Coronavirus Disease 2019 (COVID-19) has claimed more than 1.25 million human lives since December 2019 when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Almost 50 million people have had a confirmed SARS-CoV-2 infection to date, the clinical spectrum of which ranges from asymptomatic infection to severe COVID-19 with critical illness.

It has been demonstrated that obesity is an risk factor for worse outcomes in patients with COVID-19. However, it remains unclear whether all classes of obesity are associated with worse outcomes or whether this is specific to severe obesity. In addition, it is unclear whether the association of obesity with worse outcomes is sex-specific.

It is unclear whether the association of obesity with worse outcomes is sex-specific.

The pathogenetic mechanisms involved in COVID-19 infection have not been fully elucidated, but it is known that a major cause of disease severity and death is an excessive inflammatory host response to SARS-COV-2 that is associated with high levels of circulating cytokines, such as interleukin-6 (IL-6).

Obesity is considered a state of enhanced chronic inflammation. Therefore, predisposition to systemic hyper-inflammation has been hypothesized to be one of the main mechanisms by which obesity leads to worse outcomes in COVID-19.

Our study investigated whether there is an association of obesity in men and women with in-hospital outcomes in 3530 consecutive patients who were hospitalized due to COVID-19 in a tertiary medical center in the Bronx, New York. In addition, our study attempted to assess the role of systemic inflammation using IL-6 levels as a surrogate in the outcomes of obese inpatients with COVID-19.

Our study demonstrated that obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.

Several possible pathogenetic mechanisms have been described through which obesity independently increases the risk for worse outcomes in patients with COVID-19. Severe obesity may adversely affect lung function by directly altering the mechanical properties of the lungs and chest.

Severe obesity may adversely affect lung function by directly altering the mechanical properties of the lungs and chest

Furthermore, obesity has been shown to be a state of chronic low-grade inflammation due to a poorly understood interplay between adipocytes and immune system cells that results in impaired immune function. Also, obesity is associated with a perturbed intestinal microbiota that otherwise would directly prevent the invasion of pathogens including SARS-CoV-2.

Finally, the fact that ACE2 is also expressed in adipose tissue, mainly in visceral fat, suggests that severely obese individuals can host significantly higher viral load leading to local inflammation at the ectopic fat tissue level and making this population more prone to develop severe COVID-19 and this effect may not be easily measurable by measuring systemic cytokine levels.

Particular attention should be paid in protecting the population living with severe obesity from SARS-CoV-2 with priority to vaccination access, remote work, telemedicine, and other measures given the higher risk of adverse outcomes once they are diagnosed with COVID-19. In addition, patients with severe obesity diagnosed with COVID-19 should be treated with particular attention given the high risk for worse outcomes.