Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
Type
ArticleAuthor/s
Koutsakos, MariosRowntree, Louise C
Hensen, Luca
Chua, Brendon Y
van de Sandt, Carolien E
Habel, Jennifer R
Zhang, Wuji
Jia, Xiaoxiao
Kedzierski, Lukasz
Ashhurst, Thomas M
Putri, Givanna H
Marsh-Wakefield, Felix
Read, Mark N
Edwards, Davis N
Clemens, E Bridie
Wong, Chinn Yi
Mordant, Francesca L
Juno, Jennifer A
Amanat, Fatima
Audsley, Jennifer
Holmes, Natasha E
Gordon, Claire L
Smibert, Olivia C
Trubiano, Jason A
Hughes, Carly M
Catton, Mike
Denholm, Justin T
Tong, Steven Y C
Doolan, Denise L
Kotsimbos, Tom C
Jackson, David C
Krammer, Florian
Godfrey, Dale I
Chung, Amy W
King, Nicholas J C
Lewin, Sharon R
Wheatley, Adam K
Kent, Stephen J
Subbarao, Kanta
McMahon, James
Thevarajan, Irani
Nguyen, Thi H O
Cheng, Allen C
Kedzierska, Katherine
Abstract
SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute ...
See moreSARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
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See moreSARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
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Date
2021Funding information
Government of Victoria
European Commission
National Health and Medical Research Council
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