Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 delta and omicron variants

J Med Virol. 2022 Oct;94(10):5038-5043. doi: 10.1002/jmv.27916. Epub 2022 Jun 11.

Abstract

We aimed to provide in vitro data on the neutralization capacity of different monoclonal antibody (mAb) preparations against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta and omicron variant, respectively, and describe the in vivo RNA kinetics of coronavirus disease 2019 (COVID-19) patients treated with the respective mAbs. Virus neutralization assays were performed to assess the neutralizing effect of the mAb formulations casirivimab/imdevimab and sotrovimab on the SARS-CoV-2 delta and omicron variant. Additionally, respiratory tract SARS-CoV-2 RNA kinetics are provided for 25 COVID-19 patients infected with either delta variant (n = 18) or omicron variant (n = 7) treated with the respective mAb formulations during their hospital stay. In the virus neutralization assay, sotrovimab exhibits neutralizing capacity at therapeutically achievable concentrations against the SARS-CoV-2 delta and omicron variant. In contrast, casivirimab/imdevimab had neutralizing capacity against the delta variant but failed neutralization against the omicron variant except for a very high concentration above the currently recommended therapeutic dosage. In patients with delta variant infections treated with casivirimab/imdevimab, we observed a rapid decrease of respiratory viral RNA at day 3 after mAb therapy. In contrast, no such prompt decline was observed in patients with delta variant or omicron variant infections receiving sotrovimab.

Keywords: COVID-19; SARS-CoV-2; casirivimab/imdevimab; delta variant; monoclonal antibodies; omicron variant; sotromivab; virus neutralization assay.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antineoplastic Agents, Immunological*
  • COVID-19 Drug Treatment*
  • Humans
  • Membrane Glycoproteins / genetics
  • Neutralization Tests
  • RNA, Viral
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Treatment Outcome
  • Viral Envelope Proteins / genetics

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antineoplastic Agents, Immunological
  • Membrane Glycoproteins
  • RNA, Viral
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike protein, SARS-CoV-2
  • sotrovimab
  • imdevimab
  • casirivimab

Supplementary concepts

  • SARS-CoV-2 variants