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More young women being diagnosed with POTS but rural patients face extra toll

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About 800,000 people live with POTS in Australia, but with Piper living in a small regional community, knowledge of the condition was scarce and she knew no-one else with it.

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About 800,000 people live with POTS in Australia, but with Piper living in a small regional community, knowledge of the condition was scarce and she knew no-one else with it.

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https://www.abc.net.au/news/2026-08-19/pots-women-diagnosis-rural-regional-patients-healthcare-sa/107016870?

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More women being diagnosed with POTS but rural patients face extra toll

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Being diagnosed with postural orthostatic tachycardia syndrome in regional Australia means treatment is far away and local understanding of the condition is minimal.

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Congress’s 2027 budget could include new funding for Long COVID and ME

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Some 2027 budget proposals include opportunities for new Long COVID and infection-associated chronic condition (IACC) funding across the NIH, other health agencies, and the Department of Defense.

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Some 2027 budget proposals include opportunities for new Long COVID and infection-associated chronic condition (IACC) funding across the NIH, other health agencies, and the Department of Defense.

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https://thesicktimes.org/2026/08/18/congresss-2027-budget-could-include-new-funding-for-long-covid-and-me/

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The Sick Times - Chronicling the Long COVID crisis

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Congress’s 2027 budget could include new funding for Long COVID and ME - The Sick Times

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Advocates are calling on senators and representatives to include the ME/CFS Research Roadmap and new Long COVID funding in the fiscal year 2027 budget as legislators debate appropriations bills in the coming weeks.

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Is there a summer COVID-19 surge this year? Yep, it's ramping up again

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It's a big mystery as far as I'm concerned. It is the only seasonal respiratory virus that has a summer season.

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It's a big mystery as far as I'm concerned. It is the only seasonal respiratory virus that has a summer season.

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https://www.npr.org/2026/08/14/nx-s1-5927115/summer-vaccine-covid-19-surge

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Hantavirus. Ebola. West Nile. Measles. And, of course, cyclospora - that stomach parasite making people miserable across the country. Americans have plenty to worry about this summer.

But remember COVID-19? It may not be surprising that many people may have almost forgotten about COVID. Unfortunately, COVID hasn't forgotten about us.

"We're now in the midst of a growing summer surge of COVID here in the United States," says Dr. John Brooks, an infectious disease doctor at Emory University in Atlanta, Ga., who used to work at the Centers for Disease Control and Prevention. "I think most of us kind of feel like it's fading away and are certainly very grateful for that. But nationally we're seeing it ticking up pretty much everywhere."

The virus is spreading the most again in the South and West, but is also on the rise in the Northeast and Midwest. The good news is the virus is still at very low levels. And so far this summer's wave seems to be continuing the trend of getting milder each year, sending fewer people to the hospital and causing fewer deaths.

"What we're seeing is very likely evidence of growing herd immunity if you will," Brooks says. "More and more people have had one or more infections that give them some immunity against the virus and have had more than one vaccination, or maybe both. And all of that really has begun to offer us a lot of protection."

Now, that doesn't mean people don't have to worry about COVID at all anymore. The disease still makes lots of people feel awful for a week or two, foiling their summer vacations and forcing them to miss work and school.

And COVID can still cause serious disease for some people, sending them to emergency rooms, causing hospitalizations and even sometimes still causing death.

"COVID-19 is still dangerous, particularly for older adults, infants and people who are immunocompromised," says Caitlin Rivers, an epidemiologist at Johns Hopkins University in Baltimore, Md. And that is a lot of Americans. "In a typical office, if you have 20 colleagues, it's likely that one or two of them have some degree of immunocompromise. So it's very common that people have risk factors that make COVID-19 dangerous."

Unlike the flu, which only surges during the winter each year, COVID sees spikes twice a year - both in the summer and winter. The reason for that remains unclear.

"It's a big mystery as far as I'm concerned. It is the only seasonal respiratory virus that has a summer season," River says. "To my knowledge, we don't know what is causing this seasonality."

Rivers says she still masks up when she's in crowded places like busy airports, and recommends that people stay up to date on their vaccines. The next shots look like a good match for the dominant strain of COVID that's circulating and should start becoming available soon.

Unlike previous years, the CDC hasn't issued updated recommendations for the vaccines because of litigation over the Trump administration's efforts to overhaul immunizations in the U.S. The administration no longer recommends that everyone aged 6 months and older routinely get an annual shot.

But major medical groups still do recommend it. And insurers have indicated they will keep covering vaccines. The shots are likely to remain available for free through government programs like the Vaccines for Children program.

Public health experts worry that conflicting messages will cause confusion, discouraging people from getting another shot.

"The message is that COVID vaccine and flu vaccine will be available, they're covered by insurers, they're recommended by medical societies. People should get them and get them for their kids," says Clare Hannan, executive director of the Association of Immunization Managers, which advocates for immunization programs.

There's also even a, called Xocova, that people can take right after they've been exposed to the virus to cut their chances of actually getting sick from COVID.

"It is something for people to just have in the back of their mind," Brooks says. It is expected to be a useful tool in hospitals and nursing homes when exposures happen to vulnerable people.

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Is there a summer COVID-19 surge this year? Yep, it's ramping up again

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Just like all previous summers since the pandemic began, COVID-19 cases are ticking up again, even while other health threats make more headlines.

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Research, Actions to take, Press, Fact sheet, Scorecards, Newsletter, Website

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Research, Actions to take, Press, Fact sheet, Scorecards, Newsletter, Website

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https://linktr.ee/patientled

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patientled Official: TikTok, Instagram, X, Facebook | Linktree

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Long-Covid study: Gut immune system struggling to clear virus

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THE immune systems of people with long Covid may remain locked in a prolonged battle with remnants of the coronavirus, producing inflammation while failing to effectively eliminate its source, new research suggests.

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THE immune systems of people with long Covid may remain locked in a prolonged battle with remnants of the coronavirus, producing inflammation while failing to effectively eliminate its source, new research suggests.

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https://businessmirror.com.ph/2026/08/12/long-covid-study-gut-immune-system-struggling-to-clear-virus/

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Studies: Prevalence of chronic viral reactivation, treatment for post-COVID chronic cough, neuroimaging shows that ME/CFS is central in origin, Biomarkers to identify vascular changes and more...

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Studies: Prevalence of chronic viral reactivation, treatment for post-COVID chronic cough, neuroimaging shows that ME/CFS is central in origin, Biomarkers to identify vascular changes and more...

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https://longcovidweekly.substack.com/p/long-covid-weekly-188

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“Having witnessed how a single test can transform a complex disease like HIV, I am fully committed to doing my part to develop tests for Long COVID".

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“Having witnessed how a single test can transform a complex disease like HIV, I am fully committed to doing my part to develop tests for Long COVID".

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https://thesicktimes.org/2026/08/11/viper-aims-to-fast-track-long-covid-biomarkers-heres-how-it-works/

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The Sick Times - Chronicling the Long COVID crisis

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VIPER aims to fast track Long COVID biomarkers. Here’s how it works. - The Sick Times

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Led by researchers at UCSF, the research program plans to validate promising candidates for noninvasive tests that can be used to advance clinical trials.

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While many studies have indirectly suggested that energy deficits exist in the brains of people with long COVID, ME/CFS, etc., no one has directly measured them until now.

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While many studies have indirectly suggested that energy deficits exist in the brains of people with long COVID, ME/CFS, etc., no one has directly measured them until now.

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https://www.healthrising.org/blog/2026/08/02/long-covid-energy-brain/

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Long COVID Study Finds Major Energy Deficits in the Brain - Health Rising

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A long COVID study examining, for the first time, energy levels in the brain, found them to be depleted in a large region called the cingulate cortex.

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Characterizing plausible causal pathways between COVID-19 reinfections and symptom trajectories in long COVID and ME/CFS patients using digital health data

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Our findings underscore the risk of repeat infections in compounding physiological and symptomatic burden in the vulnerable Long COVID and ME/CFS populations, necessitating an integrated response that combines rigorous public health protections and equitable social policies with clinically-informed rest and pacing strategies.   N= 1179

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Our findings underscore the risk of repeat infections in compounding physiological and symptomatic burden in the vulnerable Long COVID and ME/CFS populations, necessitating an integrated response that combines rigorous public health protections and equitable social policies with clinically-informed rest and pacing strategies.   N= 1179

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https://www.nature.com/articles/s41598-026-65692-1

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Night shift workers face 88% greater risk of long COVID, study suggests

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Our findings suggest that circadian disruption plays a role in the transition from acute infection to persistent symptoms.  N=1899

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Our findings suggest that circadian disruption plays a role in the transition from acute infection to persistent symptoms.  N=1899

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https://www.cidrap.umn.edu/covid-19/night-shift-workers-face-88-greater-risk-long-covid-study-suggests

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Night shift workers face 88% greater risk of long COVID, study suggests

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People who work night shifts may face a significantly higher risk of developing long COVID, according to a study published last week in the Scandinavian Journal of Work, Environment & Health. That risk may rise even further among night shift workers who also have chronic insomnia.

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How to Manage and Treat Post Exertional Malaise (1 hour 34 mins)

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The panel shares practical approaches to pacing, reducing triggers, navigating a crash, and supporting baseline function, while also discussing emerging treatment strategies and areas of ongoing research. 

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The panel shares practical approaches to pacing, reducing triggers, navigating a crash, and supporting baseline function, while also discussing emerging treatment strategies and areas of ongoing research. 

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https://youtu.be/Na5znc92ylY?is=FnT3fK2V1tkvGiEx

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How to Manage and Treat Post-Exertional Malaise (PEM)

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Professor Rob Wüst & Professor Mark Faghy Discuss Their Work

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Professors Rob Wüst and Mark Faghy discuss biological evidence for long COVID, post-exertional malaise, patient-centred research, and the importance of collaborative, inclusive science to accelerate effective treatments and improve patient outcomes. Guest - Professor Rob Wüst & Professor Mark Faghy Note: The podcast has no bias. All conflicts of interest are highlighted with individual guests. Podcast Overview: Key Points of the Podcast This episode of Long COVID – The Answers features Professors Rob Wüst and Mark Faghy discussing advances in long COVID research and the upcoming ISLC-PAIS conference. Professor Rob Wüst explains mitochondria, post-exertional malaise (PEM), and his landmark study showing that exercise worsens mitochondrial dysfunction and muscle abnormalities in long COVID, providing biological evidence that symptoms are not psychological. Professor Mark Faghy highlights his award-winning, patient-centred research approach, where people with lived experience help shape every stage of research. He emphasizes inclusivity, safety, and collaboration to ensure studies address…

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Infection-Triggered Neurodegeneration in Long COVID: Retinal Biomarkers and Organoid Models for Mechanism and Therapy

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The team will map infection-driven neurodegenerative processes, identify candidate biomarkers, and screen for compounds capable of reversing neuronal dysfunction.

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The team will map infection-driven neurodegenerative processes, identify candidate biomarkers, and screen for compounds capable of reversing neuronal dysfunction.

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https://polybio.org/projects/infection-triggered-neurodegeneration-in-long-covid-retinal-biomarkers-and-organoid-models-for-mechanism-and-therapy/?

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Project Team

Sean J. Miller, PhD, Research Scientist in the Department of Ophthalmology and Neurology, Yale School of Medicine

Brian P. Hafler, MD, PhD, Ophthalmologist Specializing in the Treatment of Complex Retinal Diseases, Yale School of Medicine

Project Summary
This project investigates infection-triggered neurodegenerative protein aggregation as a potential driver of neurological symptoms in Long COVID. It focuses on identifying non-invasive retinal biomarkers and building human organoid models to define how persistent viral signals-such as circulating SARS-CoV-2 proteins-may induce neuronal stress, vascular dysfunction, and chronic neuroimmune activation.

To achieve this, the team combines advanced retinal imaging and electrophysiology with induced pluripotent stem cell (iPSC)-derived retinal and cortical organoids. These systems are used to detect structural and functional signatures of neuronal injury and to model how viral proteins and inflammatory signals trigger aggregation of neurodegenerative proteins such as amyloid-β and α-synuclein. By linking biomarker discovery with mechanistic modeling and drug screening, the project aims to generate actionable diagnostics and identify therapeutic strategies for neurological Long COVID.
Project Background
Neurological symptoms-including cognitive dysfunction ("brain fog"), visual disturbances, and neuropsychiatric impairment-are among the most common and debilitating features of Long COVID, yet objective biomarkers and targeted therapies remain lacking. Emerging evidence suggests that persistent viral reservoirs and circulating viral proteins can drive chronic immune activation and neuronal dysfunction, but the mechanisms linking infection to long-term neurological damage are not well understood.

This project tests the hypothesis that viral persistence can induce pathological protein misfolding and aggregation-processes classically associated with neurodegenerative diseases-and that these changes can be detected through the retina, which shares key structural and functional properties with the brain. Using multimodal retinal imaging and electroretinography alongside human organoid models, the team will map infection-driven neurodegenerative processes, identify candidate biomarkers, and screen for compounds capable of reversing neuronal dysfunction. Together, this work establishes a translational framework to diagnose, model, and treat infection-associated neurological disease in Long COVID and related conditions.

Newsletter

PolyBio scientists are active at conferences and frequent guests on podcasts. Learn more about these events, get project updates, and meet the PolyBio team via our Newsletter.

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Infection-Triggered Neurodegeneration in Long COVID: Retinal Biomarkers and Organoid Models for Mechanism and Therapy - PolyBio Research Foundation

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Project SummaryThis project investigates infection-triggered neurodegenerative protein aggregation as a potential driver of neurological symptoms in Long COVID. It focuses on...

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A lesser-known SARS-CoV-2 protein may offer clues to long COVID symptoms

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A new UCLA study describes a previously unrecognized way the SARS-CoV-2 nucleocapsid protein—a structural protein less familiar than the spike protein can push the immune system into dangerous overdrive.

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A new UCLA study describes a previously unrecognized way the SARS-CoV-2 nucleocapsid protein—a structural protein less familiar than the spike protein can push the immune system into dangerous overdrive.

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https://medicalxpress.com/news/2026-08-lesser-sars-cov-protein-clues.html?

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Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Six years after the height of the COVID-19 pandemic, scientists are still uncovering surprising ways the virus can wreak havoc on the body. A new UCLA study published in Science Advances describes a previously unrecognized way the SARS-CoV-2 nucleocapsid protein-a structural protein less familiar than the spike protein that has dominated public attention and much vaccine research-can push the immune system into dangerous overdrive.

The nucleocapsid protein's main job is to package and protect the virus's genetic material. Like several other coronavirus proteins, it's also known to suppress the body's early antiviral defenses, helping the virus get a foothold.

Scientists led by virologist Melody Li set out to see whether SARS-CoV-2's version of this immune-dampening protein worked the same way as those found in SARS and MERS, earlier coronaviruses known to cause severe disease.

"Coronaviruses are notorious for encoding proteins that antagonize the body's natural antiviral defenses," said Li, an associate professor of microbiology, immunology and molecular genetics and member of the UCLA Broad Stem Cell Research Center. "When SARS-CoV-2 first appeared, almost nothing was known about it, so we wanted to find out whether it was using the same playbook."

A hidden protein with an outsized effect

The project led the researchers to a less-explored question: how the nucleocapsid protein behaves inside macrophages. These immune cells patrol tissues for signs of infection and release chemical signals called cytokines and chemokines to rally the body's defenses.

What they found upended their original hypothesis. The nucleocapsid protein appeared to be a "double-edged sword," Li said. While it still suppressed signals that trigger an early antiviral response, it also amplified inflammatory pathways in macrophages, which can fuel tissue-damaging immune responses.

"We set out looking for a protein that suppresses the immune response, and we found the opposite," said Zhenlan Yao, co-first author of the study and a former postdoctoral researcher in Li's lab, who will soon begin a research assistant professorship at Hong Kong University. "It was surprising, but it lines up with what we already know about COVID-19: The virus dampens the immune response early on, then overactivates it later-and that's when a lot of the tissue damage happens."

The researchers examined nucleocapsid proteins from several SARS-CoV-2 variants, as well as from SARS-CoV-1 and MERS-CoV, and found the pro-inflammatory effect was conserved across pathogenic coronaviruses-with the delta variant's version proving by far the most inflammatory.

"It's a bit like a thief trying to slip past a bank's security system, but instead of staying quiet, it trips the alarm," Li said. "We don't think these viruses intend to do this-a virus's whole goal is to spread, not to make its host severely sick. But this looks like an unintended side effect that, in the case of COVID, ends up fueling the disease."

In the body, that immune "alarm" does not stay confined to macrophages. When these cells become overactivated, they release inflammatory signals that can affect nearby tissues, including the cells that line blood vessels.

Cracks in the body's protective barriers

To investigate whether those effects could help explain COVID-19 complications involving the brain and heart, the team turned to two human cell-based models: a stem cell-derived model of the blood-brain barrier and a model of the coronary artery lining.

These barriers are made of endothelial cells, which line blood vessels and help control what passes from the bloodstream into surrounding tissues. In the brain, this barrier is especially tight, helping protect delicate neural tissue from pathogens, toxins and other harmful substances.

When the researchers exposed both models to fluid containing signals from macrophages producing the delta variant's nucleocapsid protein, the heart barrier broke down significantly-a phenomenon known as vascular leakage.

Because the heart depends on tight, selective blood vessel linings to function normally, the finding points to a possible mechanism that could help explain the cardiac injury seen in severe cases of COVID-19.

Rethinking how severe COVID-19 is treated

The findings also suggest a path toward more targeted COVID-19 treatments.

Severe cases can be treated with broad anti-inflammatory drugs like corticosteroids, which dampen harmful inflammation but do not specifically target the viral mechanisms that may be driving it. A therapy or vaccine that targets the nucleocapsid protein, Li said, could potentially rein in hyperinflammation more precisely and, in doing so, help protect the blood vessel barriers that support brain and heart health.

And because macrophages play a similar double-edged role in many infections beyond COVID-19, she said, the same mechanism could turn out to matter well beyond this one virus.

"It's critical to keep studying COVID-19 so that we can constantly improve patient care-not everyone responds well to vaccines, and people who are immunocompromised often have limited treatment options," said Pablo Alvarez, co-first author of the study and a former graduate student in Li's lab. "These studies can also help us prepare for future coronavirus outbreaks."

Publication details

Zhenlan Yao et al, SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages, Science Advances (2026). DOI: 10.1126/sciadv.aea2780

Journal information: Science Advances

Key medical concepts

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A lesser-known SARS-CoV-2 protein may offer clues to long COVID symptoms

# data[].attributes.attachment_link.description
Six years after the height of the COVID-19 pandemic, scientists are still uncovering surprising ways the virus can wreak havoc on the body. A new UCLA study published in Science Advances describes a previously unrecognized way the SARS-CoV-2 nucleocapsid protein-a structural protein less familiar than the spike protein that has dominated public attention and much vaccine research-can push the immune system into dangerous overdrive.

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By studying the health records of millions of people across the United States, RECOVER researchers helped uncover initial discoveries about Long COVID and contributed findings that shaped the next phases of the initiative’s research.

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By studying the health records of millions of people across the United States, RECOVER researchers helped uncover initial discoveries about Long COVID and contributed findings that shaped the next phases of the initiative’s research.

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https://recovercovid.org/news/recovers-electronic-health-record-study-revealed-early-answers-about-covid-and-long-covid?

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RECOVER: Researching COVID to Enhance Recovery

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RECOVER’s electronic health record study revealed early answers about COVID and Long COVID

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RECOVER’s electronic health record study, which completed analyses in May, examined the health data of over 60 million people to advance Long COVID research.

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Impact of SARS-CoV-2 variants and demographic factors on COVID-19 severity in pediatric patients

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This study examined the associations between SARS-CoV-2 variants, demographic factors, and COVID-19 severity in a large diverse pediatric population. N=14,292 EHRs

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This study examined the associations between SARS-CoV-2 variants, demographic factors, and COVID-19 severity in a large diverse pediatric population. N=14,292 EHRs

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https://recovercovid.org/publications/impact-sars-cov-2-variants-and-demographic-factors-covid-19-severity-pediatric?utm_source=ACC+Communicat

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RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.title
RECOVER: Researching COVID to Enhance Recovery

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The long-term effects of COVID are real. Join the NIH in the search for answers.

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Functional outcomes of children after SARS-CoV-2 infection: An EHR-based cohort study

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This study is important because it highlights that doctors should ask about school, daily activities, and emotional well-being when caring for young people who've had COVID-19.  N=686

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This study is important because it highlights that doctors should ask about school, daily activities, and emotional well-being when caring for young people who've had COVID-19.  N=686

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https://recovercovid.org/publications/functional-outcomes-children-after-sars-cov-2-infection-ehr-based-cohort-study?

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RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.title
RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.description
The long-term effects of COVID are real. Join the NIH in the search for answers.

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RECOVER: Researching COVID to Enhance Recovery HomeMenu FindingsPublicationsSSRI/SNRI and Long COVID in children and adolescents with neuropsychiatric conditions: A cohort study from the RECOVER Initiative

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These findings are important because they suggest that children, teens, and young adults taking SSRIs or SNRIs may experience different long-term symptoms after getting COVID-19, which doctors should monitor.  N= 110K EHR's

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These findings are important because they suggest that children, teens, and young adults taking SSRIs or SNRIs may experience different long-term symptoms after getting COVID-19, which doctors should monitor.  N= 110K EHR's

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https://recovercovid.org/publications/ssrisnri-and-long-covid-children-and-adolescents-neuropsychiatric-conditions-cohort

EHR's= Electronic Health Records

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RECOVER: Researching COVID to Enhance Recovery

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Short Summary
This summary was prepared by the RECOVER Initiative.

Publication Details

DOI: 10.1038/s44220-026-00675-9

Abstract

Long COVID has been an important health concern in children and adolescents, yet factors associated with its development remain incompletely understood. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for pediatric neuropsychiatric conditions and may influence immune and autonomic pathways involved in postinfectious symptoms. Here we show associations between SSRI/SNRI use and Long coronavirus disease (COVID)-related outcomes in a retrospective cohort of 110,955 children and adolescents with pre-existing neuropsychiatric conditions across 37 US health systems participating in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) consortium. SSRI/SNRI use was not associated with clinician-recorded Long COVID diagnosis but showed heterogeneous associations with individual symptoms. Lower risks were observed for some symptoms, including fever, chills, and hair loss, whereas higher risks were observed for neurological and systemic outcomes, including postural orthostatic tachycardia syndrome (POTS), cognitive dysfunction, and fatigue. These findings suggest that antidepressant exposure may be associated with differing post-COVID symptom patterns in youth and warrant further investigation.

Authors

Ting Zhou, Bingyu Zhang, Yiwen Lu, Jiajie Chen, Chengxi Zang, Haoyang Li, Josephine Elia, Raghuram Prasad, Jonathan Arnold, Sean N. Avedissian, L. Charles Bailey, Michael J. Becich, Wyatt P. Bensken, Yuriy Bisyuk, H. Timothy Bunnell, Leah Castro, Elizabeth A. Chrischilles, Dimitri A. Christakis, Lindsay G. Cowell, Mollie R. Cummins, Soledad Fernandez, Daniel Fort, Sandy Gonzalez, Sharon J. Herring, Mady Hornig, Wenke Hwang, Nita Jain, W. Schuyler Jones, David C. Kaelber, Kelly Kelleher, Rachel Kenney, John E. Leikauf, Rebecca Letts, Mei Liu, Aaron Thomas Martinez, Heidi T. May, Abu Saleh Mohammad Mosa, Nathan M. Pajor, Suchitra Rao, Amy L. Salisbury, Srinivasan Suresh, Aparna C. Swaminathan, Bradley W. Taylor, Neena Anne Thomas, David A. Williams, Margot Gage Witvliet, Rainu Kaushal, Fei Wang, Christopher B. Forrest, Yong Chen

Keywords

Not available

# data[].attributes.attachment_link.title
RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.description
Long COVID has been an important health concern in children and adolescents, yet factors associated with its development remain incompletely understood

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New research: muscle problems in post-COVID and ME/CFS cannot be explained by prolonged inactivity

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There are indications of abnormalities in muscle fibers, energy production, and oxygen supply. Our study underscores that patients should not be treated as if they have merely lost fitness.

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There are indications of abnormalities in muscle fibers, energy production, and oxygen supply. Our study underscores that patients should not be treated as if they have merely lost fitness.

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https://www.amsterdamumc.org/nl/vandaag/nieuw-onderzoek-spierproblemen-bij-post-covid-en-mecvs-zijn-niet-te-verklaren-door-langdurige-inactiviteit?

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Nieuw onderzoek: spierproblemen bij post-covid en ME/CVS zijn niet te verklaren door langdurige inactiviteit | Amsterdam UMC

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De verminderde inspanningscapaciteit en spierklachten bij mensen met post-covid en ME/CVS (Myalgische Encefalomyelitis/Chronisch Vermoeidheidssyndroom ) zijn niet simpelweg te verklaren door een slechte conditie of langdurige inactiviteit. De spieren van deze patiënten werken op meerdere punten anders dan die van gezonde mensen die langdurig inactief zijn geweest. Dat blijkt uit nieuw onderzoek van de Vrije Universiteit Amsterdam en Amsterdam UMC. De resultaten van het onderzoek staan vandaag in Nature Communications.

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2 Events: Patients to Researchers Roundtable, and Truvaga Vagal Nerve Stim Signal Search for ME/LC - an informal observational project

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2 Events: Patients to Researchers Roundtable, and Truvaga Vagal Nerve Stim Signal Search for ME/LC - an informal observational project

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https://www.renegade-research.org/events-list

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Upcoming Clinician’s and Research Roundtables featuring doctors and other practitioners, scientists, deeply familiar with ME/CFS, Long Covid, and/or overlapping conditions including MCAS, EDS/HSD, POTS and Orthostatic Intolerance, venous compression, CCCI/AAI and more.

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COVID-19 can wake up dormant viruses in the body, large study confirms

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Virus reactivations by SARS-CoV-2 could worsen initial symptoms and increase risk of Long Covid.  N= ~1K

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Virus reactivations by SARS-CoV-2 could worsen initial symptoms and increase risk of Long Covid.  N= ~1K

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https://www.science.org/content/article/covid-19-can-wake-dormant-viruses-body-large-study-confirms?

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New curriculum empowers future healthcare providers to recognize and treat Long COVID

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Together, they created LEARN, a free, multidisciplinary curriculum for medical trainees and practicing healthcare providers.

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Together, they created LEARN, a free, multidisciplinary curriculum for medical trainees and practicing healthcare providers.

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https://recovercovid.org/news/new-curriculum-empowers-future-healthcare-providers-recognize-and-treat-long-covid

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RECOVER: Researching COVID to Enhance Recovery

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New curriculum empowers future healthcare providers to recognize and treat Long COVID

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A free online curriculum called LEARN prepares future healthcare providers to care for people with Long COVID. Built by doctors and students at 2 RECOVER study sites, LEARN bridges a gap some medical trainees see in their training.

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Long COVID curriculum, Pressbooks, Washington state

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LEARN Long COVID: Understand the fundamentals of SARS-CoV2 transmission, infection, and post-infectious sequelae

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LEARN Long COVID: Understand the fundamentals of SARS-CoV2 transmission, infection, and post-infectious sequelae

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https://uw.pressbooks.pub/learnlongcovid/front-matter/welcome/

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Null results provide “equally important” information letting us know where the path does not lead but also allowing us to sharpen the questions that we’ll ask for the next possible treatments tested".

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Null results provide “equally important” information letting us know where the path does not lead but also allowing us to sharpen the questions that we’ll ask for the next possible treatments tested".

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https://recovercovid.org/r3-seminar-series/recover-clinical-trial-results-and-pursuit-long-covid-treatments?

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RECOVER: Researching COVID to Enhance Recovery

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During the July 14 RECOVER Research Review (R3) Seminar, panelists Craig Reist, PhD; David S. Knopman, MD; and Pam R. Taub, MD, shared findings from the RECOVER Clinical Trials (RECOVER-CT) program, the initiative's first wave of clinical trials. The trials focused on Long COVID symptoms related to thinking and memory, as well as the autonomic nervous system, which controls body functions like heart rate and blood pressure. RECOVER-CT Engagement Lead, Renee Leverty, MA, BSN, and Patient Representative Marta Cerda, JD, also explained how patient, caregiver, and community input shaped the trial design process.

RECOVER-CT designed clinical trials around symptom clusters

Dr. Reist (RTI International) provided an overview of the RECOVER-CT program. He explained that trial study plans (platform protocols) were organized around symptom clusters or biological mechanisms (processes that take place inside the body and its cells) to test different possible treatments.

A committee at the National Institutes of Health (NIH) reviewed over 200 possible treatments submitted by clinicians and researchers and prioritized RECOVER-CT interventions (potential therapies). He noted that the trial designs reflected the knowledge available when they were chosen in 2022 and 2023, a time when Long COVID was still a new disease.

Based on findings from RECOVER observational studies and input from clinicians, experts, and Patient, Caregiver, and Community Representatives, RECOVER-CT identified 5 focus areas (symptom clusters) for the trials:

1. Cognitive dysfunction (RECOVER-NEURO): Brain fog, trouble thinking clearly, memory changes, slowed attention, and other symptoms related to brain function.

2. Autonomic dysfunction (RECOVER-AUTONOMIC): Dizziness, fast heart rate, shortness of breath, upset stomach, or other changes in body functions that happen automatically.

3. Viral persistence (RECOVER-VITAL): Damage to organs or dysfunction of the immune system caused when the virus that causes COVID-19 stays in the body.

4. Sleep disturbances (RECOVER-SLEEP): Changes in sleep patterns or ability to sleep.

5. Exercise intolerance and fatigue (RECOVER-ENERGIZE): Exhaustion or low energy that interferes with daily activities.

Studying 3 non-drug interventions for improving cognitive symptoms

Dr. Knopman (Mayo Clinic) presented results from RECOVER-NEURO, a trial which studied the effect of non-drug treatments on the cognitive symptoms of Long COVID. The trial, published in JAMA Neurology in November 2025, recruited 328 adults across 22 study sites in the United States. Participants had SARS-CoV-2 infections at least 12 weeks prior to enrollment and self-reported cognitive symptoms.

The study team tested 3 interventions delivered remotely over 10 weeks:

An interactive online brain-training program (BrainHQ).

A mild electric current delivered to the scalp to stimulate the brain while participants use BrainHQ (transcranial direct current stimulation, or tDCS).

A cognitive rehabilitation program with trainings, discussions, and focus groups (PASC-CoRE).

Dr. Knopman shared that the findings from the trial showed that the 3 interventions were not effective in improving cognitive symptoms of Long COVID when compared to people who did not receive the interventions (comparator groups). However, all comparator and intervention groups showed improvement over the course of the trial, including improvement with post-exertional malaise (PEM)-and continued to improve slightly even 3 months later. Dr. Knopman added that detecting a benefit from the interventions was challenging because participants in all 5 groups improved.

Testing effectiveness of ivabradine for post-COVID POTS

Dr. Taub (University of California San Diego Health System) shared results from the RECOVER-AUTONOMIC (Ivabradine) trial, which tested whether ivabradine-a drug that lowers heart rate without lowering blood pressure-could help manage postural orthostatic tachycardia syndrome (POTS), an autonomic nervous system disorder marked by fast heart rate and orthostatic intolerance (dizziness and fatigue when standing up). She noted that roughly 31% of people with Long COVID develop POTS, but there have been very few randomized trials to treat POTS, and even fewer to treat Long COVID-related POTS.

The study, first presented at the 2026 American College of Cardiology conference, is the largest study to date in patients with POTS. It randomized 181 adults with Long COVID-related POTS to either ivabradine or placebo, with a second randomization to receive coordinated non-drug care (regular check-ins with a care coordinator plus lifestyle and equipment support) or usual care. Dr. Taub noted that study participants who received ivabradine received a lower dose of the drug compared with a pilot study. Researchers anticipated older adults participating in the study and were concerned about ivabradine lowering participants' heart rate too much.

Although RECOVER-AUTONOMIC results showed that ivabradine significantly lowered heart rate, it did not significantly improve patient-reported orthostatic intolerance. Notably, participants who received ivabradine combined with coordinated care reported greater improvement than those who received ivabradine with usual care. Dr. Taub noted future opportunities to study ivabradine's impact on people with Long COVID-related POTS, including studying higher doses of the drug and whether different groups of people may benefit more.

Null results moving science toward possible Long COVID treatments

The panelists emphasized that even when possible treatments do not show a benefit, clinical trial results still deliver valuable knowledge. Null results provide "equally important" information, Dr. Reist said, "letting us know where the path does not lead but also allowing us to sharpen the questions that we'll ask for the next possible treatments tested."

Dr. Taub compared the effort to the study of other medical conditions. Heart failure with preserved ejection fraction, a condition where the heart squeezes normally but does not fill properly, required decades of null trials before leading to an FDA-approved therapy.

"When you look at clinical trials in general, it's a lot of learning and sometimes it takes multiple trials to really get the design down," she noted. "We had a great comment from the audience that just because a trial is null, it doesn't mean that the therapy doesn't work. It could be that the design wasn't optimal." Dr. Knopman added that a central challenge in cognitive Long COVID is that the underlying biology remains unclear, which makes designing effective treatments difficult. "Until the biology is better understood, I think it's going to be a challenge to move ahead," he said.

Dr. Reist confirmed that data from these trials will be made available to other researchers through NHLBI BioData Catalyst®, a secure, cloud-based ecosystem managed by the National Heart, Lung, and Blood Institute (NHLBI), so future analyses will expand beyond the original trial teams.

Learning from Patient Representatives' past engagement to inform future research

Ms. Leverty (Duke Clinical Research Institute) and Ms. Cerda (RECOVER Patient Representative) shared findings from a study published in the Journal of Clinical and Translational Science on how RECOVER researchers and Representatives worked together to develop study plans for clinical trials.

RECOVER Representatives were included as core members of RECOVER-CT Protocol Working Groups (PWGs) along with scientific research experts. Ms. Leverty highlighted the importance of having Long COVID patients be a part of study leadership or engagement teams. The PWGs reviewed and provided feedback on the program's study plans and weighed in on eligibility criteria, endpoints (what the trials are measuring), visit schedules, participant burden, compensation, and informed consent to participate in the study.

An anonymous survey distributed to PWG members found that 82% of Representatives felt their contributions were meaningful and valued by RECOVER. However, experiences of inclusion varied, with 21% reporting low inclusion and 46% reporting high inclusion. Representatives' advice to researchers and funders included incorporating patient voices early, communicating roles clearly and often, ensuring representation reflects the broader patient population, training study teams on valuing patient input, and creating clear pathways for incorporating feedback.

Ms. Cerda, who served on the Clinical Trials Steering Committee and the RECOVER-VITAL PWG, shared her positive experience. She said she not only learned more about her own dysautonomia and POTS through her participation but also felt her patient perspective was valued by researchers when providing inputs. "Meaningful Representative engagement in rapid trial protocol development is both feasible and valuable," she said, emphasizing that clarity in roles, transparent decision-making, and intentional communication are essential.

Uncovering more answers about Long COVID

Both Ms. Cerda and Ms. Leverty acknowledged the disappointment that comes with null trial results when patients are urgently seeking answers-but also expressed hope for what is ahead. "We are so looking for any hope...and I do see hope [for clinical trial treatments] in the horizon," said Ms. Cerda, who is 6 years into her Long COVID journey.

Dr. Reist pointed to the next wave of RECOVER clinical trials through the RECOVER-Treating Long COVID (RECOVER-TLC) program. RECOVER-TLC will begin recruiting participants for 3 clinical trials this year, with enrollment for the REVERSE-LC study already open. Dr. Taub also encouraged patients to explore opportunities on ClinicalTrials.gov, which lists NIH, industry, and academic trials.

To find recordings and transcripts from previous R3 Seminars, visit the R3 Seminar Series webpage or the RECOVER YouTube channel.

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RECOVER clinical trial results and the pursuit of Long COVID treatments

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During the July 14 RECOVER Research Review (R3) Seminar, panelists Craig Reist, PhD; David S. Knopman, MD; and Pam R. Taub, MD, shared findings from the RECOVER Clinical Trials (RECOVER-CT) program, the initiative's first wave of clinical trials.

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New Study Identifies Overlapping Persistent Virus-Specific T Cell Responses in Long COVID

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PolyBio-supported research provides new evidence that Long COVID is characterized by ongoing immune responses to persistent viral proteins, further supporting the role of viral persistence and herpesvirus reactivation in the disease process.

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PolyBio-supported research provides new evidence that Long COVID is characterized by ongoing immune responses to persistent viral proteins, further supporting the role of viral persistence and herpesvirus reactivation in the disease process.

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https://polybio.org/new-study-identifies-overlapping-persistent-virus-specific-t-cell-responses-in-long-covid/?

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New Study Identifies Overlapping Persistent Virus-Specific T Cell Responses in Long COVID - PolyBio Research Foundation

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PolyBio-supported research provides new evidence that Long COVID is characterized by ongoing immune responses to persistent viral proteins, further supporting the…

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One of the hardest things about having Long COVID is how painfully slow progress towards answers and treatments is

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I’d like to share some initiatives, studies, and trials I am watching and feeling hopeful will help us assemble some puzzle pieces as a patient-communicator.

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I’d like to share some initiatives, studies, and trials I am watching and feeling hopeful will help us assemble some puzzle pieces as a patient-communicator.

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https://open.substack.com/pub/connectivedigest/p/5-things-happening-behind-the-scenes?

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5 Things Happening Behind the Scenes in Long COVID Research That Give Me Hope

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One of the hardest things about having Long COVID is how painfully slow progress towards answers and treatments is and often, because a lot of work is behind the scenes or ongoing, it can feel completely stagnant as we wait for help we needed years ago.

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Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest

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As skeletal muscle characteristics differ between patients and healthy individuals after bed rest, physical inactivity cannot solely explain the lower exercise capacity and skeletal muscle adaptations in long COVID and ME/CFS patients.

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As skeletal muscle characteristics differ between patients and healthy individuals after bed rest, physical inactivity cannot solely explain the lower exercise capacity and skeletal muscle adaptations in long COVID and ME/CFS patients.

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The findings align with previous research suggesting that racial and ethnic bias among healthcare providers often influences patient care, and it highlights the need for improved equity in healthcare settings.

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The findings align with previous research suggesting that racial and ethnic bias among healthcare providers often influences patient care, and it highlights the need for improved equity in healthcare settings.

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https://www.cidrap.umn.edu/covid-19/many-black-us-patients-long-covid-being-missed-analysis-reveals

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Many Black US patients with long COVID being missed, analysis reveals

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A new study suggests that Black patients with acute COVID-19 infection are less likely to be diagnosed as having long COVID than White patients, despite no significant difference in long-COVID symptom burden between the two groups.

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The (sick) kids aren’t alright: Observations from a teacher with Long COVID

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The quiet normalization of COVID-19 in our society has come at the great expense of school-age children and adolescents. 

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The quiet normalization of COVID-19 in our society has come at the great expense of school-age children and adolescents. 

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https://thesicktimes.org/2026/07/24/the-sick-kids-arent-alright-observations-from-a-teacher-with-long-covid/

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The Sick Times - Chronicling the Long COVID crisis

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A few months ago, one of my math students mentioned having virtually no sense of smell after more than three confirmed SARS-CoV-2 infections.

Since 2020, disease has held a constant, detrimental grip on classrooms across K-12 (and higher) education. After school holidays, I often heard coughing down the hallway for days, if not weeks. There were many days where classes had only half of their students in attendance. Even our most senior teachers constantly fought to help students retain material for a week, let alone a semester.

The quiet normalization of COVID-19 in our society has come at the great expense of school-age children and adolescents. As a teacher with Long COVID who recently left in-person work after two years in my most recent position - a decision that ultimately came down to my own health and well-being - I observed concerning student behaviors that cannot solely be chalked up to technology, "immunity debt," or whatever else pundits have blamed.

I am certain that many of my former students are among the millions with Long COVID. A study in the journal Pediatrics estimated as many as 5.8 million children were affected in the U.S. as of early 2024 - already outpacing the 4.9 million children with asthma, formerly the most common pediatric health condition. Other studies suggest that reinfections can increase the risk of developing long-term symptoms, and that Long COVID can occur even after asymptomatic cases.

Academically speaking, the neurological challenges are among the most concerning Long COVID effects. The cocktail of COVID-19 and other pathogens that ran through my school every week, not just in the winter, kept students sicker and sicker - not for a day or two, but often for over a week at a time, sometimes more than once a quarter.

When students are consistently tired, struggling to keep track of basic conversation, and unable to focus, it's no wonder that they often miss school. One 2025 study concluded that children with Long COVID were more than twice as likely to experience "illness-related chronic absenteeism" than those without, defined by at least 18 missed school days in 12 months. Studies like these can also leave out students pressured to attend school due to stringent attendance policies at public schools, especially in the U.S.

Aside from the missed material in class itself, multiple students returned from sick days with what I have called "cognitive shell shock": large and sudden gaps in prior knowledge and a deep, constant exhaustion in the classroom. For some of these students, trying to be aware and mentally present with friends at school became a Herculean feat in and of itself.

For some of these students, trying to be aware and mentally present with friends at school became a Herculean feat in and of itself.

The documented increase of COVID-linked " neuropsychiatric" diagnoses and the increased percentages of students eligible for disability support go hand in hand. In at least one of my classes, more than half the students had documented accommodations. Many of the practices behind these accommodations spread to my entire class by necessity. Though I am a strong advocate for these supports and for inclusive learning, I frequently worried about their needs and difficulties becoming impossible to manage, even in a more accessible, accommodating world.

For example, one of my students started having migraines in her preteen years - accompanied by nausea, vomiting, and extreme light sensitivity - after contracting COVID-19. It is a miracle she accomplished anything in the fluorescent purgatory of our school.

Some students have food-related symptoms, such as excessive abdominal pain and related gastrointestinal symptoms that keep them from eating a meal, let alone learning and working. Others still have extreme food sensitivities. After returning from a period of illness, a student of mine relayed efforts to our staff of trying multiple diets for foods she could tolerate again, as most of her previously safe foods were no longer tolerable. One diet she tried was gluten-free; research has suggested that COVID-19 may be associated with higher rates of celiac disease in children.

Food sensitivities like these could also potentially be associated with mast cell activation syndrome (MCAS) and related conditions. These strong histamine reactions can include many categories of debilitating symptoms, far beyond the typical ones associated with food or seasonal allergies. Some of my students with chronic issues found themselves in the restroom for ten minutes or more every period, even though they cared deeply about learning and being in the classroom.

It would be wrong of me to argue that everything I have cited is caused exclusively by COVID-19. At the same time, research has suggested that mental health worsens directly after SARS-CoV-2 infection, including (but not limited to) the manifestation of mood swings.

I found myself unexpectedly emotionally regulating my classroom daily, on top of the over 1,000 decisions that come with a day of classroom management. My older students could not persist through difficult feelings, redirect attention to their work after interruption, or push through grade-level academic challenges. My students were passionate about the world around them and hyperaware of it because of the internet, but they could not build the skills to critically analyze potential misinformation or correctly interpret statistics.

What can we do to support children who already have Long COVID and keep all children in better health? We gain nothing from spiraling, though I spent many a planning period doing just that. I suggest two pathways of action and advocacy for schools:

First, speak directly with teachers and school officials about student illness and its impact.

Many teachers have numbed themselves to the problem of chronic illness in the classroom. Others do not feel safe self-advocating out of fear of accusations of politicization or risk to their employment. This was a great risk that I faced: Many parents would not speak with me directly or respect me because I masked daily in the classroom.

Teachers and administrative school officials may be more willing to provide support when they have resources and toolkits at their disposal. Long COVID Kids has created an educational toolkit of videos about Long COVID in the school system, and the RECOVER initiative hosts a wealth of relevant pediatric research studies.

As some schools, especially public schools, have stringent attendance policies that cannot be easily overcome, administrators could reduce transmission rates by supporting teachers in accommodating students who are sick at home. This could include sending material home with appropriate audio-visual supports, having reasonable deadline flexibility, or other actions as discussed and agreed upon by students, parents, teachers, and administrators. Proper understanding and appreciation for this issue may open advocacy for other actions, such as students wearing face masks when experiencing symptoms of illness, or teachers wearing masks themselves. Many public schools also have unions, which could be rallied to support and protect COVID-cautious actions.

Many parents would not speak with me directly or respect me because I masked daily in the classroom.

Second, advocate to parents and school boards for clean air.

Clean air has been important for classroom health and wellness long before 2020. Studies have shown that higher air filtration in schools significantly reduces student absence rates and improves test scores. It can also reduce pollution exposure. One study even calculated a " cost per absence day " for sick students, a tangible number that any stakeholder could be forced to confront.

Most teachers would be quite pleased to receive an air purifier donation to their classroom, especially if replacement filters are provided. You may connect with a larger group of interested and supportive parents by attending a school board meeting. If you are worried that the word "COVID" will lead others to dismiss you, consider advocating for clean air from the angle of keeping students healthy, at school, and learning. Then, connect them with funding supporters, such as Clean Air for Schools, Purifan, and the Foundation for Clean Air, to remove or reduce the financial burden.

Additionally, consider making it personal to the extent that you are comfortable. When I have mentioned that I am immunocompromised to parents and colleagues, I have found increased support - and this sometimes has allowed me to engage with them in curious, nonjudgmental conversation about how their health has changed in the last six years.

A better world is possible, though I am sorry we have to fight for it this much. Many of my former students are passionate, thoughtful people. They want things to be better, but drown in the torrent of nihilistic news about everything, everywhere, all the time. On top of this sense of helplessness, their own health and wellness are often completely out of their hands. Parents often override children's wishes to rest and take care of themselves, whether out of necessity or personal insistence.

In a time where teenagers have very few safe spaces left, let alone ones that promote standards of health and safety, school may be one of the only avenues for us to uphold the best living conditions possible. If we want kids to have the opportunity to learn, to grow, to be, then we must do what we can to keep them alive and well. To quote Madeline Lane-McKinley from her book Solidarity with Children, "We cannot allow ourselves or each other to surrender the future."

If we want kids to have the opportunity to learn, to grow, to be, then we must do what we can to keep them alive and well. To quote Madeline Lane-McKinley from her book Solidarity with Children, "We cannot allow ourselves or each other to surrender the future."

Flynn Lovelace (he/him) is an instructor and Long COVID advocate in the United States. You can follow him on and .

All articles by The Sick Times are available for other outlets to republish free of charge. We request that you credit us and link back to our website.

The Sick Times is dedicated to independent Long COVID journalism, without denial, minimizing, or gaslighting.
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Help us produce more unique news and commentary stories like this one.

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The (sick) kids aren't alright: Observations from a teacher with Long COVID - The Sick Times

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This section provides guidance on recognizing PEM in pediatric patients, pacing strategies tailored to age and developmental level, and communication approaches that empower both the child and family to participate in care planning.

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Disability-focused career paths can show up in different ways. Whether you are a researcher who studies public health disparities, a medical doctor who treats patients with disabilities or the head of a state-run agency that works to advance health policy initiatives for the disability population — each is important. Although these roles look different on […]

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Northwestern Medicine study finds women experience more severe neurological symptoms of long COVID than men

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The new study published showed for the first time that women report more neurologic symptoms of long COVID and experience worse impacts on quality of life and cognitive function than men. 

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The new study published showed for the first time that women report more neurologic symptoms of long COVID and experience worse impacts on quality of life and cognitive function than men. 

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Northwestern Medicine study finds women experience more severe neurological symptoms of long COVID than men

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July 21, 2026 – A new study from Northwestern Medicine shows that adult women experience more severe neurological symptoms of long COVID than adult men.While past studies have found that women are more frequently affected by long COVID than men, the new study published today in the Annals of Clinical and Translational Neurology…

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Evaluation of orthostatic dizziness and lightheadedness in older adults: symptoms not to be taken lightly

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Orthostatic symptoms can arise from the interaction of age-related changes in cardiovascular and autonomic regulation, multiple medical conditions, polypharmacy, reduced baroreflex sensitivity and impaired cerebral autoregulation.

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Orthostatic symptoms can arise from the interaction of age-related changes in cardiovascular and autonomic regulation, multiple medical conditions, polypharmacy, reduced baroreflex sensitivity and impaired cerebral autoregulation.

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https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1803374/full

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Frontiers | Evaluation of orthostatic dizziness and lightheadedness in older adults: symptoms not to be taken lightly

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Orthostatic dizziness and lightheadedness are frequent complaints in patients age 60 and above, whereas various common and uncommon etiologies need to be con…

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Plasma Cytokine and Caspase-1p20 Profiles in Pre-Pandemic and Long COVID-Associated Postural Orthostatic Tachycardia Syndrome

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These findings suggest an immunological relationship between primary viral insult and chronic dysautonomia, suggesting that clinical successes in Long COVID research may be applicable to the broader POTS population.  N=236

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These findings suggest an immunological relationship between primary viral insult and chronic dysautonomia, suggesting that clinical successes in Long COVID research may be applicable to the broader POTS population.  N=236

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https://www.mdpi.com/2227-9059/14/7/1605?

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William T. Gunning and John W. Spatafore and Michael P. Morran and Beverly L. Karabin and Benjamin R. Hart and Blair P. Grubb

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Plasma Cytokine and Caspase-1p20 Profiles in Pre-Pandemic and Long COVID-Associated Postural Orthostatic Tachycardia Syndrome

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Background: Prior to the COVID-19 pandemic, the etiology of postural orthostatic tachycardia syndrome (POTS) remained elusive. Since the pandemic, a newly recognized disorder, termed Long COVID, has emerged with a significant subset of patients developing dysautonomia and a multitude of comorbidities consistent with POTS. Aim: The aim of this study was to determine if pre-pandemic POTS and Long COVID POTS share a common inflammatory-associated biomarker profile. Methods: Volunteers were recruited for four study groups; patients diagnosed with POTS prior to the pandemic, Long COVID-associated POTS, SARS-CoV-2-recovered controls, and naïve controls. All participants completed a COMPASS-31 survey and a medical history questionnaire. Plasma biomarkers of the innate and adaptive immune system were quantified using a custom multiplex bead assay and ELISAs. Results: Both POTS cohorts demonstrated indistinguishable and significant elevations in 14 of the 15 measured biomarkers including markers of the NLRP3 axis (Caspase-1p20, interleukins IL-1β, IL-18), regulatory cytokine IL-10, and immune activation markers (sCD40L, sCD40, sCD30) compared to controls. Multivariate PERMANOVA analysis revealed no significant difference in global cytokine profiles between the two POTS cohorts. Random Forest classification accurately distinguished POTS from controls, with IL-18 emerging as the most important feature. Conclusions: These associative findings suggest that pre-pandemic POTS and Long COVID-associated POTS share a distinct inflammatory profile among measured cytokines. The identification of IL-18 as a key biomarker, alongside Caspase-1p20 and other inflammatory cytokines, are compatible with inflammasome-related signaling. Further investigation is necessary to characterize the role of the inflammasome, platelet activation, and immune dysregulation in POTS and Long COVID.

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Drug manufacturers have quietly discontinued trials in long COVID and related illnesses, leaving patients in the lurch.

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Drug manufacturers have quietly discontinued trials in long COVID and related illnesses, leaving patients in the lurch.

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https://cen.acs.org/pharmaceuticals/drug-development/long-covid-pots-mecfs-drug-trials-ethics/104/web/2026/07

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Access to potential long COVID drugs dwindles as trials falter

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Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection

# data[].attributes.headline
Our study shows that the antibody repertoire in children varies with the clinical presentation of SARS-CoV-2. 

# data[].attributes.subject
Our study shows that the antibody repertoire in children varies with the clinical presentation of SARS-CoV-2. 

# data[].attributes.body
https://recovercovid.org/publications/antibody-repertoire-associated-clinically-diverse-presentations-pediatric-sars-cov-2?utm_source=ACC+Communications&utm_campaign=bf8fd634a1-RECOVER_REPORT_JUNE_2026_COPY_01&utm_medium=email&utm_term=0_-a1c4c7645f-602921403

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RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.title
RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.description
The long-term effects of COVID are real. Join the NIH in the search for answers.

# data[].attributes.headline
RECOVER Patient, Caregiver, and Community Representatives continue to inform and contribute to RECOVER research in concrete ways, and  help make sure the experiences and needs of people living with Long COVID are reflected in the initiative’s work.

# data[].attributes.subject
RECOVER Patient, Caregiver, and Community Representatives continue to inform and contribute to RECOVER research in concrete ways, and  help make sure the experiences and needs of people living with Long COVID are reflected in the initiative’s work.

# data[].attributes.body
https://recovercovid.org/news/recover-mid-year-2026-progress-and-whats-ahead#representatives

# data[].attributes.attachment_link.provider_name
RECOVER: Researching COVID to Enhance Recovery

# data[].attributes.attachment_link.title
RECOVER at mid-year: 2026 progress and what’s ahead

# data[].attributes.attachment_link.description
In 2026 so far, RECOVER has published new research findings across nearly all its different studies and will soon be enrolling participants for the next phases of the adult observational study and clinical trials.

# data[].attributes.attachment_link.title
Repurposing Rapamycin: A Report On the First Biomarker-Driven Treatment Trial for ME/CFS

# data[].attributes.attachment_caption
SARS-CoV-2 spike-driven reactivation of latent herpesviruses as a mechanistic link to post-viral diseases

# data[].attributes.headline
Evidence reviewed is consistent with a model in which long COVID may represent a ME/CFS-like biology, showing PEM, dysautonomia, cognitive dysfunction, and profound fatigue potentially associated with persistent SARS-CoV-2 antigenic signaling (particularly spike) that sustains TLR2/TLR4-MyD88-NF-κB/IL-6 inflammation, disrupts mitochondrial bioenergetics and immunometabolism, and promotes immune exhaustion.

# data[].attributes.subject
Evidence reviewed is consistent with a model in which long COVID may represent a ME/CFS-like biology, showing PEM, dysautonomia, cognitive dysfunction, and profound fatigue potentially associated with persistent SARS-CoV-2 antigenic signaling (particularly spike) that sustains TLR2/TLR4-MyD88-NF-κB/IL-6 inflammation, disrupts mitochondrial bioenergetics and immunometabolism, and promotes immune exhaustion.

# data[].attributes.body
https://www.cell.com/trends-open/fulltext/S3117-3470(26)00049-0

# data[].attributes.attachment_caption
West Virginia Has One of the Highest Chronic Disease Burdens in the Nation. Congress Has a Plan to Address One of the Worst. It Just Hasn’t Funded It. 

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Physicians across this state are seeing patients who cannot recover from an illness, whose fatigue never lifts, whose symptoms worsen with even minor exertion — and we have almost nothing to offer them. As a clinician, that is not acceptable. 

# data[].attributes.subject
Physicians across this state are seeing patients who cannot recover from an illness, whose fatigue never lifts, whose symptoms worsen with even minor exertion — and we have almost nothing to offer them. As a clinician, that is not acceptable. 

# data[].attributes.body
https://wvpress.org/wvpa-sharing/west-virginia-has-one-of-the-highest-chronic-disease-burdens-in-the-nation-congress-has-a-plan-to-address-one/

# data[].attributes.attachment_link.title
West Virginia Has One of the Highest Chronic Disease Burdens in the Nation. Congress Has a Plan to Address One of the Worst. It Just Hasn’t Funded It. - West Virginia Press Association

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By Senator/Dr. Tom TakuboFor Senator/Dr. Tom Takubo I went into pulmonology because West Virginia has some of the worst lung disease in the country.

# data[].attributes.headline
Two inexpensive, widely available medications provided modest short-term relief from fatigue in people with long COVID, according to a large clinical trial.  

# data[].attributes.subject
Two inexpensive, widely available medications provided modest short-term relief from fatigue in people with long COVID, according to a large clinical trial.  

# data[].attributes.body
https://www.cidrap.umn.edu/covid-19/2-common-drugs-may-offer-short-term-improvements-long-covid-related-fatigue

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2 common drugs may offer short-term improvements in long-COVID-related fatigue

# data[].attributes.attachment_link.description
Two inexpensive, widely available medications provided modest short-term relief from fatigue in people with long COVID, according to a large clinical trial published this week in The Lancet Infectious Diseases.

# data[].attributes.headline
The new Medicaid work requirements threaten the ability of people with chronic, complex conditions to maintain their access to care.

# data[].attributes.subject
The new Medicaid work requirements threaten the ability of people with chronic, complex conditions to maintain their access to care.

# data[].attributes.body
https://scholars.org/contribution/supporting-vermonters-serious-health

# data[].attributes.attachment_link.title
Supporting Vermonters with Serious Health Conditions to Maintain Medicaid Coverage

# data[].attributes.attachment_link.description
Many people with serious health conditions, chronic illnesses, and disabilities rely on Medicaid to access care. Without ongoing treatment and support, these individuals experience worsening health complications, increased disability, higher use of emergency care and hospitalization, and premature death. The new Medicaid work requirements threaten the ability of people with chronic, complex conditions to maintain their access to care.

# data[].attributes.headline
Longitudinal analyses of physical activity with long-term follow-up are needed to evaluate whether the indicators of cardiovascular fitness and decreases in physical activity translate into an increased risk of cardiovascular disease.

# data[].attributes.subject
Longitudinal analyses of physical activity with long-term follow-up are needed to evaluate whether the indicators of cardiovascular fitness and decreases in physical activity translate into an increased risk of cardiovascular disease.

# data[].attributes.body
https://www.cidrap.umn.edu/covid-19/having-long-covid-worsens-heart-related-fitness-study-finds

# data[].attributes.attachment_link.title
Having long COVID worsens heart-related fitness, study finds

# data[].attributes.attachment_link.description
People with long COVID often report fatigue and other symptoms that make it challenging for them to enjoy life like they once did.

# data[].attributes.headline
Long-lasting vision problems following mild cases of COVID-19 may stem from persistent inflammation and nerve damage, even as the results of standard eye examinations appear normal, according to a study in Nature.

# data[].attributes.subject
Long-lasting vision problems following mild cases of COVID-19 may stem from persistent inflammation and nerve damage, even as the results of standard eye examinations appear normal, according to a study in Nature.

# data[].attributes.body
https://www.cidrap.umn.edu/covid-19/persistent-vision-problems-after-covid-linked-ongoing-inflammation-nerve-damage

# data[].attributes.attachment_link.title
Persistent vision problems after COVID linked to ongoing inflammation, nerve damage

# data[].attributes.attachment_link.description
Long-lasting vision problems following mild cases of COVID-19 may stem from persistent inflammation and nerve damage, even as the results of standard eye examinations appear normal, according to a study today in Nature Communications.

# data[].attributes.attachment_caption
Eye problems after COVID-19 can now be explained

# data[].attributes.headline
Mild COVID-19 can cause severe and long-lasting eye problems. The study also explains why it has been difficult for sufferers to get help: the abnormal eye behavior cannot be detected by standard methods, and researchers have developed a diagnostic model to detect COVID-related eye problems.

# data[].attributes.subject
Mild COVID-19 can cause severe and long-lasting eye problems. The study also explains why it has been difficult for sufferers to get help: the abnormal eye behavior cannot be detected by standard methods, and researchers have developed a diagnostic model to detect COVID-related eye problems.

# data[].attributes.body
https://www.eurekalert.org/news-releases/1134768

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Your request has been denied. If you are a human and believe this was an error, please contact us at webmaster@eurekalert.org for assistance.

# data[].attributes.headline
Bateman Horne Center: PATIENT RESOURCES: RESOURCE PDFs, PARTNERSHIPS, and OUTREACH/MONTHLY EVENTS 

# data[].attributes.subject
Bateman Horne Center: PATIENT RESOURCES: RESOURCE PDFs, PARTNERSHIPS, and OUTREACH/MONTHLY EVENTS 

# data[].attributes.body
https://t-sml.mtrbio.com/public/smartlink/BHCPatientResources

# data[].attributes.headline
Lived experience may be listened to, but it is rarely granted the same level of authority. This matters because lived experience is not simply a personal story. It is knowledge developed through ongoing learning that emerges from engagement with systems, institutions and the realities of everyday life.

# data[].attributes.subject
Lived experience may be listened to, but it is rarely granted the same level of authority. This matters because lived experience is not simply a personal story. It is knowledge developed through ongoing learning that emerges from engagement with systems, institutions and the realities of everyday life.

# data[].attributes.body
https://theconversation.com/lived-experience-is-often-dismissed-but-we-should-recognise-it-as-a-form-of-expertise-285356

# data[].attributes.attachment_link.title
Lived experience is often dismissed – but we should recognise it as a form of expertise

# data[].attributes.attachment_link.description
People living with disabilities or through poverty and racism develop deep practical knowledge of how institutions function. They should be seen as experts.

# data[].attributes.headline
This guide is the product of a dedicated interdisciplinary team of clinicians, educators, researchers, and lived experience experts who share a common mission: to improve care for individuals living with ME/CFS, Long COVID, and other infection-associated chronic conditions(IACCs).

# data[].attributes.subject
This guide is the product of a dedicated interdisciplinary team of clinicians, educators, researchers, and lived experience experts who share a common mission: to improve care for individuals living with ME/CFS, Long COVID, and other infection-associated chronic conditions(IACCs).

# data[].attributes.body
https://batemanhornecenter.org/wp-content/uploads/2025/05/Clinical-Care-Guide-First-Edition-2025-1.pdf

# data[].attributes.headline
This suggests that dysfunction in the brain’s natural cleaning system may be a key driver of this condition.

# data[].attributes.subject
This suggests that dysfunction in the brain’s natural cleaning system may be a key driver of this condition.

# data[].attributes.body
https://news.griffith.edu.au/2026/07/03/brains-waste-clearing-ability-impaired-in-me-cfs-patients/

# data[].attributes.attachment_link.title
Brain’s waste-clearing ability impaired in ME/CFS patients - Griffith News

# data[].attributes.attachment_link.description
The brain’s waste clearance system is impaired in people living with ME/CFS which can lead to various symptoms including brain fog.

# data[].attributes.attachment_caption
Nowhere to go for seriously ill post-COVID patients
I feel like an undeliverable parcel.

# data[].attributes.headline
Both have had severe post-COVID for over five years. They need 24-hour care, but there is no place available anywhere because their illness is not formally permanent.

# data[].attributes.subject
Both have had severe post-COVID for over five years. They need 24-hour care, but there is no place available anywhere because their illness is not formally permanent.

# data[].attributes.body
https://www.volkskrant.nl/kijkverder/v/2026/postcovid-longcovid-patienten-revalidatie-ziekenhuis~v3102909/

# data[].attributes.attachment_link.title
Nergens plek voor ernstig zieke postcovidpatiënten: ‘Ik voel me een onbestelbaar postpakketje’

# data[].attributes.attachment_link.description
Linda Nugteren (39) en Nicole van Keulen (45) hebben allebei al ruim vijf jaar ernstige postcovid. Ze hebben 24 uur per dag zorg nodig, maar er is nergens plek omdat hun ziekte formeel niet blijvend is.

# data[].attributes.headline
Research:  Identified metabolic dysfunction in the brains of people with Long COVID who experience PEM, People who have Long COVID are more likely to exit the workforce, A new clinical trial will assess Maraviroc in combination with Atorvastatin.

# data[].attributes.subject
Research:  Identified metabolic dysfunction in the brains of people with Long COVID who experience PEM, People who have Long COVID are more likely to exit the workforce, A new clinical trial will assess Maraviroc in combination with Atorvastatin.

# data[].attributes.body
https://thesicktimes.org/2026/06/30/research-updates-june-30/

# data[].attributes.attachment_link.provider_name
The Sick Times - Chronicling the Long COVID crisis

# data[].attributes.attachment_link.title
Research updates, June 30 - The Sick Times

# data[].attributes.attachment_link.description
A recent imaging study in Sage Journals identified metabolic dysfunction in the brains of people with Long COVID who experience PEM. The study assessed 40 people with the disease from a Long COVID clinic with an advanced imaging technique that can detect various cancers and neurologic conditions.

# data[].attributes.headline
Long-term sickness absence declined in the early phase of the COVID-19 pandemic but subsequently remained at relatively high levels. 

# data[].attributes.subject
Long-term sickness absence declined in the early phase of the COVID-19 pandemic but subsequently remained at relatively high levels. 

# data[].attributes.body
https://academic.oup.com/occmed/advance-article-abstract/doi/10.1093/occmed/kqag062/8723731?

# data[].attributes.attachment_link.title
Incidence of long-term sickness absence in Japan following the COVID-19 pandemic

# data[].attributes.attachment_link.description
AbstractBackground. Although the COVID-19 pandemic has caused widespread disruptions to working life, its impact on long-term sickness absence (LTSA) remai

# data[].attributes.headline
PLRC:  Study on Algorithmic Dependence in Long COVID Phenotypes, Two New Opinion Papers: Recommended Outcome Measures & Patient Review in Research, Long COVID Treatment Guide Webinar and New Publications.

# data[].attributes.subject
PLRC:  Study on Algorithmic Dependence in Long COVID Phenotypes, Two New Opinion Papers: Recommended Outcome Measures & Patient Review in Research, Long COVID Treatment Guide Webinar and New Publications.

# data[].attributes.body
https://4xde2.r.sp1-brevo.net/mk/mr/sh/1t6AVsd2XFnIGLpfgBMI6nKtXXzgBO/zvD7GncDfJwy

# data[].attributes.attachment_link.title
Quarterly Newsletter: Three New Papers led by PLRC, Long COVID Treatment Guide Webinar, and Two New Papers Co-Authored by PLRC

# data[].attributes.headline
MIT researchers on reproductive health and IACI, and labs' research and findings on nailfold capillaroscopy, which visualizes capillaries and provides insights into microvasculature and blood flow. 

# data[].attributes.subject
MIT researchers on reproductive health and IACI, and labs' research and findings on nailfold capillaroscopy, which visualizes capillaries and provides insights into microvasculature and blood flow. 

# data[].attributes.body
https://www.youtube.com/watch?v=uTrIW28lpps

# data[].attributes.attachment_link.title
Emerging Long COVID Research - June 2026

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In this comic strip, cartoonist Summer Pierre shares her family’s many challenges navigating health and managing everyday life following her daughter’s onset of Long COVID at age 12.

# data[].attributes.subject
In this comic strip, cartoonist Summer Pierre shares her family’s many challenges navigating health and managing everyday life following her daughter’s onset of Long COVID at age 12.

# data[].attributes.body
https://publichealthinsider.com/2026/06/24/uncertain-and-ongoing-a-parents-story-of-long-covid/

# data[].attributes.attachment_link.title
Uncertain and Ongoing: A parent’s story of Long COVID – PUBLIC HEALTH INSIDER

# data[].attributes.attachment_link.description
Adolescence is already an intense time for parenting, but what happens when you add a life altering condition to the mix? In this comic strip, cartoonist Summer Pierre shares her family’s many challenges navigating health and managing everyday life following her daughter’s onset of Long COVID at age 12.

# data[].attributes.headline
 “I think this is one of the most complex diseases that I have encountered in my decades as a physician. To the world I would say Long COVID is real. Nobody would choose this on purpose.”

# data[].attributes.subject
 “I think this is one of the most complex diseases that I have encountered in my decades as a physician. To the world I would say Long COVID is real. Nobody would choose this on purpose.”

# data[].attributes.body
https://fnih.org/patient-engagement/patient-voices-fnih/doctor-navigates-new-reality-long-covid-caregiver/

# data[].attributes.attachment_link.title
Doctor Navigates New Reality as Long COVID Caregiver | FNIH

# data[].attributes.attachment_link.description
Molly Phelps, MD, thought her family’s COVID-19 infection had passed — until her husband Kevin’s lingering symptoms revealed the reality of Long COVID.

# data[].attributes.attachment_caption
For those who rely on the sport for identity and community, leaving it behind can feel like a form of grief

# data[].attributes.headline
Matt Fitzgerald had to stop running after getting long Covid in 2020. Unlike with most injuries, he said, he also couldn’t tolerate other forms of exercise.

# data[].attributes.subject
Matt Fitzgerald had to stop running after getting long Covid in 2020. Unlike with most injuries, he said, he also couldn’t tolerate other forms of exercise.

# data[].attributes.body
https://www.nytimes.com/2026/06/30/well/move/running-loss-grief.html

# data[].attributes.headline
This comprehensive guide for the diagnosis and management of MCAS in Primary Care is designed to help GPs recognize and treat MCAS with confidence. 

# data[].attributes.subject
This comprehensive guide for the diagnosis and management of MCAS in Primary Care is designed to help GPs recognize and treat MCAS with confidence. 

# data[].attributes.body
https://www.mastcellaction.org/articles/comprehensive-guide-for-primary-care-physicians

# data[].attributes.attachment_link.title
Comprehensive Guide to MCAS for Primary Care Physicians | Mast Cell Action

# data[].attributes.headline
Our findings imply that LC immunopathology is driven by a qualitative T cell dysfunction characterized by CD4+ non-proliferative activation and consistent with persistent antigen stimuli...(N=104)

# data[].attributes.subject
Our findings imply that LC immunopathology is driven by a qualitative T cell dysfunction characterized by CD4+ non-proliferative activation and consistent with persistent antigen stimuli...(N=104)

# data[].attributes.body
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1823850/full

# data[].attributes.attachment_link.readable_text
ORIGINAL RESEARCH article

Front. Immunol. , 29 June 2026

Sec. T Cell Biology

Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1823850

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ORIGINAL RESEARCH article

Front. Immunol. , 29 June 2026

Sec. T Cell Biology

Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1823850

Abstract
Objective:
The pathogenesis of Long COVID (LC) remains poorly understood, with the analysis of immune responses often obscured by variables such as vaccination and reinfection. This study aimed to determine the primary immunological footprint of LC by examining a specific cohort that minimizes these confounding factors.
Methods:
We analyzed a Brazilian cohort of patients recruited between September 2020 and February 2021, during the first wave of the pandemic (Wuhan-Hu-1 variant), comprising mostly unvaccinated individuals. We assessed humoral responses to SARS-CoV-2 and latent viruses in 104 patients. Additionally, we investigated the immune signatures of CD4⁺ T cells in a subset of 6 LC and 4 recovered control (RC) unvaccinated patients, recruited 1 to 2 months after symptom onset, utilizing a combination of flow cytometry and single-cell RNA sequencing.
Results:
Systemic humoral responses to SARS-CoV-2 and reactivated latent viruses were comparable between the LC and RC groups, as were the overall distributions of CD4⁺ T cell subsets. However, single-cell RNA sequencing revealed distinct immune signatures. Antigen-responsive CD4⁺ T cells in LC patients demonstrated a signature of acute activation, characterized by the upregulation of genes such as CD38 and interferon-stimulated genes, including IFITM1. Furthermore, gene set enrichment analysis indicated that LC patients exhibit increased expression of interferon-alpha/gamma signatures compared to RC. Analysis of the T cell receptor repertoire presented no evidence of clonal expansion.
Discussion:
Our findings imply that LC immunopathology is driven by a qualitative T cell dysfunction characterized by CD4⁺ non-proliferative activation more than one month after symptom onset. This pattern is consistent with persistent antigen stimuli, though the underlying mechanism and its therapeutic implications require further investigation.

Introduction

Long COVID (LC), a multisystemic condition persisting beyond acute SARS-CoV-2 infection, represents a significant global health challenge affecting millions of people worldwide ( 1). Current evidence suggests that LC pathogenesis involves a complex interplay between viral persistence, chronic inflammation, autoimmunity, and reactivation of latent viruses, such as Epstein-Barr and herpesvirus ( 2, 3). Therefore, individuals with LC are anticipated to exhibit distinct cellular and humoral immune signatures compared to recovered controls (RC) ( 3- 5). Exploring the adaptive immune response is essential to understanding immunity in LC. Perturbations in CD4⁺ T cell function, T-cell receptor (TCR) repertoire diversity, and sustained antibody responses to SARS-CoV-2 or reactivated pathogens may indicate underlying immune dysregulation ( 2, 5, 6).

CD4⁺ T cells play a central role in antiviral and humoral responses. However, their specific role in LC development remains incompletely characterized ( 3, 7). Recently, perturbations in CD4⁺ T cell function, including altered activation states and dysregulated inhibitory receptor expression, have been identified as playing a role in LC pathogenesis ( 5, 8). A proteomic study identified inflammatory phenotypes associated with LC, such as NF-κB and type 2 interferon signaling pathways ( 9). However, another study analyzing plasma from patients in Sweden and the United Kingdom found no significant differences, even though healthy controls exhibited higher neutralizing antibodies against SARS-CoV-2 ( 10). This study was conducted in 2022, after the rollout of the vaccine. A critical challenge in LC research has been distinguishing its unique immunological footprint from confounding factors such as COVID-19 vaccination and/or reinfection, which have complicated comparative studies years into the pandemic. Isolating LC-specific immune alterations remains challenging in cohorts exposed to vaccines or those with recurrent infections, both of which independently modulate adaptive immunity.

The heterogeneity of LC further complicates research efforts, with multiple potential mechanistic drivers and clinical manifestations requiring careful stratification of patient populations. 1,7 To address these challenges, we evaluated CD4⁺ T cell activity in patients with LC compared to recovered patients (RC). We analyzed patients from Brazil's first pandemic year (March 2020-March 2021), in which predominantly only ancestral (Wuhan-Hu-1) and Gamma SARS-CoV-2 variants were circulating ( 11, 12). These two variants had a negligible risk of reinfection and with reinfection being less likely within the first few months post infection ( 13), this reduced the influence of confounders in the immune signature due to vaccination or reinfection. This approach enables a more accurate assessment of the differences in immune signatures between LC and RC participants, providing valuable insights into the fundamental immunological mechanisms underlying LC pathogenesis.

Methods

Study design and participants

This cross-sectional study included 104 participants (79 with Long COVID [LC] and 25 recovered controls [RC]) selected from a previously described cohort ( 14). Individuals were recruited at the reference state Post-COVID Center in Salvador, Bahia, Brazil, between September 2020 and March 2021. Inclusion criteria specified at least one month since symptom onset of COVID-19 confirmed by RT-PCR, serology, or compatible computed tomography scan of the chest. Exclusion criteria included age under 18 years, presence of cognitive disorders, and pregnancy.

Participants underwent multidisciplinary evaluation at the outpatient clinic and were classified based on acute-phase disease severity as mild (no hospitalization), moderate (hospitalized but not requiring intensive care unit), or severe (requiring intensive care unit admission). Data were collected by trained physicians and nurses using standardized forms and managed via REDCap. Participants were classified as LC if they presented persistent symptoms for more than four weeks after disease onset, according to the CDC definition at the time of recruitment (2020-2021) ( 15).

To reduce confounding by age and sex, samples from the RC group were matched to the LC group by age (± 3 years) and sex at a 1:1 ratio, with replacement. To ensure representative LC symptom coverage, we performed cluster analysis evaluating 1,094 participants with complete symptom information using Gower distance and Partitioning Around Medoids method, resulting in 8 symptom clusters (Supplementary Methods). For single-cell analysis, a subset of 21 unvaccinated participants (16 LC, 5 RC) with available PBMC samples was selected after excluding 3 vaccinated individuals (Supplementary Methods). The study was approved by the institutional review boards of Bahia State University (UNEB, protocol no. 38281720.2.0000.0057) and Santo Antônio Hospital (OSID, protocol no. 33366030.5.0000.0047), and all participants provided written informed consent.

Sample collection and processing

Whole blood was collected from participants in heparin or EDTA-coated tubes, with processing initiated within four hours of collection. PBMCs were isolated from heparin tubes using Ficoll gradient separation and cryopreserved in cell freezing medium (90% heat-inactivated fetal bovine serum with 10% DMSO) until further use.

Humoral response assessment

Antibody responses against SARS-CoV-2 Spike RBD, Nucleocapsid, EBV EBNA1, and CMV pp65 were assessed via ELISA in all plasma samples (n=101), as previously described ( 16). Briefly, heat-inactivated plasma samples were serially diluted and incubated on 96-well plates coated with recombinant proteins. Negative control plasma was pooled from healthy donors unexposed to SARS-CoV-2, while positive control plasma from convalescent donors was used to normalize results across experiments. The limit of detection was defined as 1:3 (Supplementary Methods).

Neutralizing antibody activity was measured using a SARS-CoV-2 pseudovirus neutralization assay ( 16). Recombinant SARS-CoV-2-spike pseudotyped VSV-ΔG-GFP with the D614G mutation was incubated with serially diluted heat-inactivated plasma and added to confluent Vero cell monolayers. After 16 hours, cells were fixed and imaged to quantify infection. Neutralization titers (ID50) were calculated using the One-Site Fit Log IC50 model in GraphPad Prism 8.0.

CD4+ T cell analysis

CD4⁺ T cells were evaluated using an activation-induced marker (AIM) assay, as previously described ( 17). Briefly, cryopreserved PBMCs were thawed, washed and cultured for 24 hours at 37 °C and 5% CO ₂ with SARS-CoV-2 MPs containing spike and non-spike epitopes (1μg/mL), DMSO (negative control), or staphylococcal enterotoxin B (1μg/mL, positive control). Cells were pre-incubated with anti-human CD40 blocking antibody (0.5μg/mL) for 15 minutes prior to stimulation.

Following stimulation, cells were stained with fluorochrome-conjugated antibodies against CD4, CD45RA, CCR7, CD27, OX40, 41BB, CD19, CD14, and CD16 (Supplementary Methods) and analyzed on a FACSAria IIu cell sorter (BD Biosciences). CD4⁺ T cells were classified into naïve (CCR7⁺CD45RA⁺), central memory (CCR7⁺CD45RA −), effector memory (CCR7 −CD45RA −), and terminally differentiated effector memory (CCR7 −CD45RA⁺) subsets. AIM⁺ cells were identified as OX40⁺41BB⁺. Three populations (naïve, total memory, and AIM⁺) were sorted for subsequent single-cell RNA sequencing, with viability confirmed before experiments.

Single-cell RNA sequencing

For sorted cells, indexed V(D)J, 5' Feature Barcode, and GEX libraries were prepared using the Chromium Next GEM Single Cell 5' v2 Dual Index kit with Feature Barcoding (10x Genomics). Pools of cells of the same subtype from five to seven individuals were obtained following the Cell Multiplexing Oligo Labeling protocol. Libraries were sequenced on Illumina NovaSeq platform.

Initial data processing used CellRanger v7.1.0 (10x Genomics) ( 18) for demultiplexing and alignment to human reference genome GRCh38. Quality control excluded doublets identified by scDblFinder v1.16.0 and cells with <200 or >6,000 detected genes or >10% mitochondrial RNA content. Data analysis was performed using Seurat v5.0.3 (Supplementary Methods).

After log-normalization (10,000 reads), dimensionality reduction was performed using PCA on the 2,000 most variable genes, excluding MALAT1, ribosomal, and mitochondrial genes. The first 22 principal components (accounting for 80% of variance) were selected. Batch effects were corrected using Harmony v1.2.0, and data were visualized using UMAP with default Seurat implementation. Clustering used FindNeighbors (k=10) and FindClusters functions (Supplementary Methods).

Cell type annotation employed SingleR v2.4.0 with four reference datasets: Blueprint Encode Data, Database Immune Cell Expression Data, Human Primary Cell Atlas Data, and Monaco Immune Data. Annotations were consolidated into four categories: naïve, memory, regulatory (Tregs), and activated T cells. T cell receptor (TCR) sequences were integrated with transcriptomic profiles by merging clonotype and AIRR metadata files. TCR β-chain sequences were clustered using CD-HIT v4.8.1 at 85% sequence identity and matched against the VDJdb database for antigen specificity annotation, including SARS-CoV-2, CMV, EBV, and autoantigens (Supplementary Methods).

Statistical analysis

Differences in antibody titers and neutralization titers between the LC and RC groups were evaluated using the Wilcoxon rank sum test. Categorical variables were compared using Pearson's chi-squared test. The difference in CD4⁺ T cell subset proportions between groups was evaluated using compositional data transformation (isometric log-ratio) followed by Permutational Multivariate Analysis of Variance (PERMANOVA), with 9999 permutations.

Differential gene expression analysis employed a pseudobulk approach, aggregating single-cell data by summing expression counts for each gene across cells of the same cell type and individual, using a modified version of the Libra R package. Individuals with fewer than 10 cells per cell type comparison were excluded to minimize bias from low cell representation. DESeq2 with Wald test was used for statistical testing, with significant genes identified at false discovery rate (FDR)-adjusted p-value <0.1.

Gene set enrichment analysis (GSEA) was performed using fgsea v1.30.0 in pre-ranked mode. Genes were scored using the formula: score = −log ₁₀(p-value) × sign(log ₂FC). We used the MSigDB v2024.1.Hs Hallmark gene sets ( 19), a curated collection of 50 well-defined biological processes. Genes not expressed in any sample were removed from gene sets to reduce bias ( 20). Pathway enrichment was defined as FDR <0.05. Similarities in gene dysregulation patterns between groups were evaluated by the Normalized Enrichment Score. All analyses were performed in R v4.3.3.

Results

This study cohort consisted of 79 individuals with LC and 25 recovered controls (RC), mostly unvaccinated at the time of infection (101 - 97.1%) and with no history of reinfection following their primary infection, during the first year of the pandemic (Table 1, Supplementary Figure 2). A sub-cohort of 16 LC and 5 RC participants, all of whom were unvaccinated at the time of sample collection, underwent single-cell CD4⁺ analysis; among them, only 10 (6 LC and 4 RC) were analyzed after quality control. There were no significant demographic or comorbidity differences between the groups (Table 1, Supplementary Figure 3).

Characteristic

All participants

p-value

T-cell study

p-value

Recovered,
N = 25

Long-COVID, N = 79

Recovered,
N = 4

Long-COVID, N = 6

Characteristics of the participants.

The p-values are from the Wilcoxon rank sum test or Pearson's Chi-squared test. Numbers are N(%) or otherwise specified.

First, we evaluated key components of virus-specific immunity. Analysis of humoral responses revealed no statistically significant differences in anti-Spike IgG antibody titers or SARS-CoV-2 neutralizing antibody activity between the LC and RC groups. Furthermore, serological analysis showed no evidence of differential reactivation of latent viruses, with comparable IgG titers for both Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) (Figure 1).

To investigate the role of CD4⁺ T cells in LC pathogenesis, we classified CD4⁺ T cells into three subsets using flow cytometry: total memory ( CCR7⁺CD45RA⁻, CCR7⁻CD45RA⁻, CCR7⁻CD45RA⁺), naïve ( CCR7⁺CD45RA⁺), and activation-induced markers (AIM⁺) ( OX40⁺41BB⁺). Total memory and naïve groups were capped at a maximum of 2900 cells. The number of AIM⁺ cells per sample and the distribution of the subpopulations are shown in Figure 2. Naïve and central memory were the most prevalent subpopulations; the distributions of naïve, central memory, effector memory, and terminally differentiated effector memory were similar between LC and RC participants, as indicated by a PERMANOVA p-value of 0.53 (Figure 2).

To further characterize CD4⁺ T cells, we performed single-cell RNA sequencing (scRNA-seq) of the groups sorted in the flow cytometry (naïve, total memory, and AIM⁺ cells). We further classified the T cells within each sorting based on the expression profiles of marker genes from the scRNA-seq: naïve, activated, memory, and regulatory (TReg) (Figure 3). Most cells (87%) sorted as naïve in the flow cytometry were annotated as naïve based on their gene expression profiles, reinforcing the sorting accuracy and overall data quality. Within the AIM⁺ sorted population, the proportions of subsets by gene expression were Tregs (39%), activated (17%), memory (31%), and naïve (12%) T cells, indicating that AIM⁺ sorting successfully enriched antigen-responsive cells (Supplementary Figure 4).

To ensure rigorous quality control in the bioinformatics analysis comparing LC vs. RC, individuals with fewer than 10 cells detected in any subset of sorting and gene expression were excluded. This filtering step minimized bias from low cell representation and enhanced the reliability of downstream analyses. We compared the transcriptional profiles of cells classified by gene expression annotation within each flow-cytometry sorting gate. We used the notation Gene-expression_sorting, to refer to groups within each sorting. We identified 12 differentially expressed genes (DEGs) in activated_AIM⁺ cells (2 RC and 3 LC patients), with 10 upregulated genes in LC patients. Among these genes, IFITM1 and CD38 were notably overexpressed in the LC group (Figure 4A, Supplementary Table 1). We also identified 15 DEGs in the Treg_AIM⁺ cells (2 RC and 4 LC patients), which were upregulated in the LC group (Figure 4B, Supplementary Table 2). Lastly, in the Naïve_Naïve,(4 RC and 6 LC patients) we identified 10 DEGs in this group, all of which were downregulated in the LC group (Figure 4C, Supplementary Table 3). The remaining groups ( Memory_Memory and Naïve_Memory) did not exhibit any DEGs.

In the gene set enrichment analysis (GSEA), activated_AIM+ CD4⁺ cells were enriched for interferon alpha and gamma responses in LC (Figure 5), whereas Tregs_AIM+ were enriched for IL-2 signaling responses (Figure 5). Naïve_Naïve cells from LC showed increased interferon alpha and gamma responses, IL-2, IL-6, and TNF-α signaling responses, and overall inflammatory responses compared to RC (Figure 5, Supplementary Figure 5).

To determine whether the observed transcriptomic activation was associated with the expansion of SARS-CoV-2-specific T cells, we analyzed the TCR sequences obtained from the scRNA-seq data. We identified TCR clonotypes specific to SARS-CoV-2 using public databases. We did not find any significant differences in the overall clonal diversity of the TCR repertoire between the LC and RC groups (Figure 6). We also did not find evidence of clonal expansion among the sorted CD4⁺ T cells (activated, total memory, and naïve). (Supplementary Figure 6).

Discussion

Our study provides important insights into the immunological mechanisms underlying LC, particularly focusing on CD4+ T cell dysregulation in an unvaccinated cohort with minimal reinfection risk. This unique cohort allowed us to isolate LC-specific immune alterations without the confounding effects of vaccination or reinfection. We found that while individuals with LC do not differ from those with RC in the quantity and quality of their humoral response or the overall distribution of CD4⁺ T-cell subsets, their antigen-responsive T-cells exhibit a distinct immune signature. Indeed, we observe a strong interferon signature more than 1 month after symptom onset in individuals with LC.

The genes of AIM⁺ CD4⁺ T-cells exhibited differential expression patterns between LC and recovered individuals. Notably, LC patients showed upregulation of acute activation markers, such as CD7 and CD38, along with the interferon-stimulated gene IFITM1, indicating active immune stimulation. Although IFITM1 is broadly associated with antiviral activity, in vitro evidence suggests it may facilitate SARS-CoV-2 entry during acute infection ( 21), though its relevance in the post-acute setting remains unclear. CD38 is a classic marker of activation in viral infections ( 22, 23). The role of CD7 in CD4⁺ T cells is not well known. It has been mostly studied in the context of tumor biology, where CD7⁻CD4⁺ T cells have been observed in T-cell lymphoma ( 24). A 2024 study showed that CD7⁺ CD4⁺ T cells are associated with cytolytic activity in autoimmunity ( 25). Our findings of active immune response were further substantiated by gene set enrichment analysis, which revealed significant enrichment of interferon-gamma and interferon-alpha response pathways in activated cells from the LC group. The SARS-CoV-2-specific CD8⁺ T cells from LC patients showed increased expression of co-inhibitory receptors, suggesting a state of T cell dysfunction that may contribute to persistent symptoms ( 10). In contrast, Yin et al. ( 5) examined a similarly unvaccinated, low-reinfection-risk population eight months post-disease and did not observe differences in activation markers, such as CD38, on CD4⁺ or CD8⁺ T cells when comparing the LC group to the recovered group. Instead, their study showed a differential expression of exhaustion markers, including PD-1 and CTLA-4. Considering the timing of patient recruitment between our study (1-2 months post disease) and Yin et al. (8 months post disease). One possible interpretation, when considering these two independent cohorts, is that immune activation in the early months post-infection may precede a transition toward exhaustion at later timepoints. However, this comparison is limited by differences in cohort characteristics, including disease severity and geographic setting, and would require longitudinal confirmation within a single cohort.

Despite the findings of immune activation in SARS-CoV-2-specific CD4⁺ T-cells, our analysis did not reveal a difference in response towards SARS-CoV-2 antigen. We found no evidence of clonal expansion of T-cell receptors in any CD4⁺ cell population. The absence of detectable differences in viral-specific T-cell frequencies between LC and RC could partially be attributed to the relatively small sample size, which limits statistical power, and the possible lack of matches in the VDJdb database. The combination of immune activation markers without corresponding clonal expansion is consistent with a model in which a low-level antigen stimulus sustains inflammatory signaling without eliciting a proliferative T-cell response. One candidate source for such stimulation is a tissue-resident viral antigen reservoir, which has been documented in other studies ( 2, 26, 27), although our data cannot directly test this mechanism. Whether this state precedes T-cell exhaustion, as observed in other post-viral conditions, remains to be determined.

Lastly, we have also evaluated alternative hypotheses of LC, such as the reactivation of a latent virus ( 2, 28, 29). Our analysis showed no significant difference in EBV-specific or CMV-specific IgG antibody titers between the LC and RC groups. The frequency of TCR against those viruses was similar in both groups. These results are similar to those of Williams et al. ( 30), who did not find a difference in the immune response of CD4⁺/CD8⁺ T-cells towards SARS-CoV-2, EBV, and CMV comparing LC and RC patients.

The primary strength of our study lies in the use of a cohort of mostly unvaccinated, non-reinfected individuals from the first wave of the pandemic, which provides an invaluable baseline for understanding the primary immunopathology of LC. We also provided a detailed clinical characterization of the individuals. We also combined flow cytometry and scRNA-seq on unvaccinated individuals to obtain complementary insights. Flow cytometry allowed us to quantify a predefined set of surface proteins, while scRNA-seq provides a broad, comprehensive transcriptomic profile at single-cell resolution ( 31). A previous study comparing human peripheral blood mononuclear cells found that the correlation between protein expression measured by cytometry and mRNA levels from scRNA-seq was relatively weak, with r-squared values ranging from 0.47 to 0.66 ( 32, 33). Therefore, since each technique targets different cellular components and relies on different markers to define subpopulations, their annotations do not always completely overlap. However, the benefit of applying scRNA-seq to a pre-sorted cell population is that its high resolution can uncover substantial heterogeneity within populations that were previously identified and isolated by flow cytometry. In this way, flow cytometric sorting serves as a useful pre-filter, providing an initial standardization of cell populations before transcriptomic analysis.

However, the study has limitations. First, the small sample size for the scRNA-seq precluded the assessment of the immune expression by different symptom clusters, as previous studies have shown that LC is not a homogenous condition, and it is likely to differ in immunological patterns ( 34, 35). The limited sample size also reduced the statistical power to detect differences and the generalizability of our findings. We initially planned to analyze samples from 9 RC and 27 LC participants, but due to technical problems with experiments and a limited number of AIM⁺ cells sorted, only 6 LC and 4 RC participants presented adequate numbers of cells for single-cell RNASeq analysis. Similarly, we used an FDR threshold of 0.1 for differential expression to account for the possible similarity in immune profiles between LC and RC. This more permissive threshold allowed us to detect subtle but potentially biologically relevant changes, at the cost of an increased risk of false positives among the identified genes. Second, analysis regarding TCR repertoire relied on the VDJdb, a repository containing high-quality, validated TCR sequences, however it can show low sensitivity to uncommon epitopes ( 36). Third, this cross-sectional study is a single snapshot in time; longitudinal follow-up is essential to understand the trajectory of this T-cell immune pattern. Fourth, our findings are based primarily on transcriptomic analysis, and the lack of available cell samples precluded functional validation of key pathways at the protein level. Finally, our analysis of peripheral blood may not fully capture the immunological events occurring within tissue sites of potential viral persistence.

In conclusion, by studying an unvaccinated cohort, we provide evidence of transcriptomic alterations in the CD4⁺ T-cell compartment in LC, characterized by immune activation signatures in antigen-responsive cells that are uncoupled from both clonal expansion and the systemic humoral response. These findings, observed in a small cohort, warrant validation in larger longitudinal studies.

Statements

Data availability statement

Sequence data that support the findings of this study have been deposited in the NCBI GEO database with the primary accession code GSE334857.

Ethics statement

The study was approved by the institutional review boards of Bahia State University (UNEB, protocol no. 38281720.2.0000.0057) and Santo Antônio Hospital (OSID, protocol no. 33366030.5.0000.0047). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

TC-S: Formal Analysis, Writing - original draft, Visualization, Methodology, Investigation. BG: Investigation, Writing - review & editing, Methodology. CA: Investigation, Writing - review & editing. JS: Investigation, Writing - review & editing. BP: Investigation, Writing - review & editing. ÍD: Investigation, Writing - review & editing. SN: Writing - review & editing, Investigation. AM: Writing - review & editing. APB: Writing - review & editing, Investigation. MB: Writing - review & editing. MC: Writing - review & editing. JC: Writing - review & editing. VR: Investigation, Writing - review & editing. CC: Investigation, Writing - review & editing. AR-H: Methodology, Writing - review & editing, Software, Investigation, Visualization, Formal Analysis. VM-C: Methodology, Investigation, Supervision, Writing - review & editing, Software, Formal Analysis. RK: Writing - review & editing, Investigation, Supervision. CRC: Investigation, Writing - review & editing. AB: Funding acquisition, Writing - review & editing, Resources. MB-N: Resources, Writing - review & editing, Funding acquisition. NT: Investigation, Writing - review & editing. JD: Validation, Conceptualization, Writing - review & editing, Investigation, Supervision. VB: Writing - review & editing, Supervision, Data curation, Project administration, Writing - original draft, Conceptualization, Investigation, Visualization, Funding acquisition.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This study was supported by CNPq/MCTI/CT-Saúde (53/2022 _ Grant number 409004/2022-7); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 - and by CNPq 409004/2022-7; FAPESB (Pronex N° 008/2014) and FAPESB (N° 01/2020). MB-N, AB, CRC, and VB are supported by CNPq, the Brazilian National Research Council. TC-S acknowledges institutional support from the Royal Society (NIF\R1\231435), CRC acknowledges the financial support from FAPESP (2023/03257-4), and VM-C is funded by FONDAP-ANID (15130011 and 1523A0008) and Anillo-ANID (ATE220016). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. VB gratefully acknowledges financial support of the Fulbright U.S. Student Program, sponsored by the U.S. Department of State and the Brazilian-American Fulbright Commission, which provided funding for a Fulbright Senior Visiting Fellowship at the LJI.

Acknowledgments

We would like to express our sincere gratitude to the study participants and investigators of the Post COVID-Center (CPC) study group. We thank Dr. Shane Crotty for providing access to essential equipment for conducting our experiments and for institutional support.

Conflict of interest

CC was employed by Albert Einstein Israelite Hospital. All other authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2026.1823850/full#supplementary-material
Supplementary Table 1
Log2 Fold changes and p-values of differentially expressed genes in the comparison activated_AIM+.
Supplementary Table 2
Log2 Fold changes and p-values of differentially expressed genes in the comparison Treg_AIM+.
Supplementary Table 3
Log2 Fold changes and p-values of differentially expressed genes in the comparison Naïve_Naïve.
Supplementary Figure 1
Dimensionality reduction through t-Distributed Stochastic Neighbor Embedding (t-SNE). Evaluating the presence of cough, fatigue, dyspnea, pain symptoms (headache, thoracic and muscle pain), and changes in taste and smell.
Supplementary Figure 2
Number of participants with each combination of symptoms and related cluster.
Supplementary Figure 3
Number of participants with each combination of symptoms and related cluster for the T-cell study.
Supplementary Figure 4
Percentage of cells by gene expression profile (scRNA-seq) within each sorting (flow cytometry).
Supplementary Figure 5
GSEA by cell sorting. (A) AIM⁺, (B) Memory, (C) Naïve6.
Supplementary Figure 6
TCR Expansion overall and by cell sorting. (A) Overall, (B) AIM⁺, (C) Memory, (D) Naive.

References

Wanga V . Long-term symptoms among adults tested for SARS-coV-2 - United states, january 2020-april 2021. MMWR Morb Mortal Wkly Rep. (2021) 70:1235-41. doi: 10.15585/mmwr.mm7036a1

Keywords

ancestral, COVID-19, long covid, single cell RNA (scRNA), unvaccinated

Citation

Cerqueira-Silva T, Goodwin B, Araújo C, Silva JJ, Pereira BJ, da Silva ÍBS, Nunes S, Marinho A, Barreto AP, Barreto M, Chalhoub M, Caldas JR, Rao V, Coelho C, Rojas-Hidalgo A, Maracaja-Coutinho V, Khouri R, Cardoso CR, Barral A, Barral-Netto M, Tavares NM, Dan J and Boaventura VS (2026) CD4⁺ T cell signature in long COVID: insights from an unvaccinated cohort. Front. Immunol. 17:1823850. doi: 10.3389/fimmu.2026.1823850

Updates

Copyright

*Correspondence: Viviane S. Boaventura, viviane.boaventura@fiocruz.br

†These authors share first authorship

‡These authors share senior authorship

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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# data[].attributes.attachment_link.title
Frontiers | CD4+ T cell signature in long COVID: insights from an unvaccinated cohort

# data[].attributes.attachment_link.description
ObjectiveThe pathogenesis of Long COVID (LC) remains poorly understood, with the analysis of immune responses often obscured by variables such as vaccination...

# data[].attributes.attachment_caption
Type I unconventional protein secretion of the SARS-CoV-2 nucleocapsid protein promotes inflammatory cytokine release

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Our findings shed a light on the secretion mechanism of this pro-inflammatory NP (viral nucleocapsid protein), highlighting it as a potential therapeutic target for COVID-related systemic inflammation.  (N=113 hospitalized patients)

# data[].attributes.subject
Our findings shed a light on the secretion mechanism of this pro-inflammatory NP (viral nucleocapsid protein), highlighting it as a potential therapeutic target for COVID-related systemic inflammation.  (N=113 hospitalized patients)

# data[].attributes.body
https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00691-1

# data[].attributes.headline
Overall, our study highlights the role of age and health conditions, particularly immunosuppression, as risk factors for persistent SARS-CoV-2 infections and contributors to viral mutation during such infections.  N =738,944

# data[].attributes.subject
Overall, our study highlights the role of age and health conditions, particularly immunosuppression, as risk factors for persistent SARS-CoV-2 infections and contributors to viral mutation during such infections.  N =738,944

# data[].attributes.body
https://www.nature.com/articles/s41467-026-74445-7

# data[].attributes.attachment_link.title
Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections - Nature Communications

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Using Denmark’s genomic surveillance linked to health registries, the authors identify immunosuppression as a key risk factor for persistent SARS-CoV-2 infections and show these infections accumulate mutations associated with treatment resistance.

# data[].attributes.attachment_caption
Workforce exit and work productivity loss in adults with and without post-COVID-19 condition: The PRIME post-COVID cohort study

# data[].attributes.headline
Productivity loss due to absenteeism and presenteeism was up to 3x higher in those with long COVID and 2x higher in 'recovered' participants, with more frequent reports of work incapacity and financial strain.  N=3,342

# data[].attributes.subject
Productivity loss due to absenteeism and presenteeism was up to 3x higher in those with long COVID and 2x higher in 'recovered' participants, with more frequent reports of work incapacity and financial strain.  N=3,342

# data[].attributes.body
https://www.ijidonline.com/article/S1201-9712(26)00548-5/fulltext

# data[].attributes.headline
Find out if you may be affected by Medicaid Work Requirements:

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Find out if you may be affected by Medicaid Work Requirements:

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https://dvha.vermont.gov/medicaid-work-requirements-screening-tool

# data[].attributes.attachment_link.title
Medicaid Work Requirements: Informational Screening Tool | Department of Vermont Health Access

# data[].attributes.attachment_link.description
Beginning in January 2027, a new federal law makes many Vermonters complete work requirements (also known as community engagement requirements) to get or keep Medicaid.

# data[].attributes.headline
Changes start: January 1, 2027: The law makes new requirements to get and keep Medicaid. These new requirements are “community engagement” and 6-month renewals. 

# data[].attributes.subject
Changes start: January 1, 2027: The law makes new requirements to get and keep Medicaid. These new requirements are “community engagement” and 6-month renewals. 

# data[].attributes.body
https://dvha.vermont.gov/medicaidchanges

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Federal Medicaid Changes: Vermont Impact | Department of Vermont Health Access

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On or before January 1, 2027, the Department of Health shall collaborate to:(1) identify existing evidence-informed standards, best practices, and training for primary care providers regarding long COVID and distribute these resources through the Department’s website and to primary care providers; and(2) in collaboration, identify support services or other resources for long COVID 

# data[].attributes.subject
On or before January 1, 2027, the Department of Health shall collaborate to:(1) identify existing evidence-informed standards, best practices, and training for primary care providers regarding long COVID and distribute these resources through the Department’s website and to primary care providers; and(2) in collaboration, identify support services or other resources for long COVID 

# data[].attributes.body
https://legislature.vermont.gov/bill/status/2026/H.46

# data[].attributes.attachment_link.description
An act relating to the Rare Disease Advisory Council

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Many patients with long COVID originally only had mild to moderate symptoms of the virus, but weeks or months after their original symptoms...

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Many patients with long COVID originally only had mild to moderate symptoms of the virus, but weeks or months after their original symptoms...

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https://www.uvm.edu/larnermed/medcommunications/news/menson-discusses-long-covid-vtdigger-article

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Menson Discusses Long COVID in VTDigger Article

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Larner Assistant Professor of Medicine Katherine Menson, D.O., pulmonary and critical care physician at the University of Vermont Medical Center, commented…

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Senate Health and Welfare - 2026-03-27 - 9:00am

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VT Senate: Clinical and Patient Information Overview of Long COVID with 3 testimonies.

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VT Senate: Clinical and Patient Information Overview of Long COVID with 3 testimonies.

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https://goldendomevt.com/meetings/Senate/Health_%26_Welfare/2026-03-27_09-00/transcript.html

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Testimony on Long COVID for Sen Lyons and Health Committee

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Senate concurrent resolution recognizing March 2026 as International Long COVID Awareness Month in Vermont.Whereas, in May 2023, the World Health Organization terminated its COVID-19 emergency,and over 20 million Americans live with the long-term effects of the COVID-19 virus, a malady known as long COVID, and this situation represents a major public health and economic challenge....

# data[].attributes.subject
Senate concurrent resolution recognizing March 2026 as International Long COVID Awareness Month in Vermont.Whereas, in May 2023, the World Health Organization terminated its COVID-19 emergency,and over 20 million Americans live with the long-term effects of the COVID-19 virus, a malady known as long COVID, and this situation represents a major public health and economic challenge....

# data[].attributes.body
https://legislature.vermont.gov/Documents/2026/Docs/RESOLUTN/SCR008/SCR008%20As%20adopted%20by%20the%20Senate%20Official.pdf

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Sustained Reduction in Cardiopulmonary Fitness in Long COVID: A Report from the RECOVER-adult Cohort Study

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Long COVID is associated with worse cardiovascular fitness. Additional studies are needed to determine if Long COVID is a novel risk factor for incident cardiovascular disease. N=1475

# data[].attributes.subject
Long COVID is associated with worse cardiovascular fitness. Additional studies are needed to determine if Long COVID is a novel risk factor for incident cardiovascular disease. N=1475

# data[].attributes.body
https://www.sciencedirect.com/science/article/pii/S2772963X26003443

# data[].attributes.attachment_caption
What does it mean to recover from long covid?

# data[].attributes.headline
This raises important questions. Should we adopt the language of remission rather than recovery, as is common in other chronic conditions? 

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This raises important questions. Should we adopt the language of remission rather than recovery, as is common in other chronic conditions? 

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https://www.bmj.com/content/393/bmj-2026-100054

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Prejudices against patients are reinforced when a news outlet’s most in-depth, academic-sounding articles on Long Covid attempt to undermine the reality of the disease.

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Prejudices against patients are reinforced when a news outlet’s most in-depth, academic-sounding articles on Long Covid attempt to undermine the reality of the disease.

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https://fair.org/home/media-wont-stop-psychologizing-long-covid/

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Since 2020, it has been well-documented that many people suffer new chronic symptoms following a Covid infection, including cognitive impairment, shortness of breath, fatigue, loss of smell, joint pain, vertigo, chronic tachycardia, tinnitus and more-similar to what was reported during the first SARS pandemic. In July 2021, the US government gave the condition known as "post-acute sequelae of Covid-19" (PASC) an ICD-10 (International Classification of Disease) code, identifying it as an official disease, as well as recognition as a disability. Patients popularized the term "Long Covid" to describe the condition.

There are still unanswered questions about how Long Covid functions and how its various subtypes relate. But the evidence of disease burden keeps piling on. In the last year alone, new studies have indicated that: 1) the prevalence of Long Covid may be much higher than assumed; 2) Long Covid is costing the world's economy billions; and 3) some autoimmune symptoms of Long Covid can be transferred from humans into mice via autoantibodies.

You won't find many articles about these studies and breakthroughs in national corporate media. Instead, you will find lengthy articles arguing that Long Covid is a psychological condition-that mass psychogenesis is a better explanation for millions of newly chronically sick people (and animals) than the Covid virus.

'The truth' is out there

The psychologizing of Long Covid has been a recurrent theme in the national media since 2020, especially in outlets that cultivate a high-minded audience. The idea has appeared in the New York Times ( 8/18/21), New Yorker ( 10/20/21), New Republic ( 12/8/22), Slate ( 3/19/23, 3/26/23), Time ( 11/15/23) and Wired ( 6/1/26), among others. Media outlets that trumpet their journalistic integrity and commitment to facts have used their prestige to launder an unproven, anti-science conspiracy theory, often with headlines that refer to " the truth " about Long Covid.

The Atlantic (e.g. 9/12/22, 9/26/22) has been a notable exception, where journalist Ed Yong did award-winning Long Covid coverage from a scientific and patient-centered perspective. Mother Jones (e.g., 8/6/24, 7/19/24) also has disability coverage that consistently frames Long Covid as a medical crisis.

Perhaps surprisingly, the conservative New York Post (e.g., 2/16/24, 7/27/25, 2/1/26, 2/10/26) reports frequently on advances in Long Covid research, covering stories ignored by the centrist and liberal outlets listed above, although the Post ( 2/15/24, 12/4/25) has also published contrary opinion pieces.

Most of the skeptical coverage on Long Covid draws on the history of the psychologization of chronic diseases that Covid commonly causes, especially Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS). The disease causes energy and exercise limitations, sometimes severe. Studies estimate about 50% of people with Long Covid meet the criteria for ME/CFS.

Despite more than 30 years of research confirming the biological mechanisms involved in ME/CFS-which are acknowledged by the CDC -experts are often drowned out in the media by a cadre of psychiatrists and others determined to frame it as a mental health issue.

To varying degrees, articles that psychologize Long Covid tend to acknowledge that the physical symptoms experienced by patients are real, just unlikely to be caused by the Covid virus or any other biological origin. They often point to a vague mind-body paradigm as an explanation, but one in which the mind controls the body far more than the reverse. Overall, these articles emphasize that patients would benefit more from mental health and/or social service solutions than research and medicine.

The 'brain retraining' solution

A recent piece in Wired ( 6/1/26), titled "The Painful Truth About Long Covid," advocated for a model known as "brain retraining" to treat Long Covid. This approach focuses on rewiring the brain to not overreact to perceived threats, based on the belief that the overreaction, not the exposure, is the primary driver of symptoms. The article cited some patients who say they benefited from the approach.

The author, Alan Levinovitz, previously disclosed his views more bluntly on X last year, posting, "I happen to believe 60-80% of Long Covid is...psychogenic symptoms/illness."

In Wired, Levinovitz took aim at claims that Long Covid patients with ME/CFS are limited in their ability to exercise. He argued that the problem isn't exercise, but the belief that exercise is harmful. "Patients cursed themselves by believing their symptoms had a strictly biological cause," he wrote.

Levinovitz cited an influential British study from 2011, known as the PACE trial, which determined that Cognitive-Behavioral Therapy and guided exercise were appropriate treatments for ME/CFS. While he acknowledged that the PACE trial faced backlash and fell out of favor, he failed to mention that scientists determined the study was invalid due to improper methodologies. Levinovitz portrayed patient advocates as misguided zealots who have interfered with progress by pushing back on PACE and exercise/mind-body approaches.

The Wired article has faced mass outrage and criticism from patients, scientists, doctors and journalists. Articles and social media threads have debunked its claims on scientific grounds, citing its omission of key studies, including mind-body studies that did not support the model's effectiveness. People mentioned in the article have spoken out against how they were represented. Some critics have shared their own experiences with brain retraining, describing it as a cult-like multi-level marketing scheme.

After publication, Levinovitz spent days fighting with critics online, dismissing research findings and issuing personal attacks, even going after one woman's efforts to crowdfund for her medical care. (He has since deleted some posts, and acknowledged that he misstated facts in one thread.)

A petition is circulating, calling for the article's retraction, signed by more than 1,700 people. Wired 's only response has been to issue an "update," acknowledging two corrections. One was significant: The author mistakenly referred to Myalgic Encephalomyelitis as "Myalgic Encephelitis." The outlet has not responded to questions from FAIR about the article, including about whether it was factchecked.

The 'functional' theory

Long Covid advocates similarly campaigned against a 2022 article in the New Republic (12/8/22) by journalist Natalie Shure, which argued that the disease might be a functional neurological disorder (FND), a popular belief among the skeptical crowd. Formerly known as conversion disorder, FNDs are thought to be psychological in origin. They are often used as a catch-all for diseases without clear explanation-a modern-day "hysteria " diagnosis. Like Levinovitz, Shure doubted that exercise can be seriously harmful for people with ME/CFS.

A letter published in the Public Herald ( 1/25/23), signed by over 200 medical doctors, researchers and patients (including myself), gave a point-by-point rebuttal to Shure's article. The New Republic issued only a small correction, but never again published Shure, who had been a consistent contributor until then.

Shure, as it happens, is married to Dr. Adam Gaffney, an early and vocal skeptic of Long Covid. In a February 2021 blog post, he wrote that we should "question the causal link between the virus and some 'Long Covid' symptoms." He also argued that Long Covid was showing up mostly in wealthy white people. In fact, studies show that Black and Hispanic people have higher rates of the disease than whites.

In August 2021, the New York Times ( 8/18/21) published an op-ed by Gaffney and Dr. Zackary Berger with a "truth about Long Covid" headline. It argued that funding should not be wasted on researching Long Covid, but that patients could benefit from counseling and social services. Since Gaffney's op-ed, research has uncovered mitochondrial dysfunction, vascular issues and reactivation of Epstein-Barr in Long Covid patients.

A Time magazine article ( 11/15/23) echoed Gaffney's concerns about research funding. "But what if the medical research community spends years and hundreds more millions of dollars digging a dry hole?" the article by Steven Phillips and Michelle Williams asked.

This rhetoric has a familiar antecedent: "What if someone showed you that billions of tax dollars may have been spent chasing the wrong cause of AIDS?" Nightline ( 4/4/94) asked in a 1994 segment titled "Is HIV the Causative AIDS Agent?" The idea that AIDS had a different cause than HIV was popular during the first six or so years of the pandemic, before the discovery of HIV medications. Still, the theory appeared in Harper's Magazine ( 3/06) as late as 2006, and on Joe Rogan's podcast multiple times ( 11/7/12, 2/13/24).

During the 1980s, AIDS deniers promoted homophobic ideas that the disease was caused by lifestyle choices or spiritual malaise. With Long Covid, skeptics promote lifestyle judgments around exercise and mental health. Patients who are bedbound are accused of "deconditioning" and/or an irrational fear of exercise.

Since 2020, numerous professional athletes, who probably do not fear exercise, have described a sudden onset of incapacity following infection, not from weeks or months spent deconditioning in bed.

The biomarker issue

"There is no 'Long Covid,'" Levinovitz posted on X, just after publishing his article advocating for brain retraining to treat it. "Nothing about Long Covid adds up," his Wired story ( 6/1/26) started, citing conflicting information about prevalence.

These articles exploit the fact that Long Covid is a misunderstood and heterogenous illness to make it seem unintelligible and impossible. But Long Covid/PASC has always been defined as an umbrella diagnosis. Per the ICD-10, PASC includes anyone who has suffered chronic symptoms post-infection for three or more months. That can include gastroparesis, kidney disease, cognitive impairment or an immune system disorder. The Long Covid skeptics are rarely clear about which symptoms and conditions they believe would respond to therapy, exercise and mind-body awareness.

Most Long Covid skeptics treat the fact that the disease doesn't have a single "biomarker" as an easy way to invalidate it. As Levinovitz wrote, "Part of the definitional problem for long Covid is the absence of definitive biomarkers: genes, antibodies, any unique physiological signature of the illness."

Evidence of absence is not absence of evidence. Long Covid research is still advancing, with limited funding relative to its impact. A unique biomarker, like indication of persistent viral activation, might one day be discovered in people with chronic symptoms.

Biomarkers are not necessary to define a disease. Some diseases, like Sjogren syndrome and migraines, are diagnosed clinically, based on symptoms. Many diseases, including multiple sclerosis, Alzheimer's disease and lupus, were diagnosed clinically until biomarkers were discovered, and even those markers aren't always considered absolute indicators.

Long Covid may not have a single biomarker yet, but patients often do have biomarkers, like abnormal lymphocytes, irregular tachycardia and/or reactivated infections. Providers willing to order those tests often don't take insurance and can be hard to locate.

Both Shure and Gaffney further question if it's possible to even identify a Long Covid patient. To them, the fact that many alleged patients didn't have antibodies showing after a Covid infection was a slam-dunk reason to doubt Long Covid. But studies show that a significant percentage of infected people do not seroconvert-create antibodies-and those patients are more likely to develop Long Covid.

Investigative journalism or opinion?

Most of the articles psychologizing Long Covid look like long-form investigative journalism. They include data and quotes from purported experts, often the same group of contrarians. Yet few of these articles were written by health journalists. Shure is an exception, a journalist who writes often about health issues, though usually from a sociopolitical perspective.

Levinovitz is a professor of religion who has written one article on Long Covid in the past, as well as a book arguing that people's food sensitivities are often psychological. In Wired ( 6/1/26), he refers to the arguments around Long Covid as a "religious war."

In 2023, Slate ( 3/19/23) published a much-criticized article that attempted to discount Long Covid altogether. It was written by Jeff Wise, who reports mostly on aviation and psychology. He is best known for his work on the missing flight MH370, although he received criticism, including from aviation experts, for pushing conspiracy theories in a documentary on that subject.

Wise published a book in 2009 titled Extreme Fear: The Science of Your Mind in Danger, which might explain his interest in Long Covid. He has argued online that ME/CFS patients face a fear of exercise. Some of these writers seem to be applying their specialized thought experiments to Long Covid.

Slate ( 3/26/23) published a second article in 2023, headlined "Is Long Covid Linked to Mental Illness?" that cited Gaffney and argued for a possible psychosomatic understanding of the disease. The writer, Grace Huckins, is a neuroscience PhD student interested in mind-body connections.

"As of yet, there is no conclusive proof that stress or mental illness can contribute to Long Covid," she wrote. She then posed a bunch of hypotheticals, including:

If psychological factors have a considerable role to play in generating and maintaining Long Covid, then psychological treatments should be studied just as rigorously as drugs like Paxlovid.

Huckins did not acknowledge that psychiatric medications like low-dose Abilify are often given off-label to treat Long Covid, but not for their psychological properties.

Most of these writers previously disclosed their skeptical views on Long Covid before publishing long-form stories on the illness. Why are news outlets outsourcing articles about one of the most important health stories of the decade to ax-grinders? If the media wanted to inform the public about Long Covid, there are many qualified writers who share information and findings, in journals like Nature and outlets like the Sick Times.

National corporate media have created a controversy-"is Long Covid a real medical disease?"-which never existed in any serious form among the experts who research Covid, instead of investigating the actual nuanced debates in that field, like whether viral persistence drives symptoms. These media have given credibility to writers eager to entertain the supposed controversy, while marginalizing writers who start from the premise, widely shared among actual researchers, that Long Covid is a medical disease.

There is a similar trend in the media when it comes to trans issues, as FAIR ( 12/1/25) previously reported. The media consider sources to be "neutral" when they aren't "deeply involved in the issue," which excludes both medical experts and people actually receiving gender-affirming care.

Old media habits

Long Covid is not the only disease or disability to be treated skeptically and/or psychologized in the media. Media treatment of chronic disease and disability is a consequence of newsrooms with poor disability representation.

As I wrote about for FAIR ( 1/12/26), media have a habit of assuming that claims of disability and disease are overstated, including when students say they need accommodation. A New York Times series ( 11/9/21) posited that pain is largely driven by the mind, not broken bones or pinched nerves, so it could be treated with psychotherapy.

Stories psychologizing Long Covid also support a media agenda to minimize the Covid pandemic generally ( FAIR.org, 1/10/23). The Biden administration declared the pandemic over after the introduction of vaccines, and stopped collecting consistent data on transmission and death. Outlets like NPR followed suit, regularly referring to the current era as " post-Covid." Yet Covid wastewater levels show that the virus has continued surging in the years since, sometimes to levels higher than in 2020.

By neglecting to report seriously on Long Covid, corporate media often miss a huge part of the stories they tell. For instance, some media outlets (e.g., ABC News, 2/3/25) did report on a 2025 CDC study that more than 1 million children in the US have Long Covid, which was data from 2023. A more recent study indicates that Long Covid is now the No. 1 chronic illness in children in the US, surpassing asthma.

Yet Long Covid isn't mentioned in media reports on the crisis in chronic student absenteeism (e.g., New York Times, 2/2/24; Washington Post, 5/7/22; New Yorker, 1/15/24), or the crisis in childhood test scores and cognition (e.g., AP, 6/10/26; New Yorker, 6/12/26). Instead, the media tend to scratch their collective head and blame anxiety, screens and lockdowns.

The media tendency to ignore, deny and/or psychologize Long Covid causes significant harm to both patients and the general public, who are not being warned of the risk. Patients face disbelief and bigotry from families, workplaces and even doctors, who often get more information from the media than from journals. The gulf between medical research and practice is estimated to be 17 years on average.

Prejudices against patients are reinforced when a news outlet's most in-depth, academic-sounding articles on Long Covid attempt to undermine the reality of the disease.

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Media Won't Stop Psychologizing Long Covid

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Media outlets that trumpet their journalistic integrity have used their prestige to launder an unproven, anti-science conspiracy theory about Long Covid.

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Since President Trump took office, hundreds of experts advising on science and research issues have been dismissed. One committee was on long COVID, an issue that doctors are desperate for help with. (4 Min)

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Since President Trump took office, hundreds of experts advising on science and research issues have been dismissed. One committee was on long COVID, an issue that doctors are desperate for help with. (4 Min)

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https://www.npr.org/2026/06/22/nx-s1-5859208/a-look-at-the-science-thats-been-lost-on-long-covid

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A look at the science that’s been lost on long COVID

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Since President Trump took office, hundreds of experts advising on science and research issues have been dismissed. One committee was on long COVID, an issue that doctors are desperate for help with.

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PolyBio took its biggest step yet with the Long COVID Cure Initiative, launched in March of this year, courtesy of a $10 million donation from Todd Park and Steve Pagliuca, each of whom has family members affected by long COVID.

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PolyBio took its biggest step yet with the Long COVID Cure Initiative, launched in March of this year, courtesy of a $10 million donation from Todd Park and Steve Pagliuca, each of whom has family members affected by long COVID.

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https://www.healthrising.org/blog/2026/06/17/tissues-long-covid-me-cfs/

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Visible At Last? Are Long COVID and ME/CFS Tissue Diseases? The PolyBio 2026 Symposium Pt I - Health Rising

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Geoff’s Narration The GIST The 2026 PolyBio Spring Symposium – Pt I One way to gauge the health of a field is by the number of conferences/symposia it supports. From the looks of things, the long–COVID and ME/CFS fields are moving up: The International ME/CFS conference – May 7-8 […]

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Our results demonstrate dynamic changes in ADAR expression and editing across the three stages.

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Our results demonstrate dynamic changes in ADAR expression and editing across the three stages.

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https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1857062/full

ADAR= adenosine deaminase acting on RNA: Affects RNA stability and fx

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Aiswarya Mukundan Nair and Helen Piontkivska

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Frontiers | SARS-CoV-2-induced dysregulation in ADAR editing patterns persists post viral clearance in individuals with mild COVID-19

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IntroductionInnate immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection activates multiple interferon stimulated genes (…

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“These findings challenge the hypothesis that pre-existing mental health conditions are responsible for long COVID,” the authors wrote. “This is particularly important because the occurrence of long COVID outside of mental or psychological factors has often been overlooked or dismissed.”

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“These findings challenge the hypothesis that pre-existing mental health conditions are responsible for long COVID,” the authors wrote. “This is particularly important because the occurrence of long COVID outside of mental or psychological factors has often been overlooked or dismissed.”

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https://www.cidrap.umn.edu/covid-19/people-pre-existing-physical-mental-conditions-face-similar-risk-long-covid

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A recent in the Journal of Medical Virology by researchers at Johns Hopkins Bloomberg School of Public Health found that having physical or mental comorbidities prior to having COVID-19 raised the risk of long COVID.

"While our findings align with other studies showing increased odds of developing long COVID among individuals with mental health disorders, our results indicated that these elevated odds are not unique to those with mental health comorbidities," the authors wrote. "We found no meaningful difference in the odds of developing long COVID between participants with pre-existing mental health comorbidities and those with other non-mental health comorbidities."

Understanding the role of mental illness in long COVID

Researchers have been trying to understand the role of pre-existing mental diseases in increasing the likelihood of long COVID, a post-infection condition with an array of lingering symptoms.

The researchers looked at 9,637 participants in the Johns Hopkins COVID Long Study. Of this group, 3,635 (38%) reported having a prior mental condition with or without other health conditions, with 2,237 (62%) diagnosed as having long COVID.

These findings challenge the hypothesis that pre-existing mental health conditions are responsible for long COVID.

A second cohort of 3,616 people (38%) had pre-existing non-mental comorbidities, with 2,294 (63%) diagnosed as having long COVID. The last group of 2,386 people (25%) reported no prior health conditions, with 1,287 (54%) diagnosed as having long COVID.

The researchers found that the groups that had pre-existing physical or mental conditions were at similar risk for developing long COVID. People without prior health comorbidities were less likely to be diagnosed as having long COVID.

"These findings challenge the hypothesis that pre-existing mental health conditions are responsible for long COVID," the authors wrote. "This is particularly important because the occurrence of long COVID outside of mental of psychological factors has often been overlooked or dismissed."

The researchers also noted that there is a "strong relationship" between having several long-COVID symptoms and the onset of new depression or anxiety. The reasons for this could include the underlying mechanisms of long COVID or the stress of managing and living with a chronic illness that may not improve.

The Ebola outbreak in the Democratic Republic of the Congo (DRC) and Uganda rages, with BNO News reporting and 204 deaths today and the Africa Centre for Disease Control and Prevention (Africa CDC) telling partners it has received only about 10% of the funding pledged to help fight the outbreak.

Donors have pledged $910 million, but less than $90 million had been released for the affected countries, according to Africa CDC today during a press briefing. The new case numbers reflect 38 new infections and six new deaths.

Today the US Centers for Disease Control and Prevention (CDC) announced during a press conference it will release $107 million in emergency funding for the Ebola response in the DRC and Uganda. CDC officials also said they were engaged in twice-weekly calls with the US World Cup host cities to enhance surveillance of the disease at games, but the overall Ebola threat to Americans is low.

WHO publishes new clinical guidelines

Yesterday the World Health Organization (WHO) released a new comprehensive guide for the clinical management of filovirus disease, which include all types of Ebola and Marburg viruses. The new guidelines highlight the importance of early supportive care to improve patient survival and health outcomes, outlining 16 evidence-based recommendations.

"The current Bundibugyo virus outbreak is a stark reminder of the need for diligent, holistic and person-focused medical care, to save lives and preserve human dignity. We encourage governments and authorities to integrate these new recommendations into preparedness and outbreak response, to ensure high-quality care for everyone," said WHO Director-General Adhanom Ghebreyesus, PhD.

Among the guidelines are rapid testing, patient isolation, rehydration therapy, and early and precise use of intravenous fluids and vasoactive medications to treat shock in patients.

Drugmakers GSK and Spero Therapeutics announced yesterday that the US Food and Drug Administration (FDA) has approved their investigational oral antibiotic for complicated urinary tract infections (cUTIs).

Marketed under the brand name Utebzi, tebipenem pivoxil is the first and only oral carbapenem antibiotic approved in the United States. The antibiotic targets cUTIs caused by multidrug-resistant organisms, which have been typically treated with intravenous (IV) carbapenems.

More than three million cUTIs occur in the United States annually, and roughly one-third of patients experience treatment failure because of drug resistance.

"With antibiotic resistance continuing to rise, patients and healthcare professionals need new treatment options," GSK Chief Scientific Officer Tony Wood, PhD, said in a company press release .

Trial data show noninferiority compared with IV carbapenems

The FDA approval was based on the results of the PIVOT-PO trial, which found that tebipenem pivoxil was noninferior to IV imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis (kidney infection), based on the overall response at the test-of-cure visit.

Tebipenem pivoxil's overall success rate (a composite of clinical cure plus microbiologic eradication) was 58.5%, compared with 60.2% for imipenem-cilastatin, for an adjusted treatment difference of -1.3%. (The noninferiority margin was -10%).

The safety profile was similar to that of imipenem-cilastatin and other carbapenems. The trial was stopped early for efficacy.

With antibiotic resistance continuing to rise, patients and healthcare professionals need new treatment options.

Tebipenem pivoxil was initially developed by Spero Therapeutics. In 2022, GSK signed a licensing agreement with Spero to develop and commercialize the drug in all markets except Asia. That deal provided the financing for Spero to conduct the PIVOT-PO trial, which involved 1,690 patients hospitalized with cUTIs, including pyelonephritis.

"Through our partnership with GSK, we look forward to this much-needed oral treatment option reaching cUTI patients to help reduce the burden of the disease," said Spero Therapeutics President and CEO Esther Rajavelu, MBA.

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People with pre-existing physical, mental conditions face similar risk of long COVID

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The research provider a greater understanding of factors that might contribute to persistent symptoms.

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Immune system may attack nervous system in some Long COVID patients

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Researchers linked antibodies that attack the body’s nervous system to some neurological symptoms of Long COVID. The results may point to possible treatments for some people with Long COVID.

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Researchers linked antibodies that attack the body’s nervous system to some neurological symptoms of Long COVID. The results may point to possible treatments for some people with Long COVID.

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https://www.nih.gov/news-events/nih-research-matters/immune-system-may-attack-nervous-system-some-long-covid-patients

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This study is one of the first large-scale analyses in Korea to classify symptom patterns of long COVID (PASC) among adults and to examine differences in Health-Related Quality of Life (HRQoL) across symptom profiles. N=629

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This study is one of the first large-scale analyses in Korea to classify symptom patterns of long COVID (PASC) among adults and to examine differences in Health-Related Quality of Life (HRQoL) across symptom profiles. N=629

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https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0351506

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Abstract

Background

Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.

Objectives

In this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.

Methods

We conducted an online survey of 629 adults in Korea who experienced persistent symptoms ≥12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2®. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.

Results

A four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes ( p  < .001), with a clear gradient of decreasing scores from low to high symptom burden. The independent predictors of lower HRQoL included lower education, presence of chronic disease, poor subjective health, hospitalization during acute infection, and prolonged symptom persistence. The model explained 32.9% of the variance in HRQoL.

Conclusions

Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.

Citation: Kim S-j, Kim J (2026) Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis. PLoS One 21(6): e0351506. https://doi.org/10.1371/journal.pone.0351506

Editor: Kokouvi Kassegne, Shanghai Jiao Tong University School of Medicine, CHINA

Received: October 20, 2025; Accepted: May 28, 2026; Published: June 16, 2026

Copyright: © 2026 Kim, Kim. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was supported by research fund from Chosun University (K206904007, 2024). The funder did not play any role in the conduct or publication of the study.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The World Health Organization (WHO) defined Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) in 2021 as "symptoms that begin within 3 months of the onset of coronavirus disease (COVID-19) infection, last for at least 2 months, and cannot be explained by an alternative diagnosis" [ 1]. The U.S. Centers for Disease Control and Prevention (CDC) described a wide range of persistent, recurrent, or worsening symptoms beyond 3 months after diagnosis as Post-COVID Conditions, whereas the United Kingdom's National Institute for Health and Care Excellence (NICE) referred to symptoms that persist beyond 12 weeks as Post-COVID-19 syndrome [ 2, 3]. Although these definitions collectively include the sequelae that persist after the acute phase of infection, differences in diagnostic criteria, duration, and terminology make it difficult to compare study results and integrate clinical guidelines. Therefore, the term PASC, encompassing the definitions of all three institutions, has been widely adopted in academic contexts.

PASC symptoms vary in onset, intensity, and duration among individuals, and multiple symptoms often co-occur to form distinct symptom clusters [ 14]. Variable-centered approaches are limited in capturing such heterogeneous patterns. Recent studies have applied person-centered methods, such as latent class analysis (LCA) and latent profile analysis (LPA), to demonstrate that the PASC is not a single homogeneous condition [ 14]. For example, four symptom profiles were identified in a U.S. cohort and five in a longitudinal study conducted in the United Kingdom, with clusters characterized as fatigue-cognitive, respiratory, and pain-dominant types [ 15, 16]. However, most of these studies focused on Western populations, and few simultaneously examined symptom typology and HRQoL. In Korea, research on PASC symptom subtypes remains scarce, resulting in scant evidence on the characteristics of the Korean population. As HRQoL comprehensively reflects patients' experiences and functional impairments and serves as a key basis for healthcare resource allocation, studies investigating HRQoL differences across PASC symptom profiles are urgently needed.

In this study, we aimed to (1) identify distinct symptom profiles of PASC among Korean adult COVID-19 survivors using LPA, and (2) examine differences in HRQoL and associated factors across the identified profiles. The findings are expected to provide empirical evidence for developing tailored management strategies for PASC and serve as a practical foundation for establishing Korean population-specific PASC assessment and management guidelines, as well as related health policies.

Materials and methods

Study design

This descriptive cross-sectional study was conducted to classify latent symptom profiles based on PASC symptoms among Korean adult COVID-19 survivors using LPA, and to identify the differences and influencing factors of HRQoL across the identified profiles.

Participants

The study population consisted of Korean adults who had recovered from COVID-19 and were clinically diagnosed with SARS-CoV-2 infection at a medical institution, with at least one symptom persisting for > 12 weeks after the initial infection [ 2, 3]. Initially, 880 individuals participated in the online survey. Of them, 230 were excluded for not meeting the inclusion criteria, such as missing information regarding the date of COVID-19 diagnosis, confirmation based solely on self-testing, or having post-COVID symptoms lasting < 12 weeks. Among the remaining 650 participants, responses were further screened for data quality, and cases showing careless or inconsistent responding were excluded. Specifically, exclusion criteria included (1) highly repetitive response patterns across multiple items and (2) logical inconsistencies between related variables, such as discrepancies in COVID-19 diagnosis, symptom duration, or post-COVID symptom reporting. Based on this screening process, 21 additional cases were excluded, resulting in a final sample of 629 participants.

There is no universal rule for determining the sample size required for LPA; however, simulation studies suggest that when the number of latent classes ranges from four to six, a sample size exceeding 500 generally ensures model stability and classification accuracy [ 17, 18]. Therefore, the final sample of 629 participants was considered adequate for LPA.

Measures

General characteristics and pre-COVID-19 health status.

The participants' general characteristics included age, sex, occupation, educational level, marital status, alcohol consumption, and smoking behavior. Each item was assessed using a self-administered checklist. Pre-COVID-19 health status was evaluated based on the presence of chronic diseases and the participants' subjective perception of health. Chronic disease status was determined using a checklist of nine chronic conditions, including hypertension, diabetes mellitus, cancer, and stroke. Participants who reported at least one condition were classified as having a chronic disease. Subjective health status was assessed using a two-point Likert scale ("healthy" vs. "unhealthy")

COVID-19-related characteristics.

COVID-19-related characteristics included the number of COVID-19 vaccinations received, number of confirmed infections, whether participants visited a hospital for treatment during the acute phase, the presence of a caregiver during the infection, and the time point at which symptoms resolved after diagnosis.

PASC symptoms.

PASC symptoms were assessed using the Long COVID Symptom Tool (LCST) developed by Jeong [ 19], with permission from the author. This instrument consists of 26 items covering symptoms, such as fatigue, cough, difficulty concentrating, and anxiety. Each item was rated on a six-point Likert scale ranging from 0 ("no symptoms") to 5 ("extremely severe symptoms"). The sex-specific item "menstrual cycle changes" was analyzed only among female respondents. The overall symptom severity score was calculated as the mean of all items by dividing the total score by the number of symptoms, with higher scores indicating greater overall symptom burden. For male participants, the sex-specific item was not applicable and was excluded from the calculation; therefore, the mean score was computed based on the number of available items for each individual.

Health-related quality of life (HRQoL).

HRQoL was assessed using the validated Korean version of the Medical Outcomes Study 36-Item Short Form Health Survey Version II (SF-36 v2®) developed by Ware and Sherbourne [ 20, 21]. The official license for use was obtained from QualityMetric Incorporated (license no. Quo-03539-Y1P6WO), and scoring was performed using the SF-36 v2® Health Outcomes™ Scoring Software [ 22].

The SF-36 consists of 36 items that yield two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The PCS includes 10 items on physical functioning (PF), 4 items on role limitations due to physical problems (RP), 5 items on general health perceptions (GH), and 2 items on bodily pain (BP). The MCS includes 4 items on vitality (VT), 2 on social functioning (SF), 3 on role limitations due to emotional problems (RE), and 5 on mental health (MH).

In this study, the eight domain scores were converted to a 0-100 scale and the mean of these converted scores was used as a single HRQoL index. Higher scores indicated better HRQoL.

Data collection

Data were collected from November 1 to December 31, 2023. Participants were recruited from two major online COVID-19 communities hosted on Naver, the largest internet portal in South Korea: Long COVID 119 (1,109 members) and Coronara (40,676 members). Before recruitment, official approval to post the study announcement was obtained from the administrators of both communities. A detailed notice describing the purpose of the study, participation procedures, and ethical safeguards was posted on the communities' main announcement boards and pinned to ensure continuous visibility during the recruitment period.

Individuals who wished to participate accessed the survey through a link provided in an announcement (Google Forms). On the first page, participants were presented with a study information sheet and an online informed consent form; only those who selected "Agree" were able to proceed to the main questionnaire.

Ethical considerations

This study was approved by the Institutional Review Board (IRB) of Chosun University (Approval no. 2-1041055-AB-N-01-2023-45) prior to data collection. Before they could access the survey link, participants were provided with a study information sheet and an online informed consent form describing the study purpose, estimated duration, potential risks and benefits, data protection measures, and the right to voluntary participation and withdrawal. Only participants who selected "I agree" could proceed to the main questionnaire.

All responses were collected anonymously without any identifiable information, such as IP addresses, and were securely stored in an encrypted research-dedicated database. Access to the dataset was restricted to the research team. The data will be retained for 3 years after study completion and then permanently deleted. A small token of appreciation was given to participants upon completion of the survey. This study was conducted in accordance with the principles of the Declaration of Helsinki and Personal Information Protection Act of the Republic of Korea.

Data analysis

All statistical analyses were performed using SPSS Statistics (version 26.0; IBM Corp., Armonk, NY, USA) and Mplus version 8.0 (Muthén & Muthén, Los Angeles, CA, USA). Descriptive statistics were used to summarize the participants' general and COVID-19-related characteristics and the distribution of PASC symptoms, using frequencies and percentages for categorical variables and means with standard deviations for continuous variables.

LPA was performed using 26 PASC symptom items by applying the maximum likelihood estimation with robust standard errors (MLR). Latent profile analysis was conducted using individual item responses rather than aggregated summary scores. Models with one to six latent classes were sequentially tested. Model selection was based on the following criteria: the lowest information criteria values (Akaike Information Criterion [AIC], Bayesian Information Criterion [BIC], and sample-size adjusted BIC (saBIC), a significant Lo-Mendell-Rubin adjusted likelihood ratio test (LMR-LRT) and bootstrap likelihood ratio test (BLRT) with p  < 0.05, an entropy value ≥ 0.80, and a minimum class size of 10% of the total sample.

Differences in HRQoL across latent classes were examined using one-way analysis of variance (ANOVA). Multiple linear regression analysis was then performed to identify factors associated with HRQoL, with HRQoL as the dependent variable, and independent variables including dummy variables for latent class membership and participant characteristics that showed significant associations in the preliminary univariate analyses ( p  < 0.05).

All analyses were conducted using complete data without missing values, and two-tailed tests were used with a significance level of p  < 0.05.

Results

General characteristics of the participants and COVID-19-related factors

The mean age of the 629 participants was 36.25 ± 9.62 years; participants in their 30s (42.0%) comprised the largest proportion, followed by those aged ≤ 29 years (25.1%) and those in their 40s (23.4%), while only 3.2% of the participants were aged ≥ 60 years. Women comprised 64.4% of the participants. Regarding employment status, 76.3% were currently employed and 74.4% had completed a college degree or higher. A total of 26.4% reported following a religion and 55.5% were unmarried.

In terms of health behaviors, drinking alcohol 2-4 times per month was the most common (35.3%), followed by never drinking (29.3%), and drinking less than once per month (21.6%). Non-smokers and current smokers accounted for 63.8% and 12.6% of the participants, respectively. Before COVID-19 infection, 11.4% had at least one chronic disease, while 84.9% rated their subjective health status as "healthy."

Regarding COVID-19-related factors, 41.7% of the participants had received two vaccine doses, followed by 32.9% with three doses, and 11.0% with four or more doses, while 6.5% were unvaccinated. Most participants (77.6%) were diagnosed with COVID-19 once, 20.0% twice, and 2.4% were diagnosed three or more times. A total of 15.7% reported visiting a hospital for treatment during the acute phase and 41.5% had a caregiver during the infection. At the time of the survey, 43.4% reported that their symptoms were still persistent, 38.8% had symptoms resolve within 13-24 weeks, and 11.8% within 6-9 months ( Table 1).

Frequency and severity of PASC symptoms

Table 2 presents the frequency (percentage) and severity (mean ± standard deviation) of the 26 PASC symptoms. The most frequently reported symptoms, experienced by > 85% of the participants, were fatigue (90.6%), cough (86.3%), and post-exertional malaise (PEM) (85.2%). Other commonly reported symptoms included sore throat (81.1%), shortness of breath (dyspnea) (79.8%), sleep disturbance (79.5%), cognitive impairment (78.7%), gustatory dysfunction (loss of taste) (78.5%), fever (78.2%), and palpitations (78.2%). The least frequently reported symptom was nausea, which was experienced by 73.9% of the participants ( Table 2).

Regarding symptom severity, fatigue (3.22 ± 1.19) and PEM (3.08 ± 1.23) had the highest mean severity scores, followed by cough (2.82 ± 1.29), sore throat (2.53 ± 1.25), cognitive impairment (2.46 ± 1.31), headache (2.43 ± 1.33), olfactory dysfunction (loss of smell) (2.39 ± 1.36), and gustatory dysfunction (loss of taste) (2.39 ± 1.33). Nausea had the lowest mean severity (1.64 ± 0.97) ( Table 2).

Model-fit comparison of latent profile models

Table 3 presents the model-fit indices for the latent profile models with two to six classes (k = 2-6). The information criteria (AIC, BIC, and saBIC) consistently decreased as the number of classes increased; however, the rate of reduction diminished beyond the four-class model (ΔAIC = 453.48 from four- to five-class; ΔAIC = 324.47 from five- to six-class), indicating convergence. The BIC and saBIC values exhibited similar trends.

Regarding the model comparison tests, BLRT was significant across all models, whereas the LMR-LRT reached statistical significance only for the four-class model ( p  = 0.035), suggesting no further improvement with additional classes. Entropy values, indicating classification accuracy, were high for all models (≥ 0.97), with the four-class model also demonstrating an entropy of 0.97.

In the four-class model, the class proportions were 23.3% (Class 1), 44.1% (Class 2), 15.9% (Class 3), and 16.7% (Class 4), satisfying the criterion of at least 10% per class and indicating no imbalance in class size. In contrast, models with five or more classes produced very small groups (2.4%).

Considering the change in information criteria, the significance of LMR-LRT, high entropy values, stable class proportions, and interpretability, the four-class model was determined to be the optimal solution ( Table 3).

Characteristics of latent PASC symptom profiles

The four-class model derived from the LPA was identified as the optimal solution. The characteristics of each latent class are as follows.

Class 1 (n = 146, 23.3%) showed the lowest mean symptom severity score (0.38 ± 0.26) among the four groups and was labeled the low-symptom profile.

Class 2 (n = 278, 44.1%) demonstrated a mean symptom severity score of 1.55 ± 0.27, which was higher than that of Class 1 but lower than those of Classes 3 and 4. This group was labeled as having a moderate multisystem profile.

Class 3 (n = 105, 15.9%) had a mean severity score of 2.59 ± 0.32, higher than those of Classes 1 and 2 but lower than that of Class 4, indicating a high-symptom group. This class showed the highest scores for fatigue and PEM (3.78 ± 0.96) and was labeled the fatigue/PEM-dominant profile.

Class 4 (n = 100, 16.7%) exhibited the highest overall mean severity score (3.25 ± 0.42). Most of the 26 symptoms in this class had mean scores of ≥ 3.0, indicating a substantial symptom burden. Accordingly, this group was labeled as having a high multisystem burden profile ( Fig 1).

Note. Mean scores for 26 symptoms are plotted on a 0-5 Likert scale (higher scores indicate worse symptoms). Profiles are ordered by overall severity: Low-symptom, Moderate multisystem, Fatigue/PEM-dominant, and High multisystem burden. The sex-specific item ('Menstrual cycle changes') was calculated among female respondents only. PEM = post-exertional malaise.

Differences in HRQoL

The mean HRQoL score among the participants was 70.79 ± 8.53. Statistically significant differences in HRQoL were observed across age, education level, smoking status, pre-existing chronic disease, subjective health status, number of COVID-19 vaccine doses, hospital visits for acute COVID-19 treatment, time to symptom resolution after diagnosis, and latent symptom profile class.

By age group, participants aged ≤ 29 years showed the highest mean HRQoL (72.92 ± 5.63), followed by those in their 40s (71.03 ± 7.85), whereas those in their 50s had the lowest HRQoL (68.97 ± 7.80; p = .003). Regarding education level, participants with a college degree or higher reported significantly higher HRQoL (71.87 ± 7.38) than those with middle school education or lower (62.86 ± 9.01; p  < .001).

In terms of smoking status, non-smokers had the highest HRQoL (72.00 ± 7.97), followed by current smokers (70.78 ± 7.58) and former smokers (67.54 ± 9.62; p < .001). Participants with pre-existing chronic diseases reported lower HRQoL (65.63 ± 10.02) than those without (71.46 ± 8.09; p < .001). Similarly, those who perceived their health as "healthy" (71.68 ± 8.19) had significantly higher HRQoL than those who perceived themselves as "unhealthy" (65.81 ± 8.74; p  < .001).

With regard to vaccination status, HRQoL differed significantly by the number of doses received: participants with four or more doses had the lowest HRQoL (66.38 ± 11.37), followed by unvaccinated individuals (68.05 ± 9.60), those with one dose (69.74 ± 7.39), two doses (71.27 ± 7.42), and three doses (72.45 ± 8.20; p < .001). Participants who visited a hospital for acute COVID-19 treatment reported lower HRQoL (66.63 ± 8.88) than those who did not (71.76 ± 8.12; p  < .001).

Regarding symptom resolution period, participants whose symptoms resolved within 13-24 weeks after diagnosis had the highest HRQoL (74.40 ± 6.31), whereas those whose symptoms persisted at the time of the survey had the lowest HRQoL (67.69 ± 8.73; p  < .001).

Across the latent symptom-profile classes, mean HRQoL scores were as follows: Class 1 (low-symptom profile), 71.68 ± 9.09; Class 2 (moderate multisystem profile), 72.87 ± 8.12; Class 3 (fatigue/PEM-dominant profile), 68.42 ± 8.88; and Class 4 (high multisystem burden profile), 66.21 ± 5.76 ( p < .001). The HRQoL showed a stepwise decline with increasing symptom burden ( Table 4).

Predictors of HRQoL

To identify the predictors of HRQoL, multiple linear regression analysis was performed, including the participant characteristics that showed significant differences in HRQoL in the univariate analyses (age, level of education, smoking status, pre-existing chronic disease, subjective health status, number of COVID-19 vaccine doses, hospital visits for acute COVID-19 treatment, and time to symptom resolution after diagnosis), along with the latent symptom profile class. Categorical variables were dummy coded before being included in the regression models.

The overall regression model was statistically significant ( F = 13.50, p < .001), with the included independent variables explaining approximately 32.9% of the variance in HRQoL scores ( R²  = .329). The Durbin-Watson statistic was 1.69, indicating no autocorrelation of the residuals. Tolerance values ranged from 0.11 to 0.94, and variance inflation factors (VIFs) ranged from 1.05 to 9.32, confirming the absence of multicollinearity. Examination of the residual plots and standardized residuals indicated that the assumptions of linearity, homoscedasticity, and normality were satisfied.

Among the independent variables, participants with a college education or higher showed significantly higher HRQoL than those with middle school education or lower ( β = .29, p = .004). HRQoL was also significantly higher among participants without pre-existing chronic diseases ( β = .10, p = .008) and among those who perceived themselves as healthy ( β = .14, p < .001). Conversely, participants who visited a hospital for acute COVID-19 treatment had significantly lower HRQoL ( β = -.11, p  = .004).

Compared with participants whose symptoms persisted at the time of the survey, those whose symptoms resolved within 13-24 weeks ( β = .23, p < .001) and within 6-9 months ( β = .10, p = .006) reported significantly higher HRQoL. Regarding latent symptom-profile class, participants in Class 2 (moderate multisystem profile) ( β = -.09, p = .024) and Class 4 (high multisystem burden profile) ( β = -.17, p < .001) had significantly lower HRQoL than those in Class 1 (low-symptom profile). Interestingly, participants in Class 3 (fatigue/PEM-dominant profile) had higher HRQoL compared with those in Class 1 ( β = .02, p < .001) ( Table 5). These results represent associations after adjustment for potential confounding variables, whereas the descriptive comparisons are based on unadjusted mean differences across classes.

Discussion

A clear gradient was observed in the HRQoL analysis, indicating that quality of life decreased progressively with increasing symptom burden. Notably, however, although the moderate multisystem profile (Class 2) showed the highest mean HRQoL in the unadjusted comparisons, this pattern was attenuated in the regression analysis after adjustment for covariates. This discrepancy likely reflects differences in the distribution of sociodemographic and clinical characteristics across classes, such as educational attainment, subjective health status, and the burden of chronic conditions, which may independently influence HRQoL. In contrast, the fatigue/PEM-dominant profile (Class 3) exhibited relatively higher HRQoL in the adjusted model, suggesting that specific symptom patterns may be differently associated with HRQoL compared to overall symptom burden when individual characteristics are taken into account. Overall, this pattern reflects the influence of covariate adjustment, indicating that the observed differences in HRQoL across latent classes should be interpreted in the context of underlying participant characteristics rather than as simple unadjusted group differences.

Education level, presence of chronic diseases, subjective health perception, history of hospital visits for acute COVID-19 treatment, and time-to-symptom resolution were identified as independent predictors of HRQoL. The multiple regression model explained approximately 32.9% of the variance in HRQoL ( R² = .329), which was comparable to or slightly higher than the explanatory power reported in previous studies on HRQoL among patients with PASC [ 13]. These findings suggest that multidimensional risk factors should be considered when developing strategies for managing PASC in Korean adults.

When compared with findings from Western studies, the four symptom profiles identified in this study were consistent in that they all included a high-burden group characterized by a combination of fatigue, cognitive impairment, and pain. A longitudinal study in the United Kingdom reported fatigue/cognitive-dominant and respiratory/pain-type clusters [ 15], whereas a large-scale data analysis in the U.S identified a high multisystem burden group [ 16]. The fatigue/PEM-dominant class observed in this study is consistent with the abovementioned findings and notably overlaps with the PEM commonly reported among patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [ 24], supporting the potential pathophysiological continuity between PASC and ME/CFS.

However, the proportion of the low-symptom class was relatively high (23%) in the Korean sample, which was probably due to the characteristics of online recruitment. Individuals who voluntarily participate in online surveys often exhibit higher health-related anxiety, which could result in differences in the actual population distribution of low-symptom cases [ 6, 7]. In addition, the "respiratory-dominant" phenotype commonly reported in Western studies was not clearly observed in this study. This discrepancy may be related to clinical characteristics specific to Asian populations, differences in vaccination rates, or variations in the dominant viral strains during different epidemic periods [ 5, 9]. Therefore, nationwide population-based surveys and linkage studies incorporating clinical data are warranted.

The mean HRQoL level among the participants was significantly lower than that of the general Korean adult population and comparable to that reported in patients with heart failure or multiple sclerosis [ 13]. Given the relatively high prevalence of several symptoms observed in this study, these findings should be interpreted with caution. In particular, individuals with persistent symptoms showed markedly lower HRQoL scores, indicating that PASC can have substantial long-term effects on physical, mental, and social functioning [ 8, 9, 13, 25]. Educational attainment emerged as an important protective factor, likely reflecting its close association with health literacy and access to resources [ 18, 19]. Conversely, the presence of chronic disease and hospitalization during the acute phase of COVID-19 were associated with lower HRQoL, suggesting a "double burden" effect in which PASC exacerbates pre-existing conditions [ 10, 11].

The number of COVID-19 vaccine doses was associated with HRQoL in a nonlinear pattern rather than a simple linear association, which may indicate interactions with factors such as the persistence of post-vaccination symptoms or reinfection experiences, as reported in previous studies, warranting further investigation [ 12]. Notably, this association should be interpreted with caution, as individuals with different vaccination histories may differ systematically in age, pre-existing health conditions, and healthcare access, all of which can independently influence HRQoL. Therefore, the observed relationship may partly reflect underlying differences in population characteristics rather than a direct effect of vaccination alone. Hospitalization during the acute phase and delayed symptom resolution were major predictors of lower HRQoL. In particular, participants whose symptoms persisted for > 6 months exhibited markedly reduced HRQoL, underscoring the urgent need to establish a long-term management system for post-COVID sequelae [ 4, 20].

From a policy perspective, our findings support long-term vaccination strategies and investments in PASC rehabilitation programs. In Korea, studies have estimated that several hundred thousand individuals may experience PASC [ 5, 7], and the absence of a long-term management system can lead to substantial social and economic costs [ 11, 12]. Beyond the individual burden of reduced quality of life, PASC is also associated with productivity loss and increased healthcare expenditure. The United Kingdom's OpenSAFELY study reported higher annual primary care costs among patients with long-term sequelae [ 12, 13], a finding that may serve as a relevant policy reference in Korea. Therefore, early intervention and optimized resource allocation are essential for reducing the cost burden.

When developing national PASC management guidelines, it is crucial to incorporate tailored management strategies based on symptom profiles. Management approaches that distinguish between the low- and high-symptom groups can enhance policy efficiency and clinical effectiveness. Furthermore, the inclusion of PASC-related support items in the national health insurance system and the expansion of community-based rehabilitation and psychosocial support services are urgently warranted [ 21, 22].

This study is the first in Korea to apply LPA for classifying PASC symptom patterns using a large sample of COVID-19 survivors (n = 629). In particular, 26 symptom domains and HRQoL were simultaneously assessed using the SF-36 v2® instrument, allowing for a multidimensional analysis of the association between symptom burden and HRQoL. The use of an officially licensed assessment tool and a high entropy value (>.97) support the methodological rigour and classification accuracy of the latent classes identified in this study.

Nevertheless, this study has several limitations. First, because this study employed a cross-sectional design, causal relationships between latent symptom profiles and HRQoL could not be determined. Second, the participants were recruited through online communities, which may have led to an overrepresentation of individuals with more severe symptoms, resulting in potential selection bias. Therefore, caution is warranted when generalizing these findings to the broader population of individuals with PASC. Third, major variables, including symptom experience, vaccination, and hospitalization, were based on self-reported data, which may have introduced recall and information biases. Fourth, objective biological indicators (such as laboratory or imaging findings) were not included, limiting the ability to directly examine the association between symptom profiles and underlying physiological mechanisms. Fifth, HRQoL was calculated as a single composite index by averaging the eight domain scores of the SF-36 v2® after conversion to a 0-100 scale. However, because the SF-36 is inherently a multidimensional instrument, reporting domain-specific scores and summary measures ( PCS/MCS) is generally recommended, and the validity of a single total score remains unestablished [ 20- 22]. Therefore, potential limitations in construct validity, as well as dilution of domain-specific effects, should be considered when interpreting the findings of this study. In particular, the use of a composite score may have obscured differential patterns between physical and mental components of HRQoL across symptom profiles. Future studies should incorporate both domain-specific scores and standardized summary measures (PCS, MCS, and norm-based scores) to provide a more comprehensive and interpretable assessment of HRQoL and to enhance comparability across studies.

However, this study is significant because it identified the heterogeneity of PASC symptom profiles and differences in HRQoL among Korean adults using a large-scale dataset. Future research should adopt a longitudinal design to track changes in symptom profiles and HRQoL trajectories over time. In particular, investigating the relationships between objective biomarkers (such as autonomic nervous system indices and inflammatory markers) and symptom profiles could help elucidate the underlying biological mechanisms. Additionally, randomized controlled trials applying tailored interventions, such as exercise, cognitive-behavioral therapy, and psychological support, according to symptom profiles, are warranted. Finally, expanding the research to include children, older adults, and vulnerable populations will enhance the comprehensiveness of future policy recommendations [ 27].

In conclusion, this study identified four heterogeneous symptom profiles among Korean adults with PASC and demonstrated the independent effects of profile-specific clinical characteristics on HRQoL. These findings provide fundamental evidence for the development of Korean population-specific PASC assessment tools and the establishment of tailored management strategies and health policies.

References

1. 17. Nylund KL, Asparouhov T, Muthén BO. Deciding on the Number of Classes in Latent Class Analysis and Growth Mixture Modeling: A Monte Carlo Simulation Study. Structural Equation Modeling: A Multidisciplinary Journal. 2007;14(4):535-69.

2. 18. Spurk D, Hirschi A, Wang M, Valero D, Kauffeld S. Latent profile analysis: A review and "how to" guide of its application within vocational behavior research. J Vocat Behav. 2020;120:103445.

3. 19. Jeong JH. Symptom clusters and quality of life in people with long coronavirus disease. Jeonju (Republic of Korea): Jeonbuk National University. 2023.

4. 24. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-15.

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# data[].attributes.attachment_link.title
Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis

# data[].attributes.attachment_link.description
Background Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.

# data[].attributes.headline
Vaccine may be cardioprotective, especially for older adults and those with comorbidities. (N= >1M)

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Vaccine may be cardioprotective, especially for older adults and those with comorbidities. (N= >1M)

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https://www.statnews.com/2026/06/15/covid-vaccination-cardiovascular-protection-jama-study/

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Covid vaccination cut risk of adverse heart events, large study finds

# data[].attributes.attachment_link.description
Covid vaccination was also tied to a nearly 24% reduction in all-cause cardiac events in a large study, surprising researchers.

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Researchers caution the evidence is preliminary but say the findings underscore a familiar message for cancer survivors and others at risk: avoid severe viral infections, using vaccines and other reasonable precautions.

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Researchers caution the evidence is preliminary but say the findings underscore a familiar message for cancer survivors and others at risk: avoid severe viral infections, using vaccines and other reasonable precautions.

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https://www.latimes.com/science/story/2026-06-15/what-covid-teaches-doctors-about-relationship-viruses-cancer

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What COVID is teaching doctors about the relationship between viruses and cancer

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The pandemic has left some evidence that viral infection may play a role in reawakening dormant cancer cells already present in a patient’s body before infection.

# data[].attributes.headline
Specifically, long COVID was associated with a higher risk of angina (chest pain) and myocardial infarction (heart attack). N=8,332

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Specifically, long COVID was associated with a higher risk of angina (chest pain) and myocardial infarction (heart attack). N=8,332

# data[].attributes.body
https://www.cidrap.umn.edu/covid-19/long-covid-patients-more-likely-develop-heart-disease-study-finds

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Long-COVID patients are more likely to develop cardiovascular disease (CVD), according to a recent analysis of a national survey published in the journal

Long COVID is a chronic illness in which people experience lingering symptoms after an initial COVID-19 infection. The diagnosis is not well understood, though many patients report cardiovascular complications

The study confirms that CVD is more common among long-COVID patients: 11.9% of those with long COVID have CVD compared with 6.8% without this diagnosis. In an adjusted analysis, long COVID was associated with 37% higher odds of any CVD diagnosis (odds ratio [OR], 1.37).

Specifically, long COVID was associated with a higher risk of angina (chest pain; OR, 1.81) and myocardial infarction (heart attack; OR, 1.50), but not coronary heart disease (OR, 1.23) or stroke (OR, 1.28). The 95% confidence intervals for the final two conditions ranged below 1, indicating no elevated risk.

Interestingly, those with pre-existing CVD were not more likely to report new long-COVID symptoms. The findings echo those of a study from Sweden published earlier this year.

More long-COVID research needed

The analysis used self-reported data from the 2022 Medical Expenditure Panel Survey, which included 8,332 participants with a history of COVID-19.

People were categorized as having pre-existing CVD if they received this diagnosis in the year before they got COVID-19. New-onset CVD was assessed in two ways: if the diagnosis occurred in the same year or following year of a COVID-19 illness, or if it occurred within a year after COVID-19.

Scientists say their findings show the need for additional research to improve health interventions for long COVID, which affects an estimated 17.8 million Americans .

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Long-COVID patients more likely to develop heart disease, study finds

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People with long COVID are more likely to experience angina and myocardial infarction, according to a national survey.

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They found that people with long COVID used nearly every type of healthcare service more frequently than those who recovered fully from COVID or were never infected. N=28K

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They found that people with long COVID used nearly every type of healthcare service more frequently than those who recovered fully from COVID or were never infected. N=28K

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https://www.cidrap.umn.edu/covid-19/paper-spotlights-high-healthcare-burden-and-costs-long-covid

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A new study suggests that post-COVID-19 condition (PCC), commonly known as long COVID, has placed a substantial burden on healthcare systems in the years since the onset of the pandemic and is associated with significantly higher healthcare use and costs compared with either COVID infection without lingering symptoms or no history of infection.

For the , published in the International Journal of Infectious Diseases , researchers led by a team at the University of Groningen in the Netherlands analyzed data from nearly 28,000 participants in a large population-based study in the Netherlands that examined the health and health-related behaviors of more than 150,000 Dutch adults. They found that people with long COVID used nearly every type of healthcare service more frequently than those who recovered fully from COVID or were never infected.

The researchers defined long COVID as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation."

High costs of long COVID

The researchers estimated that average annual healthcare costs for people with long COVID were €1,136 ($1,315 US) per person, compared with €616 ($713) for people who had COVID without developing ongoing symptoms and €678 ($785) for those who were never infected.

"Except for hospitalizations, costs of the PCC group were substantially higher than costs of the COVID-19 group," note the researchers.

Primary care visits accounted for the largest share of costs across all groups. Average annual primary care costs per participant in the long COVID group were roughly twice as high as costs in the other two groups (PCC, €434 [$502]; COVID-19, €202 [$234]; control, €216.50 [$250.50]).

Heavy healthcare burden

On average, long-COVID patients consulted with general practitioners (GPs, or primary care practitioners) twice per year. "The relatively high number of GP consultations in the PCC group can likely be explained by the persistence of a wide diversity of symptoms as well as the absence of an effective care pathway," write the researchers.

Long-COVID patients also averaged six physical therapy visits annually, making it the most commonly used primary care service among that cohort. But the largest difference in primary care use among those with long COVID and those without lingering symptoms or no history of infection was observed for occupational therapy.

Occupational therapy consultation rates were more than eight times higher among those with long COVID than those who were uninfected and more than 20 times higher among those who got COVID but didn't develop lingering symptoms (PCC to control, 8.7 times; PCC to COVID-19, 20.3 times). Because myalgia (muscle pain) is a common symptom among long-COVID patients, it's not surprising that physical therapy and occupational therapy visits were relatively high among this group, note the authors.

These numbers reveal the longitudinal impact of PCC on patients, their families, and society, and address the need for dedicated care to this particular group of patients.

Consultation rates for speech therapy were eight times higher among those with long COVID compared with those who were never infected and 14 times higher among those without lingering symptoms (PCC to control, 8.0 times; PCC to COVID-19, 14.2 times).

Long-COVID patients also had the most annual secondary care visits in nine of 15 specialties compared with the other two groups, with the highest difference observed in the "unspecified specialty" category, followed by pulmonology, which focuses on breathing problems.

In addition, people with long COVID received more hours of in-home nursing care and were more likely to attend day-treatment rehabilitation programs. Long-COVID patients also reported significantly greater dependence on informal care from family members and friends-roughly 15 hours per week for people with long COVID, compared with 3.4 in the COVID group and 5.3 hours in the control group.

When the researchers included the value of that unpaid care in their calculations, annual costs for long COVID patients rose nearly 25%.

Findings may help create more efficient care

The emergency phase of the pandemic has ended and the number of new long-COVID cases across the world has decreased, write the authors, yet a significant percentage of long-COVID patients experience persistent symptoms two years after infection. The authors cite previous research suggesting that long-COVID patients who are discharged from the hospital report lower quality of life, decreased exercise capacity, increased mental health issues, and more healthcare use two years after infection.

"These numbers reveal the longitudinal impact of PCC on patients, their families, and society, and address the need for dedicated care to this particular group of patients," write the researchers. They note that their findings reveal what types of healthcare are primarily used by long-COVID patients and conclude that the data may help policymakers in creating more efficient care pathways for these patients.

"Given that healthcare resources, such as budgets and personnel in both primary and secondary care, are generally growing scarcer, it is important to monitor resource use to identify bottlenecks throughout the care pathway," they conclude.

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Paper spotlights high healthcare burden and costs of long COVID

# data[].attributes.attachment_link.description
A new study suggests that post-COVID-19 condition (PCC), commonly known as long COVID, has placed a substantial burden on healthcare systems in the years since the onset of the pandemic and is associated with significantly higher healthcare use and costs compared with either COVID infection without lingering symptoms or no history of infection.

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The interim final rule released by the CMS means being sick with extreme exhaustion and memory challenges related to her treatments may not be enough for Brandon to evade the new work requirements. 

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The interim final rule released by the CMS means being sick with extreme exhaustion and memory challenges related to her treatments may not be enough for Brandon to evade the new work requirements. 

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https://www.wcax.com/2026/06/12/too-sick-work-can-they-prove-it-new-medicaid-rule-worries-patients/

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Too sick to work, but can they prove it? New Medicaid rule worries patients

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The new Medicaid restrictions, which Democrats have criticized, were part of Trump’s big tax and policy law in 2025.

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SARS-CoV-2 history associated with ↑ risk of 6 allergic conditions over 18 months. ( asthma, hay fever, food allergy, eczema, medication allergy, and hives)

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SARS-CoV-2 history associated with ↑ risk of 6 allergic conditions over 18 months. ( asthma, hay fever, food allergy, eczema, medication allergy, and hives)

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https://www.medscape.com/viewarticle/covid-history-may-prompt-new-allergies-2026a1000jkz?src=rss

*changed to common allergy names

# data[].attributes.attachment_link.keywords[]
covid-19; coronavirus; 2019 novel coronavirus; 2019-ncov; wuhan coronavirus; corona virus; covid19; novel coronavirus; sars-cov-2

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post-acute sequelae of sars-cov-2 infection; post-acute sequelae of sars-cov-2 infection (pasc); long covid

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otolaryngology; ent specialty; ent speciality

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Data from a large study of children and adults showed an increased risk of developing atopic diseases in those with a history of SARS-CoV-2 infection.

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Major cardiotropic and cardioactive viruses—including SARS COV 2, influenza virus, HIV, arboviruses (dengue/chikungunya, Zika), enteroviruses (coxsackie), and human CMV—contribute to myocardial injury.

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Major cardiotropic and cardioactive viruses—including SARS COV 2, influenza virus, HIV, arboviruses (dengue/chikungunya, Zika), enteroviruses (coxsackie), and human CMV—contribute to myocardial injury.

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https://journals.asm.org/doi/10.1128/jvi.00383-26

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INTRODUCTION

Viruses have existed long before human history and are ubiquitous in the human environment. Humans acquire viral infections through multiple routes, including the respiratory tract (e.g., inhalation of aerosols or droplets), the gastrointestinal tract (e.g., ingestion of contaminated food or water), contact transmission-either direct (person-to-person) or indirect (via contaminated objects or surfaces)-and vector-borne transmission via arthropods such as mosquitoes and ticks, which is particularly relevant for arboviruses. Importantly, only a subset of viruses exhibit clinically meaningful cardiac tropism or trigger host responses that culminate in cardiovascular injury. Nonetheless, viral infections can affect the cardiovascular system through direct and indirect mechanisms and are increasingly recognized as contributors to an elevated risk of major cardiovascular diseases ( 1). A substantial body of evidence supports a close association between viral infection and cardiac pathology. Viral illness may precipitate a spectrum of cardiovascular manifestations, including myocarditis, pericarditis, arrhythmias, and acute or chronic heart failure ( 2-5). Proposed mechanisms include direct injury to cardiomyocytes and other cardiac-resident cells, immune-mediated damage (e.g., exaggerated inflammation, cytokine-driven injury, and autoimmunity), and perturbations of cardiac electrophysiology that promote conduction abnormalities and malignant arrhythmias. In addition, systemic effects of infection-such as endothelial dysfunction, plaque destabilization, and a prothrombotic state-may precipitate acute ischemic events and cerebrovascular complications ( 6-8). Multiple viral pathogens have been implicated in major adverse cardiovascular events (MACEs). These include severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, HIV, arboviruses (dengue virus [DENV], chikungunya virus [CHIKV], Zika virus [ZIKV]), enteroviruses (coxsackievirus B3 [CVB3]), and human cytomegalovirus (HCMV). Reported MACEs encompass acute myocardial infarction, stroke, heart failure exacerbation or new-onset heart failure, clinically significant arrhythmias, and myocarditis ( 3, 9-14).

VIRAL INFECTIONS ASSOCIATED WITH CARDIOVASCULAR DISEASES

SARS-CoV-2

Since the initial reports in 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has resulted in more than 7 million deaths worldwide ( 15). The most common proximate cause of death in severe cases is respiratory failure due to viral pneumonia and acute respiratory distress syndrome ( 16). However, cardiovascular complications-including acute heart failure, clinically significant arrhythmias, and thromboembolic events-also substantially contribute to morbidity and mortality ( 17).

SARS-CoV-2 entry into host cells is primarily mediated by binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2), followed by membrane fusion and/or receptor-mediated endocytosis ( 18). ACE2 is a membrane-bound carboxypeptidase that also serves as a functional viral receptor; it is highly expressed in several organs, including the lungs, kidneys, and heart, and soluble ACE2 can be detected in plasma ( 19, 20). SARS-CoV and SARS-CoV-2 share substantial sequence homology (approximately 76% amino acid identity), and ACE2 is a key determinant of host range and transmissibility for related coronaviruses ( 21-23). Within the heart, experimental studies indicate that SARS-CoV-2 shows relatively higher tropism for cardiomyocytes and pericytes than for macrophages, fibroblasts, or endothelial cells, although these findings may vary by model system and disease context ( 24, 25). Moreover, increased myocardial ACE2 expression reported in conditions such as heart failure and diabetes has been proposed as a potential factor influencing susceptibility and/or disease severity in patients with pre-existing cardiovascular risk ( 24, 26-29).

Cardiac involvement in COVID-19 is clinically heterogeneous, encompassing myocarditis or myocarditis-like syndromes, pericarditis, arrhythmias, heart failure (including de novo dysfunction and exacerbation of established disease), and vascular complications such as coronary inflammation and thrombosis ( 30-33). Epidemiological studies have identified COVID-19 as a risk factor for acute myocardial infarction and ischemic stroke, consistent with these vascular clinical manifestations ( 34). Mechanistically, SARS-CoV-2-associated cardiac injury is likely multifactorial, reflecting a variable contribution from direct viral infection of cardiac cells, immune-mediated injury, microvascular dysfunction, and systemic inflammation with prothrombotic and hemodynamic consequences ( 35) ( Fig. 1). Consistent with this, epidemiologic studies have demonstrated that biochemical and/or imaging evidence of myocardial injury is associated with worse outcomes and higher mortality in hospitalized patients ( 36). Substantial evidence from autopsy and tissue-based studies has demonstrated the presence of SARS-CoV-2 RNA, antigen, and related viral material in cardiovascular tissues, including myocardial tissue and coronary arteries ( 8, 37). However, these findings do not uniformly establish widespread productive cardiomyocyte infection in all cases, and viral RNA may be undetectable in some myocardial samples at the time of examination, likely reflecting heterogeneity in disease stage, tissue sampling, and viral persistence ( 38, 39). This observation may indicate that indirect immune or inflammatory mechanisms predominate in a substantial proportion of patients. However, alternative explanations must be considered, including that the virus had already been cleared by the host immune response prior to sampling, or that the focal nature of viral myocarditis combined with limited tissue sampling could lead to false-negative results. Collectively, these findings underscore that indirect mechanisms play a significant role in the pathogenesis of virus-associated cardiovascular injury while also highlighting the diagnostic challenges in confirming direct cardiac infection in human studies. Experimental models provide additional insight into potential direct effects on cardiomyocytes. In human pluripotent stem cell-derived cardiomyocytes, SARS-CoV-2 infection has been associated with impaired contractility, induction of inflammatory mediators, sarcomere disruption, and cell death, collectively compromising electrical and mechanical function ( 6, 40). In a mouse model with cardiomyocyte-restricted SARS-CoV-2 infection, transient viral replication in the heart triggered macrophage-predominant immune infiltration and subsequent deterioration in cardiac function, supporting the concept that primary cardiac infection can be sufficient to drive myocardial dysfunction in vivo ( 41). These mechanistic observations, while informative, should be interpreted alongside human tissue data indicating substantial interindividual variability in the degree of myocardial viral burden and inflammatory injury.

Fig 1 Mechanism of SARS-CoV-2-induced myocardial injury. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; ACE: angiotensin-converting enzyme; ACE2: angiotensin-converting enzyme 2; TMPRSS2: transmembrane serine protease 2.

Beyond the acute phase, a subset of patients experience persistent symptoms and organ dysfunction after SARS-CoV-2 infection (post-acute sequelae of COVID-19, often termed "long COVID"). Emerging evidence suggests that ongoing cardiovascular manifestations may occur in this context, including persistent myocardial inflammation and dysautonomia, although the underlying biology is not fully defined ( 42). In some studies, SARS-CoV-2 viral RNA and related viral material have been identified in cardiac tissues for months after the initial infection, with distribution across distinct cardiac regions, including myocardial tissue and coronary arteries. Such findings support the possibility that persistent viral material and/or sustained immune activation may contribute to post-COVID myocardial and vascular pathology in a subset of patients. ( 8, 37, 43). Importantly, population-based data from the United Kingdom indicate that the risk of acute myocarditis following SARS-CoV-2 vaccination is lower than the risk observed after SARS-CoV-2 infection in unvaccinated individuals, supporting an overall favorable risk-benefit profile of vaccination for myocarditis prevention at the population level ( 44). Overall, SARS-CoV-2 can affect the heart during acute infection and may also impose longer-term cardiovascular risk, either by inducing new pathology or by exacerbating pre-existing cardiovascular diseases. Accordingly, elucidating the mechanisms, incidence, and trajectory of cardiovascular sequelae after SARS-CoV-2 infection remains an important priority with direct implications for prevention, risk stratification, and long-term management.

Influenza virus

The mechanisms by which influenza contributes to cardiac injury appear to be multifactorial. Both influenza A and B viruses have been implicated in cardiac complications, potentially through cytokine-mediated cardiotoxicity and immune dysregulation, including autoimmune responses directed against cardiac antigens ( 49-52). Cardiac injury may occur via direct infection of cardiac cells or indirectly through systemic inflammation with induction of inflammatory mediators, acute-phase reactants, and procoagulant factors, which together can promote endothelial dysfunction, microvascular injury, and thrombosis ( 46, 49, 53). In line with these mechanisms, epidemiologic studies have reported a significant association between recent influenza infection and acute myocardial infarction ( 54), supporting the concept that influenza can trigger plaque destabilization and/or a prothrombotic milieu leading to acute coronary syndromes. Experimental studies further support a direct role of influenza virus in cardiac pathology. Kenney and colleagues showed that influenza-infected Ifitm3 −/− mice developed significant cardiac electrical abnormalities, including bradycardia and irregular RR intervals, consistent with direct cardiac involvement. Importantly, by using a recombinant influenza virus that was specifically attenuated for replication in cardiomyocytes but retained replication competence in the lungs, they further demonstrated that pulmonary inflammation alone was not sufficient to drive the cardiac phenotype. Rather, direct cardiomyocyte infection and replication were required for the development of influenza-associated cardiac dysfunction and fibrosis in this model ( 46, 55, 56). Recent research has further elucidated a unique cellular route for influenza virus dissemination to the heart and its local pathogenic mechanisms within cardiac tissue. Work by Downey et al. revealed that the influenza virus can traffic to the heart via a specialized immune cell subset termed progenitor DC3 (pro-DC3). This study also established that, in the context of direct cardiomyocyte infection, type I interferon signaling within cardiomyocytes itself is cardiopathogenic, uncovering a novel intracellular mechanism by which viral infection precipitates cardiac injury ( 52). Complementary animal data indicate that both pathogenic and attenuated human influenza A viruses can infect multiple cardiac cell types-including cardiomyocytes and components of the specialized conduction system (e.g., Purkinje cells)-as well as cardiac endothelial cells, and that cardiac infection may occur independently of pulmonary viral titers, suggesting tissue-specific determinants of viral dissemination and tropism ( 7).

Collectively, available data support several non-mutually exclusive pathways for influenza-associated cardiac injury, including direct cardiomyocyte injury, systemic and interferon-driven inflammatory responses, excessive cytokine signaling, myocardial fibrosis and remodeling, hypoxia-related supply-demand mismatch, and destabilization of coronary atherosclerotic plaques ( 46, 52, 57-59). Importantly, influenza vaccination reduces the risk of infection and is associated with fewer influenza-related cardiovascular complications. By preventing infection and attenuating systemic inflammatory responses, vaccination may thereby reduce the incidence of influenza-associated myocarditis and heart failure exacerbations ( 60). Nevertheless, the relative contribution of each pathogenic pathway likely varies across patient populations and clinical phenotypes, and the mechanisms underlying influenza-associated cardiac events in humans are not fully resolved. Further mechanistic and translational studies are therefore needed to refine risk stratification and to inform personalized diagnostic and therapeutic strategies aimed at reducing the burden of influenza-related cardiovascular complications.

HIV

HIV remains a major global public health challenge, with an estimated 44.1 million cumulative deaths to date. According to the latest World Health Organization report, approximately 40.8 million people were living with HIV by the end of 2024, with about 65% residing in the WHO African Region ( 61). HIV primarily infects and depletes CD4+ T lymphocytes, which are critical for host immune competence. In the absence of treatment, progressive CD4+ T-cell loss leads to severe immunodeficiency and, ultimately, acquired immunodeficiency syndrome (AIDS) ( 62). With improved access to and effectiveness of antiretroviral therapy (ART), HIV infection has transitioned to a chronic, manageable condition. Consequently, people living with HIV/AIDS increasingly experience non-AIDS comorbidities, including cardiovascular disease (CVD), often at a younger age than HIV-negative populations ( 63, 64). Cardiovascular and other circulatory system disorders have emerged as prominent causes of morbidity among people living with HIV/AIDS, driven by a multifactorial pathogenesis that includes persistent immune activation and chronic inflammation, HIV-associated endothelial dysfunction, and metabolic disturbances related in part to ART exposure ( 65, 66). Epidemiological and clinical studies indicate that CVD is now a leading contributor to HIV-associated morbidity and mortality, with a significantly elevated cardiovascular risk observed in people living with HIV/AIDS compared with the general population ( 67). Importantly, although ART can achieve durable suppression of plasma viremia, it does not eradicate latent viral reservoirs. Viral proteins may continue to contribute to pathogenesis even under virologic suppression. The HIV-1 accessory protein Nef has been implicated in viral virulence, immune dysregulation, and persistence. In Nef transgenic (Nef-TG) mouse models, Nef expression has been associated with impaired cardiac function, adverse myocardial remodeling, and increased fibrosis, culminating in heart failure and premature death. Mechanistically, Nef-mediated inhibition of autophagy and induction of aging-associated markers have been proposed to promote cellular senescence, potentially contributing to cardiovascular aging in people living with HIV/AIDS ( 68).

CVB3

Enteroviruses are among the most frequently implicated pathogens in viral myocarditis, with group B coxsackieviruses (CVBs), particularly CVB3, historically linked to both acute myocarditis and subsequent progression to chronic inflammatory cardiomyopathy and dilated cardiomyopathy ( 76). The association between acute myocarditis and CVB infection was recognized as early as the mid-1950s, when multiple studies reported isolation of coxsackieviruses from myocardial or pericardial specimens in patients with acute myocarditis ( 12, 77). A central determinant of cardiac susceptibility to coxsackievirus infection is the coxsackievirus and adenovirus receptor (CAR), which mediates viral attachment and entry. Beyond its role in viral uptake, CAR participates in cytoskeletal organization and intracellular signaling, suggesting that CAR engagement and downstream perturbations may contribute to myocardial dysfunction during infection ( 78, 79). Infection of cardiomyocytes can trigger direct cytopathic injury and a robust inflammatory response, resulting in interstitial edema, necrosis, and impaired contractility. Clinically, patients may present with chest pain, palpitations, or dyspnea, and severe cases can progress to dilated cardiomyopathy and heart failure ( 80, 81) ( Fig. 2). Experimental studies further support mechanistic links between CVB infection and contractile and electrical instability. In transgenic murine models expressing CVB3, investigators have observed reduced stroke volume and cardiac output, mild QTc prolongation, intracellular Ca²⁺ overload, contractile dysfunction, and mitochondrial dysregulation. These abnormalities disrupt excitation-contraction coupling and may increase susceptibility to stress-induced arrhythmias ( 82, 83).

Fig 2 Mechanism of CVB3 infection leading to myocarditis. CVB3: coxsackieviruses B3; CAR: coxsackievirus-adenovirus receptor; DAF: decay-accelerating factor; DCM: dilated cardiomyopathy.

Host immune responses are critical determinants of disease severity and outcome in CVB3 myocarditis, contributing to both viral control and immunopathology. Recent work has identified several potentially targetable pathways, including complement signaling (e.g., C4/C3 axis) with links to ferroptotic cell death in infected cardiomyocytes, macrophage-derived VEGF-C-mediated remodeling of cardiac lymphatics, metabolic reprogramming of neutrophils by α-lipoic acid, and attenuation of inflammation via blockade of IL1RAP, which has been reported to reduce disease severity in acute CVB3 myocarditis and experimental autoimmune myocarditis models ( 84-87). In addition, mitochondrial calpain-1 has been reported to suppress NLRP3 inflammasome activation via mitochondrial pathways, thereby mitigating inflammation and cardiac dysfunction in CVB3-induced viral myocarditis ( 88). Mitochondrial quality control, extracellular vesicle signaling, and noncoding RNAs also appear to modulate CVB3 pathogenesis. Parkin-dependent mitophagy has been implicated in regulating the development and progression of viral myocarditis. Exosomes derived from cardiac progenitor cells have been reported to inhibit CVB3 replication and modulate mTOR signaling with functional improvement in experimental viral myocarditis, whereas miR-19a/19b has been implicated in promoting viral biosynthesis and replication, thereby exacerbating myocardial injury ( 89-91). Nonpharmacologic approaches, such as low-intensity pulsed ultrasound, have also been reported to attenuate CVB3-induced cardiac inflammation in experimental settings ( 92).

Despite substantial mechanistic progress, clinical management remains largely supportive. Most translational and clinical research on enterovirus-related cardiovascular diseases has focused on myocarditis and its progression to inflammatory cardiomyopathy, whereas other potential cardiac manifestations are comparatively less well characterized. Moreover, there are currently no widely used, enterovirus-specific vaccines or approved antiviral therapies for CVB myocarditis, underscoring the need for effective preventive and disease-modifying strategies for enterovirus-associated myocardial disease.

Human cytomegalovirus

HCMV is a globally prevalent β-herpesvirus that establishes lifelong infection. Following primary infection, HCMV is commonly asymptomatic in immunocompetent hosts and then persists in a latent state with intermittent reactivation. Infected individuals may shed virus for prolonged periods, thereby serving as a reservoir for transmission ( 93). Although HCMV typically causes limited clinical disease in immunocompetent individuals, it can lead to significant morbidity in immunocompromised patients, particularly in the setting of transplantation and other forms of iatrogenic or disease-related immunosuppression. Accumulating evidence links HCMV infection to cardiovascular pathology, including myocarditis, transplant vasculopathy, atherosclerosis/arteriosclerosis, and hypertension ( 13, 94-97). In immunosuppressed patients, viral reactivation is common and has been proposed to contribute to cardiovascular injury through sustained inflammatory and vascular effects ( 98). In addition, latency and intermittent reactivation may provide a mechanistic basis for chronic or recurrent inflammatory cardiac phenotypes, including myocarditis, although causality and the magnitude of effect likely vary by host factors and clinical context.

Overall, HCMV is associated with a range of cardiovascular conditions, particularly in immunosuppressed hosts and transplant settings. However, the extent to which HCMV is a causal driver versus a modifier of cardiovascular risk remains incompletely defined, and the dominant pathogenic pathways in the human heart-spanning direct tissue infection, immune dysregulation, and vascular inflammation-require further clarification.

Arthropod-borne viruses (arboviruses)

DENV, CHIKV, and ZIKV are prevalent arboviruses transmitted mainly by hematophagous arthropods (predominantly Aedes mosquitoes) and impose a disproportionate burden in low- and middle-income countries ( 106). Although these infections most commonly present as acute febrile illnesses, cardiovascular involvement is increasingly recognized and may contribute to severe diseases and mortality ( 107-109).

Chikungunya virus (CHIKV) infection can also involve the cardiovascular system ( 113). Human pathological studies have provided direct evidence of cardiac involvement, demonstrating the presence of CHIKV within cardiac tissue. In addition, CHIKV RNA has been detected in the heart as part of a broader pattern of multi-organ infection, accompanied by inflammatory cell infiltration in several affected organs, including the heart ( 114). These findings support the concept that direct viral invasion, together with associated inflammatory responses, may contribute to CHIKV-related cardiac pathology. Reported cardiovascular manifestations include hypotension, shock, circulatory failure, arrhythmias, myocarditis, dilated cardiomyopathy, and heart failure ( 14). A systematic synthesis of available studies estimated a global incidence of cardiac complications of ~32.81% ( 110). Furthermore, beyond the acute phase, CHIKV infection is associated with an increased risk of death from cerebrovascular disease, ischemic heart disease, and diabetes, indicating potential long-term cardiovascular sequelae ( 113). Elevated circulating cardiovascular biomarkers in fatal cases further support the presence of endothelial and/or myocardial injury ( 115). Experimental data indicate that CHIKV can directly infect cardiac tissue in immunocompetent mice and human primary cardiac cells, with cardiac fibroblasts representing a major target cell population. In immunocompetent hosts, cardiac infection is effectively controlled and cleared through a local type I interferon response. By contrast, loss of IFN-I signaling leads to increased cardiac viral burden, broader viral dissemination, and enhanced apoptosis within the heart ( 116, 117). In addition, MAVS signaling is required for efficient viral clearance from cardiac tissue; in its absence, persistent infection is associated with focal myocarditis and vasculitis of large vessels adjacent to the heart ( 118). These findings provide mechanistic insight into CHIKV-cardiac tissue interactions, although the precise pathways linking viral persistence to specific cardiovascular phenotypes remain incompletely defined.

ZIKV is best known for neurotropism and congenital diseases, but cardiovascular involvement has been described. In addition to typical symptoms (rash, headache, low-grade fever, arthralgia, myalgia, and conjunctivitis), some patients present with cardiovascular manifestations and may exhibit elevations in myocardial injury biomarkers ( 119). Case reports describe ZIKV-associated myocarditis and arrhythmias, including atrial fibrillation ( 10, 119, 120). In vivo, ZIKV-induced myocardial immune activation and myocarditis have been reported mainly in juvenile mice or in IFN-α/β receptor-deficient models, whereas adult wild-type mice generally show minimal permissiveness to infection ( 121). In adult A129 mice, ZIKV infection has been associated with electrocardiographic abnormalities, increased myocardial enzyme levels, downregulation of connexin 43 (Cx43), and disruption of gap junction architecture, findings consistent with acute myocardial injury and potential arrhythmogenic remodeling ( 122). However, these observations arise largely from susceptibility-enhanced models and should not be overinterpreted as direct evidence for the role of innate immunity or type I interferon pathways in immunocompetent adult hosts. More definitive conclusions regarding these mechanisms require appropriately supported data from mouse-adapted viral strains, humanized models, or human studies.

Taken together, ecological and societal drivers-including climate change, urbanization, and increased population mobility-are expanding the geographic range and outbreak potential of arboviruses, particularly in tropical and subtropical regions. Although cardiac involvement is an important and potentially life-threatening complication of DENV, CHIKV, and ZIKV infections, current evidence is heterogeneous, and mechanistic studies are relatively few. Further work is needed to clarify the incidence and risk factors for cardiovascular complications, define causal mechanisms (including the roles of direct viral tropism versus immune-mediated injury), and identify actionable targets for prevention, surveillance, and treatment.

MECHANISMS OF VIRAL-INDUCED CARDIAC DISEASES

Direct infection and indirect pathways

Immune-mediated damage

In the pathogenesis of viral myocardial injury, dysregulated immune responses play a key role ( 123, 124), primarily involving two mechanisms. The first is molecular mimicry, wherein viral epitopes structurally resemble cardiac self-antigens, leading to cross-reactive immune responses that attack myocardial tissue ( 125, 126). CVB3 is a typical example; the antiviral antibodies it induces can cross-react with cardiomyocyte antigens, not only promoting the infiltration of immune cells such as T lymphocytes and macrophages but also-through an excessive humoral response-causing the deposition of immune complexes within myocardial tissue. This, in turn, activates the complement system and triggers immune complex-mediated inflammation, continuously disrupting myocardial structure and function ( 127). Additionally, excessive or sustained inflammatory responses represent another core mechanism. Acute infections can induce a "cytokine storm," as seen in Zika virus infection, which triggers a cytokine release syndrome characterized by massive release of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, resulting in severe collateral tissue damage ( 128-130). Chronic infections, on the other hand, manifest as persistent immune activation. For example, in HIV infection, ongoing viral replication and immune dysregulation lead to CD4⁺ T-cell depletion, heightened T-cell activation, and sustained inflammatory signaling, which are considered central drivers of increased cardiovascular complication risk ( 131-133). These immune-mediated mechanisms, whether through autoimmune cross-reactivity or uncontrolled inflammatory responses, collectively contribute to myocarditis and may progress to cardiomyopathy.

Effects of viruses on cardiac electrophysiology

Viral infections can perturb cardiac electrophysiology and thereby promote arrhythmias through both direct effects on the cardiac conduction system and indirect, inflammation-mediated mechanisms. Coxsackievirus B3 (CVB3), for example, can infect cardiomyocytes via receptor-mediated entry involving the coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF/CD55). This may enable viral invasion of conduction tissue and disruption of normal impulse generation and propagation, predisposing to rhythm disturbances ( 134). Following SARS-CoV-2 infection, clinical observations have described sinus node dysfunction and atrioventricular (AV) conduction abnormalities, including sinus bradycardia and varying degrees of AV block ( 135). In HIV infection, viral proteins have been implicated in electrophysiological remodeling and may contribute directly to arrhythmogenic substrates in HIV-associated cardiac disease ( 136). Although the relative contributions of direct viral tropism versus secondary effects vary across patients, systemic inflammation, hypoxemia, autonomic imbalance, fever, electrolyte disturbances, and drug-related effects can all further modulate arrhythmic risk in the setting of acute infection. More broadly, immune-mediated myocardial injury and myocarditis can impair electrical coupling and conduction by damaging cardiomyocytes and the specialized conduction system and by altering the electrophysiological properties of surviving cells. Inflammatory cytokines, edema, microvascular dysfunction, and subsequent fibrosis can remodel ion channel expression and gap-junction integrity, thereby changing cardiomyocyte excitability, conduction velocity, and automaticity, and increasing susceptibility to both atrial and ventricular arrhythmias ( 137-141) ( Table 1; Fig. 3).

TABLE 1 Cardiac manifestations caused by viral infection

Virus

Cardiac disease

Pathogenic mechanism

HCMV

Myocarditis, heart failure, infection after heart transplantation

latent infection ( 102), inflammasome-mediated myocardial remodeling ( 104)

Arboviruses (DENV, CHIKV, ZIKV)

Myocarditis, pericarditis, heart failure, arrhythmia, myocardial dysfunction, myocardial infarction

virulence ( 143), immune response ( 111), inflammatory pathways ( 118, 144), autophagy ( 145)

Fig 3 Mechanisms by which viruses trigger heart disease.

TREATMENT STRATEGIES FOR VIRUS-RELATED CARDIAC DISEASES

Antiviral therapy

Immunomodulatory therapy

Immunomodulatory therapy is an important adjunct in selected forms of virus-related cardiac diseases, particularly when immune-mediated injury contributes substantially to myocardial dysfunction. Because antiviral immune responses can themselves drive cardiomyocyte damage, carefully modulating inflammation may reduce myocardial injury and improve clinical outcomes ( 153-155). Commonly discussed immunomodulatory approaches include glucocorticoids and intravenous immunoglobulin (IVIG), although the benefit of these interventions depends on patient selection, timing, and-critically-the presence or absence of ongoing myocardial viral replication. Glucocorticoids can suppress excessive inflammation and attenuate immune-mediated myocardial injury ( 154, 156). Accordingly, their use generally requires caution and is most defensible when active viral infection has been excluded or is considered unlikely. Prednisone has been reported to be beneficial in virus-negative inflammatory cardiomyopathy/myocarditis, supporting the concept that immunosuppression may be helpful in carefully phenotyped patients ( 150). In contrast, in patients with evidence of persistent myocardial viral infection, antiviral-oriented immunomodulation may be considered. The applicability of such an approach depends on the specific viral pathogen. For instance, in patients with persistent myocardial infection by enteroviruses or adenoviruses, therapy with interferon (IFN)-β has been associated with viral clearance and prevention of left ventricular functional deterioration. It is important to note, however, that the consequences of enhancing IFN signaling are context-dependent and may not be beneficial-and could potentially be harmful-in the setting of infections by other viruses ( 157). Beyond broad immunosuppression, more targeted immune modulation is under investigation. Experimental studies suggest that regulating T-cell trafficking can reduce CVB3-induced myocardial inflammation and fibrosis, thereby improving myocarditis severity and downstream remodeling ( 158, 159). These findings underscore the therapeutic potential of strategies that attenuate pathogenic immune pathways while preserving, or even enhancing, effective viral clearance. Overall, treatment development is challenged by the dual contribution of direct viral cytotoxicity and immune-mediated injury. Immunostimulatory approaches may accelerate viral elimination and could be advantageous early in infection, yet they risk amplifying inflammatory myocardial damage. Conversely, immunosuppressive therapies may relieve immune-mediated injury but can impair viral control and thereby worsen virus-driven pathology. Accordingly, a key unmet need is the development of biomarkers and diagnostic strategies (including myocardial virology, where feasible) that enable individualized selection and timing of immunomodulatory therapy. Immunomodulation is also a major area of interest in HIV-associated cardiac disease, where persistent immune activation and inflammation may contribute to endothelial dysfunction, myocardial injury, and adverse remodeling even under effective ART. Future work should define how best to calibrate immunomodulatory interventions in this setting-optimizing viral control while minimizing immune-mediated myocardial damage and avoiding impairment of host defenses-through mechanistic studies and rigorously designed clinical trials.

Therapies to improve and support cardiac function

In patients with severe virus-related cardiac diseases-particularly those with acute myocarditis, decompensated heart failure, or malignant arrhythmias-hemodynamic stabilization and guideline-directed supportive care are central to management. Pharmacologic support may include diuretics to relieve congestion, vasodilators to reduce preload/afterload when blood pressure permits, and inotropic agents for patients with low cardiac output and evidence of end-organ hypoperfusion. These measures aim to optimize cardiac performance and reduce myocardial workload while the acute inflammatory and/or infectious process resolves. Arrhythmia management should be individualized according to the arrhythmia subtype, hemodynamic impact, and underlying myocardial involvement. In the context of SARS-CoV-2 infection, antiarrhythmic therapy (including class III agents in selected patients) may be used when clinically indicated, with careful attention to proarrhythmic risk, drug-drug interactions, and QT-interval monitoring ( 160). For patients at high risk of sudden cardiac death or with sustained ventricular tachyarrhythmias, device therapy such as an implantable cardioverter-defibrillator (ICD) may be considered in accordance with established indications and timing recommendations (often after reassessment of ventricular function once acute myocarditis has stabilized) ( 161). For patients with heart failure, treatment should follow contemporary heart failure guidelines, including beta-blockers and renin-angiotensin system inhibition (ACE inhibitors or angiotensin II receptor blockers, and, where appropriate, other guideline-directed agents), alongside diuretics for volume management. In refractory cases with progressive respiratory or circulatory failure, advanced organ support may be required. This can include invasive mechanical ventilation for severe hypoxemia and temporary mechanical circulatory support-such as extracorporeal membrane oxygenation (ECMO) in selected patients with cardiogenic shock-to maintain perfusion and oxygenation while allowing time for myocardial recovery and definitive etiologic therapy ( 162). For advanced, persistent heart failure despite optimal medical therapy, durable mechanical circulatory support such as left ventricular assist devices (LVADs) can be considered in carefully selected patients, including those with HIV infection when otherwise appropriate and consistent with transplant/LVAD candidacy criteria ( 163). Overall, the primary goal of cardiac support is to stabilize physiology, prevent secondary organ injury, and "bridge" patients through the acute phase to recovery or further interventions as needed.

Treatment of long-term cardiovascular sequelae

Persistent or new symptoms occurring ≥12 weeks after acute SARS-CoV-2 infection are commonly referred to as long COVID (post-COVID-19 condition). Frequently reported cardiovascular-related complaints include fatigue, dyspnea, chest pain, and palpitations ( 164). Epidemiologic studies indicate that prior SARS-CoV-2 infection is associated with an increased risk of subsequent cardiovascular complications, including arrhythmias, myocarditis, pericarditis, ischemic cardiac disease, heart failure, and thromboembolic events ( 165). In parallel, post-infection evaluations have described abnormalities on cardiac magnetic resonance imaging (CMR) in some patients, as well as elevated cardiac biomarkers (e.g., troponin), persistent chest pain, and palpitations after apparent recovery; collectively, these findings support an increased incidence of cardiovascular events following SARS-CoV-2 infection, although the prevalence and clinical significance vary across cohorts and are influenced by baseline risk, infection severity, and ascertainment methods ( 163, 166). At present, management of cardiovascular manifestations in long COVID is largely individualized and symptom-directed, guided by standard cardiovascular diagnostic pathways to exclude alternative etiologies and to identify treatable conditions. For example, patients with chest pain suggestive of vasospastic or microvascular angina may benefit from anti-anginal therapy (e.g., calcium-channel blockers and/or nitrates) when clinically appropriate, while β-blockers (or alternatives such as ivabradine, depending on local practice and contraindications) may be considered for troublesome palpitations or inappropriate sinus tachycardia. Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), has been reported after SARS-CoV-2 infection. First-line therapy generally emphasizes non-pharmacologic measures (adequate hydration, increased salt intake when not contraindicated, compression garments, and graded recumbent exercise/physical reconditioning), with pharmacologic options reserved for persistent symptoms. Medications used in selected patients include volume-expanding agents (e.g., fludrocortisone), vasoconstrictors (e.g., midodrine), and heart-rate-lowering therapies (e.g., β-blockers), tailored to blood pressure profile and comorbidities. For patients with prominent fatigue syndromes, management typically focuses on pacing, sleep optimization, rehabilitation strategies, and treatment of comorbid mood, pain, or sleep disorders. Evidence for specific pharmacologic therapies (including immunomodulators or mitochondrial supplements such as coenzyme Q10) remains limited, and such interventions should be presented as investigational or adjunctive rather than as established standard of care. Similarly, in patients suspected of mast cell activation-related symptoms, H1/H2 antihistamines, mast cell stabilizers, and/or leukotriene receptor antagonists may be considered on a case-by-case basis. NSAIDs may be used for symptom relief (e.g., fever, myalgias, pleuritic pain), but they should be used cautiously in patients with heart failure, renal dysfunction, or elevated cardiovascular risk, consistent with general cardiovascular practice ( 35, 167).

CONCLUSIONS AND FUTURE PERSPECTIVES

Over the past decade, the field of viral cardiology has undergone a profound paradigm shift. Historically centered on acute viral myocarditis-prototypically modeled by Enteroviruses such as Coxsackievirus B3-our understanding has evolved to recognize cardiotropic viruses as systemic drivers of a broad spectrum of major adverse cardiovascular events (MACEs), including acute myocardial infarction, heart failure, and chronic vascular dysfunction. This transition, significantly accelerated by the global COVID-19 pandemic, has been underpinned by technological advances such as single-cell sequencing, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), and advanced cardiac magnetic resonance (CMR) imaging. Consequently, our mechanistic understanding has expanded to encompass novel viral trafficking routes (e.g., pro-DC3-mediated dissemination) and the complex, dual nature of immune responses, such as type I interferon signaling in cardiac protection versus injury.

Despite these unprecedented insights, critical knowledge gaps persist. It remains clinically challenging to disentangle direct viral cytopathic effects from indirect immune-mediated injuries, primarily due to the focal nature of infections and the limitations of endomyocardial biopsies. Furthermore, the mechanistic underpinnings of long-term cardiovascular sequelae-exemplified by "Long COVID" and premature cardiovascular aging in people living with HIV-remain poorly defined, particularly regarding the roles of persistent viral reservoirs and low-grade chronic inflammation in subclinical myocardial remodeling. Compounding these issues is a glaring lack of pathogen-specific antiviral and immunomodulatory therapies validated by large-scale clinical trials.

To address these challenges, future research must pivot toward precision medicine and long-term prevention strategies. First, the development of non-invasive, high-sensitivity biomarkers is urgently needed to distinguish active viral replication from post-viral autoimmunity, thereby guiding the optimal timing and modality of interventions. Parallel to this, therapeutic discovery should shift from broad-spectrum immunosuppression to targeting pathogenic inflammatory cascades-such as the NLRP3 inflammasome-without compromising the host's innate antiviral capacity. Furthermore, establishing large-scale longitudinal cohorts integrating multi-omics data is essential for tracking post-infection cardiovascular trajectories and facilitating the early identification of individuals at high risk for chronic sequelae, such as heart failure or accelerated atherosclerosis. Ultimately, prioritizing vaccine development against emerging cardiotropic viruses, building on the established cardioprotective efficacy of existing vaccines, represents a fundamental strategy for reducing the global burden of cardiovascular disease.

In summary, mitigating the cardiovascular impact of viral infections requires transitioning from a reactive clinical approach to a proactive, preventative paradigm. By seamlessly integrating clinical epidemiology with advanced molecular biology, the field is well-positioned to develop highly effective strategies to improve cardiovascular outcomes in an increasingly interconnected and virus-exposed world.

ACKNOWLEDGMENTS

This work was supported by grants from the National Natural Science Foundation of China (no. 882570588 and 82460105), Yunnan Key Research and Development Program (202303AC100026, 202403AC100033), Yunnan Provincial Science and Technology Department (no. 202301AT070270), the Program Innovative Research Team in Science and Technology in Kunming Medical University (CXTD202202), Yunnan Provincial Science and Technology Department (202401AY070001-303), First-Class Discipline Team of Kunming Medical University (2024XKTDTS12, 2024XKTDPY12), the Yunnan Talent Support Plan (202505AS350006), Science and Technology Projects of Yunnan Universities Serving Key Industries (FWCY-BSPY2025074), Yunnan Provincial Department of Education Scientific Research Fund Project (2025Y0411), Yunnan Science and Technology Talent and Platform Program (202105AG070012), and Graduate Student Innovation Foundation of Kunming Medical University (2025S185).

All figures in this article were drawn using BioRender.com. We thank the platform for providing efficient tool support for scientific research drawings.

He-Min Yu: Conceptualization, Methodology, Formal Analysis, Writing-Original Draft; Ming-Liang Zhu: Data curation; Yan-Li Zhao: Visualization, Investigation; Jia-Xiang Tan: Resources, Supervision; Shao-Chao Luo: Conceptualization; Pan-Pan Pang: Supervision, Writing-Review & Editing; Chang-Bo Zheng: Conceptualization, Funding Acquisition, Resources, Supervision, Writing-Review & Editing.

REFERENCES

61.

Information & Contributors

Published In

Editor: Suchetana Mukhopadhyay, Indiana University Bloomington, Bloomington, Indiana, USA

History

Published online: 9 June 2026

Keywords

1. viral infection

2. cardiac diseases

3. antiviral therapy

4. prevention and risk factor control

Topics

Authors

School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China

Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Kunming Medical University, Kunming, Yunnan, China

Author Contributions: Conceptualization, Formal analysis, Methodology, and Writing - original draft.

School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China

Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, Yunnan, China

Author Contributions: Supervision and Writing - review and editing.

School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China

Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Kunming Medical University, Kunming, Yunnan, China

Author Contributions: Conceptualization, Funding acquisition, Resources, Supervision, and Writing - review and editing.

Editor

Indiana University Bloomington, Bloomington, Indiana, USA

Notes

The authors declare no conflict of interest.

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Research progress on the association between viruses and cardiac diseases | Journal of Virology

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Viruses have existed long before human history and are ubiquitous in the human environment. Humans acquire viral infections through multiple routes, including the respiratory tract (e.g., inhalation of aerosols or droplets), the gastrointestinal tract (e.g., ingestion of contaminated food or water), contact transmission-either direct (person-to-person) or indirect (via contaminated objects or surfaces)-and vector-borne transmission via arthropods such as mosquitoes and ticks, which is particularly relevant for arboviruses.

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"I think this World Cup is a test case to show the system that we built for wastewater monitoring,"

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"I think this World Cup is a test case to show the system that we built for wastewater monitoring,"

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https://www.medpagetoday.com/special-reports/features/121671

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Here’s How Experts Are Watching for Infectious Disease Threats During the World Cup

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This could be the bellwether of mass wastewater surveillance and help prep for L.A. Olympics

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The exciting (and unusual) aspects of this work include the potential to uncover the precise drivers of the intense immune dysregulation found, and possibly of ME/CFS and long COVID themselves. Nobody else has gotten this far.

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The exciting (and unusual) aspects of this work include the potential to uncover the precise drivers of the intense immune dysregulation found, and possibly of ME/CFS and long COVID themselves. Nobody else has gotten this far.

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https://www.healthrising.org/blog/2026/06/09/t-cell-long-covid-me-cfs/

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Hitting the Target? ME/CFS and long COVID T-Cell Researchers on Uncovering the Precise Drivers of the Illnesses - Health Rising

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Dr. Selin and company believe they can solve one of the key mysteries of ME/CFS and long COVID: exactly why the T-cells are getting pummeled.

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The alignment between ACOG and AAFP reflects what's best for pregnant patients and families, said AAFP chief medical officer Margot Savoy, MD, MPH. She said her organization is dedicated to ensuring every pregnant patient has access to these lifesaving vaccines.

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The alignment between ACOG and AAFP reflects what's best for pregnant patients and families, said AAFP chief medical officer Margot Savoy, MD, MPH. She said her organization is dedicated to ensuring every pregnant patient has access to these lifesaving vaccines.

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https://www.cidrap.umn.edu/influenza-vaccines/leading-ob-gyn-society-breaks-cdc-recommended-vaccines-pregnant-women-including

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Leading OB-GYN society breaks from CDC on recommended vaccines for pregnant women, including COVID-19

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All pregnant people should get the COVID-19, respiratory syncytial virus (RSV), influenza, and Tdap vaccines, according to new recommendations from the American College of Obstetricians and Gynecologists (ACOG.)

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Researchers finally find explanation for common disease: Chronic fatigue can be traced back to a specific event in the body.

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NL: But Ponting and his colleagues have discovered that the symptoms are not imagined. The condition arises from a violent chain reaction, which begins with a very common phenomenon that affects us all. And that breakthrough could soon lead to new treatments. (Paywall)

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NL: But Ponting and his colleagues have discovered that the symptoms are not imagined. The condition arises from a violent chain reaction, which begins with a very common phenomenon that affects us all. And that breakthrough could soon lead to new treatments. (Paywall)

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https://wibnet.nl/gezondheid/onderzoekers-vinden-eindelijk-verklaring-voor-veelvoorkomende-ziekte-chronische-vermoeidheid-is-terug-te-voeren-op-een-specifieke-gebeurtenis-in-het-lichaam

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Onderzoekers vinden eindelijk verklaring voor veelvoorkomende ziekte: Chronische vermoeidheid is terug te voeren op een specifieke gebeurtenis in het lichaam

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Je bent gevloerd en kunt je moeilijk concentreren, en hoeveel je ook rust, je raakt die uitputting maar niet kwijt. Dat is het dagelijks leven van miljoenen mensen – maar tientallen jaren dachten veel artsen dat de klachten tussen de oren zaten. Nu hebben onderzoekers aangetoond dat ze het mis hadden.

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The PolyBio Spring 2026 Symposium featured IACI project updates from PolyBio-supported research collaborators on May 22, 2026. 

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The PolyBio Spring 2026 Symposium featured IACI project updates from PolyBio-supported research collaborators on May 22, 2026. 

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https://2026-spring-symposium-polybio.netlify.app/

Full Recording: https://www.youtube.com/watch?v=tD5gWVEjudQ&t=1s

Interactive forum: https://polybio.org/spring-2026-symposium/

Notable: Dr. Van Elzakker 2:17:44, Dr. Tim Heinrich 3:43:41

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Resia Pretorius · Stellenbosch University

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PolyBio Spring 2026 Symposium — Talk Summaries

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Plain-language and technical summaries of the 28 research talks presented at the PolyBio Spring 2026 Symposium.

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“I used to think that a lot of the acute infections are inconsequential in the long term,” said Al-Aly. Today, he sees things differently.“The pandemic sort of proved this to be a wrong model of thinking.” 

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“I used to think that a lot of the acute infections are inconsequential in the long term,” said Al-Aly. Today, he sees things differently.“The pandemic sort of proved this to be a wrong model of thinking.” 

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https://san.com/cc/can-every-infection-become-a-chronic-disease/

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Can every infection become a chronic disease?

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During the pandemic, long COVID emerged as a medical curiosity. Now, it is changing how scientists think about infections.

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Symptoms tied to food insecurity, job loss: About 47% of AIAN respondents reported having COVID-19, and 40% said they had long COVID, compared with 30% among non-AIAN adults. (>20K)

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Symptoms tied to food insecurity, job loss: About 47% of AIAN respondents reported having COVID-19, and 40% said they had long COVID, compared with 30% among non-AIAN adults. (>20K)

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https://www.cidrap.umn.edu/covid-19/survey-highlights-greater-burden-long-covid-native-americans

AIAN: American Indian and Alaska Natives

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From 2021 to 2023, American Indian and Alaska Natives (AIANs) reported higher rates of COVID-19 and long COVID than their non-AIAN counterparts, according to a non-peer-reviewed published on the Research Square preprint platform.

Led by a researcher from the US National Bureau of Economic Research, the study team surveyed more than 20,000 adult respondents, including public-use files (datasets stripped of identifying information) and an oversample of AIANs, to the California Health Interview Survey from 2021 to 2023.

The goal was to estimate associations between demographic, socioeconomic, and health characteristics and COVID-19 infection, long-COVID symptoms, vaccination status, testing behavior, food insecurity, job loss, and fewer work hours.

By the end of 2020, "AIAN communities had approximately 1.6 times the number of confirmed cases, 2.4 times the number of hospitalizations, and twice the mortality rates associated with COVID-19 relative to the U.S. population overall," the authors noted.

Symptoms tied to food insecurity, job loss

About 47% of AIAN respondents reported having COVID-19, and 40% said they had long COVID, compared with 30% among non-AIAN adults. Obesity and poverty were risk factors for both infection and long COVID.

Lower vaccination rates among rural AIAN respondents further highlight structural barriers to preventive care that have been documented in previous studies, including geographic isolation, limited health care infrastructure, and historical mistrust of health institutions.

AIAN adults were less likely to be fully vaccinated against COVID-19 than their non-AIAN peers. Vaccination was tied to lower odds of job loss and reductions in hours or income in only public-use files, while persistent symptoms were linked to severe food insecurity and job loss.

"Lower vaccination rates among rural AIAN respondents further highlight structural barriers to preventive care that have been documented in previous studies, including geographic isolation, limited health care infrastructure, and historical mistrust of health institutions," the researchers wrote.

Long-COVID symptoms such as fatigue can reduce work capacity and limit workers' ability to maintain employment. "These effects may be particularly consequential for workers in occupations requiring in-person interaction or physical labor, which are more common in some AIAN communities and may also increase exposure to infectious disease," the authors wrote.

"As a result, persistent health effects associated with COVID-19 may reinforce existing economic vulnerabilities in communities that already experience higher rates of poverty and limited access to health care resources," they added.

Idaho's Department of Health and Welfare (DHW) said it's investigating a spate of illnesses tied to raw, or unpasteurized, milk. Since May 15, department officials said almost 60 people have been identified as having illnesses after drinking raw milk, and at least 45 of those people tested positive for campylobacteriosis, a bacterial infection.

Most of the sickened people reported getting raw milk from two different milking operations, one in northern Idaho and one in southern Idaho.

"Both milking operations are working in collaboration with DHW and local public health agencies to identify and fix any potential sources of contamination," DHW said.

Campylobacteriosis can appeartwo to five days after exposure. Symptoms include diarrhea (sometimes bloody), fever, stomach cramps, nausea, and vomiting. Infections can be more severe in young children, the elderly, and those who are immunocompromised, but most people recover within one week of symptom onset.

The Food and Drug Administration's Animal and Plant Health Inspection Service (APHIS) has confirmed a second case of New World screwworm (NWS) in Texas. APHIS said late last week that the case was found in a one-month-old calf in Zavala County, more than five miles from the first confirmed infection. Caused by the larvae of Cochliomyia hominivorax, a parasitic fly, NWS is a serious threat to livestock, wildlife, pets, and in rare cases, people. The larvae burrow into living tissue, causing severe wounds. APHIS said other samples collected from the surrounding area have been tested and were negative.

An analysis of over 1,800 whole genome sequences from US measles cases suggests the nation is likely to lose its measles elimination status, ProPublica reports . The analysis, which includes sequences from measles cases released as recently as last month, shows the measles virus currently spreading in Utah-the largest current outbreak in the United States-is very closely related to the strain that spread in West Texas beginning in January 2025. Mutations found in cases in Texas and Utah were also present in sequences from infected patients in other states. Measles was declared eliminated in the United States in 2000, but continuous transmission over a 12-month period threatens that status. The Centers for Disease Control and Prevention is conducting its own sequencing analysis and will present its findings to the Pan American Health Organization later this year.

Three African countries reported polio cases last week, according to the latest update from the Global Polio Eradication Initiative. Central African Republic confirmed its first two cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) this year, with onsets of paralysis on April 20 and 26. Malawi reported a cVDPV2 case with paralysis on December 22, 2025, for its first case of 2025. Nigeria reported a cVDPV2 case with paralysis onset on May 2, marking its 25th case this year.

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Survey highlights greater burden of long COVID in Native Americans

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In total, 40% of American Indian and Alaska Natives said they had persistent symptoms, relative to 30% of their non-native peers.

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We focus on two convergent mechanisms: (1) the activation of glial Toll-like receptor (TLR)4/TLR2 signaling, which initiates a chronic neuroinflammatory cascade, and (2) the disruption of host proteostasis, which seeds neurodegenerative proteinopathies like alpha-synuclein and tau aggregation. 

# data[].attributes.subject
We focus on two convergent mechanisms: (1) the activation of glial Toll-like receptor (TLR)4/TLR2 signaling, which initiates a chronic neuroinflammatory cascade, and (2) the disruption of host proteostasis, which seeds neurodegenerative proteinopathies like alpha-synuclein and tau aggregation. 

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https://www.sciencedirect.com/science/article/pii/S1879625726000519

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Post-viral neurological syndromes, such as post-acute sequelae of COVID-19, present a paradox of severe symptoms despite minimal CNS viral replication. The 'protein-as-pathogen' model, where shed viral proteins act as soluble neurotoxins, is now central to understanding this phenomenon. This review presents the opinion that the most critical recent developments are not that these proteins are toxic, but how their mechanisms converge. We synthesize evidence from the last two years showing that proteins from diverse, highly infectious virus families with zoonotic potential (e.g. Coronaviridae, Flaviviridae, Orthomyxoviridae) engage shared host pathways. We focus on two convergent mechanisms: (1) the activation of glial Toll-like receptor (TLR)4/TLR2 signaling, which initiates a chronic neuroinflammatory cascade, and (2) the disruption of host proteostasis, which seeds neurodegenerative proteinopathies like alpha-synuclein and tau aggregation. This framework positions post-viral syndromes as mechanistically related disorders and identifies pan-viral therapeutic targets, such as TLR inhibitors and autophagy activators.

Data Availability

No data were used for the research described in the article.

# data[].attributes.attachment_link.title
Beyond brain fog: viral proteins as convergent drivers of neuroinflammation and proteinopathy

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Post-viral neurological syndromes, such as post-acute sequelae of COVID-19, present a paradox of severe symptoms despite minimal CNS viral replication...

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Prioject: Stratification of ME/CFS by mycotoxin exposure

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This work will significantly advance the field by providing stratification of ME/CFS by mycotoxin exposure and providing novel insights into environmentally driven immune reprogramming in ME/CFS.

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This work will significantly advance the field by providing stratification of ME/CFS by mycotoxin exposure and providing novel insights into environmentally driven immune reprogramming in ME/CFS.

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https://reporter.nih.gov/search/5w7xmrOYnUq1OuRlHWaNew/project-details/11347476

# data[].attributes.attachment_caption
“The Message of Hope” An interview with renowned ME/CFS researcher Dr. Nancy Klimas

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"Clinically, ME/CFS, Gulf War illness, and many Long COVID patients look almost identical".

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"Clinically, ME/CFS, Gulf War illness, and many Long COVID patients look almost identical".

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https://michaela.substack.com/p/the-message-of-hope

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An interview with renowned ME/CFS researcher Dr. Nancy Klimas

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This Brain Inflammation Collaborative webinar featured Dr. Leonard Jason,  presenting on pacing as an intervention for managing post-exertional malaise (PEM), and Anvita Guda (BIC) explained how the unhide platform’s pacing notifications work using wearable device data to help patients monitor and manage their activity levels.. 

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This Brain Inflammation Collaborative webinar featured Dr. Leonard Jason,  presenting on pacing as an intervention for managing post-exertional malaise (PEM), and Anvita Guda (BIC) explained how the unhide platform’s pacing notifications work using wearable device data to help patients monitor and manage their activity levels.. 

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Living Within The Energy Envelope: Research Updates & Interventions for People with ME/CFS - braininflammation

unhide: https://unhidenow.org/how-it-works/

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Living Within The Energy Envelope: Research Updates & Interventions for People with ME/CFS - braininflammation

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This Brain Inflammation Collaborative webinar featured Dr. Leonard Jason, a renowned ME-CFS researcher and patient, presenting on pacing as an intervention for managing post-exertional malaise (PEM). Dr. Jason shared his pioneering research from the 1990s on the energy envelope theory. He presented multiple studies showing the effectiveness of pacing interventions, including case studies, as well […]

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A new study co-led by Yale scientists reveals that antibodies from some long COVID patients attacked brain and nerve tissues, a finding that could point toward treatments. 

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A new study co-led by Yale scientists reveals that antibodies from some long COVID patients attacked brain and nerve tissues, a finding that could point toward treatments. 

# data[].attributes.body
https://news.yale.edu/2026/05/28/yale-study-links-some-long-covid-patients-autoimmune-responses

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Yale study links some long COVID patients to autoimmune responses

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A new study co-led by Yale scientists reveals that antibodies from some long COVID patients attacked brain and nerve tissues, a finding that could point toward treatments.

# data[].attributes.headline
POTS is one specific cause of OI, not the whole picture. Orthostatic intolerance is a broader category, and the absence of a POTS diagnosis does not rule out other causes of OI, including other forms of dysautonomia. 

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POTS is one specific cause of OI, not the whole picture. Orthostatic intolerance is a broader category, and the absence of a POTS diagnosis does not rule out other causes of OI, including other forms of dysautonomia. 

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https://batemanhornecenter.org/when_its_not_pots/

# data[].attributes.attachment_link.title
When “It’s Not POTS” Doesn’t Mean “It’s Not Dysautonomia”

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A new NIH/NIAID strategic vision signals increased attention to post-infectious conditions like ME/CFS and Long COVID.

# data[].attributes.headline
Instead of a disorder of perception, the existing scientific literature describes a multi-system disease of bioenergetic failure, immune dysregulation, and vascular dysfunction.

# data[].attributes.subject
Instead of a disorder of perception, the existing scientific literature describes a multi-system disease of bioenergetic failure, immune dysregulation, and vascular dysfunction.

# data[].attributes.body
https://likeannopeningbandforthesun.substack.com/p/revisiting-the-painful-truth-of-long?

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Despite being set up to protect vulnerable participants, these boards are ill-equipped to ensure research is safe, especially regarding post-exertional malaise (PEM).

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Despite being set up to protect vulnerable participants, these boards are ill-equipped to ensure research is safe, especially regarding post-exertional malaise (PEM).

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https://thesicktimes.org/2026/06/02/research-ethics-boards-need-urgent-training-on-long-covid-and-myalgic-encephalomyelitis/

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The Sick Times - Chronicling the Long COVID crisis

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Research ethics boards need urgent training on Long COVID and myalgic encephalomyelitis - The Sick Times

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Last year, researchers in Ontario, Canada started recruiting participants for a Long COVID trial testing the feasibility of exercise and rehabilitation. Like many other studies of exercise, it doesn’t use validated measures for post-exertional malaise (PEM). But the Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation (PREFACER) study, run by researchers at Western University, stands out because it involves deceiving participants — undermining informed consent and potentially violating Canadian ethical research standards.