| Title | Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Laurence J, J Mulvey J, Seshadri M, Racanelli A, Harp J, Schenck EJ, Zappetti D, Horn EM, Magro CM |
| Journal | Clin Immunol |
| Volume | 219 |
| Pagination | 108555 |
| Date Published | 2020 10 |
| ISSN | 1521-7035 |
| Keywords | Acute Kidney Injury, Adult, Antibodies, Monoclonal, Humanized, Betacoronavirus, Biomarkers, Complement Activation, Complement C4b, Complement C5, Complement Inactivating Agents, Complement Membrane Attack Complex, Coronavirus Infections, COVID-19, Cytokine Release Syndrome, Female, Fibrin Fibrinogen Degradation Products, Humans, Immunity, Humoral, Male, Mannose-Binding Protein-Associated Serine Proteases, Middle Aged, Neutrophils, Pandemics, Peptide Fragments, Pneumonia, Viral, SARS-CoV-2, Severe Acute Respiratory Syndrome |
| 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 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19. |
| DOI | 10.1016/j.clim.2020.108555 |
| Alternate Journal | Clin Immunol |
| PubMed ID | 32771488 |
| PubMed Central ID | PMC7410014 |
| Grant List | P30 CA008748 / CA / NCI NIH HHS / United States |
Related Faculty:
Cynthia M. Magro, M.D.