B cell dysregulation during acute COVID-19 is transient.

Publication date: Sep 05, 2025

COVID-19 is still a significant health concern worldwide. B cell responses to COVID-19 have been extensively studied in acute severe disease, but less so during extended follow-up or mild disease. Persisting immunological changes together with herpesvirus reactivations during acute COVID-19 have been suggested as contributing factors for post-acute sequelae of COVID-19 (PASC). Here, we evaluated the natural kinetics of B cell subpopulations together with serological markers of increased B cell activity during acute COVID-19 and long-term follow-up. We also measured human herpesvirus reactivations during acute COVID-19. We collected plasma and peripheral blood mononuclear cell samples from 120 SARS-CoV-2 positive patients (outpatients = 56, inpatients = 64) at up to five timepoints during acute disease and recovery (up to 460 days since symptom onset, dsso). We determined circulating B cell and Th cell subpopulations using flow cytometry, and measured free light chains, in addition to Epstein-Barr virus (EBV) serology, and herpesvirus qPCR from the plasma samples. The presence of anosmia as a proxy for PASC was self-reported at 3-12 months post-COVID. All changes in B cell subpopulation proportions normalized within 200 dsso. Likewise, the acute alterations observed in circulating T follicular helper and T follicular regulatory cell proportions stabilized soon after. Free light chains were high in acute COVID-19, especially in inpatients, but normalized during follow-up. EBV and human herpesvirus 6B (HHV-6B) reactivations were significantly more common in inpatients than outpatients, with reactivation in 47 and 19% of inpatients and 4. 3 and 0% of outpatients respectively. Anosmia was not significantly associated with any herpesvirus reactivation. The circulating B cell and Th cell subpopulations experience transitional changes during SARS-CoV-2 infection, but these changes recover in follow-up. EBV and HHV-6B reactivations are common in inpatients, but they are not associated with persisting anosmia.

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