# data[].attributes.headline
Using Previous Pandemics to Prepare for the Future

# data[].attributes.subject
Using Previous Pandemics to Prepare for the Future

# data[].attributes.body
This article, that was published in 2014, showcases the political issues regarding the 2009 H1N1 Pandemic along with the strategies that did work out positively. Historical references such as this should be the basis of our future pandemic preparedness in knowing what to invest in, what to focus policy towards, and what topic to surveil.

"Beyond institutional, political, and managerial difficulties, the most fundamental constraints on pandemic preparedness are the limits of scientific understanding and technical capacity" (Fineberg 2014).

# data[].attributes.attachment_link.title
Pandemic Preparedness and Response — Lessons from the H1N1 Influenza of 2009 | NEJM

# data[].attributes.attachment_link.description
Review Article from The New England Journal of Medicine — Pandemic Preparedness and Response — Lessons from the H1N1 Influenza of 2009

# data[].attributes.body
This article describes the use of a Stay-At-Home order in the United States as an example of "national coordination". The Stay-At-Home order showcases the government's role in coordination with the CDC, local governments, and federal adminstration. In addition, in the case of a pandemic, establishing a sense national responsibility is vital in ensuring less American Covid-19 cases.  The United States Stay-At-Home order helped reduce the spread of the virus, seeing an 30.2% decrease of cases in the first week after its introduction.

# data[].attributes.attachment_link.readable_text
Abstract

Governments issue "stay at home" orders to reduce the spread of contagious diseases, but the magnitude of such orders' effectiveness is uncertain. In the United States these orders were not coordinated at the national level during the coronavirus disease 2019 (COVID-19) pandemic, which creates an opportunity to use spatial and temporal variation to measure the policies' effect with greater accuracy. Here, we combine data on the timing of stay-at-home orders with daily confirmed COVID-19 cases and fatalities at the county level in the United States. We estimate the effect of stay-at-home orders using a difference-in- differences design that accounts for unmeasured local variation in factors like health systems and demographics and for unmeasured temporal variation in factors like national mitigation actions and access to tests. Compared to counties that did not implement stay-at-home orders, the results show that the orders are associated with a 30.2 percent (11.0 to 45.2) reduction in weekly cases after one week, a 40.0 percent (23.4 to 53.0) reduction after two weeks, and a 48.6 percent (31.1 to 61.7) reduction after three weeks. Stay-at-home orders are also associated with a 59.8 percent (18.3 to 80.2) reduction in weekly fatalities after three weeks. These results suggest that stay-at-home orders reduced confirmed cases by 390,000 (170,000 to 680,000) and fatalities by 41,000 (27,000 to 59,000) within the first three weeks in localities where they were implemented.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

None.

Author Declarations

All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.

Yes

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data used in this paper are publicly available on internet sites.

# data[].attributes.attachment_link.title
The Effect of Stay-at-Home Orders on COVID-19 Cases and Fatalities in the United States

# data[].attributes.attachment_link.description
Governments issue "stay at home" orders to reduce the spread of contagious diseases, but the magnitude of such orders' effectiveness is uncertain. In the United States these orders were not coordinated at the national level during the coronavirus disease 2019 (COVID-19) pandemic, which creates an opportunity to use spatial and temporal variation to measure the policies' effect with greater accuracy.

# data[].attributes.body
This image illustrates vital information used to keep employees safe while working on site. Infographics like these are essential in providing both awareness and education to everyday people in keeping everyone safe. These guidelines are also most likely taken from the CDC website, which can also be linked towards the topic of having available resources/information ready in case of either question or emergency.

# data[].attributes.body
This image showcases the pandemic preparation essentials that everyday people can take for themselves. These items, such as a first aid kit with thermometer, can help detect illness quickly and establish a self-imposed quarantine on individuals. Little decisions and items like this can save lives but also encourage people to do their part in a pandemic. This is especially relevant to essential workers like grocery store workers and nurses, who interact with hundreds of people a day.

# data[].attributes.headline
The Different Disciplines of Pandemic Preparedness

# data[].attributes.subject
The Different Disciplines of Pandemic Preparedness

# data[].attributes.body
This image showcases the many different aspects allotted to the topic of pandemic preparedness. As a quick note, most of these agenda items involve international help. For example, "establish a pre-negotiated platform for tools and supplies" along with "establish a new global surveillance system" are only effective when all 195 countries are contributing their share. This will take lots of coordination and leadership but would not only provide for a safer global health but also save millions of lives.

# data[].attributes.headline
Metabolic Health and Lifestyle Medicine as Pandemic Preparedness

# data[].attributes.subject
Metabolic Health and Lifestyle Medicine as Pandemic Preparedness

# data[].attributes.body
This article demonstrates the use of improving population lifestyle choices as a way of pandemic preparedness. As seen in this pandemic, most Covid-19 symptoms only worsened with the help of one's pre-existing conditions. If we were to target the source of the pre-existing conditions, we can then mitigate the symptoms and even death count of pandemic wide viruses.

# data[].attributes.attachment_link.readable_text
Thomas R. Wood BM, BCh, PhD , Guðmundur F. Jóhannsson MD ,

Department of Emergency Medicine, Landspítali University Hospital, Reykjavík, Iceland
Search for more papers by this author

Corresponding Author

Department of Pediatrics, University of Washington, Seattle, Washington

Institute for Human and Machine Cognition, Pensacola, Florida
Correspondence
Thomas R. Wood, Department of Pediatrics, University of Washington, Seattle, WA 98195.
Search for more papers by this author

Abstract

The recent impact of SARS-CoV-2 and coronavirus disease 2019 (COVID-19) has shown major differences in infrastructure and approach across healthcare systems worldwide. One thing we can already be certain of is that governments and policy makers worldwide will place a greater focus on pandemic preparedness in the future. However, as well as ensuring that robust pipelines for rapid test, highly effective treatment or vaccine, and personal protective equipment (PPE) production are in place, we must address underlying resilience and susceptibility of our populations to infectious disease. Although the true spread and case fatality rate of SARS-CoV-2 may not be known for several months or even years, what is becoming increasingly clear is the significant degree to which underlying conditions associated with suboptimal metabolic health appear to be associated with poor outcomes in those with COVID-19. Considering the nature of these underlying conditions, such as obesity and hypertension, lifestyle-based approaches are likely to be one of our best tools in order to address ongoing and future disease burden during pandemics.

The recent impact of SARS-CoV-2 and coronavirus disease 2019 (COVID-19) has shown major differences in infrastructure and approach across healthcare systems worldwide. One thing we can already be certain of is that governments and policy makers worldwide will place a greater focus on pandemic preparedness in the future. However, as well as ensuring that robust pipelines for rapid test, highly effective treatment or vaccine, and personal protective equipment (PPE) production are in place, we must address underlying resilience and susceptibility of our populations to infectious disease. Although the true spread and case fatality rate of SARS-CoV-2 may not be known for several months or even years, what is becoming increasingly clear is the significant degree to which underlying conditions associated with suboptimal metabolic health appear to be associated with poor outcomes in those with COVID-19. Considering the nature of these underlying conditions such as obesity and hypertension, lifestyle-based approaches are likely to be one of our best tools in order to address ongoing and future disease burden during pandemics.

Based on the largest available studies at time of writing, the comorbidities particularly associated with hospitalization and poor outcome in patients with COVID-19 are age, obesity, hypertension, and diabetes. For instance, one study in New York City found that, of 5700 patients hospitalized with COVID-19, 57%, 42%, and 34% had hypertension, obesity, and diabetes, respectively. Of 72 314 cases from the Chinese Center for Disease Control and Prevention, reported case fatality rate was elevated in those with comorbid conditions: at least 10% for cardiovascular diseases, 7% for diabetes, and 6% for hypertension. Importantly, however, the diabetes diagnoses associated with increased risk have not routinely been separated by type (1 or 2) or duration, and this is a key area of future research. As outlined below, with metabolic derangement (eg, systemic insulin resistance) and hyperglycemia potentially underlying changes in the immune system seen in the comorbid conditions associated with worse COVID-19 outcome, it is possible that the well-controlled type 1 diabetic is not at increased risk. In studies of COVID-19 patients requiring invasive mechanical ventilation in Italy and New York City, the latter as a preprint at time of writing, both age and obesity were significant contributors to risk, with the mechanical disadvantage of ventilation in obese patients a potential contributor. In the United Kingdom, the Office of National Statistics (ONS) reported that the most common comorbid condition in COVID-19 deaths was ischemic heart disease, which is also tightly associated with obesity, metabolic syndrome, and glycemic control. Similarly, a report from the Intensive Care National Audit and Research Centre (ICNARC) on 8 May 2020 stated that of the first 8250 critically ill COVID-19 cases in the United Kingdom (64% of whom required mechanical ventilation within 24 h of admission), 73% were overweight or obese, which was significantly greater than the 60% of critically ill historical controls admitted for viral pneumonia ( P < .001, Chi-squared test by authors).

A major driver of morbidity and mortality in those at risk appears to be a dysregulated immune response characterized by lymphopenia and an associated "cytokine" storm. This cytokine storm is typically associated markedly higher levels of cytokines such as IL-6, IL-10, and TNF-α, as well as elevated lactate dehydrogenase (LDH) and C-reactive protein, which may reflect systemic injury responses as well as both direct (eg, myocarditis) and indirect injury to the heart and lungs. As we learn more, it seems likely that the COVID-19 cytokine storm is at least partly rooted in the immune dysregulation seen as a result of metabolic disease, a phenomenon explored in the burgeoning field of "immunometabolism." These changes include a shift toward greater innate immune responses, relative lymphopenia, and a decrease in the balance of the T-helper (Th) system of cytokines resulting in reduced Th1-type cytokines and increased Th2-type cytokines. These changes are associated both the with ongoing disease process as well as periods of acute hyperglycaemia. Though the Th1/Th2 classification is oversimplified, and cytokines from both branches are increased in COVID-19, it has been hypothesized that relative increases in the Th2 response contribute in inhibition of inflammatory resolution in severe COVID-19. Hyperactivation of the Th2 system is thought to underlie the increase in mortality seen in mice who received a prototype vaccine for the related SARS-CoV-1 virus and were then exposed to a viral challenge. The preclinical literature has also documented the course of the immune response to viral challenge in rodents with diet-induced obesity, with influenza A as the model infection. At baseline, obese mice have higher levels of pro-inflammatory cytokines in the lungs, but they display as slower initial immune response that results in a higher overall viral load and increased inflammatory response later on in the course of the infection. This potentially explains the anecdotal reports of COVID-19 progression occurring in two phases, with an initial brief resolution of certain symptoms followed by a later significant deterioration.

Another critical aspect of immune overactivation in severe COVID-19 appears to be involvement of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome, one of many inflammasomes that make up the innate immune system. Tonic NLRP3 activation increases in the elderly and is also associated with the progression and severity of obesity and other metabolic diseases. Activation of NLRP3 during the immune response drives a necrotic-type cell death known as pyroptosis, one hallmark of which is the release of intracellular LDH. As increased LDH is seen in severe COVID-19, this has led many to suggest that NLRP3 overactivation and pyroptosis, particularly in the respiratory tissues, is a significant contributor to COVID-19 morbidity. Overactivation of the NLRP3 pathway may also partly explain why males appear to be at greater risk for poor COVID-19 outcomes; in older adults, a greater activation of the innate immune system, including the nucleotide-binding oligomerization domain (NOD) pathway of which NLRP3 is a subset, is seen in males compared to females.

Though the diseases associated with worse outcome are based on specific diagnostic criteria, it is likely that these immunometabolic changes lie along a continuum as health changes over time. Considering that recent estimates in the United States suggest that less than 20% of adults have optimal metabolic health, a sliding scale exists that could still place the majority of adults at some degree of increased risk of susceptibility to certain infectious diseases. More broadly, the comorbidities associated with increased risk of severe COVID-19 can also all be characterized as having the presence of low-grade chronic inflammation, as well as the presence of many of the hallmarks of aging, which together are pathognomonic for the process of "inflammaging." Indeed, a group of researchers with significant experience in the of field of aging and biomarkers of biological age have released a preprint proposing that COVID-19 is an emergent disease of aging. Previous studies of patients with the related SARS-CoV-1 and MERS (Middle East Respiratory Syndrome) coronaviruses also suggest that in addition to age, similar comorbidities to those that predispose to worse outcomes in COVID-19 played a role in mortality risk. During the unrelated Influenza A (H1N1) pandemic, both obesity and hypertension were also identified as risk factors for poor outcome. Both preclinical models and clinical data from the H1N1 pandemic also suggest that diabetes, particularly when associated with hyperglycemia and glycemic variability, is associated with worse outcomes after infection with influenza. Glycemic variability has similarly been found to be associated with outcomes in type 2 diabetics with COVID-19. This suggests that regardless of the virus type, taking steps to improve population metabolic and immune health will play a crucial role in reducing the impact of future pandemics. Though they are clearly important in the current SARS-CoV-2 pandemic, in the context of long-term population health, the diseases associated with inflammaging and poor metabolic health should become a key focus as we prepare for future pandemics, which are most likely to be due to a strain of influenza.

A ray of hope for those hoping to improve health and reduce risk at the population level is the fact that the majority of at-risk comorbidities are thought to be largely driven by lifestyle factors, with lifestyle-based interventions such as lifestyle medicine having a rapidly expanding evidence base to support their use as the cornerstone of disease treatment, prevention, and reversal. Even age, traditionally thought to be an unmodifiable risk factor for disease and mortality, may be partially modifiable, with biological age and immune age superseding chronological age as predictors of outcome. Increased relative biological age, which can be inferred from a number of potential biomarkers, is tightly linked to lifestyle factors such as smoking, being sedentary, excessive alcohol intake, and a poor-quality diet.

Regardless whether the exact underlying mechanisms are currently understood, it is clear that the tenets of lifestyle medicine have extraordinary power to improve the health of the population, both overall as well as in the face of unknown future pandemics. For instance, a wide variety of dietary approaches have been shown to be effective in providing long-term weight loss, reductions in blood pressure, improved glycemic control, and even reversal of type 2 diabetes. These include the dietary approaches to stop hypertension (DASH) and Mediterranean diets. More severe disease may benefit from more restrictive approaches for a short period, including low-fat whole food plant-based diets, low-carbohydrate ketogenic diets, and severe caloric restriction. Time-restricted eating may also be beneficial by increasing the fasting window and spontaneously improving diet quality and reducing caloric intake. Importantly, if long-term improvements in weight and metabolic health are the goal, any and all of these dietary tools should remain in our toolkit based on the disease and individual patient, avoiding tacit ideological support of any single approach. In addition to larger dietary changes, targeted approaches to nutrient status may also be beneficial, with two reports (with one only available as a conference abstract) suggesting at least of 90% acute respiratory distress syndrome (ARDS) cases have Vitamin D deficiency. Multiple recent preprints have also suggested vitamin D deficiency/insufficiency being associated with worse outcomes in COVID-19, with the greatest benefit seemingly being associated with vitamin D levels above 30 ng/mL (75 nmol/L). Although randomized controlled trials of vitamin D supplementation in those who are deficient do seem to reduce the incidence of acute respiratory tract infections, supplementation with vitamin D in critically ill patients at high risk of mortality does not appear to be beneficial after admission to intensive care. An increased prevalence of vitamin D deficiency may partly explain the higher COVID-19 risk seen in BAME (Black, Asian, and Minority Ethic) populations, who are at greater risk of Vitamin D deficiency in northern latitudes as well as being as greater risk of metabolic disease. In the United Kingdom, this apparent increase in COVID-19 risk in BAME populations, as well as the apparent overrepresentation of those from BAME backgrounds in the death toll of the UK healthcare workers, has resulted in significant and much-needed funding from the National Institute for Health Research (NIHR) and the UK Research and Innovation (UKRI) for research examining the associations between ethnicity and COVID-19 outcome. As information on the demographics associated with poor COVID-19 outcomes will only continue to increase and evolve, platforms such as OpenSAFELY and the Oxford rapid COVID-19 Evidence Service will remain crucial to ongoing data collection and understanding of those at greater risk, and potential reasons why.

Beyond diet, regular movement is associated with significant improvements in glycemic control, often independent of weight loss. Importantly, this does not need to be a daunting task. Coined by Francois et al in 2014, small regular movement or exercise "snacks" (eg, 2-6 min of simple movement every 30-60 min or before meals) are associated with improved glycemic control, including when compared to energy-matched long single training sessions. Simple walking is also associated with decreased mortality that plateaus around 10 000 steps per day. Beyond that, both resistance training (and resulting improvements in strength and muscle mass) and aerobic exercise are associated with reduced risk of obesity, hypertension, metabolic disease, and survival after critical illness. Lifestyle medicine also has significant scope to improve sleep quantity and quality, both of which are associated with immune function and overall mortality. Initiatives such as group consultations and social prescribing can even help to tackle loneliness and social isolation, which are associated with both altered inflammatory processes and increased mortality. The majority of lifestyle medicine interventions can also be implemented and tracked using simple telemedicine and digital health solutions. These have become increasingly prevalent in the modern healthcare system, with a further increase due to social distancing during COVID-19, and are likely to become a cornerstone of future health care as a result, particularly for vulnerable populations.

As the SARS-CoV-2 pandemic curve appears to be flattening in many countries, the priority is to ensure that developing nations are supported in their response to the first wave, whereas surveillance and a heightened test, track, and trace strategy anticipate and mitigate further waves. There will be an increased interest in planning for future pandemics to reduce the likelihood of healthcare systems becoming overwhelmed with patients such that care needs to be rationed, with the attendant risk of accentuating inequality in access to adequate healthcare. Although improving essential infrastructure will be an important aspect of this planning, proactively improving population health will also be crucial in order to minimize the future burden on health care during a pandemic. Lifestyle medicine is poised to be at the forefront of these efforts and should be increasingly promoted as part of healthcare policy in order to improve the resiliency and health of the population in an unknowable future.

ACKNOWLEDGMENT

The authors would like to sincerely thank Dr. Fraser Birrell for his input during the writing process. There was no funding associated with this work.

CONFLICT OF INTEREST

TRW is a director of the British Society of Lifestyle Medicine.

Abstract

The recent impact of SARS-CoV-2 and coronavirus disease 2019 (COVID-19) has shown major differences in infrastructure and approach across healthcare systems worldwide. One thing we can already be certain of is that governments and policy makers worldwide will place a greater focus on pandemic preparedness in the future. However, as well as ensuring that robust pipelines for rapid test, highly effective treatment or vaccine, and personal protective equipment (PPE) production are in place, we must address underlying resilience and susceptibility of our populations to infectious disease. Although the true spread and case fatality rate of SARS-CoV-2 may not be known for several months or even years, what is becoming increasingly clear is the significant degree to which underlying conditions associated with suboptimal metabolic health appear to be associated with poor outcomes in those with COVID-19. Considering the nature of these underlying conditions, such as obesity and hypertension, lifestyle-based approaches are likely to be one of our best tools in order to address ongoing and future disease burden during pandemics.

The recent impact of SARS-CoV-2 and coronavirus disease 2019 (COVID-19) has shown major differences in infrastructure and approach across healthcare systems worldwide. One thing we can already be certain of is that governments and policy makers worldwide will place a greater focus on pandemic preparedness in the future. However, as well as ensuring that robust pipelines for rapid test, highly effective treatment or vaccine, and personal protective equipment (PPE) production are in place, we must address underlying resilience and susceptibility of our populations to infectious disease. Although the true spread and case fatality rate of SARS-CoV-2 may not be known for several months or even years, what is becoming increasingly clear is the significant degree to which underlying conditions associated with suboptimal metabolic health appear to be associated with poor outcomes in those with COVID-19. Considering the nature of these underlying conditions such as obesity and hypertension, lifestyle-based approaches are likely to be one of our best tools in order to address ongoing and future disease burden during pandemics.

Based on the largest available studies at time of writing, the comorbidities particularly associated with hospitalization and poor outcome in patients with COVID-19 are age, obesity, hypertension, and diabetes. For instance, one study in New York City found that, of 5700 patients hospitalized with COVID-19, 57%, 42%, and 34% had hypertension, obesity, and diabetes, respectively. Of 72 314 cases from the Chinese Center for Disease Control and Prevention, reported case fatality rate was elevated in those with comorbid conditions: at least 10% for cardiovascular diseases, 7% for diabetes, and 6% for hypertension. Importantly, however, the diabetes diagnoses associated with increased risk have not routinely been separated by type (1 or 2) or duration, and this is a key area of future research. As outlined below, with metabolic derangement (eg, systemic insulin resistance) and hyperglycemia potentially underlying changes in the immune system seen in the comorbid conditions associated with worse COVID-19 outcome, it is possible that the well-controlled type 1 diabetic is not at increased risk. In studies of COVID-19 patients requiring invasive mechanical ventilation in Italy and New York City, the latter as a preprint at time of writing, both age and obesity were significant contributors to risk, with the mechanical disadvantage of ventilation in obese patients a potential contributor. In the United Kingdom, the Office of National Statistics (ONS) reported that the most common comorbid condition in COVID-19 deaths was ischemic heart disease, which is also tightly associated with obesity, metabolic syndrome, and glycemic control. Similarly, a report from the Intensive Care National Audit and Research Centre (ICNARC) on 8 May 2020 stated that of the first 8250 critically ill COVID-19 cases in the United Kingdom (64% of whom required mechanical ventilation within 24 h of admission), 73% were overweight or obese, which was significantly greater than the 60% of critically ill historical controls admitted for viral pneumonia ( P < .001, Chi-squared test by authors).

A major driver of morbidity and mortality in those at risk appears to be a dysregulated immune response characterized by lymphopenia and an associated "cytokine" storm. This cytokine storm is typically associated markedly higher levels of cytokines such as IL-6, IL-10, and TNF-α, as well as elevated lactate dehydrogenase (LDH) and C-reactive protein, which may reflect systemic injury responses as well as both direct (eg, myocarditis) and indirect injury to the heart and lungs. As we learn more, it seems likely that the COVID-19 cytokine storm is at least partly rooted in the immune dysregulation seen as a result of metabolic disease, a phenomenon explored in the burgeoning field of "immunometabolism." These changes include a shift toward greater innate immune responses, relative lymphopenia, and a decrease in the balance of the T-helper (Th) system of cytokines resulting in reduced Th1-type cytokines and increased Th2-type cytokines. These changes are associated both the with ongoing disease process as well as periods of acute hyperglycaemia. Though the Th1/Th2 classification is oversimplified, and cytokines from both branches are increased in COVID-19, it has been hypothesized that relative increases in the Th2 response contribute in inhibition of inflammatory resolution in severe COVID-19. Hyperactivation of the Th2 system is thought to underlie the increase in mortality seen in mice who received a prototype vaccine for the related SARS-CoV-1 virus and were then exposed to a viral challenge. The preclinical literature has also documented the course of the immune response to viral challenge in rodents with diet-induced obesity, with influenza A as the model infection. At baseline, obese mice have higher levels of pro-inflammatory cytokines in the lungs, but they display as slower initial immune response that results in a higher overall viral load and increased inflammatory response later on in the course of the infection. This potentially explains the anecdotal reports of COVID-19 progression occurring in two phases, with an initial brief resolution of certain symptoms followed by a later significant deterioration.

Another critical aspect of immune overactivation in severe COVID-19 appears to be involvement of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome, one of many inflammasomes that make up the innate immune system. Tonic NLRP3 activation increases in the elderly and is also associated with the progression and severity of obesity and other metabolic diseases. Activation of NLRP3 during the immune response drives a necrotic-type cell death known as pyroptosis, one hallmark of which is the release of intracellular LDH. As increased LDH is seen in severe COVID-19, this has led many to suggest that NLRP3 overactivation and pyroptosis, particularly in the respiratory tissues, is a significant contributor to COVID-19 morbidity. Overactivation of the NLRP3 pathway may also partly explain why males appear to be at greater risk for poor COVID-19 outcomes; in older adults, a greater activation of the innate immune system, including the nucleotide-binding oligomerization domain (NOD) pathway of which NLRP3 is a subset, is seen in males compared to females.

Though the diseases associated with worse outcome are based on specific diagnostic criteria, it is likely that these immunometabolic changes lie along a continuum as health changes over time. Considering that recent estimates in the United States suggest that less than 20% of adults have optimal metabolic health, a sliding scale exists that could still place the majority of adults at some degree of increased risk of susceptibility to certain infectious diseases. More broadly, the comorbidities associated with increased risk of severe COVID-19 can also all be characterized as having the presence of low-grade chronic inflammation, as well as the presence of many of the hallmarks of aging, which together are pathognomonic for the process of "inflammaging." Indeed, a group of researchers with significant experience in the of field of aging and biomarkers of biological age have released a preprint proposing that COVID-19 is an emergent disease of aging. Previous studies of patients with the related SARS-CoV-1 and MERS (Middle East Respiratory Syndrome) coronaviruses also suggest that in addition to age, similar comorbidities to those that predispose to worse outcomes in COVID-19 played a role in mortality risk. During the unrelated Influenza A (H1N1) pandemic, both obesity and hypertension were also identified as risk factors for poor outcome. Both preclinical models and clinical data from the H1N1 pandemic also suggest that diabetes, particularly when associated with hyperglycemia and glycemic variability, is associated with worse outcomes after infection with influenza. Glycemic variability has similarly been found to be associated with outcomes in type 2 diabetics with COVID-19. This suggests that regardless of the virus type, taking steps to improve population metabolic and immune health will play a crucial role in reducing the impact of future pandemics. Though they are clearly important in the current SARS-CoV-2 pandemic, in the context of long-term population health, the diseases associated with inflammaging and poor metabolic health should become a key focus as we prepare for future pandemics, which are most likely to be due to a strain of influenza.

A ray of hope for those hoping to improve health and reduce risk at the population level is the fact that the majority of at-risk comorbidities are thought to be largely driven by lifestyle factors, with lifestyle-based interventions such as lifestyle medicine having a rapidly expanding evidence base to support their use as the cornerstone of disease treatment, prevention, and reversal. Even age, traditionally thought to be an unmodifiable risk factor for disease and mortality, may be partially modifiable, with biological age and immune age superseding chronological age as predictors of outcome. Increased relative biological age, which can be inferred from a number of potential biomarkers, is tightly linked to lifestyle factors such as smoking, being sedentary, excessive alcohol intake, and a poor-quality diet.

Regardless whether the exact underlying mechanisms are currently understood, it is clear that the tenets of lifestyle medicine have extraordinary power to improve the health of the population, both overall as well as in the face of unknown future pandemics. For instance, a wide variety of dietary approaches have been shown to be effective in providing long-term weight loss, reductions in blood pressure, improved glycemic control, and even reversal of type 2 diabetes. These include the dietary approaches to stop hypertension (DASH) and Mediterranean diets. More severe disease may benefit from more restrictive approaches for a short period, including low-fat whole food plant-based diets, low-carbohydrate ketogenic diets, and severe caloric restriction. Time-restricted eating may also be beneficial by increasing the fasting window and spontaneously improving diet quality and reducing caloric intake. Importantly, if long-term improvements in weight and metabolic health are the goal, any and all of these dietary tools should remain in our toolkit based on the disease and individual patient, avoiding tacit ideological support of any single approach. In addition to larger dietary changes, targeted approaches to nutrient status may also be beneficial, with two reports (with one only available as a conference abstract) suggesting at least of 90% acute respiratory distress syndrome (ARDS) cases have Vitamin D deficiency. Multiple recent preprints have also suggested vitamin D deficiency/insufficiency being associated with worse outcomes in COVID-19, with the greatest benefit seemingly being associated with vitamin D levels above 30 ng/mL (75 nmol/L). Although randomized controlled trials of vitamin D supplementation in those who are deficient do seem to reduce the incidence of acute respiratory tract infections, supplementation with vitamin D in critically ill patients at high risk of mortality does not appear to be beneficial after admission to intensive care. An increased prevalence of vitamin D deficiency may partly explain the higher COVID-19 risk seen in BAME (Black, Asian, and Minority Ethic) populations, who are at greater risk of Vitamin D deficiency in northern latitudes as well as being as greater risk of metabolic disease. In the United Kingdom, this apparent increase in COVID-19 risk in BAME populations, as well as the apparent overrepresentation of those from BAME backgrounds in the death toll of the UK healthcare workers, has resulted in significant and much-needed funding from the National Institute for Health Research (NIHR) and the UK Research and Innovation (UKRI) for research examining the associations between ethnicity and COVID-19 outcome. As information on the demographics associated with poor COVID-19 outcomes will only continue to increase and evolve, platforms such as OpenSAFELY and the Oxford rapid COVID-19 Evidence Service will remain crucial to ongoing data collection and understanding of those at greater risk, and potential reasons why.

Beyond diet, regular movement is associated with significant improvements in glycemic control, often independent of weight loss. Importantly, this does not need to be a daunting task. Coined by Francois et al in 2014, small regular movement or exercise "snacks" (eg, 2-6 min of simple movement every 30-60 min or before meals) are associated with improved glycemic control, including when compared to energy-matched long single training sessions. Simple walking is also associated with decreased mortality that plateaus around 10 000 steps per day. Beyond that, both resistance training (and resulting improvements in strength and muscle mass) and aerobic exercise are associated with reduced risk of obesity, hypertension, metabolic disease, and survival after critical illness. Lifestyle medicine also has significant scope to improve sleep quantity and quality, both of which are associated with immune function and overall mortality. Initiatives such as group consultations and social prescribing can even help to tackle loneliness and social isolation, which are associated with both altered inflammatory processes and increased mortality. The majority of lifestyle medicine interventions can also be implemented and tracked using simple telemedicine and digital health solutions. These have become increasingly prevalent in the modern healthcare system, with a further increase due to social distancing during COVID-19, and are likely to become a cornerstone of future health care as a result, particularly for vulnerable populations.

As the SARS-CoV-2 pandemic curve appears to be flattening in many countries, the priority is to ensure that developing nations are supported in their response to the first wave, whereas surveillance and a heightened test, track, and trace strategy anticipate and mitigate further waves. There will be an increased interest in planning for future pandemics to reduce the likelihood of healthcare systems becoming overwhelmed with patients such that care needs to be rationed, with the attendant risk of accentuating inequality in access to adequate healthcare. Although improving essential infrastructure will be an important aspect of this planning, proactively improving population health will also be crucial in order to minimize the future burden on health care during a pandemic. Lifestyle medicine is poised to be at the forefront of these efforts and should be increasingly promoted as part of healthcare policy in order to improve the resiliency and health of the population in an unknowable future.

ACKNOWLEDGMENT

The authors would like to sincerely thank Dr. Fraser Birrell for his input during the writing process. There was no funding associated with this work.

CONFLICT OF INTEREST

TRW is a director of the British Society of Lifestyle Medicine.

# data[].attributes.attachment_link.title
Metabolic health and lifestyle medicine should be a cornerstone of future pandemic preparedness

# data[].attributes.attachment_link.description
Thomas R. Wood BM, BCh, PhD , Guðmundur F. Jóhannsson MD , Department of Emergency Medicine, Landspítali University Hospital, Reykjavík, Iceland Search for more papers by this author Corresponding Author Department of Pediatrics, University of Washington, Seattle, Washington Institute for Human and Machine Cognition, Pensacola, Florida Correspondence Thomas R.

# data[].attributes.body
Pandemics are worldwide disease outbreak disasters that not only affect the people but also the economic and social systems in place. In order to prevent such an event, there are many pandemic preparation methods that can take place to lessen the impact. These bigger-picture methods are mostly at the will of both local and global governments. International assistance and communication are instrumental in pandemic preparedness policy. Every day people and societies themselves can prepare through the use of education along with making good lifestyle choices.