Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection

Phetsouphanh, C.; Darley, D.; Howe, A.; Munier, C. M. L.; Patel, S. K.; Juno, J. A.; Burrell, L. M.; Kent, S. J.; Dore, G. J.; Kelleher, A. D.; Matthews, G.

A proportion of patients surviving acute COVID-19 infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID (the ADAPT study) compared to age/gender matched subjects without long COVID, healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found an elevated diffuse serum inflammatory cytokine profile in symptomatic long COVID subjects that was maintained at 8 months post-infection and was not observed in asymptomatic COVID-19 survivors. This inflammatory profile consisted of 15 cytokines that positively correlated; revealing an apparent diffuse, potentially coordinated, low level up regulation of a spectrum of immune and inflammatory mediators. In addition, we found an absence of subsets of un-activated naive T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. In contrast, individual serum cytokines from the interferon I and III classes, T cell activation markers and plasma ACE2, while elevated in the serum of people previously infected with SARS-CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.