Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19. •SARS-CoV-2 infection in COVID-19 is associated with sustained complement activation.•Severe COVID-19 involves a pro-inflammatory/hypercoaguable state linked to complement.•Complement deposition in skin of 3 COVID-19 cases recalcitrant to therapy is shown.•Anti-C5 therapy with eculizumab led to 1 complete and 2 partial clinical remissions.•Our data may inform guidelines for earlier intervention with anti-C agents in COVID-19.