Clin Immunol

. 2020 Aug 6;108555.
doi: 10.1016/j.clim.2020.108555. Online ahead of print.
Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19

Jeffrey Laurence 1 , J Justin Mulvey 2 , Madhav Seshadri 3 , Alexandra Racanelli 4 , Joanna Harp 5 , Edward J Schenck 4 , Dana Zappetti 4 , Evelyn M Horn 6 , Cynthia M Magro 7



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.

Keywords: COVID-19; Complement; Coronavirus; Eculizumab; Lectin pathway; MASP2.