Association between Coronavirus Disease 2019 Vaccination and Fatigue Outcomes: Postvaccine Syndrome Risk in a Cross-sectional Study

A BSTRACT Background: Postvaccination fatigue has emerged as a significant concern following coronavirus disease 2019 (COVID-19) immunization, yet the relationship between vaccination history, prior COVID-19 infection, and fatigue outcomes remains incompletely understood. This study investigated the prevalence and predictors of postvaccine fatigue and its severity. Methods: Across-sectional study was conducted among 775 vaccinated individuals (53.3% female, predominantly under 60 years). Data on vaccination history, COVID-19 infection status, and fatigue outcomes were collected. Fatigue prevalence, severity (0–10 scale), and long-term persistence were assessed. Statistical analyses included Pearson correlations, logistic regression for fatigue occurrence, and linear regression for severity prediction. Results: Postvaccine fatigue affected 76.0% of participants, with 20.9% experiencing long-term symptoms. Mean fatigue severity was 4.78 (standard deviation = 2.58), with affected individuals scoring 5.53 versus 2.43 in unaffected participants. Fatigue rates varied by dose: 67.9% (first dose), 78.8% (second dose), and 75.2% (third dose). Strong correlations emerged between fatigue occurrence and severity ( r = 0.516, P < 0.001). Logistic regression identified prior COVID-19 infection as the strongest predictor (odds ratios [OR] = 2.277, 127.7% increased odds), while counterintuitively, higher vaccine doses showed protective effects (OR = 0.469, 53.1% decreased odds). Female gender modestly increased risk (OR = 1.143). Conclusion: Postvaccination fatigue is highly prevalent but shows a complex relationship with vaccination history. Prior COVID-19 infection substantially increases fatigue risk, while multiple vaccine doses may offer protective effects. These findings warrant further investigation into immunological mechanisms underlying postvaccine fatigue syndromes.