Post-acute non-specific symptoms following COVID-19 vaccination: a Danish population-based study

Post-acute non-specific symptoms such as headaches, muscular pain, and fatigue are frequently reported following COVID-19 vaccination, raising concerns about adverse events. As vaccine-hesitant individuals may be more likely to experience symptoms of vaccines, this study investigates whether COVID-19 vaccination increases the odds of post-acute non-specific symptoms, stratified by COVID-19 vaccine hesitancy.

This longitudinal study uses repeated measurements from the BiCoVac cohort-a random sample of 913 116 Danish citizens aged 16-65 years. Data were collected through national registers and questionnaires (May 2021-June 2022). Non-specific symptoms were identified by using the 25-item Bodily Distress Syndrome checklist and analysed by using logistic and linear regression models comparing vaccinated and unvaccinated individuals. Models were fitted with robust standard errors and inverse probability of selection weights.

A total of 132 776 observations were collected from 61 316 COVID-19 vaccine-unconcerned individuals, 52 325 observations from 25 272 COVID-19 vaccine-sceptical individuals, and 10 242 observations from 5064 COVID-19 vaccine-concerned individuals. Among the vaccine-unconcerned individuals, those vaccinated had lower odds of most symptoms compared with unvaccinated individuals >4 weeks post-vaccination [e.g. muscular pain: odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.47-0.68]. A similar tendency was found for vaccine-sceptical individuals, although with attenuated estimates. Conversely, among vaccine-concerned individuals, we observed a tendency for higher odds of most symptoms >4 weeks post-vaccination compared with unvaccinated individuals (e.g. muscular pain: OR = 1.23, 95% CI: 0.91-1.67).

For most individuals aged 16-65 years, we found no evidence of post-acute symptoms after COVID-19 vaccination. Vaccinated vaccine-concerned individuals were, however, more likely to report most symptoms, potentially due to reporting bias or nocebo effects.