Comparison of Adverse COVID-19 Vaccines Reactions between First and Second Doses, First Booster and Fourth Doses in General Medicine

Background: Differential characteristics of the adverse reactions between the different COVID-19 vaccinations shots are not clearly known. Objective: Comparison of adverse reactions that led to consultation with the general practitioner between first and second, third (first booster) and fourth (second booster) doses of COVID-19 vaccines. Methodology: Several longitudinal studies are compared, with the same methodology and population, of adverse COVID-19 vaccines reactions that were the reason for medical consultation, in people with first and second doses from February to July 2021, first booster from November 2021 to August 2022 and fourth dose (second booster) of bivalent mRNA from October 1, 2022 to February 28, 2023. Results: A total of 109 adverse COVID-19 vaccines reactions with the first and second doses, 21 adverse COVID-19 vaccines reactions in vaccinated people with first booster, and 4 adverse COVID-19 vaccines reactions in vaccinated people with fourth dose (second booster) were included. The only statistically significant differences were that the adverse reactions of first and second doses vs. first and second boosters were occurred in people < 65 years [p= .00041], were more certain and probable [p= .027042], and more mild and moderate [p= .005912]. There were no differences by chronic diseases or symptoms. Conclusion: Adverse reactions were more severe, more unlikely/conditional, and occurred in older people with the boosters than with the first or second dose of the COVID-19 vaccine. However, these differences must be taken with caution and could be explained by older people being more vaccinated with booster, and by the knowledge of the population over time, which may change the reason for consultation with general practitioner towards adverse reactions severe and less known. Our data support the safety of COVID-19 vaccines, including the first and second booster.