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

Phetsouphanh and colleagues show that individuals with long COVID have persistent activation of the innate and adaptive immune system at 8 months after infection and define a set of analytes associated with long COVID. A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-beta) and type III IFN (IFN-lambda 1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-beta, PTX3, IFN-gamma, IFN-lambda 2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.