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They don’t struggle to They They don’t struggle to breathe—but COVID-19 is starving them of oxygenOne alarming symptom robs many patients of blood oxygen well before they notice. Doctors are racing to understand it.

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They don’t struggle to They They don’t struggle to breathe—but COVID-19 is starving them of oxygenOne alarming symptom robs many patients of blood oxygen well before they notice. Doctors are racing to understand it.

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May, 2020

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Standing in her patient's living room, Mari Seim was perplexed. The man, in his 60s, had fallen ill with flu-like symptoms more than a week before. His breathing rate had climbed, so his daughter called the Taarnaasen Medical Center, the clinic where Seim works as a general practitioner, just outside Oslo, Norway. With COVID-19 at the forefront of her mind, Seim set out to check on the man, and she wasn't prepared for what she found.

"He was sitting in a chair, and he was smiling," she says. "He didn't seem bothered in any way."

Yet his breaths came in rapid succession, nearly triple the normal rate. A faint blue tinted his lips and fingers. She truly didn't grasp how sick he was until she measured the oxygen levels in his blood. A normal percentage would sit well above 90. The number Seim saw was 66. For a split second, Seim thought she had the device turned upside down. She checked again. The reading was the same, and she immediately called an ambulance.

The patient had what seems to be a pervasive but initially overlooked feature of COVID-19: silent hypoxia. Unlike many other respiratory diseases, COVID-19 can slowly starve the body of oxygen without initially causing much shortness of breath. By the time some patients have trouble breathing or feel pressure in the chest- among the symptoms the U.S. Centers for Disease Control and Prevention lists as emergency warning signs -they are already in dire straits.

Silent hypoxia has surprised many doctors. Some patients are running so low on oxygen, health-care workers would normally expect them to be incoherent or in shock. Instead, they're awake, calm, and responsive. They chat with the physicians. They use their cell phones. While the basic physiology behind why these patients don't immediately feel short of breath is well understood, scientists are still trying to come to grips with exactly how COVID-19 ravages the body, and why this disease, in particular, can quietly take your breath away.

The roots of breathlessness

Frequently, breathlessness parallels the loss of elasticity in the lung tissue. Many respiratory diseases can stiffen the lungs, due to inflammation, scarring, or the buildup of fluid and pus. That stiffening can hinder the movement of the bellows in our chest, creating a sensation of air being squeezed from the body.

Lung stiffness also impacts a patient's ability to expel carbon dioxide, and the buildup of this gas is a potent trigger for our urge to inhale. The body's levels of carbon dioxide usually sit in a narrow range. If CO ₂ increases, your brain gets an emergency alert-that's the feeling of breathlessness.

For many COVID-19 patients, it seems neither of these triggers are pulled at the disease's onset, says Cameron Baston, a pulmonary and critical care physician at Penn Medicine. Early in the course of the disease, many patients' lungs remain stretchy, like a balloon, so they can breathe freely in and out. As their oxygen levels slowly decline, their breathing rate gradually increases to compensate, which blows out loads of the body's carbon dioxide. The result is a sneaky onset of hypoxia, with some patients developing dangerously low levels of oxygen without the increases in carbon dioxide that would commonly alert the body to the problem.

"In almost all clinical experience that physicians have, problems with the lung involve both problems with oxygen absorption and carbon dioxide elimination," says Richard Levitan, an emergency physician who volunteered to spend 10 days treating COVID-19 pneumonia at New York's Bellevue Hospital. "This disease is different."

Doctors have previously observed silent hypoxia among high-altitude climbers and pilots, Levitan notes. As you ascend into the skies, the atmospheric pressure drops, which means fewer oxygen molecules are available for any given breath, yet rapid breathing still expels carbon dioxide. He stresses that the cause, and therefore the treatments, behind high-altitude diseases and COVID-19 are vastly different, contrary to some claims circulating online. But one of the body's reactions to this reduced oxygen-breathing faster-is similar.

This process has also been studied in pilots, who train in low-oxygen (hypobaric) chambers to recognize the subtle symptoms of silent hypoxia, in case the cabin depressurizes while flying, says William Ottestad, who specializes in hypobaric medicine as a doctor for the Norwegian Special Operations Command. "It's also been coined the silent killer because of its insidious character," he adds. That's because a sudden drop in cabin pressure can cause pilots to fall unconscious and crash.

In these cases, the low carbon dioxide levels that result from rapid breathing cause oxygen to bind more strongly to hemoglobin, the protein that carries oxygen within red blood cells. This means more oxygen can be delivered to tissues in need, as long as the heart continues to pump strongly, explains Ottestad, who is also an anesthesiologist with Oslo University Hospital's air ambulance department.

The COVID-19 experience may parallel what happens in pilots. The rapidly breathing patients frequently retain decent heart function early in the disease, and thus still have the ability to pump blood to their extremities. Ottestad speculates that without their low carbon dioxide levels, COVID-19 patients would perhaps suffer from even lower oxygen levels than measured, which could make a severe case of the virus even worse.

There have not yet been thorough studies of whether early detection of silent hypoxia can improve COVID-19 outcomes. But prolonged hypoxia may strain the heart and perhaps other bodily systems, and Baston points to the improved life expectancies for patients with chronic obstructive pulmonary disease (COPD) who are given supplemental oxygen.

Breathing under the microscope

For now, much remains unknown about how the coronavirus causes silent hypoxia, Ottestad says. "We are all kind of baffled by this." But hypotheses exist.

One hinges on the fact that oxygen moves from the lungs to the blood by transiting from tiny air sacs known as alveoli to the blood vessels. SARS-CoV-2, the virus behind the pandemic, invades by attaching spikes on its viral surface to protein receptors scattered on top of cells called ACE2, which are abundant throughout the lungs and their many air sacs. Once the germ establishes itself in enough cells, the ensuing battle between the body's immune response and the virus sparks a torrent of damage.

Such an effect could hinder the passage of oxygen from alveoli to the blood, while carbon dioxide-which passes much more readily from the blood out through the lungs-is less impacted, Ottestad says. He points to two small autopsy studies that suggest COVID-19 causes early-onset inflammation of the tissues around the alveoli.

Another possibility may be that the disease creates a mismatch between oxygen's movement in the lungs and the flow of blood, says pulmonologist William Janssen, the head of critical care medicine at National Jewish Health. Usually, blood vessels constrict so that the flow is greatest to highly aerated regions of the lung, where oxygen is picked up, and lowest to areas lacking airflow. But this safeguard could be abnormal in COVID-19 patients, meaning more blood is flowing to damaged lung areas, while less is passing through healthy parts.

Blood flow to oxygen-rich zones of the lung might alternatively be hindered by tiny clots in the blood vessels, notes Enid Neptune, a pulmonary and critical care specialist at Johns Hopkins Medicine. Many have pointed to elevated blood clotting as a possible deadly facet of COVID-19. Some doctors are debating the use of blood thinners in COVID-19 patients to prevent clotting, but Janssen cautions that larger trials should be conducted before this practice becomes the norm.

What's more, the mechanism behind silent hypoxia as seen with COVID-19 may not be unique to the disease, says Penn Medicine's Baston, who works with patients suffering from particularly severe and rare lung diseases. While uncommon, some of his past patients have become silently hypoxic from other illnesses, such as bacterial pneumonia.

"What COVID-19 has done is taken things that we see and pushed it into every community hospital across the country," Baston says.

Worried about silent hypoxia?

The curious presentation of COVID-19 has led many health-care professionals to search for more effective routes for treatment. Many now suggest holding off on using mechanical ventilation for patients unless their condition is advanced. Instead, they are trying less invasive supportive care early on, such as supplemental oxygen and placing patients in a prone position on their bellies to allow for better oxygen flow.

Levitan says that raising awareness of this silent symptom of COVID-19 could help by getting people to head to a hospital earlier in the course of disease, before they decline severely and require mechanical ventilation. A simple, at-home gadget known as a pulse oximeter could help people who develop other symptoms to also monitor for silent hypoxia, Levitan says.

"This is not a panacea. It's not going to prevent all death," he says. But "we need to give people a sense of hope and more information, so they can wrap their head around what's happening."

A collaboration among multiple Norwegian health-care centers and a Spanish university is recruiting COVID-19 patients for a study using an array of biosensors, including pulse oximetry, for remotely tracking patients' conditions. The hope is to potentially catch patients early in the disease's progression, as well as reduce the need for patients with mild cases to remain in medical centers for extended periods.

Other doctors generally agree that use of a home pulse oximeter is useful for monitoring disease progression. But Janssen stresses that this should be done in consultation with a medical professional. As fear of COVID-19 spread, he worries that patients have been afraid to enter medical care centers and possibly risk catching the disease, curbing lines of communication to doctors and encouraging self-diagnosis.

He gives one simple piece of advice: "If you're sick, call your doctor."

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They don't struggle to breathe-but COVID-19 is starving them of oxygen

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Standing in her patient's living room, Mari Seim was perplexed. The man, in his 60s, had fallen ill with flu-like symptoms more than a week before. His breathing rate had climbed, so his daughter called the Taarnaasen Medical Center, the clinic where Seim works as a general practitioner, just outside Oslo, Norway.

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Guideline for oxygen use in healthcare and emergency settings -British Thoracic Society

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Guideline for oxygen use in healthcare and emergency settings -British Thoracic Society

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The 2017 guidance is based on new evidence about how effective prescribing and delivery of emergency oxygen for patients can improve health and saved lives.

Visit our Oxygen Clinical Resource page where you will find a number of useful documents to download.
December 2019 Update
The BTS Standards of Care Committee has recently considered whether the publication of the new evidence in the form of a systematic review and meta-analysis ¹ provides grounds for an update to certain recommendations within the BTS Guideline for oxygen use in healthcare and emergency settings ².

The current recommendations state that the recommended target saturation range for acutely ill patients not at risk of hypercapnic respiratory failure is 94-98% and for those with known COPD, or other known risk factors for hypercapnic respiratory failure, a target saturation range of 88-92% is suggested, pending the availability of blood gas results. In response to the conclusions drawn from the systematic review and meta-analysis on mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA) ¹, the BTS Standards of Care Committee notes that the major thrust of the guideline was to mandate the use of controlled vs liberal oxygen therapy; thus, the overall messages from the BTS guideline ² and the systematic review ¹ are aligned in stating that controlling oxygen to a target saturation is paramount. The IOTA meta-analysis showed higher oxygen saturations were associated with higher mortality, but the optimal target range was not clearly defined. An interim update of the BTS guideline is not required at the present time.

1. Chu DK et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet (2018) 391(10131):1693-1705

2. O'Driscoll BR et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax (2017) 72(Suppl 1):ii1-ii90

December 2019

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Emergency Oxygen | British Thoracic Society | Better lung health for all

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The 2017 guidance is based on new evidence about how effective prescribing and delivery of emergency oxygen for patients can improve health and saved lives. Visit our Oxygen Clinical Resource page where you will find a number of useful documents to download.

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Oxygen therapy: emergency use and long term treatment (2015)

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Oxygen therapy: emergency use and long term treatment (2015)

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The Pharmaceutical Journal

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Clinical guide for the optimal use of Oxygen therapy during the coronavirus pandemic

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Oxygen Resources

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NHS England will not routinely commission hyperbaric oxygen therapy for diabetic lower limb ulceration in accordance with the criteria outlined in this document.

In creating this policy NHS England has reviewed this clinical condition and the options for its treatment. It has considered the place of this treatment in current clinical practice, whether scientific research has shown the treatment to be of benefit to patients, (including how any benefit is balanced against possible risks) and whether its use represents the best use of NHS resources.

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NHS England will not routinely commission hyperbaric oxygen therapy for diabetic lower limb ulceration in accordance with the criteria outlined in this document. In creating this policy NHS England has reviewed this clinical condition and the options for its treatment.

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The use of high-flow nasal oxygen in COVID-19

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The use of high-flow nasal oxygen in COVID-19

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C.Lyons1andM.CallaghaN (2020)

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Here are a collection of links and resources that you may find useful relating to both home and emergency oxygen.

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The British Thoracic Society exists to improve standards of care for people who have respiratory diseases and to support and develop those who provide that care.

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Ford,S (2018)Giving oxygen in hospital ‘often unnecessary and can cause harm’

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Ford,S (2018)Giving oxygen in hospital ‘often unnecessary and can cause harm’

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Nursing Times article

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Oxygen should be regarded as a drug. It is prescribed for hypoxaemic patients to increase alveolar oxygen tension and decrease the work of breathing. The concentration of oxygen required depends on the condition being treated; the administration of an inappropriate concentration of oxygen can have serious or even fatal consequences.

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The NICE British National Formulary (BNF) sites is only available to users in the UK, Crown Dependencies and British Overseas Territories.

If you believe you are seeing this page in error please contact us.

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The NICE British National Formulary (BNF) sites is only available to users in the UK, Crown Dependencies and British Overseas Territories. If you believe you are seeing this page in error please contact us.

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live S (2016) Practical procedures: oxygen therapy. Nursing Times; 112: 1/2, 12-14.

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live S (2016) Practical procedures: oxygen therapy. Nursing Times; 112: 1/2, 12-14.

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Great KS3 BBC description

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When animals breathe in, oxygen molecules enter the lungs and pass through the lung walls into the . The blood carries oxygen to the cells of the body, where it takes part in a chemical reaction with glucose. This chemical reaction is called respiration .

Respiration happens all the time in every living thing: it is how the cells receive . If an animal or plant does not have enough oxygen, it will not be able to and will die.

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When animals breathe in, oxygen molecules enter the lungs and pass through the lung walls into the . The blood carries oxygen to the cells of the body, where it takes part in a chemical reaction with glucose. This chemical reaction is called respiration .