Association of mRNA SARS-CoV-2 vaccination with fatigue and functional recovery in patients with post-acute sequelae of COVID-19 (PASC)

Background Patients with post-acute sequelae of SARS-CoV-2 (PASC) fear SARS-CoV-2 vaccine-linked symptom aggravation. Data on objective functional outcomes are limited.Methods We performed a retrospective analysis of an observational cohort at a post-COVID outpatient clinic at Hannover Medical School with standardized assessments at baseline and follow-up visit (3–6 months) in adults with confirmed SARS-CoV-2 infection and PASC. Participants were classified as vaccination (receipt of an additional SARS-CoV-2 vaccine dose between visits) or no vaccination. Primary outcomes were fatigue (Fatigue Assessment Scale) and exercise capacity (6-minute walk distance). Propensity scores matching (1:1 nearest-neighbor, ATT; caliper 0.2 SD) was performed using logistic regression. Group differences were assessed using t-tests/χ2 tests with Benjamini-Hochberg adjustment. Longitudinal changes were analyzed using linear mixed-effects models.Results Of 193 eligible patients, 174 were analyzed, 148 remained after matching (74 per group). No significant differences between the groups were observed at baseline or follow-up after adjustment for multiple comparisons. Both groups improved over time, with no statistically significant difference in fatigue or exercise capacity.Conclusions Fatigue and functional performance improved over time regardless of vaccination status. We found no statistically significant association between mRNA SARS-CoV-2 vaccination and worsening symptoms or impaired recovery, although smaller effects cannot be excluded.