Shared Clinical and Immunological Features of Post-Acute COVID-19 and Post-Acute COVID-19 Vaccination Syndromes
- 1Institute for Clinical Immunology, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Hoelkeskampring 40, 44625 Herne, Germany
Abstract
BackgroundPost-acute COVID-19 syndrome (PACS) can cause persistent disability involving fatigue, post-exertional malaise, neurocognitive symptoms, and autonomic manifestations. A clinically overlapping condition has been reported following COVID-19 vaccination and termed post-acute COVID-19 vaccination syndrome (PACVS), but its underlying mechanisms remain poorly understood. We investigated whether immune dysregulation, autoreactivity, antigen persistence, and viral reactivation--mechanisms implicated in PACS--are also present in PACVS.
MethodsThis cross-sectional study included 28 PACS patients, 29 PACVS patients, and 16 convalescent controls (CCG). Clinical manifestations were assessed using ME/CFS-related symptom questionnaires and the Bell Score. T-cell phenotypes and T cells reactive to SARS-CoV-2 Spike, {beta}1/{beta}2-adrenergic receptor, and M3/M4 muscarinic receptor antigens were analyzed by multicolor flow cytometry. Circulating Spike protein and GPCR autoantibodies were quantified by ELISA, and EBV load by qPCR.
ResultsPACS and PACVS showed substantial clinical overlap, although several symptoms were more severe in PACS. GPCR autoantibody profiles were comparable between patient groups, while {beta}2-adrenergic receptor autoantibodies were increased compared with CCG. Only three of 57 conventional immunophenotyping parameters differed between PACS and PACVS in unadjusted analyses, whereas both groups showed multiple alterations compared with CCG. Circulating Spike protein was detected in both patient groups, with the highest prevalence in PACVS. {beta}1/{beta}2- and M3/M4-reactive CD4+ T cells were increased, whereas Spike-specific CD4+ T cells were reduced compared with CCG. EBV reactivation was rare.
ConclusionsPACS and PACVS exhibit substantial clinical and immunological overlap, including GPCR-directed autoreactivity and altered receptor-reactive T-cell responses. These shared immune-mediated features suggest overlapping pathophysiological mechanisms and warrant investigation of whether therapeutic strategies currently explored for PACS may also be relevant to PACVS.
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BibTeX
@misc{dinser2026shared,
title = {{Shared Clinical and Immunological Features of Post-Acute COVID-19 and Post-Acute COVID-19 Vaccination Syndromes}},
author = {J. Dinser and M. Anft and L. Wiemers and S. Skrzypczyk and E. Kohut and J. Kurek and U. Stervbo and F. S. Seibert and T. H. Westhoff and K. Rosiewicz and N. Babel},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.26363380},
url = {https://www.medrxiv.org/content/10.64898/2026.09.18.26363380v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Shared Clinical and Immunological Features of Post-Acute COVID-19 and Post-Acute COVID-19 Vaccination Syndromes
AU - J. Dinser
AU - M. Anft
AU - L. Wiemers
AU - S. Skrzypczyk
AU - E. Kohut
AU - J. Kurek
AU - U. Stervbo
AU - F. S. Seibert
AU - T. H. Westhoff
AU - K. Rosiewicz
AU - N. Babel
PY - 2026
DA - 2026/09/18
PB - medRxiv
DO - 10.64898/2026.09.18.26363380
UR - https://www.medrxiv.org/content/10.64898/2026.09.18.26363380v1
AB - BackgroundPost-acute COVID-19 syndrome (PACS) can cause persistent disability involving fatigue, post-exertional malaise, neurocognitive symptoms, and autonomic manifestations. A clinically overlapping condition has been reported following COVID-19 vaccination and termed post-acute COVID-19 vaccination syndrome (PACVS), but its underlying mechanisms remain poorly understood. We investigated whether immune dysregulation, autoreactivity, antigen persistence, and viral reactivation--mechanisms implicated in PACS--are also present in PACVS. MethodsThis cross-sectional study included 28 PACS patients, 29 PACVS patients, and 16 convalescent controls (CCG). Clinical manifestations were assessed using ME/CFS-related symptom questionnaires and the Bell Score. T-cell phenotypes and T cells reactive to SARS-CoV-2 Spike, {beta}1/{beta}2-adrenergic receptor, and M3/M4 muscarinic receptor antigens were analyzed by multicolor flow cytometry. Circulating Spike protein and GPCR autoantibodies were quantified by ELISA, and EBV load by qPCR. ResultsPACS and PACVS showed substantial clinical overlap, although several symptoms were more severe in PACS. GPCR autoantibody profiles were comparable between patient groups, while {beta}2-adrenergic receptor autoantibodies were increased compared with CCG. Only three of 57 conventional immunophenotyping parameters differed between PACS and PACVS in unadjusted analyses, whereas both groups showed multiple alterations compared with CCG. Circulating Spike protein was detected in both patient groups, with the highest prevalence in PACVS. {beta}1/{beta}2- and M3/M4-reactive CD4+ T cells were increased, whereas Spike-specific CD4+ T cells were reduced compared with CCG. EBV reactivation was rare. ConclusionsPACS and PACVS exhibit substantial clinical and immunological overlap, including GPCR-directed autoreactivity and altered receptor-reactive T-cell responses. These shared immune-mediated features suggest overlapping pathophysiological mechanisms and warrant investigation of whether therapeutic strategies currently explored for PACS may also be relevant to PACVS.
ER -