Fig 1.

COVID-19 immunologic mechanisms for CS and the possible role of biologics. When SARS-CoV-2 PAMPs and/or DAMPs bind to TLRs on the surface of resident alveolar macrophages, they become activated and secrete TNF, IL-1β, and IL-6. In increased levels, these cytokines will be the hallmark of the CS responsible for the ARDS and CS in COVID-19. The different targets of biologics are illustrated in the figure. Specifically, the downstream effect of IL-6 can be blocked with tocilizumab, sarilumab, or siltuximab and the effects of IL-1β with anakinra or canakinumab. CD8⁺ T cells produce IFN-γ, causing direct tissue damage, whereas activated CD4⁺ T cells, in the presence of transforming growth factor β and IL-6, will differentiate into the T_H17-cell subset, responsible for secreting IL-17A and IL-17F, which, among numerous roles, target macrophages, dendritic cells, endothelial cells, and fibroblasts to increase the production of IL-1, IL-6, and TNF. DAMP, Damage-associated molecular pattern; PAMP, pathogen-associated molecular pattern; TLR, Toll-like receptor; TMPRSS2, transmembrane protease, serine 2.