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.
Keywords: SARS-CoV-2; biomarkers; prediction.
【저자키워드】 SARS-CoV-2, Biomarkers, prediction., 【초록키워드】 COVID-19, Treatment, coronavirus disease, Transcriptome, Coronavirus disease 2019, coronavirus, clinical trial, Biomarkers, Hospitalized, Decision making, disease severity, monoclonal antibody, neutrophil, transcriptomics, Infection, risk, progression, severe acute respiratory syndrome Coronavirus, Neutrophil-to-lymphocyte ratio, Disease progression, Randomized, lymphocyte, Viral, Accuracy, Laboratory parameters, understanding, Placebo, Viral RNA, respiratory, transcriptomic profile, Sotrovimab, antibody treatment, marker, NLR, severe disease, risk for disease, Predictive, serologic test, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, severe coronavirus disease, Nasopharyngeal samples, Study participants, profiles, clinical decision, participant, normalization, e parameters, parameter, effective, decrease, greater, identify, facilitate, provide, occur, study participant, 1:1, 【제목키워드】 Antibody therapy, COVID-19 progression,