Complement and coagulation: key triggers of COVID-19-induced multiorgan pathology.

Ghebrehiwet, Berhane; Peerschke, Ellinor I

In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the virus struck was indeed overwhelming, scientists throughout the world have also been up to the task of deciphering the mechanisms by which SARS-CoV-2 induces the multisystem- and multiorgan-inflammatory response that, collectively, contribute to the high mortality rate in affected individuals. In this issue of the JCI, Skendros et al., is one such team who report that the complement system plays a substantial role in creating the hyper-inflammation and thrombotic microangiopathy that appear to contribute to the severity of COVID-19. In support of the hypothesis that the complement system along with neutrophils and platelets contributes to COVID-19, the authors presented empirical evidence showing that treatment with the complement inhibitor, compstatin Cp-40, inhibited the expression of tissue factor in neutrophils. These results confirm that the complement axis plays a critical role and suggests that targeted therapy using complement inhibitors is a potential therapeutic option to treat COVID-19 induced inflammation.