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

Clin Immunol. 2020 Oct:219:108555. doi: 10.1016/j.clim.2020.108555. Epub 2020 Aug 6.

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.

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

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / complications
  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / immunology*
  • Acute Kidney Injury / virology
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • Biomarkers / metabolism
  • COVID-19
  • Complement Activation / drug effects
  • Complement C4b / antagonists & inhibitors
  • Complement C5 / antagonists & inhibitors
  • Complement Inactivating Agents / therapeutic use*
  • Complement Membrane Attack Complex / antagonists & inhibitors
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / immunology*
  • Cytokine Release Syndrome / virology
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Immunity, Humoral / drug effects
  • Male
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Mannose-Binding Protein-Associated Serine Proteases / immunology
  • Middle Aged
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Pandemics
  • Peptide Fragments / antagonists & inhibitors
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / complications
  • Severe Acute Respiratory Syndrome / drug therapy
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / virology

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Complement C5
  • Complement Inactivating Agents
  • Complement Membrane Attack Complex
  • Fibrin Fibrinogen Degradation Products
  • Peptide Fragments
  • fibrin fragment D
  • Complement C4b
  • complement C4d
  • eculizumab
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases