tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], J Justin Mulvey[SUP] 2 [/SUP], Madhav Seshadri[SUP] 3 [/SUP], Alexandra Racanelli[SUP] 4 [/SUP], Joanna Harp[SUP] 5 [/SUP], Edward J Schenck[SUP] 4 [/SUP], Dana Zappetti[SUP] 4 [/SUP], Evelyn M Horn[SUP] 6 [/SUP], Cynthia M Magro[SUP] 7 [/SUP]
Affiliations
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 FiO[SUB]2[/SUB] 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.
. 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[SUP] 1 [/SUP], J Justin Mulvey[SUP] 2 [/SUP], Madhav Seshadri[SUP] 3 [/SUP], Alexandra Racanelli[SUP] 4 [/SUP], Joanna Harp[SUP] 5 [/SUP], Edward J Schenck[SUP] 4 [/SUP], Dana Zappetti[SUP] 4 [/SUP], Evelyn M Horn[SUP] 6 [/SUP], Cynthia M Magro[SUP] 7 [/SUP]
Affiliations
- PMID: 32771488
- DOI: 10.1016/j.clim.2020.108555
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 FiO[SUB]2[/SUB] 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.