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 YC Tong; Denise L Doolan; Tom C Kotsimbos; David C Jackson; Florian Krammer; Dale Godfrey; Amy W Chung; Nicholas JC King; Sharon R Lewin; Adam K Wheatley; Stephen J Kent; Kanta Subbarao; James McMahon; Irani Thevarajan; HO Nguyen Thi; Allen C Cheng; Katherine Kedzierska

Journal article

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 Show all

CELL REPORTS MEDICINE | ELSEVIER | Published : 2021

DOI: 10.1016/j.xcrm.2021.100208

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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..

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University of Melbourne Researchers

Amy Chung Author Microbiology and Immunology

Dale Godfrey Author Microbiology and Immunology

Jennifer Juno Author Microbiology and Immunology

Lukasz Kedzierski Author Veterinary and Agricultural Sciences

Adam Wheatley Author Microbiology and Immunology

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Grants

Awarded by NHMRC

Awarded by Research Grants Council of the Hong Kong Special Administrative Region, China

Awarded by Victorian Government MRFF award

Awarded by MRFF

Awarded by European Union

Funding Acknowledgements

We thank all of the participants in the study and Jeni Mitchell, Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, Jill Garlick, Janine Roney, and Anne Paterson for support with the cohorts. This research included samples from the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases (SETREP-ID). We acknowledge the SETREP-ID investigators and sites, Barbara Scher for setting up the ethics and governance for SETREP-ID, the Australian Partnership for Preparedness Research for Infectious Disease Emergencies (APPRISE) for funding of SETREP-ID, and Ajantha Solomon, Judy Chang, and Ashanti Dantanaranaya for SETREP-ID biobanking. This work was supported by the NHMRC Leadership Investigator Grant to K.K. (no. 1173871); the NHMRC Program Grant to D.L.D. (no. 1132975); the Research Grants Council of the Hong Kong Special Administrative Region, China (no. T11-712/19-N) to K.K.; the Jack Ma Foundation to K.K., K.S., D.I.G., and A.W.C.; the a2 Milk Foundation to K.S.; the Victorian Government MRFF award (no. 2002073) to S.J.K., D.I.G., and A.K.W.; MRFF Award (no. 1202445) to K.K.; MRFF Award (no. 2005544) to K.K., S.J.K., J.J., A.W.C., and A.K.W.; NHMRC program grant no. 1149990 to S.J.K.; NHMRC project grant no. 1162760 to A.K.W.; NHMRC program grant (no. 1071916) to K.K. and D.C.J.; NHMRC program grant (no. 1113293) to D.I.G.; the Merridew Foundation to N.J.C.K. and D.L.D.; NHMRC Principal Research Fellowship (no. 1137285); NHMRC Investigator grant (no. 1177174) to K.S.; NHMRC Career Development Fellowship (no. 1145033) to S.Y.C.T.; and NHMRC Senior Principal Research Fellowships (nos. 1117766 and 1136322) to D.I.G. and S.J.K. S.R.L. is supported by an NHMRC Program Grant (no. 1149990) and a Practitioner Fellowship (no. 1135851). L.H., J.R.H., and W.Z. are supported by the University of Melbourne International Research Scholarship and the Melbourne International Fee Remission Scholarship. X.J. is supported by the China Scholarship Council-University of Melbourne Joint Scholarship. C.E.v.d.S. is supported by the European Union's Horizon 2020 research and innovation program Marie Sklodowska-Curie grant (no. 792532). T.M.A. and F.M.-W. are International Society for Advancement of Cytometry Marylou Ingram Scholars. G.H.P. is supported by the Australian Government Research Training Program (RTP) Scholarship. J.A.J. is supported by an NHMRC Early Career Fellowship (no. 1123673). E.B.C. is supported by NHMRC Peter Doherty Fellowship no. 1091516. The Melbourne WHO Collaborating Centre is supported by the Australian Government Department of Health. We acknowledge all DRASTIC (the use of cytokines as a predictor of disease severity in critically ill COVID-patients) investigators from Austin Health and Fiona James, Effie Mouhtouris, and Ana Copaescu for laboratory work and DRASTIC study coordination. The graphical abstract was created with BioRender.com.