Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
Authors:
- 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
Details:
Cell Reports Medicine, Volume 2, Issue 3, 2021-03-16
Article Link: Click here
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.