• Jeffrey Laurence, J Justin Mulvey, Madhav Seshadri, Alexandra Racanelli, Joanna Harp, Edward J Schenck, Dana Zappetti, Evelyn M Horn, and Cynthia M Magro.
• Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA. Electronic address: jlaurenc@med.cornell.edu.
• Clin. Immunol. 2020 Oct 1; 219: 108555.

AbstractRespiratory 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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