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Background: Several different types of vaccines have been developed for the prevention of coronavirus disease (COVID-19). Despite several local and systemic side-effects to COVID-19 vaccination reported, the vaccines are still considered the best intervention to tackle the spread of the virus and reduce the severity of COVID-19 infection. However, the reported side-effects continue to have a crucial role in public confidence in the vaccine and its acceptance. This study aimed to investigate the short-term side-effects reported by the healthcare workers (HCWs) in Saudi Arabia after receiving the first dose of the Oxford/AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccine. Methods: A prospective cohort study was conducted among HCWs in the Jazan region of southwestern Saudi Arabia. Healthcare workers who had received the first dose of the COVID-19 vaccine and agreed to participate in the study were followed up for 3 weeks post vaccination through a weekly online survey. Information was collected on local and/or systemic side-effects reported following vaccine administration. Participants’ general and demographic information was also collected. Results: A total of 57.2% (250/437) of the HCWs who participated in this study reported at least one side-effect. Injection site pain and redness (80.0%), fever (73.2%), whole-body pain/fatigue (56.4%), and headache (48.8%) were the most commonly reported side-effects. Moreover, 12.4% of the participants who reported side-effects needed to see a physician, and only one female participant was admitted to the hospital. Multivariate regression analyses revealed that nationality (Saudi, adjusted odds ratio (aOR) = 3.65; 95% CI = 2.40, 5.55) and residency (Jazan governorate, aOR = 0.38; 95% CI = 0.15, 0.95) were the significant factors associated with reporting COVID-19 post-vaccination side-effects, while the number of reported side-effects was found to be significantly influenced by occupation (medical, aOR = 0.42; 95% CI = 0.26, 0.66; p &lt; 0.001) and gender (female, aOR = 0.61; 95% CI = 0.38, 0.97; p = 0.038). Conclusions: Findings of the present study support the safety of the Oxford/AstraZeneca COVID-19 vaccine among HCWs in Saudi Arabia. All the reported side-effects were mild-to-moderate side-effects. The findings may help convince vaccine-hesitant individuals and skeptics to accept the COVID-19 vaccine.

Prospective Evaluation of Side-Effects Following the First Dose of Oxford/AstraZeneca COVID-19 Vaccine among Healthcare Workers in Saudi Arabia