Figure 3.

The virus–immune system interaction and relevant immunometabolic dysregulation underlying the association between obesity and the severe course of COVID-19. SARS-CoV-2 is notorious for its broad tissue tropism, including susceptibility that has been demonstrated in the airway, lung, intestine, kidney tubule, pancreatic duct, blood vessel, neuron, and adipocyte cells, implicating metabolic and immune disruption caused by direct viral infections in multiple systems. Studies indicate an extensive virus-immune system interaction at both innate and adaptive immune levels, with emphasis on the viral antagonism against the antiviral IFN system, hyper-inflammation incited by massive cell death upon immunopathies induced by the virus–host interaction, as well as various disruptions in adaptive immunity per T-cell- and B-cell-mediated responses. Some metabolic disruption of lipid biosynthesis has also been correlated to COVID-19 progression, but its long-term effect on the development of metabolic disorders in convalescent patients warrants further studies. PANoptosis, massive inflammatory cell death including Pytoptosis, Apoptosis, and Necroptosis. Other abbreviations are as listed in Figure 2 legend.