In vitro to clinical efficacy: Neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 strains

J Infect Chemother. 2024 Dec 30:102604. doi: 10.1016/j.jiac.2024.102604. Online ahead of print.

Abstract

Introduction: Neutralizing antibodies have been approved for coronavirus disease 2019 (COVID-19) treatment; however, no study has clarified the link among their neutralizing effect in vitro, the period of infectious virus shedding, and symptoms in the acute phase. Here, we aimed to assess the duration of virus shed and fever in patients with mild COVID-19 stratified by their characteristics and type of neutralizing antibody administered.

Methods: We evaluated the efficacy of neutralizing antibodies in terms of the duration of infectious virus excretion and fever in three groups: patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta strain treated with REGEN-CoV2 (REGN-CoV2 group) and patients infected with Omicron strain treated with S309 (S309 group) or untreated (untreated group).

Results: REGN-CoV2 was significantly more effective in reducing viral load than S309; furthermore, S309 treatment did not show a significant reduction in fever duration when compared to no treatment. Mutations in the spike protein receptor-binding domain may reduce the binding ability of REGN-CoV2 and S309: the 50% inhibitory concentration (IC50) of REGN-CoV2 for the conventional and Delta strains was 0.013 and 0.019 μg/mL, respectively, and that of S309 for the Omicron strain was 53.1 μg/mL.

Conclusion: Laboratory evaluations are helpful for analyzing the clinical efficacy of neutralizing antibodies, and this study will help in not only considering effective treatments for COVID-19 but also addressing the threat of future unknown viral infections.

Keywords: COVID-19; SARS-CoV-2; clinical efficacy; mutation; neutralizing antibody.