Figure 3.

Mediator cascades causing complications during pneumonia in COVID‐19 patients. The classical pathway of complement can be activated by immunocomplexes formed by SARS‐CoV‐2 and specific IgG or IgM (A). Complement activation causes the release of pro‐inflammatory, vasoactive, and chemoattractant components that increase local inflammation. The lectin pathway of complement may be activated by virus‐IgA immunocomplexes, through MBL binding to both viral N‐glycan and IgA (B). Activation of MBL‐associated MASP may cause thrombin activation and triggering of coagulation. Both classic and lectin pathways of complement activation on the external membrane of infected cells releasing viruses may cause deposition of late complement factor and formation of the membrane attack complex (MAC) causing cell damage (C) and release of cellular components. Non‐neutralizing specific IgG and IgA binding the virus may concur to increased infection and inflammation as a consequence of antibody‐dependent enhancement (ADE) of infectivity. Ig with low affinity or non‐neutralizing effect may cause infection and activation of macrophages via Fc receptors (D). In addition, Ig binding the S protein of SARS‐CoV‐2 may cause its conformational changes making more efficacious the binding to the ACE‐2 receptor and the viral fusion with the cell membrane (D)