Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Integrated immune dynamics define correlates of COVID-19 severity and antibody responses (#105)

Marios Koutsakos 1 , Louise C Rowntree 1 , Luca Hensen 1 , Brendon Y Chua 1 2 , Carolien E van de Sandt 1 3 , Jennifer R Habel 1 , Wuji Zhang 1 , Xiaoxiao Jia 1 , Lukasz Kedzierski 1 4 , Thomas M Ashhurst 5 6 , Givanna H Putri 7 8 , Felix Marsh-Wakefield 7 9 10 , Mark N Read 8 11 , Davis N Edwards 8 11 , Bridie Clemens 1 , Chinn Yi Wong 1 , Francesca L Mordant 1 , Jennifer A Juno 1 , Fatima Amanat 12 13 , Jennifer Audsley 14 , Natasha E Holmes 15 16 17 , Carly M Hughes 18 , Mike Catton 19 , Justin Denholm 14 20 , Steven YC Tong 20 21 , Denise L Doolan 22 , Tom C Kotsimbos 23 24 , David C Jackson 1 2 , Florian Krammer 12 , Dale I Godfrey 1 25 , Amy W Chung 1 , Nicholas JC King 5 6 26 27 , Sharon R Lewin 14 20 28 , Adam K Wheatley 1 29 , Stephen J Kent 1 29 30 , Kanta Subbarao 1 31 , James McMahon 28 32 , Irani Thevarajan 14 20 , Allen C Cheng 33 34 , Katherine Kedzierska 1 2 , Thi HO Nguyen 1
  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
  2. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan
  3. Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam
  4. Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne
  5. Australia Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute and The University of Sydney, Sydney
  6. Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney
  7. Charles Perkins Centre, The University of Sydney, Sydney
  8. School of Computer Science, The University of Sydney, Sydney
  9. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney
  10. Vascular Immunology Unit, Department of Pathology, The University of Sydney, Sydney
  11. The Westmead Initiative, Faculty of Engineering, The University of Sydney, Sydney
  12. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York
  13. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York
  14. The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne
  15. Department of Medicine and Radiology, The University of Melbourne, Melbourne
  16. Data Analytics Research and Evaluation (DARE) Centre, Austin Health and The University of Melbourne, Heidelberg
  17. Department of Infectious Diseases, Austin Hospital, Heidelberg
  18. Monash Infectious Diseases, Monash Medical Centre, Monash Health, Melbourne
  19. Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne
  20. Victorian Infectious Diseases Services, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne
  21. Menzies School of Health Research, Charles Darwin University, Darwin
  22. Centre for Molecular Therapeutics, Australian Institute of Tropical Health & Medicine, James Cook University, Cairns
  23. Respiratory Medicine Laboratory, Department of Medicine, Central Clinical School, Monash University, Melbourne
  24. Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne
  25. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne
  26. Viral Immunopathology Laboratory, Discipline of Pathology, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney
  27. Sydney Nano, the University of Sydney, Sydney
  28. Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne
  29. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne
  30. Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University, Melbourne
  31. World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza, at The Peter Doherty Institute for Infection and Immunity , Melbourne
  32. Department of Infectious Diseases, Monash Medical Centre, Melbourne
  33. School of Public Health and Preventive Medicine, Monash University, Melbourne
  34. Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne

Abstract:

SARS-CoV-2 causes a spectrum of illness, ranging from asymptomatic to severe COVID-19. Early in March when WHO declared the COVID-19 pandemic, we provided the first evidence that the breadth of robust immune responses to SARS-CoV2 can be measured in peripheral blood prior to patient recovery. This was a longitudinal case study of one patient. As the immunological basis for severity remains ill-defined, we have now analysed 78 SARS-CoV-2-infected individuals at acute and/or convalescent timepoints, up to 102 days post-symptom onset, quantifying 184 innate and adaptive immunological parameters. Acute hospitalised COVID-19, including ward and intensive care unit (ICU) patients, was associated with high levels of IL-6, IL-18 and IL-10, elevated neutrophil-to-lymphocyte and neutrophil-to-T cell ratios, and high proportions of activated CD38+ neutrophils, CD38+ eosinophils, CD38+HLA-DRlo monocytes, CD38+CD56dim NK cells, CD38+ γδ T cells, antibody-secreting cells, PD-1+ICOS+ circulating T follicular helper (cTFH) cells, CD38+HLA-DR+CD4+ T cells, effector CD27-CD45RA+ and CD38+CD8+ T cells. During convalescence, elevated seroconversion and neutralising antibodies were prominent and correlated with acute CXCR3+ cTFH cell activation. Strikingly, ICU patients with severe COVID-19 displayed higher levels of soluble IL-6R, IL-18, and hyperactivation of innate, adaptive and myeloid compartments than ward patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients during acute and convalescent phases of SARS-CoV-2 infection, and integrate key cellular pathways of complex perturbed immune networks that underpin severe COVID-19. We observed a typical immune response in people displaying mild to moderate infections and that this immune response was not controlled in time in patients suffering from severe disease. Our data also provides important insights into potential biomarkers and immunotherapies for severer cases such as higher IL-18, IL-6R, IL-6 and CD38 expression on innate and adaptive immune cells.