Apple-shaped obesity; a risky soil for cytokine-accelerated severity in COVID-19

Obesity is one of the most significant risk factors for the deterioration and mortality associated with COVID-19 [1]. A certain proportion of COVID-19 patients experience marked elevations of inflammatory mediators, termed “cytokine storm”, resulting in the deterioration of the respiratory condition [2,3]. In the present study, we elucidate that the high visceral adipose tissue (VAT) burden was more closely related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients than other obesity-associated markers, including body mass index (BMI). To explore a novel stratification of COVID-19 patients, we infected mouse-adapted SARS-CoV-2 in several obese mice, revealing that VAT-dominant ob/ob mice and diet-induced obesity obese mice died after infection with low-titer mouse-adapted SARS-CoV-2 virus due to the subsequent cytokine storm, whereas none of the subcutaneous adipose tissue (SAT) dominant db/db mice or control lean wild-type mice died. SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased production of inflammatory cytokine represented by IL-6. As well as the anti-IL-6 treatment, the prevention of obesity by leptin administration improved the survival of SARS-CoV-2 infected ob/ob mice by reducing the viral protein burden and excessive immune responses.