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 Audsley, Natasha 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

Cell Reports Medicine, Volume 2, Issue 3, 100208, March 16, 2021. DOI:

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.