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 () and Gail V. Matthews ()
Additional contact information
Chansavath Phetsouphanh: University of New South Wales
Brendan Jacka: University of New South Wales
Sara Ballouz: Garvan Institute for Medical research
Katherine J. L. Jackson: Garvan Institute for Medical research
Daniel B. Wilson: University of New South Wales
Bikash Manandhar: University of New South Wales
Vera Klemm: University of New South Wales
Hyon-Xhi Tan: University of Melbourne
Adam Wheatley: University of Melbourne
Anupriya Aggarwal: University of New South Wales
Anouschka Akerman: University of New South Wales
Vanessa Milogiannakis: University of New South Wales
Mitchell Starr: St. Vincent’s Centre for Applied Medical Research
Phillip Cunningham: St. Vincent’s Centre for Applied Medical Research
Stuart G. Turville: University of New South Wales
Stephen J. Kent: University of Melbourne
Anthony Byrne: St. Vincent’s Hospital Sydney and Faculty of Medicine and Health (UNSW)
Bruce J. Brew: Peter Duncan Neurosciences Unit- St Vincent’s Centre for Applied Medical Research
David R. Darley: St. Vincent’s Hospital
Gregory J. Dore: University of New South Wales
Anthony D. Kelleher: University of New South Wales
Gail V. Matthews: University of New South Wales

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47720-8

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