Kaiser Study: Severe Obesity Boosts Risk of COVID-19 Death, Especially for the Young

Severe obesity puts those with coronavirus disease 2019 (COVID-19) at particularly high risk of death, more so than related risk factors such as diabetes or hypertension, according to a study of patient records that researchers from Kaiser Permanente published today.

The study, appearing in Annals of Internal Medicine,¹ showed that obesity is especially dangerous for men and younger patients who contract COVID-19, and that obesity stood out from racial, ethnic, or socioeconomic disparities when isolated from those factors.

Data from the 6916 patients in the study show that compared with those at normal body mass index (BMI) of 18.5 to 24 kg/m², the risk of death more than doubled for patients with a body mass index (BMI) of 40 to 44 kg/m² (relative risk of 2.68; 95% CI, 1.43 to 5.04) and nearly doubled again for those with a BMI of 45 kg/m² (relative risk of 4.18; 95% CI, 2.12 to 8.26).

“This risk was most striking among those aged 60 years or younger and men,” the authors wrote.

In an accompanying editorial, David A. Kass, MD, a cardiologist at John Hopkins University, wrote that these findings, when taken with prior research, “should put to rest the contention that obesity is common in severe COVID-19 because it is common in the population. Obesity is an important independent risk factor for serious COVID-19 disease.”²

Genentech funded the study.

Kaiser Permanente’s study stands out from others for a number of reasons: it gathered data not just on patients in the hospital, and authors had access to comprehensive patient data that allowed them to isolate the effect of obesity from multiple individual clinical and socioeconomic factors, including 20 different comorbidities, prior medication use, alcohol or smoking status, health care use, median household income, household education level, and the population density of the neighborhood.

Researchers even adjusted for time, because they knew that with each passing week, testing practices, social distancing, and clinical treatments changed as doctors and health officials shifted their pandemic response. The study covered patients treated from February 13 to May 2, 2020.

The authors note that they did not find a statistically significant link between Black or Hispanic race/ethnicity or neighborhood-level variables on death risk, amid “widespread concern” about the outsize share of COVID-19 deaths in minority communities. Because Kaiser Permanente is a capitated health care system, the authors speculated that patients may have greater access to care than in some parts of the United States.

Still, they noted their findings show the need to treat severe obesity as an independent risk factor and create appropriate interventions, especially in young men.

“We present findings that can inform decisions much earlier in the triage process, including in the ambulatory setting,” they wrote. “Our finding that severe obesity, particularly among younger patients, eclipses the mortality risk posed by other obesity-related conditions, such as history of myocardial infarction, diabetes, hypertension, or hyperlipidemia, suggests a significant pathophysiologic link between excess adiposity and severe COVID-19 illness.”

Kass, the Johns Hopkins cardiologist, elaborated on what might be behind these findings. “That the risks are higher in younger patients is probably not because obesity is particularly damaging in this age group; it is more likely that other serious comorbidities that evolve later in life take over as dominant risk factors,” he wrote.

His assessment was stark: COVID-19 makes it hard to breathe, and excess fat only makes this worse.

“As a cardiologist who studies heart failure, I am struck by how many of the mechanisms that are mentioned in reviews of obesity risk and heart disease are also mentioned in reviews of obesity and COVID-19,” Kass wrote. Things like sleep apnea and increased inflammation are all at work, damaging lungs and particularly the air sacs that do the heavy lifting in the respiratory system.

Not only does being severely obese make it harder to breathe, but the adipose tissue fuels mechanisms that act like magnets for SARS-CoV-2, the virus that causes the COVID-19.

“Fat deposited in skeletal muscle may be sought after by top-end steakhouses but, in vivo, it compromises muscle metabolic efficiency, nutrient uptake, and performance,” Kass wrote. “It requires more muscle force to displace the diaphragm downward when a substantial fat mass lies below it. Abdominal obesity also makes it more difficult to breathe in a prone position that is favored to improve ventilation in patients with COVID-19.”

“Among more specific mechanisms is expression of angiotensin-converting enzyme (ACE) 2 protein in adipose tissue. This is the docking protein for SARS-CoV-2 to enter a cell, and fat has higher levels than the lungs and so may serve as a viral refuge and replication site, prolonging virus shedding,” he wrote.

The Kaiser Permanente authors noted that other trials are examining the role of certain mainstay therapies in COVID-19, including recombinant ACE2 and angiotensin II receptor blockers (ARBs).

They note that while fighting COVID-19 is the immediate task, it has pointed to the need to confront obesity. “Principally, we demonstrate the leading role severe obesity has over other highly correlated risk factors, providing a clear target for early intervention.

“Our findings also reveal the distressing collision of 2 pandemics: COVID-19 and obesity. As COVID-19 continues to spread unabated, we must focus our immediate efforts on containing the crisis at hand. Yet our findings also underscore the need for future collective efforts to combat the equally devastating, and potentially synergistic, force of the obesity epidemic.”

References

1. Tartof SY, Qian L, Hong V. Obesity and mortality among patients diagnosed with COVID-19: results from an integrated health care organization. Ann Intern Med. Published online August 12, 2020. doi:10.7326/M20-3742
2. Kass DA. COVID-19 and severe obesity: a big problem? Ann Intern Med. Published online August 12, 2020. doi:10.7326/M20-5677