Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection

Chansavath Phetsouphanh; Brendan Jacka; Sara Ballouz; Katherine J L Jackson; Daniel B Wilson; Bikash Manandhar; Vera Klemm; Hyon-Xhi Tan; Adam Wheatley; Anupriya Aggarwal; Anouschka Akerman; Vanessa Milogiannakis; Mitchell Starr; Phillip Cunningham; Stuart G Turville; Stephen J Kent; Anthony Byrne; Bruce J Brew; David R Darley; Gregory J Dore; Anthony D Kelleher; Gail V Matthews

doi:10.1038/s41467-024-47720-8

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection

Nat Commun. 2024 Apr 17;15(1):3315. doi: 10.1038/s41467-024-47720-8.

Authors

Chansavath Phetsouphanh¹, Brendan Jacka², Sara Ballouz^{3

4}, Katherine J L Jackson³, Daniel B Wilson², Bikash Manandhar², Vera Klemm², Hyon-Xhi Tan⁵, Adam Wheatley⁵, Anupriya Aggarwal², Anouschka Akerman², Vanessa Milogiannakis², Mitchell Starr⁶, Phillip Cunningham⁶, Stuart G Turville², Stephen J Kent⁵, Anthony Byrne⁷, Bruce J Brew⁸, David R Darley⁹, Gregory J Dore^{2

9}, Anthony D Kelleher^#^{10

11}, Gail V Matthews^#^{12

13}

Affiliations

¹ The Kirby Institute, University of New South Wales, Sydney, NSW, Australia. cphetsouphanh@kirby.unsw.edu.au.
² The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
³ Garvan Institute for Medical research, Sydney, NSW, Australia.
⁴ School of Computer Science and Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW, Australia.
⁵ Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Victoria, VIC, Australia.
⁶ NSW State Reference Laboratory for HIV, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.
⁷ Heart Lung Clinic, St. Vincent's Hospital Sydney and Faculty of Medicine and Health (UNSW), Sydney, NSW, Australia.
⁸ Peter Duncan Neurosciences Unit- St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.
⁹ St. Vincent's Hospital, Darlinghurst, NSW, Australia.
¹⁰ The Kirby Institute, University of New South Wales, Sydney, NSW, Australia. akelleher@kirby.unsw.edu.au.
¹¹ St. Vincent's Hospital, Darlinghurst, NSW, Australia. akelleher@kirby.unsw.edu.au.
¹² The Kirby Institute, University of New South Wales, Sydney, NSW, Australia. gmatthews@kirby.unsw.edu.au.
¹³ St. Vincent's Hospital, Darlinghurst, NSW, Australia. gmatthews@kirby.unsw.edu.au.

^# Contributed equally.

Abstract

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4⁺ T cells, PD-1, and TIM-3 expression on CD4⁺ and CD8⁺ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

MeSH terms

Antibodies, Viral
CD8-Positive T-Lymphocytes
COVID-19*
Humans
Post-Acute COVID-19 Syndrome*
Quality of Life
SARS-CoV-2

Substances

Antibodies, Viral