Potential mechanisms linking obesity to severe COVID-19 outcomes
Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms
The article by Sattar et al. in Circulation describes potential mechanisms that may link obesity to severe COVID-19 illness. Obesity is discussed from a cardiovascular, cardiorespiratory and inflammatory perspective and the authors describe how obesity and excess ectopic fat may contribute severe COVID-19 outcomes from these viewpoints. Finally, recommendations for future research and with respect to public health are given.
Obesity linked with severe COVID-19 outcomes
Several reports have linked obesity to more severe COVID-19 outcomes and mortality [1-3]. Patients with COVID-19 admitted to an intensive treatment unit and a BMI>35 kg/m² had a seven-fold higher risk to require invasive mechanical ventilation compared to those with a BMI<25 kg/m² . The likelihood of COVID-19 patients (<60 years of age) to be admitted to critical care was 1.8 times higher for those with a BMI 30-34 kg/m² and 3.6 times higher for those with BMI>35 kg/m², compared to patients with a BMI<30 kg/m² .
Cardiovascular, respiratory, metabolic and thrombotic consequences of obesity
Obesity is causally related to hypertension, coronary heart disease, stroke, atrial fibrillation, heart failure, renal disease and diabetes. Furthermore, obesity can increase the effect of CV risk factors . Obesity and excess ectopic fat can also lead to impairment of insulin resistance and reduced beta-cell function, which limit the ability to evoke an appropriate metabolic response during an immunologic challenge. Furthermore, obesity can enhance thrombosis. Pro-thrombotic disseminated intravascular coagulation and high rates of venous thromboembolism have been associated with COVID-19. Obesity also affects lung function and diminishes forced expiratory volume and forced vital capacity. Together, these cardiometabolic, thrombotic and cardiorespiratory consequences of obesity could lead to an impaired metabolic response, increased CV susceptibility to immune-driven vascular effects and thrombotic effects, and decreased cardiorespiratory fitness, which could contribute to increased severity of COVID-19.
Role of obesity in dysregulated immune response and greater viral exposure
Obesity has been associated with higher circulating Interleukin 6 and C-reactive protein levels. Adipose tissue in obese individuals also has increased expression of cytokines and adipokines. Furthermore, tissue leukocyte expression is dysregulated and tissue regulatory (M2) phenotypic cells are replaced by inflammatory macrophage subsets. It has been shown that obesity impairs adaptive immune responses to influenza virus . Viral shedding may be greater in obese individuals, which could potentially lead to a greater viral exposure. This is especially relevant if multiple family members have obesity, or in communities with a high prevalence of obesity. Together, obesity may lead to a dysregulated immune response and increased viral shedding, which could impact the outcome of COVID-19 infection.
Implications for future research and public health
Further research is required to determine whether obesity is an independent risk factor for susceptibility to infection. BMI should be considered in predictive instruments for those most at risk of severe outcomes. Moreover, mechanistic understanding of the relation between obesity and COVID-19 is important as it may suggest therapeutic interventions which could potentially reduce the risk of severe COVID-19 outcomes. People should be encouraged to adopt sustainable changes in lifestyle (i.e. improving diet and increasing activity levels) to reduce the risk of severe COVID-19 illness. The authors note that this may be challenging during lockdown regulations and that the expected economic downturn may worsen obesity. The COVID-19 pandemic has highlighted that more should be done to prevent obesity and governments should address this issue, according to the authors.