Improvement of immune dysregulation and health-related quality of life in individuals with long COVID at 24-months following SARS-CoV-2 infection

This study investigated the humoral and cellular immune responses in individuals with long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24-months. LC participants showed elevated spike and nucleocapsid IgG levels, higher neutralizing capacity, and increased spike- and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells at 3- and 8-months, but these differences did 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 24-month timepoint revealed similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC. No significant differences in exhaustion scores or antigen-specific T cell clones were 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 were associated with improvements in health-related quality of life. ADAPT is an ongoing prospective, observational cohort study of patients seen at St Vincent’s Hospital Sydney (Australia) who tested PCR positive for SARS-CoV-2 infection. Each patient is followed for a period of 24-months from the time of diagnosis, with up-to 8 pre-specified timepoint collections. This analysis studied 10 individuals with long-COVID and 10 age and sex matched controls, all of which had an acute COVID19 infection in March 2020. PBMCs collected at 4, 8 and 24 month timepoints were sequenced with 10x and assessed for transcriptional differences.