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Cell reports. Medicine
03 16, 2021;2 (3): 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 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
Author Information
  1. Marios Koutsakos: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  2. Louise C Rowntree: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  3. Luca Hensen: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  4. Brendon Y Chua: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  5. Carolien E van de Sandt: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  6. Jennifer R Habel: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  7. Wuji Zhang: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  8. Xiaoxiao Jia: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  9. Lukasz Kedzierski: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  10. Thomas M Ashhurst: Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute and University of Sydney, Sydney, NSW, Australia.
  11. Givanna H Putri: Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
  12. Felix Marsh-Wakefield: Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
  13. Mark N Read: Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
  14. Davis N Edwards: School of Computer Science, University of Sydney, Sydney, NSW, Australia.
  15. E Bridie Clemens: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  16. Chinn Yi Wong: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  17. Francesca L Mordant: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  18. Jennifer A Juno: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  19. Fatima Amanat: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  20. Jennifer Audsley: Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  21. Natasha E Holmes: Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC, Australia.
  22. Claire L Gordon: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  23. Olivia C Smibert: Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC, Australia.
  24. Jason A Trubiano: Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia.
  25. Carly M Hughes: Monash Infectious Diseases, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia.
  26. Mike Catton: Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  27. Justin T Denholm: Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  28. Steven Y C Tong: Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  29. Denise L Doolan: Centre for Molecular Therapeutics, Australian Institute of Tropical Health & Medicine, James Cook University, Cairns, QLD, Australia.
  30. Tom C Kotsimbos: Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia.
  31. David C Jackson: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  32. Florian Krammer: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  33. Dale I Godfrey: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  34. Amy W Chung: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  35. Nicholas J C King: Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute and University of Sydney, Sydney, NSW, Australia.
  36. Sharon R Lewin: Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  37. Adam K Wheatley: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  38. Stephen J Kent: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  39. Kanta Subbarao: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  40. James McMahon: Monash Infectious Diseases, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia.
  41. Irani Thevarajan: Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  42. Thi H O Nguyen: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
  43. Allen C Cheng: School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
  44. Katherine Kedzierska: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
PMID: 33564749 DOI: 10.1016/j.xcrm.2021.100208

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 CXCR3cT1 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.

Keywords

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

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MeSH Term

Adaptive Immunity
Adult
Aged
Antibodies, Viral
Antibody Formation
B-Lymphocytes
COVID-19
Female
Humans
Immunity, Innate
Interleukin-18
Interleukin-6
Male
Middle Aged
Receptors, CXCR3
Receptors, Interleukin-6
SARS-CoV-2
Severity of Illness Index
Th1 Cells
Young Adult

Chemicals

Antibodies, Viral
CXCR3 protein, human
Interleukin-18
Interleukin-6
Receptors, CXCR3
Receptors, Interleukin-6
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 47

Word Cloud

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