Complement and protection from tissue injury in COVID-19.

As the second wave of coronavirus disease 2019 (COVID-19) is well under way around the world, the optimal therapeutic approach that addresses virus replication and hyperinflammation leading to tissue injury remains elusive. This issue of provides further evidence of complement activation involvement in COVID-19. Taking advantage of the unique repeat access to chronic haemodialysis patients, the differential time course of C3 and C5 activation in relation to inflammation and severity of disease have been characterized. This further points to complement as a therapeutic target. Indeed, clinical trials targeting diverse components of complement are ongoing. However, a unique case of COVID-19 in a patient with pre-existent atypical haemolytic syndrome on chronic eculizumab therapy suggests that even early eculizumab may fail to prevent disease progression to a severe stage. Finally, preclinical studies in endotoxaemia, another hyperinflammation syndrome characterized by lung and kidney injury, suggest that cilastatin, an inexpensive drug already in clinical use, may provide tissue protection against hyperinflammation in COVID-19.