LAUSR

TO THE EDITOR: We read, with interest, the paper by Friedman and colleagues recently published in Obesity (Silver Spring) (1). In particular, we have appreciated their conclusions questioning the widespread belief of a peculiar and sometimes even exclusive role of obesity in the development of the hyperinflammatory and prothrombotic state observed in patients with COVID19. Increasing BMI has been previously recognized to directly correlate with a worsening prognosis in patients with SARSCoV2related infection (2), suggesting the existence of a causal mechanism that makes obesity responsible for a more severe form of the disease. The detection of an abnormal pattern of circulating cytokines such as interleukin (IL)6, IL1β, IL7, and tumor necrosis factor α in patients with COVID19 (3), in particular, in those with respiratory failure requiring ventilation support, led to the consideration of the activation of the inflammatory pathways induced by SARSCoV2 as the main prognostic factor. The severe pulmonary damage observed in COVID19 patients developing acute respiratory distress syndrome (ARDS) lies on the prompt release of both damageassociated molecular patterns and pathogenassociated molecular patterns due to the viral cytolytic effect leading to the alveolarcapillary barrier leakage. Along with that, a direct and inflammatorymediated endothelial damage has been observed in lung specimen examinations (4), with a diffuse microangiopathy promoting both local and systemic thrombotic complications. In light of these observations, several authors have identified the epidemiological interconnection between obesity and severe COVID19 in the intrinsic proinflammatory secretion from the dysfunctional adipose tissue of patients with obesity. In particular, according to this point of view, a preexistent lowgrade inflammatory state such as that characterizing obesity acts as an additional factor promoting an exaggerated inflammatory response in SARSCoV2infected patients. However, this is in contrast with previous theories proposed to unravel the relationship between obesity and infectious diseases in the context of a counterintuitive paradox, reported in several observational studies, showing improving survival aligns with increasing BMI values in patients hospitalized for sepsis (5). In this case, the adiposederived chronic lowgrade inflammation has been considered as a negative modulator of the systemic immune response, downregulating the systemic proinflammatory mediator production in response to pathogens, as in a negative feedback loop. The data from Friedman et al., which show a greater risk of developing ARDS for patients with obesity, without a correlation between BMI and inflammatory markers, suggest that, in the more severe forms resulting in respiratory failure, COVID19 becomes primarily a pulmonary affliction, resulting in a peculiar form of ARDS in which both alveolar and vascular derangement is involved without a correlation with the extent of the inflammatory response. In this sense, it seems more plausible that a higher BMI influences the prognosis of affected patients because of the detrimental effects of obesity on respiratory compliance, further reducing the respiratory reserve. Surely, further studies are needed to better define the relationship between obesity and COVID19, but, in our opinion, this analysis provides important additional data to the field, suggesting a less speculative approach when proposing novel pathophysiological theories.O