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

• Published in: Nature communications Vol. 15; no. 1; p. 3315
• Main Authors: Phetsouphanh, Chansavath, Jacka, Brendan, Ballouz, Sara, Jackson, Katherine J. L., Wilson, Daniel B., Manandhar, Bikash, Klemm, Vera, Tan, Hyon-Xhi, Wheatley, Adam, Aggarwal, Anupriya, Akerman, Anouschka, Milogiannakis, Vanessa, Starr, Mitchell, Cunningham, Phillip, Turville, Stuart G., Kent, Stephen J., Byrne, Anthony, Brew, Bruce J., Darley, David R., Dore, Gregory J., Kelleher, Anthony D., Matthews, Gail V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/91; 631/250/2502; 631/250/254; 631/250/255/2514; 631/250/256; 631/326/596/4130; 82/1; Antigens; CD4 antigen; CD8 antigen; Complications; COVID-19; Gene sequencing; Humanities and Social Sciences; Immune response (cell-mediated); Immune response (humoral); Immune system; Immunoglobulin G; Long COVID; Lymphocytes; Lymphocytes T; multidisciplinary; Nucleocapsids; PD-1 protein; Quality of life; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transcriptomics; β-Interferon; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47720-8

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. Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.