The complement system is an ancient part of innate immunity sensing
highly pathogenic coronaviruses by Mannan-binding lectin resulting in
lectin pathway-activation and subsequent generation of the
anaphylatoxins (AT) C3a and C5a as important effector molecules.
Complement deposition in endothelial cells and high blood C5a serum
levels have been reported in COVID-19 patients with severe illness,
suggesting vigorous complement activation leading to systemic thrombotic
microangiopathy (TMA). Strikingly, SARS-CoV-2-infected African Americans
suffer from high mortality. Complement regulator gene variants prevalent
in African Americans have been associated with a higher risk for severe
TMA and multi-organ injury. These findings allow us to apply our
knowledge from other complement-mediated diseases to COVID-19 infection
to better understand severe disease pathogenesis. Here we will discuss
the multiple aspects of complement activation, regulation, crosstalk
with other parts of the immune system and the options to target
complement in COVID-19 patients to halt disease progression and death.