Immune disturbances in individuals with post-COVID syndrome are not characterized by enhanced SARS-CoV-2-specific immunity.

Background Post-COVID syndrome (PCS) is characterized by persistent symptoms lasting beyond 12 weeks after SARS-CoV-2 infection. The underlying pathomechanims remain poorly understood. Methods We conducted detailed immunological analyses in 47 individuals with PCS, assessed >12 weeks post-acute SARS-CoV-2 infection, and compared them to 25 convalescent controls without symptoms. We performed immune phenotyping of T and B cell subsets, assessed SARS-CoV-2-specific responses using activation-induced marker (AIM) flow cytometry for T cells, and tetramer staining of spike-specific B cells. Cytokine levels in peptide-stimulated cell supernatants and plasma were quantified using a Luminex platform. Results PCS individuals exhibited reduced frequencies of AIM+ SARS-CoV-2-specific T cells (OX40+, PDL1+) and CD8 T cells (CD137+, CD69+) following petide stimulation with S- or N-Antigen, accompanied by diminished IFNγ and IL2 as measured in the cell culture supernatants. In contrast, non-virus specific T cell populations, including their memory differentiation, activation and helper cell differentiation status did not differ between the groups. PCS individuals showed a significant increase in total (CD19+) and activated B cells (CD86+, HLA-DR+), but not in SARS-CoV-2 spike-specific B cells (∼0.2% of total B cells). Plasma cytokine analysis revealed elevated markers associated with vascular damage and inflammation in PCS individuals. Conclusion Persistent immune disturbances in individuals with PCS are characterized by reduced SARS-CoV-2-specific T cell responses, increased B cell activation, and altered inflammatory and vascular biomarkers. These findings provide insights into the underlying mechanisms of PCS and may contribute to biomarker discovery and therapeutic development.Trialnumber: DRKS00030974registry's URL: https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html.