1. Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
- Author
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Koutsakos, M, Rowntree, LC, Hensen, L, Chua, BY, van de Sandt, CE, Habel, JR, Zhang, W, Jia, X, Kedzierski, L, Ashhurst, TM, Putri, GH, Marsh-Wakefield, F, Read, MN, Edwards, DN, Clemens, EB, Wong, CY, Mordant, FL, Juno, JA, Amanat, F, Audsley, J, Holmes, NE, Gordon, CL, Smibert, OC, Trubiano, JA, Hughes, CM, Catton, M, Denholm, JT, Tong, SYC, Doolan, DL, Kotsimbos, TC, Jackson, DC, Krammer, F, Godfrey, D, Chung, AW, King, NJC, Lewin, SR, Wheatley, AK, Kent, SJ, Subbarao, K, McMahon, J, Thevarajan, I, Thi, HON, Cheng, AC, Kedzierska, K, Koutsakos, M, Rowntree, LC, Hensen, L, Chua, BY, van de Sandt, CE, Habel, JR, Zhang, W, Jia, X, Kedzierski, L, Ashhurst, TM, Putri, GH, Marsh-Wakefield, F, Read, MN, Edwards, DN, Clemens, EB, Wong, CY, Mordant, FL, Juno, JA, Amanat, F, Audsley, J, Holmes, NE, Gordon, CL, Smibert, OC, Trubiano, JA, Hughes, CM, Catton, M, Denholm, JT, Tong, SYC, Doolan, DL, Kotsimbos, TC, Jackson, DC, Krammer, F, Godfrey, D, Chung, AW, King, NJC, Lewin, SR, Wheatley, AK, Kent, SJ, Subbarao, K, McMahon, J, Thevarajan, I, Thi, HON, Cheng, AC, and Kedzierska, K
- 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.
- Published
- 2021