Pre-infection COVID-19 vaccination and long-COVID mental fatigue severity: Findings from the Johns Hopkins COVID Long Study

BackgroundLong-COVID is a post-acute sequela of SARS-CoV-2 infection characterized by persistent, multi-system symptoms. Neurologic symptoms, such as mental fatigue, are often reported. While vaccination prior to infection is known to lessen symptom burden, its impact on mental fatigue remains unclear. ObjectiveExamine the association between vaccination and long-COVID-associated mental fatigue. MethodsWe analyzed data from the Johns Hopkins COVID Long Study, a cohort study of 22,811 participants with and without infection. Among 2,634 participants with complete longitudinal follow-up, we examined the association between pre-infection vaccination and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI; range 0-36, with lower scores indicating less fatigue). We considered three groups: long-COVID, recovered, and never infected, with the latter two groups as negative controls. We estimated the score differences between vaccinated and unvaccinated participants using covariate-adjusted quantile regression and mixed-effects linear models. ResultsAmong participants with long-COVID, receiving a booster dose was associated with lower WMFI scores across the distribution (1.5, 2.6, and 3.8 points lower at the 25th, 50th, and 75th percentiles; p [&le;] 0.02) compared to those unvaccinated. Fully vaccinated participants also had lower scores, though these differences were not statistically significant. Findings were consistent in mixed-effect linear models where boosted (4.0 points lower) and fully vaccinated (1.9 points lower) participants with long-COVID had lower WMFI scores (p < 0.05). No associations were observed among recovered or never-infected participants. ConclusionPre-infection vaccination was associated with less long-COVID-associated mental fatigue, with the greatest benefit among boosted participants.