Vir Biotechnology, San Francisco, CA, USA.
Vir Biotechnology, San Francisco, CA, USA.
Cell Rep Med. 2022 Aug 16;3(8):100721. doi: 10.1016/j.xcrm.2022.100721.
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.
了解哪些人有进展为严重 2019 冠状病毒病（COVID-19）的风险，对于临床决策和有效治疗至关重要。我们在 COMET-ICE 临床试验中研究了疾病严重程度的相关性，该试验将患者以 1:1 的比例随机分配至安慰剂组或索托维单抗（一种用于治疗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的单克隆抗体）组（ClinicalTrials.gov04545060）。实验室参数可识别出疾病严重程度较高的研究参与者，包括高中性粒细胞与淋巴细胞比值（NLR）、SARS-CoV-2 血清学检测呈阴性以及全血转录组谱。索托维单抗治疗与 NLR 和转录组谱的正常化以及鼻咽样本中病毒 RNA 的减少相关。转录组学可最敏感地检测到可能住院或死亡的参与者。为了便于及时测量，我们确定了一个具有相似预测准确性的 10 基因特征。我们确定了疾病进展风险的标志物，并证明这些参数的正常化发生在已确立感染的抗体治疗中。
