Evaluation of Adverse Effects after the Second Dose of BNT162b2 Mrna Vaccination for COVID-19: A Survey-based Analysis among Italian Healthcare Workers

Gianluigi Ferrazza1, Alessandro Nucera1, Susanna Longo1, Cristiana Ferrari2, Andrea Mazza2, Andrea Magrini2, Luca Coppeta2, Stefano Rizza1, *
1 Department of Systems Medicine, University of Rome Tor Vergata, Italy
2 Department of Occupational Medicine, University of Rome Tor Vergata, Italy


Backgrounds and Aims:

Since the start of the SARS-CoV-2 pandemic, healthcare workers have been at elevated risk of contracting COVID-19. Although COVID-19 vaccines have contributed to the eradication of, or substantial decreases in, the incidence of lethal diseases, the major determinant of COVID-19 vaccine hesitancy is a fear of associated adverse effects. Here, we performed a survey assessing the reactogenicity and safety of BNT162b2 in a real-world setting.


Data were collected from March 1 and June 14, 2021. A total of 206 hospital employees undergoing BNT162b2 mRNA vaccination completed the survey. These hospital workers received a questionnaire to collect the common and uncommon adverse effects developing 2–6 days after the second dose of the Pfizer-BioNTech vaccine.


After the second dose, female sex was found to be associated with a higher risk of vaccine-related severe systemic adverse effects than male sex (odds ratio [OR] 3.116, 95% CI 2.365–7.113). We also observed that the anti-SARS-CoV-2 receptor-binding domain titer, determined on the day when the second dose of the Pfizer-BioNTech vaccine was administered, was significantly higher in participants with severe systemic effects than those without such effects (OR 1.017, 95% CI 1.001–1.034).


Our study suggested that healthy female healthcare workers had a three-fold higher risk than healthy male healthcare workers of developing severe adverse effects after the second dose of the Pfizer-BioNTech vaccine. Further research is warranted to determine whether a high anti-SARS-CoV-2 RBD titer determined at the time of the second vaccination might indicate a disproportionate inflammatory systemic reaction leading to severe adverse effects. Our findings might contribute to a decrease in the disappearance of COVID-19 vaccine hesitancy.

Keywords: COVID-19, SARS-CoV-2, Healthcare workers, Vaccine, BNT162b2 mRNA vaccine, Adverse effect.

Abstract Information

Identifiers and Pagination:

Year: 2023
Volume: 16
DOI: 10.2174/18749445-v16-e230913-2023-159

Article History:

Electronic publication date: 13/09/2023
Collection year: 2023

© 2023 Ferrazza et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; Tel/fax: +390620908330; E-mail: stefano.rizza@uniroma2.it