Longitudinal analysis of COVID-19 patients shows age-associated T cell changes independent of ongoing ill-health

The trajectory of immunological and inflammatory changes following acute COVID-19 infection are unclear. We investigate immunological changes in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms, termed long COVID. We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed and investigated their relationship with convalescent results. We demonstrate persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naive CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naive CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common but were not associated with immunological changes.