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

Marios Koutsakos, Louise C. Rowntree, Luca Hensen, Brendon Y. Chua, Carolien E. van de Sandt, Jennifer R. Habel, Wuji Zhang, Xiaoxiao Jia, Lukasz Kedzierski, Thomas M. Ashhurst, Givanna H. Putri, Felix Marsh-Wakefield, Mark N. Read, Davis N. Edwards, E. Bridie Clemens, Chinn Yi Wong, Francesca L. Mordant, Jennifer A. Juno, Fatima Amanat, Jennifer AudsleyNatasha E. Holmes, Claire L. Gordon, Olivia C. Smibert, Jason A. Trubiano, Carly M. Hughes, Mike Catton, Justin T. Denholm, Steven Y.C. Tong, Denise L. Doolan, Tom C. Kotsimbos, David C. Jackson, Florian Krammer, Dale I. Godfrey, Amy W. Chung, Nicholas J.C. King, Sharon R. Lewin, Adam K. Wheatley, Stephen J. Kent, Kanta Subbarao, James McMahon, Irani Thevarajan, Thi H.O. Nguyen, Allen C. Cheng, Katherine Kedzierska

Research output: Contribution to journalArticlepeer-review


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. Koutsakos et al. perform a broad analysis of 184 immune features using blood samples from 85 COVID-19 cases across time and severity groups. The study defines circulating TFH1 cells as a correlate of antibody responses and sIL-6R, IL-6, and IL-18 as correlates of disease severity.

Original languageEnglish
Article number100208
Pages (from-to)1-22
Number of pages22
JournalCell Reports Medicine
Issue number3
Publication statusPublished - 4 Feb 2021


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