Obesity and COVID-19: Immune and metabolic derangement as a possible link to adverse clinical outcomes.

Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other co-morbidities. After infecting the host cells, SARS-CoV-2 may cause a hyper-inflammatory reaction through the excessive release of cytokines, a condition known as "cytokine storm", while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNF-α, IL-1, IL-6 and MCP-1 lead to oxidative stress and defective function of innate and adaptive immunity, while the activation of NLRP3 inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, while alterations in cardiac structure and function and the pro-thrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyper-inflammatory settings like that of rheumatoid arthritis has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.