Journal Article

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

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

2024

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 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