As the number of confirmed cases of COVID-19 surges past 4.7 million globally and deaths surpass 315,000, clinicians and pathologists are untiringly working to comprehend the damage produced by the coronavirus through the body. They are understanding that, yet the lungs are massively deranged, COVID-19 infection can outspread to many organs including the blood vessels and heart, gut, brain, and kidneys [1]. A systemic therapeutic approach is necessary; we thus analyzed a global interpretation of multi-organ symptoms and signs to propose a new pathogenetic hypothesis, with potential drug therapy implications, in COVID-19 people with obesity. Recent studies point to obesity as a critical risk factor for being hospitalized with COVID-19 [2,3,4]. Indeed, a high prevalence of obesity has been observed in COVID-19 patients requiring invasive mechanical ventilation [5], a robust proxy of SARS-CoV2 severity. In patients under the age of 60, those with obesity were at almost double risk of being admitted to critical care when compared with normal-weight patients [6].