Pathways to Severe COVID-19 for People with Obesity

Abstract

Increased morbidity and mortality from coronavirus disease 2019 (COVID-19) in people with obesity have illuminated the intersection of obesity with impaired responses to infections. Although data on mechanisms by which COVID-19 impacts health are being rapidly generated, there is a critical need to better understand the pulmonary, vascular, metabolic, and immunologic aspects that drive the increased risk for complications from COVID-19 in people with obesity. This review provides a broad overview of the intersection between COVID-19 and the physiology of obesity in order to highlight potential mechanisms by which COVID-19 disease severity is increased by obesity and identify areas for future investigation toward developing tailored therapy for people with obesity who develop COVID-19.

Figure 1

Clinical progression of COVID‐19. SARS‐CoV‐2 infection progresses through stages starting with Stage 1, which includes initial asymptomatic or mild symptoms associated with active viral replication. Some individuals progress to Stage 2, which includes increased pulmonary involvement with symptoms of dyspnea and hypoxemia and opacities observed with chest imaging that often must be managed with hospitalization. A subset of individuals in Stage 2 progress to more severe disease, Stage 3, which is associated with respiratory failure, elevated markers of systemic inflammation, and multisystem organ failure. Relative to normal‐weight individuals (indicated by the black line), people with obesity (indicated by the red line) have a higher risk for progressing to Stage 2 and 3 and have more severe disease at each stage. ARDS, acute respiratory distress syndrome; COVID‐19, coronavirus disease 2019; ICU, intensive care unit; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Obesity‐associated alterations in physiology and immunity that amplify responses to SARS‐CoV‐2. Obesity has broad effects on pulmonary physiology, adipose tissue biology, metabolism, and immune system function. COVID‐19 exploits these impairments in normal homeostasis leading to more severe disease and/or requiring different clinical management approaches (e.g., ventilator management) compared with people without obesity. COVID‐19, coronavirus disease 2019; EC, endothelial cells; FA, fatty acid; FRC, function residual capacity; IFN, interferon; IR, insulin resistance; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; V/Q, lung ventilation/perfusion.