Obesity as a contributor to immunopathology in pregnant and non-pregnant adults with COVID-19

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to a global public health emergency with the need to identify vulnerable populations who may benefit from increased screening and healthcare resources. Initial data suggest that overall, pregnancy is not a significant risk factor for severe coronavirus disease 2019 (COVID-19). However, case series have suggested that maternal obesity is one of the most important comorbidities associated with more severe disease. In obese individuals, suppressors of cytokine signaling are upregulated and type I and III interferon responses are delayed and blunted leading to ineffective viral clearance. Obesity is also associated with changes in systemic immunity involving a wide range of immune cells and mechanisms that lead to low-grade chronic inflammation, which can compromise antiviral immunity. Macrophage activation in adipose tissue can produce low levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Further, adipocyte secretion of leptin is pro-inflammatory and high circulating levels of leptin have been associated with mortality in patients with acute respiratory distress syndrome. The synergistic effects of obesity-associated delays in immune control of COVID-19 with mechanical stress of increased adipose tissue may contribute to a greater risk of pulmonary compromise in obese pregnant women. In this review, we bring together data regarding obesity as a key co-morbidity for COVID-19 in pregnancy with known changes in the antiviral immune response associated with obesity. We also describe how the global burden of obesity among reproductive age women has serious public health implications for COVID-19.

Keywords: COVID-19; maternal health; obesity; pneumonia; pregnancy.

FIGURE 1

Potential mechanisms for increased COVID‐19 severity in pregnancy associated with obesity. In pregnant women with lean body weight (right panel), there is typically an effective type I and III IFN responses to viruses through antigen presentation by dendritic cells and coordinated innate and adaptive immune responses. In obese pregnant women (left panel), there is an inhibition of viral clearance through blunting of type I and III IFN responses, as well as inadequate antigen presentation by dendritic cells and T‐cell dysfunction. Obesity is also associated with chronic inflammation, M1 macrophage activation, altered adipokine production (eg, leptin, adiponectin) and upregulation of suppressors of cytokine gene signaling (SOCS), which can lead to excessive lung injury. The combination of defective viral clearance, increased inflammatory lung injury and altered lung mechanics in obese pregnant patients can synergize to increase the risk of severe or critical COVID‐19 disease

FIGURE 2

Global distribution of obesity among adult women. This global map demonstrates the geographic distribution of obesity (BMI >30) in adult women (>18 y old). The highest prevalence of obesity (>30%) is concentrated within the United States, Mexico, North Africa, South Africa, the Middle East and a few additional countries. Reprinted with permission: World Health Organization 2017 | Source: Global Health Observatory (http://www.who.int/gho/en/)