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

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., and Kedzierska, Katherine (2021) Integrated immune dynamics define correlates of COVID-19 severity and antibody responses. Cell Reports Medicine, 2 (3). 100208.

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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.

Item ID: 72673
Item Type: Article (Research - C1)
ISSN: 2666-3791
Copyright Information: © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Leadership Investigator Grant no.1173871, NHMRC Program Grant no.1132975, NHMRC program grant no.1149990, NHMRC project grant no.1162760, NHMRC program grant no.1071916, NHMRC program grant no.1113293, NHMRC Principal Research Fellowship no.1137285, NHMRC Investigator grant no.1177174, NHMRC Career Development Fellowship no.1145033, NHMRC Senior Principal Research Fellowship no.1117766, NHMRC Senior Principal Research Fellowship no.1136322, NHMRC Program Grant no.1149990, NHMRC Program Grant Practitioner Fellowship no.1135851, NHMRC Early Career Fellowship no.1123673, NHMRC Peter Doherty Fellowship no.1091516
Date Deposited: 11 May 2022 00:52
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320705 Medical virology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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