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

doi:10.1016/j.xcrm.2021.100208

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

Menzies School of Health Research

Research output: Contribution to journal › Article › peer-review

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⁺cT_FH1 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 T_FH1 cells as a correlate of antibody responses and sIL-6R, IL-6, and IL-18 as correlates of disease severity.

Original language	English
Article number	100208
Pages (from-to)	1-22
Number of pages	22
Journal	Cell Reports Medicine
Volume	2
Issue number	3
DOIs	https://doi.org/10.1016/j.xcrm.2021.100208
Publication status	Published - 4 Feb 2021

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10.1016/j.xcrm.2021.100208

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Koutsakos, M., Rowntree, L. C., Hensen, L., Chua, B. Y., van de Sandt, C. E., Habel, J. R., Zhang, W., Jia, X., Kedzierski, L., Ashhurst, T. M., Putri, G. H., Marsh-Wakefield, F., Read, M. N., Edwards, D. N., Clemens, E. B., Wong, C. Y., Mordant, F. L., Juno, J. A., Amanat, F., ... Kedzierska, K. (2021). Integrated immune dynamics define correlates of COVID-19 severity and antibody responses. Cell Reports Medicine, 2(3), 1-22. [100208]. https://doi.org/10.1016/j.xcrm.2021.100208

@article{de8c016298ea4129a13cf39d3f88fea1,

title = "Integrated immune dynamics define correlates of COVID-19 severity and antibody responses",

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. 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.",

keywords = "acute COVID-19, antibody-secreting cells, CD38, convalescent COVID-19, HLA-DR, IL-18, IL-6, SARS-CoV-2, soluble IL-6 receptor, T follicular helper cells",

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

year = "2021",

month = feb,

day = "4",

doi = "10.1016/j.xcrm.2021.100208",

language = "English",

volume = "2",

pages = "1--22",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "3",

}

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, DI, Chung, AW, King, NJC, Lewin, SR, Wheatley, AK, Kent, SJ, Subbarao, K, McMahon, J, Thevarajan, I, Nguyen, THO, Cheng, AC & Kedzierska, K 2021, 'Integrated immune dynamics define correlates of COVID-19 severity and antibody responses', Cell Reports Medicine, vol. 2, no. 3, 100208, pp. 1-22. https://doi.org/10.1016/j.xcrm.2021.100208

TY - JOUR

T1 - Integrated immune dynamics define correlates of COVID-19 severity and antibody responses

AU - Koutsakos, Marios

AU - Rowntree, Louise C.

AU - Hensen, Luca

AU - Chua, Brendon Y.

AU - van de Sandt, Carolien E.

AU - Habel, Jennifer R.

AU - Zhang, Wuji

AU - Jia, Xiaoxiao

AU - Kedzierski, Lukasz

AU - Ashhurst, Thomas M.

AU - Putri, Givanna H.

AU - Marsh-Wakefield, Felix

AU - Read, Mark N.

AU - Edwards, Davis N.

AU - Clemens, E. Bridie

AU - Wong, Chinn Yi

AU - Mordant, Francesca L.

AU - Juno, Jennifer A.

AU - Amanat, Fatima

AU - Audsley, Jennifer

AU - Holmes, Natasha E.

AU - Gordon, Claire L.

AU - Smibert, Olivia C.

AU - Trubiano, Jason A.

AU - Hughes, Carly M.

AU - Catton, Mike

AU - Denholm, Justin T.

AU - Tong, Steven Y.C.

AU - Doolan, Denise L.

AU - Kotsimbos, Tom C.

AU - Jackson, David C.

AU - Krammer, Florian

AU - Godfrey, Dale I.

AU - Chung, Amy W.

AU - King, Nicholas J.C.

AU - Lewin, Sharon R.

AU - Wheatley, Adam K.

AU - Kent, Stephen J.

AU - Subbarao, Kanta

AU - McMahon, James

AU - Thevarajan, Irani

AU - Nguyen, Thi H.O.

AU - Cheng, Allen C.

AU - Kedzierska, Katherine

PY - 2021/2/4

Y1 - 2021/2/4

N2 - 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.

AB - 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.

KW - acute COVID-19

KW - antibody-secreting cells

KW - CD38

KW - convalescent COVID-19

KW - HLA-DR

KW - IL-18

KW - IL-6

KW - SARS-CoV-2

KW - soluble IL-6 receptor

KW - T follicular helper cells

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U2 - 10.1016/j.xcrm.2021.100208

DO - 10.1016/j.xcrm.2021.100208

M3 - Article

C2 - 33564749

AN - SCOPUS:85101356557

SN - 2666-3791

VL - 2

SP - 1

EP - 22

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 3

M1 - 100208

ER -

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

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