key: cord-0982435-a45l4vbj
authors: Lavie, Carl J.; Coursin, Douglas B.; Long, Micah T.
title: The Obesity Paradox in Infections and Implications for COVID-19
date: 2021-01-26
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2021.01.014
sha: f20b96871c3e7625eb74b05b875bf142956fb8ae
doc_id: 982435
cord_uid: a45l4vbj

nan

In this issue of the Mayo Clinic Proceedings, Grisholt and colleagues (9) report the mortality of patients who were hospitalized between 1/1/2011 and 9/30/2015 for non-COVID-related infections of varied sources: sepsis, pulmonary, urinary and skin. Data were drawn from the Central Denmark Region Clinical Information System, a comprehensive registry, of which 76,044 patients were admitted for infection and 35,406 also had height and weight data recorded within 30 days of hospitalization. In this subpopulation of patients with recent BMI, 25% were admitted with pneumonia, 12.5% with urinary tract infection and 11.2% with sepsis, with <10% admitted for skin and <5% with gastrointestinal infection.

For this study, the authors compared the risk of death in patients with a normal weight range (BMI 18.5-25 kg/m 2 ) to patients who were underweight (BMI <18.5 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ) and obese (BMI ≥30 kg/m 2 ). The authors reported an obesity paradox, with lower mortality in hospitalized infected patients with obesity compared to normal weight individuals. Underweight patients, however, had the highest overall mortality rate [adjusted 90 mortality: aHR 1.75 (CI; 1.58 -1.94)]. Compared to the US population, this Danish population exhibited a higher prevalence of smoking and had a much lower prevalence of obesity, thus also making the prevalence of moderate and severe obesity less likely, although this was not listed. The finding of considerably higher mortality in the underweight is not a major surprise, as this is seen in many other disease processes, likely due to comorbidities, like cancer or severe COPD, and less "reserve" to fight acute illnesses. However, compared with the normal BMI patients, those who were overweight and obese had 36% and 45% lower mortality, respectively.

The reasons for the obesity paradox in many conditions, including CVD, remain uncertain. Certainly, advanced HF is often associated with a state of cachexia and frailty, (10) so having higher weight and more muscle mass could itself be protective, or an associative marker of maintained vigor, but this J o u r n a l P r e -p r o o f would not explain the obesity paradox seen in less severe HF and even stable CHD. As mentioned above, an obesity paradox has been noted in other conditions, including end-stage renal disease, COPD, and PE, among other conditions, (6) (7) (8) and the results of Grisholt and colleagues (9) Vitamin D is associated with maintenance of favorable ACE-2 levels and limitation of dysregulation in the renin-angiotensin system, which both limit viral entry and subsequent acute lung injury. (19) Further, with the recent release of various COVID-19 vaccines, there is concern that obese individuals may require larger doses or a third injection, based on the fact that influenza vaccinated obese adults are twice as likely to develop influenza and influenza-like illness compared with those of healthy weight adults, despite similar levels of immune response to the influenza vaccine. (20) Since the COVID-19 vaccines potentially could be less effective in adults with obesity, especially moderate and severe obesity, careful post-vaccination surveillance is needed. Thankfully, early data on COVID-19 vaccines suggest equal efficacy in patients with obesity, but longer-term follow up is required. (12) Finally, a study in the Proceedings of 247 patients showed that higher levels of cardiorespiratory fitness (CRF) was associated with lower hospitalization rates in those infected with COVID-19. (21, 22) This same study suggested fitness was more important than adiposity in determining the risk for COVID-19

hospitalizations. (23, 24) Since physical activity and CRF may play a role in immunity against infections,

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