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Severe Acute Respiratory Syndrome Coronavirus 2 Affects the Innate Immune Response The PO System The PO system is triggered by SARS-CoV-2, as for any pathogen, through toll-like receptors (TLRs) on macrophages, the first-line cell of innate defense (Figure 1, this results in tumor necrosis factor-alpha (TNF)-induced inflammation, which has two clinically relevant molecular effects: inactivation of insulin receptor signaling on endothelial cells (see Graphical Abstract) and activation of NOX2 on macrophages ( * -) from oxygen (O2)