Acute symptoms and subsequent post-acute symptoms following COVID-19 vaccination: A Danish population-based study

Objectives Acute symptoms are common following COVID-19 vaccination, yet it remains unclear if these reactions can manifest or progress into non-specific symptoms (e.g., headache, fatigue, muscle pain) beyond the acute phase. This study examines whether acute symptoms after COVID-19 vaccination increases the odds of subsequent post-acute symptoms, and whether this varies by vaccine hesitancy. Study design Longitudinal cohort study. Methods Using repeated measurements from the BiCoVac cohort of 911,613 Danes aged 16-65, acute symptoms were defined as the number of systemic symptoms within seven days following COVID-19 vaccination, while post-acute symptoms were assessed ≥ five weeks later using the 25-item Bodily Distress Syndrome checklist. Multiple logistic regressions with inverse probability weighting and robust standard errors were used. Results We included 93,268 observations representing 61,023 individuals. Compared to participants without acute symptoms, odds of high post-acute symptom burden were higher for individuals with one-four acute symptoms (OR = 2.13 (95% CI: 1.77-2.56)) and five + acute symptoms (OR = 6.37 (95% CI: 5.07-8.01)), particularly among vaccine-concerned individuals reporting five + acute symptoms (OR = 21.40 (95% CI: 9.98-45.89)). Conclusions Findings highlight an association between acute and post-acute symptoms and further emphasize the impact of vaccine hesitancy.