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

Abstract

Highlights Narsoplimab down-modulates SARS-CoV-2-induced activation of the lectin pathway and endothelial cell damage. Narsoplimab can reduce the thrombotic risk of Covid-19 patients. All patients treated with narsoplimab improved and survived without any drug-related adverse events.

Coagulopathy, endothelial dysfunction, thrombotic microangiopathy and complement activation: potential role of complement system inhibition in COVID-19

“…BK virus and human herpesvirus 6, might be potential causative factors of TA-TMA [29,30]. A relative ADAMTS13 deficiency [31], increased circulating endothelial cell (CEC) counts and serum levels of IL-6 and IL-8 [32] are observed in COVID-19, reminiscent the findings in TMA. Urokinase plasminogen activator receptor (uPAR) is bound on the endothelium and released into the blood stream as a soluble counterpart, named suPAR, in the setting of inflammation and endothelial damage [33].…”

“…Patients with severe COVID-19 treated with narsoplimab (anti-MASP-2 antibody) under compassionate use displayed rapid and sustained reduction in markers of endothelial damage (CECs, IL-6, IL-8, CRP and LDH levels). All patients treated with narsoplimab recovered and the agents is being evaluated further in patients with severe COVID-19 [32]. As mentioned above, the laboratory and autopsy findings in COVID-19 reminiscent of one seen in TMA, which is also highly associated with pathogenic complement activation [25].…”

Immunomodulation for Severe COVID-19 Pneumonia: The State of the Art

“…In addition, a clinical trial (ChiCTR2000029765) of tocilizumab for the treatment of COVID-19 is currently underway. Other monoclonal antibodies specific for proinflammatory cytokines also show prospects for treating COVID-19, which include Canakinumab, a monoclonal antibody targeting IL-1b (56); Eculizumab, C5-targeting monoclonal antibody (57); Narsoplimab, a monoclonal antibody against mannose-binding protein-associated serine protease 2 (58); and Dupilumab, a monoclonal antibody of the immunoglobulin G4 subclass (59).…”

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

“…In contrast, Holter et al (125) did not find much difference in MBL concentrations in plasma between COVID-19 patients and controls although a transient increase of its level (at days 3-5 after hospital admission) was noted. It should be however stressed that narsoplimab, specifically targeting MASP-2, has recently been demonstrated to be a promising therapeutic agent, reducing detrimental effects of complement activation and giving no adverse reactions itself (126).…”