Internal medicine

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Innate immune system

Immunology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Medicine

Immune system

Nature Immunology

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-β) and type III IFN (IFN-λ1) 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-β, PTX3, IFN-γ, IFN-λ2/3 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. 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.

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