EBV Reprograms B Cells in an Autoimmune-Like Fashion in Patients with COVID-19

Epstein-Barr virus (EBV) reprograms B cells in autoimmune disease. Reprogrammed EBV ⁺ B cells activate nearby B and CD4 ⁺ T cells, via upregulated antigen presentation and costimulatory machinery, to drive autoimmune pathology. EBV reactivation is a known correlate of long COVID, which is a heterogeneous condition that can bear similarities to autoimmune disease. However, the mechanisms underpinning this association remain unresolved. We report on EBV metabolically reprogrammed B cells in patients with COVID-19. We find EBV ⁺ B cells provide stimulatory signals to bystander B and CD4 ⁺ T cells. SARS-CoV-2 infected participants exhibiting elevated fractions of EBV ⁺ B cells present, at convalescence, with dysregulated lipid profiles, increased autoantibody titers, and post-acute symptomology likely reflective of this metabolic reprogramming and cell-cell interactions. Enrichment of our EBV ⁺ B cell signatures seen in patients with COVID-19 is similar in patients with lupus and multiple sclerosis suggesting a potentially shared pathway of EBV-driven dysfunction across diseases.