Fig. 1

Potential processes affected by presence of autoantibodies in COVID-19. Left panel: pathogen uptake results in release of inflammatory markers and complement proteins which lead to neutrophil recruitment, activation and translocation of autoantigens. Anti-neutrophil cytoplasmic antibodies (ANCA) (anti-MPO, anti-PR3, anti-ELANE, and anti-aPL autoantibodies and anti-H3/H4), bind autoantigens and promote NETosis which induces a thrombotic response. NET contents can be recognised by anti-MPO, anti-H3/H4 and anti-ELANE autoantibodies. Autoantibodies to complement proteins (anti-MASP2, anti-C1q) interfere with complement activation. Right panel: autoantibodies bind to the B cell activating factor (BAFF) which enables production of more autoantibodies by pre-existing autoantibody producing B cells. Autoantibodies which interfere with pathogen defence include antibodies to complement, tissue antigens and cytokines which can disrupt cytokine communication (anti-GM-CSF) and cytokine clearance (anti-IFNs). SARS-CoV-2 bound to soluble ACE2 complex can be phagocytosed by macrophages and presented on the surface, inducing anti-ACE2 antibodies. Anti-ACE2 can bind soluble ACE2, reducing its capacity to act as a decoy for SARS-CoV-2, as well as have cross-reactivity with surface attached ACE, triggering further detrimental inflammation. Created with BioRender.com