Systemic and SARS-CoV-2 specific Immune Disturbances in Individuals With Post-COVID Syndrome

Post-coronavirus disease 2019 syndrome (PCS) is characterized by persistent symptoms lasting >12 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The underlying pathological mechanisms remain poorly understood.

We conducted detailed immunological analyses in 47 individuals with PCS, assessed >12 weeks after acute SARS-CoV-2 infection, and we compared them with 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.

Individuals with PCS exhibited reduced frequencies of AIM-positive SARS-CoV-2-specific T cells (OX40+PDL1+) and CD8 T cells (CD137+CD69+) following peptide stimulation with spike or nucleocapsid antigen, accompanied by diminished interferon γ and interleukin 2, as measured in the cell culture supernatants. In contrast, non-virus-specific T-cell populations, including memory differentiation, activation and helper cell differentiation status, did not differ between the groups. Individuals with PCS showed a significant increase in total (CD19+) and activated (CD86+HLA-DR+) B cells but not in SARS-CoV-2 spike-specific B cells (approximately 0.2% of total B cells). Plasma cytokine analysis revealed elevated markers associated with vascular damage and inflammation in those with PCS.

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.

DRKS00030974 (registry: https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html).