Human monoclonal antibody a possible treatment for ARDS in COVID-19

Compassionate use of a human monoclonal antibody (Narsoplimab, Omeros) to treat acute respiratory distress syndrome (ARDS) associated with COVID-19 resulted in recovery and survival of the affected patients.

Narsoplimab is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2). It has been shown to provide a number of therapeutic benefits.

Autopsy results of COVID-19 patients with ARDS show arterial thrombosis and severe endothelial damage, which is central to ARDS and thrombosis and activates the lectin pathway of complement. MASP-2, binds the nucleocapsid protein of severe ARDs-associated coronavirus-2 (SARS-CoV-2), causing 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, the authors explained.

Narsoplimab also has been evaluated in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) that also causes endothelial damage, and blocks microvascular injury-associated thrombus formation and MASP-2-mediated activation of thrombin, kallikrein, and factor XII, may be therapeutic in both HSCT-TMA and COVID-19.

Alessandro Rambaldi, MD, professor of Hematology at the University of Milan and Head of the Department of Hematology and Oncology at Papa Giovanni, and a lead investigator in the trial of narsoplimab in HSCT-TMA, requested compassionate use of the drug considering the clinical and pathologic similarities between COVID-19 and HSCT-TMA, for patients in Bergamo, the initial epicenter of the pandemic in Europe.

The six COVID-19 patients (83% men; median age, 57 years; range, 47-63) with ARDS required continuous positive airway pressure or intubation and were treated with narsoplimab. All patients had comorbidities.

At baseline, endothelial/cellular damage and/or inflammation markers were significantly elevated. Narsoplimab treatment was begun within 48 hours after the start of mechanical ventilation; patients were treated twice weekly for 2 to 4 weeks.

He said, “The patients that we treated with narsoplimab were critically ill, and the uniformly successful outcomes were truly impressive.”

The drug appeared to be well tolerated with no adverse effects.

“The pathophysiology of COVID-19 appears to be consistent with that of HSCT-TMA, and the mechanism of the lectin pathway inhibitor narsoplimab looks to be well suited to treat the often-lethal manifestations of both disorders,” Rambaldi pointed out. “The outcomes in these six patients provide further evidence of the potential role of narsoplimab in treating diseases caused by endothelial damage.”

In this study, the lectin-pathway inhibitor was used for the first time to treat COVID-19; all narsoplimab-treated patients recovered, survived and were discharged from the hospital, the authors reported.

The study findings are accepted for publication in Immunobiology. A pre-publication copy of the manuscript can be accessed at:

https://www.sciencedirect.com/science/article/pii/S0171298520304459.