Antiviral monoclonal antibody therapies may prevent hospitalization in nonsevere COVID-19

The antiviral monoclonal antibodies casirivimab-imdevimab appear to reduce the risk of hospitalization in patients with nonsevere COVID-19, as do bamlanivimab, bamlanivimab-etesevimab, and sotrovimab, according to the results of a systematic review and meta-analysis.

In addition, casirivimab-imdevimab may reduce the risk of death in patients with severe COVID-19 who do not have detectable antibodies to the SARS-CoV-2 spike protein. However, this combination, along with other interventions, does not appear to have any effect when given to severe COVID-19 patients.

“Low rates of adverse events leading to discontinuation, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO) make it difficult to make conclusions about the safety of antiviral monoclonal antibodies and convalescent plasma,” the researchers said.

A systematic search was performed using the World Health Organization COVID-19 database, a comprehensive multilingual source of global COVID-19 literature, and six Chinese databases up to 21 July 2021. Trials that randomly assigned patients with suspected, probably, or confirmed COVID-19 to antiviral antibody therapies, blood products, or standard care or placebo were identified.

After duplicate data abstraction, the researchers conducted a random-effects Bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. They also evaluated the risk of bias using a modification of the Cochrane risk of bias 2.0 tool. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.

Forty-seven trial examining convalescent plasma (n=21), intravenous immunoglobulin (IVIg; n=5), umbilical cord mesenchymal stem cells (n=5), bamlanivimab (n=4), casirivimab-imdevimab (n=4), bamlanivimab-etesevimab (n=2), control plasma (n=2), peripheral blood nonhaematopoietic enriched stem cells (n=2), sotrovimab (n=1), CT-P59 monoclonal antibody (n=1), therapeutic plasma exchange (n=1), XAV-19 polyclonal antibody (n=1), anti-SARS-CoV-2 IVIg (n=1), and INM005 polyclonal antibody (n=1) for the treatment of COVID-19 met the eligibility criteria. [BMJ 2021;374:n2231]

Hospitalization risk was lower in patients with nonsevere COVID-19 who received antiviral monoclonal antibodies versus placebo: casirivimab-imdevimab (odds ratio [OR], 0.29, 95 percent confidence interval [CI], 0.17–0.47; risk difference [RD], −4.2 percent; moderate certainty), bamlanivimab (OR, 0.24, 95 percent CI, 0.06–0.86; RD, −4.1 percent; low certainty), bamlanivimab-etesevimab (OR, 0.31, 95 percent CI, 0.11–0.81; RD, −3.8 percent; low certainty), and sotrovimab (OR, 0.17, 95 percent CI, 0.04–0.57; RD, −4.8 percent; low certainty).

These antivirals, however, did not have a significant effect on other outcomes. No remarkable difference was seen between monoclonal antibodies, and no other intervention showed any notable impact on any outcome in patients with nonsevere COVID-19.

“No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical COVID-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative,” the researchers said.

This review also failed to find evidence that convalescent plasma provides benefits to patients with COVID-19 of any severity. Evidence was consistent between trials, except one, that limited donors to those with higher neutralizing titres and enrolled high-risk patients with nonsevere COVID-19. [N Engl J Med 2021;384:610-618]

“Additional high-quality data are needed to evaluate the efficacy and safety of antiviral antibodies and blood products for the treatment of COVID-19,” they added.