Cell https://doi.org/10.1016/j.cell.2022.01.014 (2022)

Recovery from COVID-19 can take a long time. In Cell, Su et al. perform multi-omics profiling in a cohort of 209 patients with COVID-19 (71% hospitalization rate) at clinical diagnosis (T1), acute disease (T2) and 2–3 months after disease onset (T3). At T3, 44% of patients were positive for the 6 autoantibodies tested (IFN-α2 and nuclear proteins), with half of them positive at T1 (94% at subclinical levels). T3 autoantibodies associated with inflammation biomarkers at T2 and negatively correlated with titers of SARS-CoV-2 IgG. T3 respiratory symptoms associated with IFN-α2 autoantibodies; neurological symptoms with SARS-CoV-2 IgG titers; fatigue with Epstein–Barr virus reactivation at T1; and gastrointestinal symptoms with bystander activation of CMV-specific CD8+ T cells. Single-cell RNA sequencing sorted patients into four groups: a type 1, enriched in TH1, M1 and cytotoxic signatures in T cells, monocytes and NK cells, and memory signatures in B cells; type 2, enriched in TH2, M2 and plasma B cell signatures; intermediate (between types 1 and 2); and (T and NK cell) naive, all four with high monocyte polyfunctionality. The T3 type was anticipated by the transcriptomic signature at T1, which indicates that patients may be predisposed towards their post-acute status early in the infection.