NOTeD Asks: What Drives the Severity of COVID-19 Infection?

Meagan L. Grega, MD, FACLM
Covid mask and chocolate cake side by side.

THI is honored to present NOTeD guest author Meagan L. Grega, MD, FACLM. Dr. Grega is the co-founder and Chief Medical Officer of Kellyn Foundation, a 501(c)3 non-profit dedicated to making the healthy choice the easy choice. Her article below discusses how lifestyle-driven chronic diseases affect the severity of COVID-19 infection.

Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis

Though it would have seemed almost inconceivable a year ago, we have exceeded 550,000 American deaths from COVID-19, with the prediction of reaching 600,000 deaths sometime this summer. We represent <5% of the global population; but, as of March 2021, Americans account for approximately 20% of the pandemic-related deaths. Sadly, these shocking numbers only reflect the deaths from confirmed cases of COVID-19. The true death toll is likely even higher. CDC data evaluating the overall number of American deaths from all causes through October 2020 found almost 300,000 excess deaths by that point in the pandemic, with only 66% of those additional deaths caused by confirmed COVID-19 infection. The remaining excess deaths are likely multifactorial, ranging from undiagnosed COVID-19 infection to deaths due to the sequelae of lockdown policies, including medical treatment delays, missed opportunities for cancer screening and “deaths of despair” such as unintentional overdose and suicide.  One of the most concerning statistics in the CDC’s statement is that the 25–44-year-old age group has the highest percentage of excess deaths, with 26.5% more deaths than projected in a typical year. To say the last year has been unexpectedly horrifying is a massive understatement; but the truth is that the seeds of this tragedy were sown within our society long ago, growing dangerously in plain sight.

What Drives the Severity of COVID-19 Infection?

A recent study published in the Journal of the American Heart Association, entitled “Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis,” highlights the dramatic impact of largely lifestyle driven chronic diseases, such as obesity, hypertension, Type 2 diabetes and heart failure (often driven by hypertension and coronary artery disease), on the severity of COVID-19 infection. Utilizing a comparative risk assessment model, the researchers incorporated data on numbers of COVID-19 hospitalizations by age, sex and race/ethnicity from 14 states with reliable stratified data, along with national data on estimated total COVID-19 hospitalizations. Independent relationships of cardiometabolic conditions associated with COVID-19 hospitalizations were included, along with nationally representative demographics for prevalence of these cardiometabolic conditions by age, sex and race/ethnicity. Relevant cardiometabolic conditions evaluated include diabetes mellitus, hypertension, heart failure and obesity stratified into two risk groups, one with a BMI 30-40 kg/m2 and the second with a BMI> 40 kg/m2. The purpose of the study was to identify what proportion of US COVID-19 hospitalizations appear attributable to these chronic conditions, which are greatly influenced by modifiable lifestyle choices to decrease risk.

What Did the Study Find?

Throughout the study period ending November 18, 2020, an estimated 906,849 COVID-19 hospitalizations occurred in US adults. We have learned that there is a wide spectrum of outcomes for individuals infected with the SARS-CoV-2 virus, ranging from remaining completely asymptomatic to developing severe hypoxia, thromboembolic events and death. A more challenging question is, “Why?”  What factors increase an individual’s risk of serious illness if they encounter SARS-CoV-2?

Advanced age is a non-modifiable risk factor that definitely plays a role. But early studies on hospitalized patients in NYC demonstrated that comorbidities such as obesity, cardiovascular disease, diabetes and hypertension were independent predictors of hospitalization and severe COVID-19 disease. This study expands on earlier research, providing additional evidence that the ubiquitous chronic diseases found throughout American society play a role in worsening outcomes from COVID-19. Overall, four cardiometabolic conditions (obesity, hypertension, diabetes mellitus and heart failure) accounted for almost 2/3 (63.5%) of the attributable risk of hospitalization for patients with confirmed COVID-19 infection. Perhaps surprisingly, of the four cardiometabolic conditions evaluated, obesity – which increases the risk of developing the remaining three – was the most likely attributable cause for hospitalization; accounting for 30.2% of attributable risk.

This statistic should give us all pause. Nearly 43% of Americans meet the classification criteria for obesity, a number that has been increasing for several decades. In fact, it is now abnormal in the US to have a “normal” BMI (<25 kg/m2), with less than 1/3 of Americans meeting “normal” weight criteria and only 1% of Americans meeting ideal levels for all of the American Heart Association’s ‘Simple 7’ benchmarks for optimal cardiometabolic health. Many in the normal weight category are in suboptimal metabolic health with an estimated 30 million Americans suffering “normal weight obesity,” where weight is “normal” but body fat percentage and muscle mass are high and low, respectively. The vast majority of us have substantial room for improvement in regards to optimizing our cardiometabolic health and longevity.

Equally concerning is the fact that, in this study, the risk of hospitalization after COVID-19 infection for those meeting the clinical criteria for obesity was similarly high for those of younger and older age groups (total obesity >30 kg/m2 risk: 30.8% age 18-49; 31.9% age 50-64 and 28.8% age 65+). This data highlights that the prevalence of obesity in our country is a public health emergency that deserves attention, investment and innovation in behavior modification, not just pharmacotherapy, to address.  The association of obesity and COVID-19 mortality is not just an American phenomenon. Many of the hardest hit countries in terms of severe COVID-19 disease are those with high rates of adult obesity among their citizens.

Hypertension was the second most likely attributable cause for hospitalization after SARS-CoV-2 infection, accounting for 26.2% of attributable risk, followed by diabetes mellitus at 20.5% and heart failure at 11.7%. Chronic kidney disease was also a factor in their analysis, accounting for 12.9% of attributable risk. These finding are consistent with previous studies regarding the impact of chronic disease on COVID-19 outcomes. Race/Ethnicity factors also play a role, with Black and Hispanic adults demonstrating the highest proportion of COVID-19 hospitalizations attributable to obesity, hypertension, diabetes mellitus and heart failure across all age groups.

Why Do Cardiometabolic Conditions Increase Risk for Severe COVID-19 Infection?

One of the limitations of this study is that it evaluates the association of cardiometabolic conditions with COVID-19 hospitalization, but that does not equal causation of severe COVID-19 infection due to these factors. However, there are plausible biologic explanations for why conditions like obesity, hypertension, diabetes mellitus and heart failure might increase risk of poor outcomes after SARS-CoV-2 infection. Importantly, these cardiometabolic diseases have been associated with impaired immune function and decreased immune response. Chronic systemic inflammation associated with cardiometabolic disease is another potential factor that can worsen outcomes, as can related underlying endothelial dysfunction. Obesity can reduce baseline pulmonary function, increasing the risk for respiratory failure after infection with COVID-19. Additionally, increased expression of the ACE 2 receptors in adipose tissue, especially the visceral variety, likely play a role in the aggravated pathogenesis of severe COVID-19 and death in obesity. The SARS-CoV-2 spike protein accesses the ACE 2 receptor like a key into a lock, which may support a massive viral load in obese individuals and contribute to worsening severity of disease. These myriad metabolic disturbances all add up to decreased resilience in the face of a novel viral infection.

What Can We Do?

The COVID-19 pandemic, both the virus and our responses to it, will have long-lasting impacts throughout the world. The most tragic part of the story is the amount of mortality that likely could have been avoided if our population health metrics were improved. The CDC estimates that over 47% of American adults have an underlying comorbidity which puts them at increased risk of severe COVID-19 infection. We can do better. Cardiometabolic conditions like obesity, hypertension, type 2 diabetes mellitus, heart failure and chronic kidney disease are, for the most part, preventable, as well as treatable and reversible, by optimizing lifestyle choices. Healthy habits such as a predominantly whole food, plant-based dietary pattern, regular physical activity with reduced chronic sitting, prioritizing restorative sleep, avoidance of risky substances such as tobacco and excess alcohol consumption, managing stress and nurturing social connections can dramatically decrease the risk of developing chronic disease while supporting immune function and improving overall longevity and quality of life.  Albert Einstein once said, “The definition of insanity is doing the same thing over and over and expecting different results.” If we would like to see different results for ourselves and for those we love, and not just for the current and future pandemics but also for the unacceptably high number of Americans who die of cardiovascular disease, complications from diabetes and chronic kidney disease every year, we have important choices to make, both as individuals and as a society. We need to change the game and give intensive therapeutic lifestyle interventions targeted to improving cardiometabolic risk factors the attention they deserve, along with investing in overall population health through community-based programs and scalable personalized digital initiatives while shifting our social norms towards healthier habits. An old proverb asks, “When is the best time to plant a tree? Twenty years ago. When is the next best time to plant a tree? Today.” This wisdom applies to preparing for a pandemic, as well as creating strategies to combat the crushing financial cost and poor outcomes of our current chronic disease epidemic. Let’s not let this crisis fade to history in vain. It’s time to seize the opportunity for serious, deliberate and persistent change, a change that can only come through making the healthy choice the easy choice by addressing environmental nudges starting in our homes, and then our neighborhoods; schools; workplaces; and food outlets, to support lifestyle habits that will promote resilience regardless of what the future brings.