Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health

Townsend, Liam; Dyer, Adam H.; Naughton, Aifric; Kiersey, Rachel; Holden, Dean; Gardiner, Mary; Dowds, Joanne; O’Brien, Kate; Bannan, Ciaran; Nadarajan, Parthiban; Dunne, Jean; Martin-Loeches, Ignacio; Fallon, Padraic G.; Bergin, Colm; O’Farrelly, Cliona; Cheallaigh, Cliona Ni; Bourke, Nollaig M.; Conlon, Niall

OBJECTIVES: The immunological and inflammatory changes following acute COVID-19 are hugely variable. Persistent clinical symptoms following resolution of initial infection, termed long COVID, are also hugely variable, but association with immunological changes has not been described. We investigate changing immunological parameters in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms. METHODS: 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 as cardinal features of long COVID using the Chalder Fatigue Scale and 6-minute-walk test. The relationships between these clinical outcomes and convalescent immunological results were investigated. RESULTS: We identify persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common in this cohort. These symptoms were not associated with immune cell populations or circulating inflammatory cytokines. CONCLUSION: We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.