Integrated immune dynamics define correlates of COVID-19 severity and antibody responses

Journal Publication ResearchOnline@JCU
Koutsakos, Marios;Rowntree, 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
Denise Doolan
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 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.

Journal

Cell Reports Medicine

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2

ISBN/ISSN

2666-3791

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Issue

3

Pages Count

21

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Publisher

Cell press

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N/A

DOI

10.1016/j.xcrm.2021.100208