tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Aug 16;3(8):100721.
doi: 10.1016/j.xcrm.2022.100721.
Antibody therapy reverses biological signatures of COVID-19 progression
M Cyrus Maher[SUP] 1 [/SUP], Leah B Soriaga[SUP] 2 [/SUP], Anil Gupta[SUP] 3 [/SUP], Yi-Pei Chen[SUP] 2 [/SUP], Julia di Iulio[SUP] 2 [/SUP], Sarah Ledoux[SUP] 2 [/SUP], Megan J Smithey[SUP] 2 [/SUP], Andrea L Cathcart[SUP] 2 [/SUP], Kathleen McKusick[SUP] 2 [/SUP], David Sun[SUP] 2 [/SUP], Melissa Aldinger[SUP] 2 [/SUP], Elizabeth Alexander[SUP] 2 [/SUP], Lisa Purcell[SUP] 2 [/SUP], Xiao Ding[SUP] 2 [/SUP], Amanda Peppercorn[SUP] 4 [/SUP], Daren Austin[SUP] 5 [/SUP], Erik Mogalian[SUP] 2 [/SUP], Wendy W Yeh[SUP] 2 [/SUP], Adrienne E Shapiro[SUP] 6 [/SUP], Davide Corti[SUP] 7 [/SUP], Herbert W Virgin[SUP] 8 [/SUP], Phillip S Pang[SUP] 2 [/SUP], Amalio Telenti[SUP] 9 [/SUP]
Affiliations
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.
. 2022 Aug 16;3(8):100721.
doi: 10.1016/j.xcrm.2022.100721.
Antibody therapy reverses biological signatures of COVID-19 progression
M Cyrus Maher[SUP] 1 [/SUP], Leah B Soriaga[SUP] 2 [/SUP], Anil Gupta[SUP] 3 [/SUP], Yi-Pei Chen[SUP] 2 [/SUP], Julia di Iulio[SUP] 2 [/SUP], Sarah Ledoux[SUP] 2 [/SUP], Megan J Smithey[SUP] 2 [/SUP], Andrea L Cathcart[SUP] 2 [/SUP], Kathleen McKusick[SUP] 2 [/SUP], David Sun[SUP] 2 [/SUP], Melissa Aldinger[SUP] 2 [/SUP], Elizabeth Alexander[SUP] 2 [/SUP], Lisa Purcell[SUP] 2 [/SUP], Xiao Ding[SUP] 2 [/SUP], Amanda Peppercorn[SUP] 4 [/SUP], Daren Austin[SUP] 5 [/SUP], Erik Mogalian[SUP] 2 [/SUP], Wendy W Yeh[SUP] 2 [/SUP], Adrienne E Shapiro[SUP] 6 [/SUP], Davide Corti[SUP] 7 [/SUP], Herbert W Virgin[SUP] 8 [/SUP], Phillip S Pang[SUP] 2 [/SUP], Amalio Telenti[SUP] 9 [/SUP]
Affiliations
- PMID: 35977462
- 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.
Keywords: SARS-CoV-2; biomarkers; prediction.