Antibody therapy reverses biological signatures of COVID-19 progression

M. Cyrus Maher; Leah B. Soriaga; Anil Gupta; Yi Pei Chen; Julia di Iulio; Sarah Ledoux; Megan J. Smithey; Andrea L. Cathcart; Kathleen McKusick; David Sun; Melissa Aldinger; Elizabeth Alexander; Lisa Purcell; Xiao Ding; Amanda Peppercorn; Daren Austin; Erik Mogalian; Wendy W. Yeh; Adrienne E. Shapiro; Davide Corti; Herbert W. Virgin; Phillip S. Pang; Amalio Telenti

doi:10.1016/j.xcrm.2022.100721

Antibody therapy reverses biological signatures of COVID-19 progression

M. Cyrus Maher^*, Leah B. Soriaga, Anil Gupta, Yi Pei Chen, Julia di Iulio, Sarah Ledoux, Megan J. Smithey, Andrea L. Cathcart, Kathleen McKusick, David Sun, Melissa Aldinger, Elizabeth Alexander, Lisa Purcell, Xiao Ding, Amanda Peppercorn, Daren Austin, Erik Mogalian, Wendy W. Yeh, Adrienne E. Shapiro, Davide CortiHerbert W. Virgin, Phillip S. Pang, Amalio Telenti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.gov 04545060). 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.

Original language	English
Article number	100721
Journal	Cell Reports Medicine
Volume	3
Issue number	8
DOIs	https://doi.org/10.1016/j.xcrm.2022.100721
Publication status	Published - 16 Aug 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

biomarkers
prediction
SARS-CoV-2

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10.1016/j.xcrm.2022.100721

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Maher, M. C., Soriaga, L. B., Gupta, A., Chen, Y. P., di Iulio, J., Ledoux, S., Smithey, M. J., Cathcart, A. L., McKusick, K., Sun, D., Aldinger, M., Alexander, E., Purcell, L., Ding, X., Peppercorn, A., Austin, D., Mogalian, E., Yeh, W. W., Shapiro, A. E., ... Telenti, A. (2022). Antibody therapy reverses biological signatures of COVID-19 progression. Cell Reports Medicine, 3(8), Article 100721. https://doi.org/10.1016/j.xcrm.2022.100721

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title = "Antibody therapy reverses biological signatures of COVID-19 progression",

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.gov 04545060). 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 = "biomarkers, prediction, SARS-CoV-2",

author = "Maher, {M. Cyrus} and Soriaga, {Leah B.} and Anil Gupta and Chen, {Yi Pei} and {di Iulio}, Julia and Sarah Ledoux and Smithey, {Megan J.} and Cathcart, {Andrea L.} and Kathleen McKusick and David Sun and Melissa Aldinger and Elizabeth Alexander and Lisa Purcell and Xiao Ding and Amanda Peppercorn and Daren Austin and Erik Mogalian and Yeh, {Wendy W.} and Shapiro, {Adrienne E.} and Davide Corti and Virgin, {Herbert W.} and Pang, {Phillip S.} and Amalio Telenti",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = aug,

day = "16",

doi = "10.1016/j.xcrm.2022.100721",

language = "English",

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Maher, MC, Soriaga, LB, Gupta, A, Chen, YP, di Iulio, J, Ledoux, S, Smithey, MJ, Cathcart, AL, McKusick, K, Sun, D, Aldinger, M, Alexander, E, Purcell, L, Ding, X, Peppercorn, A, Austin, D, Mogalian, E, Yeh, WW, Shapiro, AE, Corti, D, Virgin, HW, Pang, PS & Telenti, A 2022, 'Antibody therapy reverses biological signatures of COVID-19 progression', Cell Reports Medicine, vol. 3, no. 8, 100721. https://doi.org/10.1016/j.xcrm.2022.100721

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T1 - Antibody therapy reverses biological signatures of COVID-19 progression

AU - Maher, M. Cyrus

AU - Soriaga, Leah B.

AU - Gupta, Anil

AU - Chen, Yi Pei

AU - di Iulio, Julia

AU - Ledoux, Sarah

AU - Smithey, Megan J.

AU - Cathcart, Andrea L.

AU - McKusick, Kathleen

AU - Sun, David

AU - Aldinger, Melissa

AU - Alexander, Elizabeth

AU - Purcell, Lisa

AU - Ding, Xiao

AU - Peppercorn, Amanda

AU - Austin, Daren

AU - Mogalian, Erik

AU - Yeh, Wendy W.

AU - Shapiro, Adrienne E.

AU - Corti, Davide

AU - Virgin, Herbert W.

AU - Pang, Phillip S.

AU - Telenti, Amalio

PY - 2022/8/16

Y1 - 2022/8/16

N2 - 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.gov 04545060). 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.

AB - 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.gov 04545060). 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.

KW - biomarkers

KW - prediction

KW - SARS-CoV-2

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U2 - 10.1016/j.xcrm.2022.100721

DO - 10.1016/j.xcrm.2022.100721

M3 - Article

C2 - 35977462

AN - SCOPUS:85135909547

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 8

M1 - 100721

ER -

Antibody therapy reverses biological signatures of COVID-19 progression

Abstract

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Keywords

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