The COVID-19 pandemic keeps the world in suspense uniting clinicians and basic researchers in their efforts to better understand disease pathogenesis and develop effective clinical interventions. 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 to apply knowledge from other complement-mediated diseases with TMA to better understand the mechanism underlying severe disease progression in COVID-19 infection.

Jörg Köhl (University of Lübeck) and Sonata Jodele (Cincinnati Children's Hospital Medical Center) discuss in their review article ‘Tackling COVID-19 infection through complement-targeted immunotherapy’ 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. The article is currently under review at the British Journal of Pharmacology in context of the Themed Issue ‘Canonical and non-canonical functions of the complement system in health and disease’ with Claudia Kemper (University of Lübeck/National Institutes of Health), Ulrich Wenzel (University Hospital Hamburg-Eppendorf) and Jörg Köhl as guest editors. A preprint is already available via the online server Authorea: Link!