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, Łukasz Kedzierski, Thomas M. Ashhurst, Givanna Putri, Felix Marsh‐Wakefield, Mark 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 Smibert, Jason A. Trubiano, Carly M. Hughes, Mike Catton, Justin T. Denholm, Steven Y. C. Tong, Denise L. Doolan, Tom 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 Cheng, Katherine Kedzierska
Abstract
1 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.