: To date, Coronavirus disease (COVID-19) has caused high morbidity and mortality worldwide. To counteract the pandemic scenario, several vaccines against the etiological factor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed and tested. At the end of December 2020, BNT162b2 (Comirnaty, Pfizer-BioNTech) was the first and only authorized vaccine in Italy for selected categories, such as healthcare workers, fragile patients and people aged over 80 years old. To master our knowledge about BNT162b2 adverse reactions (ARs), an active surveillance system based on instant messaging was realized for voluntary participants who had been vaccinated at COVID-19 Vaccination Center of the Palermo University Hospital. Overall, 293 vaccinated persons were included in this study, which were more frequently healthcare workers (n = 207, 70.6% with a median age of 36 years, IQR = 29-55) followed by health professional students (n = 31, 10.6% with a median age of 27 years, IQR = 25-29), reporting 82.6% of at least one local or systemic AR. In details, the frequency of at least one local or systemic AR after the second dose of Comirnaty (n = 235, 80.2%) was statistically significant with higher value in comparison to the first one (n = 149, 50.9%; p < 0.001). However, local pain, swelling, joint pain and muscular pain after the second dose were the symptom causing a statistically significant working limitation. The youngest persons showed a higher risk to have either local or systemic ARs (aOR = 7.5, CI 95% = 2.9-18.9), while females had a higher risk of having systemic ARs (aOR = 1.8, CI 95% = 1.1-3.0). Despite the small sample examined, this active surveillance system by instant messaging seems to detect a higher ARs prevalence with respect to data obtained by the passive surveillance. Further studies could be required in order to optimize this clinical monitoring that could be considered an efficient and timely active surveillance.
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