Antibody therapy reverses biological signatures of COVID-19 progression

Cell Rep Med. 2022 Aug 16;3(8):100721. doi: 10.1016/j.xcrm.2022.100721.

Abstract

Understanding who is at risk of progression to severe coronavirus disease 2019 (COVID-19) is key to clinical decision making and effective treatment. We study correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ClinicalTrials.gov04545060). Laboratory parameters identify study participants at greater risk of severe disease, including a high neutrophil-to-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test, and whole-blood transcriptome profiles. Sotrovimab treatment is associated with normalization of NLR and the transcriptomic profile and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provides the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identify a 10-gene signature with similar predictive accuracy. We identify markers of risk for disease progression and demonstrate that normalization of these parameters occurs with antibody treatment of established infection.

Trial registration: ClinicalTrials.gov NCT04545060.

Keywords: SARS-CoV-2; biomarkers; prediction.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • COVID-19 Drug Treatment*
  • Humans
  • RNA, Viral
  • SARS-CoV-2

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • RNA, Viral
  • sotrovimab

Associated data

  • ClinicalTrials.gov/NCT04545060