Oral Presentation Lorne Infection and Immunity 2021

Integrated immune dynamics define correlates of COVID-19 severity and antibody responses (#3)

Marios Koutsakos 1 , Louise C Rowntree 1 , Luca Hensen 1 , Brendon Y Chua 1 2 , Carolien E van de Sandt 1 3 , Jennifer A Habel 1 , Wuji Zhang 1 , Xiaoxiao Jia 1 , Lukasz Kedzierski 1 , Thomas M Ashhurst 4 , Givanna H Putri 4 , Felix Marsh-Wakefield 4 , Mark V Read 4 , Davis N Edwards 4 , Bridie E Clemens 1 , Chinn Yi Wong 1 , Francesca L Mordant 1 , Jennifer A Juno 1 , Fatima Amanat 5 , Jennifer Audsley 6 , Natasha E Holmes 7 8 , Carly M Hughes 9 , Mike Catton 10 , Justin Denholm 11 , Steven YC Tong 11 12 , Denise L Doolan 13 , Tom C Kotsimbos 14 15 , David C Jackson 1 2 , Florian Krammer 5 , Dale I Godfrey 1 , Amy W Chung 1 , Nicholas JC King 4 , Sharon R Lewin 6 14 15 , Adam K Wheatley 1 , Stephen J Kent 1 , Kanta Subbarao 1 16 , James McMahon 9 14 15 , Irani Thevarajan 6 11 , Thi HO Nguyen 1 , Allen C Cheng 14 15 , Katherine Kedzierska 1 2
  1. University of Melbourne, Peter Doherty Institute, Melbourne
  2. Hokkaido University, Hokkaido, Japan
  3. University of Amsterdam, Amsterdam, Netherlands
  4. Centenary Institute and University of Sydney, Sydney
  5. Icahn School of Medicine at Mount Sinai, New York, USA
  6. Peter Doherty Institute, Melbourne
  7. Austin Hospital, Melbourne
  8. University of Melbourne, Melbourne
  9. Monash Medical Centre, Monash Health, Melbourne
  10. Victorian Infectious Diseases Reference Laboratory, Melbourne
  11. Victorian Infectious Diseases Services, Melbourne
  12. Charles Darwin University, Darwin
  13. James Cook University, Townsville
  14. Monash University, Melbourne
  15. Alfred Hospital, Melbourne
  16. WHO Collaborating Centre for Reference and Research on Influenza, Melbourne

SARS-CoV-2 causes a spectrum of disease outcomes, ranging from asymptomatic to critical COVID-19. As immunological basis remains ill-defined, we analyzed 77 SARS-CoV-2-infected individuals at acute and/or convalescent timepoints, up to 103 days post-symptom onset, quantifying 154 innate and adaptive immunological parameters. Acute COVID-19 was associated with high levels of IL-6, IL-18 and IL-10, elevated neutrophil-to-lymphocyte and neutrophil-to-T cell ratios, frequencies of activated CD38+ neutrophils, CD38+ eosinophils, CD38+/HLA-DRlo monocytes, CD38+CD56dim NK cells, CD38+ γδ T-cells, antibody-secreting cells, CD38+ICOS+ circulating T follicular helper cells, CD38+/HLA-DR+CD4+ T-cells, and effector CD27-CD45RA+ and CD38+CD8+ T-cells. During convalescence, elevated seroconversion and neutralisation activity were prominent and were correlated with acute cTFH cell activation. Strikingly, severe COVID-19 in ICU patients displayed elevated soluble IL-6R levels, higher IL-18 concentration, and hyperactivation of innate, adaptive and myeloid compartments. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients at acute and convalescent phases of SARS-CoV-2 infection, and integrate key cellular pathways of complex perturbed immune networks that underpin severe COVID-19, providing important insights into potential biomarkers and immunotherapies.