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


ABSTRACT: 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.

SUBMITTER: Laurence J 

PROVIDER: S-EPMC7410014 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Laurence Jeffrey J   Mulvey J Justin JJ   Seshadri Madhav M   Racanelli Alexandra A   Harp Joanna J   Schenck Edward J EJ   Zappetti Dana D   Horn Evelyn M EM   Magro Cynthia M CM  

Clinical immunology (Orlando, Fla.) 20200806


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 en  ...[more]

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