key: cord-0682863-6entp07f authors: Tibiriçá, Eduardo; De Lorenzo, Andrea title: Increased severity of COVID‐19 in people with obesity: are we overlooking plausible biological mechanisms? date: 2020-05-13 journal: Obesity (Silver Spring) DOI: 10.1002/oby.22887 sha: e2a6048d04486aec0ae297c7a93dc210bdd735b2 doc_id: 682863 cord_uid: 6entp07f The relationship between obesity and more severe disease in patients with COVID‐19 is intriguing. Recent articles published in Obesity (1‐3) discuss the possible effects of increased proinflammatory cytokines and disturbances of lung function in people with obesity, but we believe that they overlook an important player in this scenario, which is endothelial dysfunction. The relationship between obesity and more severe disease in patients with COVID-19 is intriguing. Recent articles published in Obesity (1-3) discuss the possible effects of increased proinflammatory cytokines and disturbances of lung function in people with obesity, but we believe that they overlook an important player in this scenario, which is endothelial dysfunction. Endothelial dysfunction is present in obesity and is indeed a final common pathway of a cluster of comorbidities, such as hypertension, diabetes and dyslipidemia. In obesity, the severity of endothelial dysfunction correlates with the degree of visceral adiposity, and studies indicate the roles of proinflammatory factors and oxidative stress. (3) . In addition to that chronic scenario, acute endothelial damage occurs, induced by SARS-CoV-2 (which binds to the transmembrane angiotensin-converting enzyme-II receptor). Vascular endothelial cell apoptosis ensues, and in conjunction with the acute "cytokine storm", promote the settings for lung microvascular dysfunction, vascular leakage, alveolar edema and ultimately hypoxia. Proinflammatory cytokines also increase the expression of adhesion molecules, resulting in endothelial activation and procoagulant changes, worsening microvascular flow and tissue perfusion (4) . In this context, the acronym "MicroCLOTS" (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) was recently suggested to describe a progressive endothelial pulmonary syndrome with microvascular thrombosis (5) Therefore, we believe that, among several possible pathophysiologic mechanisms leading to adverse prognosis in people with obesity and COVID-19, endothelial dysfunction is a central one, as it combines the effects of obesity and its associated comorbidities with the acute effect of SARS-CoV-2. This should turn our attention into the endothelium; if we overlook that, we may be overlooking important plausible biologic mechanisms underlying the association between obesity and more serious COVID-19 outcomes. Targeting the Adipose Tissue in COVID-19. Obesity (Silver Spring) Does COVID-19 Disprove the Obesity Paradox in ARDS? Obesity (Silver Spring) The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections Cytokine release syndrome in severe COVID-19 Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis Accepted Article