Background Vaccines are a powerful choice to stop disease outbreaks, including covid-19. However, people are hesitant to take vaccinations due to uncertainty about side effects. So, this study aimed to assess covid-19 vaccine side-effect and its associated factors among healthcare workers in Dessie comprehensive specialized hospital, in Ethiopia. Methods An institution-based cross-sectional study was conducted at Dessie Comprehensive and Specialized Hospital among 351 vaccinated healthcare workers from April 25 to May 25, 2021. Self-administrated questionnaires were used by consented health workers. Variance inflation factor (VIF) was used to assess the multicollinearity of independent variables. Bivariable and multivariable binary logistic regression were used to identify significant factors of vaccine side effects. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) was reported as the effect size. Statistical significance was considered at p-value <0.05. Results Overall, of vaccinated healthcare workers, 56.98% (95% CI, 50.86–61.26%) experienced at least one side effect. The majority of the side effects were fever (44.44%), headache (39.03%), fatigue (27.35%), injection site pain (25.93%), and nausea (24.22%). Healthcare workers with (≥10 years) of work experience (AOR: 3.74, 95% CI, 1.32–10.59), Hesitancy to take the first dose of the Covid-19 vaccine (AOR: 3.01, 95% CI, 1.82–4.99), underlying chronic disease (AOR: 14.41, 95% CI, (5.07–40.92)), being on antihypertensive medication (AOR: 0.15; 95% CI (0.02–0.93)), and unsafe perception of vaccine safety (AOR:3.50; 95% CI, 1.43–8.57) were independent factors of Covax vaccine side effect development. Conclusion Overall, common vaccine side effects were identified in healthcare workers who have taken the Covax vaccine. Healthcare workers with (≥10 years) of work experience, Hesitancy to take the first dose, unsafe perception of vaccine safety, and underlined chronic disease were predictors of vaccine side effect occurrence. So, providing vaccine-related information to the community to be vaccinated is mandatory to reduce hesitancy and flaws regarding vaccine safety.
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