Hypercoagulopathy and Adipose Tissue Exacerbated Inflammation May Explain Higher Mortality in COVID-19 Patients With Obesity

Pasquarelli-do-Nascimento, Gabriel; Braz-de-Melo, Heloísa Antoniella; Faria, Sara Socorro; Santos, Igor de Oliveira; Kobinger, Gary P.; Magalhães, Kelly Grace

COVID-19, caused by SARS-CoV-2, is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Several reports from around the world have identified obesity and severe obesity as one of the strongest risk factors for COVID-19 hospitalization and mechanical ventilation. Moreover, countries with greater obesity prevalence have a higher morbidity and mortality risk of developing serious outcomes from COVID-19. The understanding of how this increased susceptibility of the people with obesity to develop severe forms of the SARS-CoV-2 infection occurs is crucial for implementing appropriate public health and therapeutic strategies to avoid COVID-19 severe symptoms and complications in people living with obesity. We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue. Individuals with obesity have increased white adipose tissue, which may act as a reservoir for a more extensive viral spread with increased shedding, immune activation and pro-inflammatory cytokine amplification. Here we discuss how obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death. Taken together, it may be crucial to better explore the role of visceral adipose tissue in the inflammatory response to SARS-CoV-2 infection and investigate the potential therapeutic effect of using specific target anti-inflammatories (canakinumab or anakinra for IL-1β inhibition; anti-IL-6 antibodies for IL-6 inhibition), anticoagulant or anti-diabetic drugs in COVID-19 treatment of people with obesity. Defining the immunopathological changes in COVID-19 patients with obesity can provide prominent targets for drug discovery and clinical management improvement.