Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab

Immunobiology. 2020 Nov;225(6):152001. doi: 10.1016/j.imbio.2020.152001. Epub 2020 Aug 9.


In COVID-19, acute respiratory distress syndrome (ARDS) and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2), the lectin pathway's effector enzyme, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), resulting in complement activation and lung injury. Narsoplimab, a fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2, inhibits lectin pathway activation and has anticoagulant effects. In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab under compassionate use. At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. Narsoplimab treatment was associated with rapid and sustained reduction of CEC and concurrent reduction of serum IL-6, IL-8, CRP and LDH. Narsoplimab was well tolerated; no adverse drug reactions were reported. Two control groups were used for retrospective comparison, both showing significantly higher mortality than the narsoplimab-treated group. All narsoplimab-treated patients recovered and survived. Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.

Keywords: COVID-19; Endothelial injury; Lectin pathway; MASP-2; Monoclonal antibody; Narsoplimab; SARS-CoV-2; Thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • C-Reactive Protein / immunology
  • C-Reactive Protein / metabolism
  • COVID-19 / complications
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Complement Pathway, Mannose-Binding Lectin / drug effects*
  • Complement Pathway, Mannose-Binding Lectin / immunology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Male
  • Mannose-Binding Protein-Associated Serine Proteases / antagonists & inhibitors
  • Mannose-Binding Protein-Associated Serine Proteases / immunology
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Retrospective Studies
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Thrombotic Microangiopathies / complications
  • Thrombotic Microangiopathies / drug therapy*
  • Thrombotic Microangiopathies / immunology


  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Interleukin-6
  • C-Reactive Protein
  • Mannose-Binding Protein-Associated Serine Proteases