Immediate adverse events following COVID-19 immunization. A cross-sectional study of 314,664 Italian subjects. Immediate adverse events following COVID-19 immunization

Main Article Content

Vincenza Gianfredi
Massimo Minerva
Giulia Casu
Michele Capraro
Greta Chiecca
Giovanni Gaetti
Rosaria Mantecca Mazzocchi
Patrizia Musarò
Pasquale Berardinelli
Paola Basteri
Beatrice Bertini
Camilla Ferri
Anna Odone
Carlo Signorelli
Valerio Fabio Alberti
Gilda Gastaldi


COVID-19, Lombardy, SARS-COV-2, vaccine, adverse events following immunization


Background and aim: The urgency of having rapidly safe and efficient COVID-19 vaccines called for the need to shorten trial phases, reduce sample sizes, and speed-up the approval process by the regulatory Agencies. In light of this, monitoring adverse effects (AEFI) (both immediate and at medium-long term) become of great importance. Aim of this cross-sectional study was to explore the associations between several factors and risk of immediate AEFI.

Methods: Data come from the electronic dataset developed ad hoc to record demographic data, anamnesis and data related to immunization, set-up in the mass vaccination site in Novegro (Milan). Novegro mass vaccination site was one of the mass vaccinations sites with the highest flow in Lombardy Region, with a maximum capacity of 5,000 vaccinations/day. The center opened in April 2021 and closed the 1st of August 2021. A multivariable logistic regression model was used. Odds ratios adjusted (aOR) for age and sex are presented. Statistical significance was set at p<0.05. Analyses were conducting using STATA.

Results: Among the total of 314,671 subjects vaccinated, 0.5% developed an immediate AEFI, on average 17.0 ± 0.43 minutes after the administration. The three most frequent AEFI recorded were vagal response (30%), anxiety reaction (24%) and dizziness (21%). AEFI were more frequently observed among women [aOR= 2.24 (95%CI= 2.00 - 2.50)], and those with at least one previous disease [aOR= 1.47 (95%CI= 1.22-1.76)].

Conclusions: In conclusion, AEFI were less likely to occur for increasing age and after the second dose. Results from this large, complete and representative sample population regarding enrich the interesting scientific debate on potential adverse events following COVID-19 immunization.


Download data is not yet available.
Abstract 34 | PDF Downloads 9


1. Signorelli C, Odone A, Gianfredi V, Bossi E, Bucci D, Oradini-Alacreu A, et al. The spread of COVID-19 in six western metropolitan regions: a false myth on the excess of mortality in Lombardy and the defense of the city of Milan. Acta Biomed. 2020;91(2):23-30.
2. Signorelli C, Odone A, Gianfredi V, Balzarini F, Bucci D, Croci R, et al. Epidemiological assessment of the first COVID-19 epidemic wave in Lombardy. A systematic review. Acta Biomed. 2021;92(S6):e2021462.
3. Paciullo F, Giannandrea D, Gianfredi V, Borgognoni F, Verdecchia P, L'Angiocola PD, et al. Epidemiology of emergency calls for time-dependent acute illnesses during COVID-19 outbreak in Umbria region (Italy). Ann Ig. 2021;33(2):198-200.
4. Bossi E, Gianfredi V, Odone A, Valsecchi D, Franchini S, Etteri M, et al. COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan. Acta Biomed. 2021;92(S6):e2021419.
5. Gianfredi V, Santangelo OE, Provenzano S. The effects of COVID-19 pandemic on the trend of measles and influenza in Europe. Acta Biomed. 2021;92(4):e2021318.
6. Gianfredi V, Mauer NS, Gentile L, Ricco M, Odone A, Signorelli C. COVID-19 and Recreational Skiing: Results of a Rapid Systematic Review and Possible Preventive Measures. International journal of environmental research and public health. 2021;18(8).
7. Signorelli C, Odone A, Gianfredi V, Bossi E, Bucci D, Oradini-Alacreu A, et al. COVID-19 mortality rate in nine high-income metropolitan regions. Acta Biomed. 2020;91(9-S):7-18.
8. Li T, Zhang T, Gu Y, Li S, Xia N. Current progress and challenges in the design and development of a successful COVID-19 vaccine. Fundamental Research. 2021;1(2):139-50.
9. European medicines Agency. Comirnaty, COVID-19 mRNA vaccine 2020 [Available from:
10. European medicines Agency. COVID-19 Vaccine Moderna 2021 [Available from:
11. European Medicines Agency. CHMP summary of positive opinion for COVID-19 Vaccine AstraZeneca 2021 [Available from:
12. European Medicines Agency. COVID-19 Vaccine Janssen (COVID-19 vaccine (Ad26.COV2-S [recombinant])) 2021 [Available from:
13. Italian Ministry of Health aoMAo. Vaccinazione anti-SARS-COV-2/COVID-19. Piano strategico. 2020 [Available from:
14. Gianfredi V, Pennisi F, Lume A, Ricciardi GE, Minerva M, Ricco M, et al. Challenges and Opportunities of Mass Vaccination Centers in COVID-19 Times: A Rapid Review of Literature. Vaccines (Basel). 2021;9(6).
15. Capolongo S, Brambilla A, Girardi A, Signorelli C. Validation Checklist for Massive Vaccination Centers. Ann Ig. 2021;33(5):513-7.
16. Signorelli C, Odone A, Gianfredi V, Capraro M, Kacerik E, Chiecca G, et al. Application of the "immunization islands" model to improve quality, efficiency and safety of a COVID-19 mass vaccination site. Ann Ig. 2021;33(5):499-512.
17. Wu Q, Dudley MZ, Chen X, Bai X, Dong K, Zhuang T, et al. Evaluation of the safety profile of COVID-19 vaccines: a rapid review. BMC medicine. 2021;19(1):173.
18. Yacoub MR, Cucca V, Asperti C, Ramirez GA, Della-Torre E, Moro M, et al. Safety of the BNT162b2 vaccine in patients with severe allergic background and mast cell disorders. Vaccine. 2021;in press.
19. Centers for Disease Control and Prevention Covid Response Team and Food Drug Administration. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine - United States, December 14-23, 2020. MMWR Morbidity and mortality weekly report. 2021;70(2):46-51.
20. Centers for Disease Control and Prevention Covid Response Team and Food Drug Administration. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID-19 Vaccine - United States, December 21, 2020-January 10, 2021. MMWR Morbidity and mortality weekly report. 2021;70(4):125-9.
21. Vigezzi GP, Lume A, Minerva M, Nizzero P, Biancardi A, Gianfredi V, et al. Safety surveillance after BNT162b2 mRNA COVID-19 vaccination: results from a cross-sectional survey among staff of a large Italian teaching hospital. Acta Biomed. 2021;92(S6):e2021450.
22. Gold MS, MacDonald NE, McMurtry CM, Balakrishnan MR, Heininger U, Menning L, et al. Immunization stress-related response - Redefining immunization anxiety-related reaction as an adverse event following immunization. Vaccine. 2020;38(14):3015-20.
23. Gianfredi V, Grisci C, Nucci D, Parisi V, Moretti M. [Communication in health.]. Recenti Prog Med. 2018;109(7):374-83.
24. Freeman D, Lambe S, Yu LM, Freeman J, Chadwick A, Vaccari C, et al. Injection fears and COVID-19 vaccine hesitancy. Psychol Med. 2021:1-11.
25. Cella P, Voglino G, Barberis I, Alagna E, Alessandroni C, Cuda A, et al. Resources for assessing parents' vaccine hesitancy: a systematic review of the literature. J Prev Med Hyg. 2020;61(3):E340-E73.
26. Gianfredi V, Moretti M, Lopalco PL. Countering vaccine hesitancy through immunization information systems, a narrative review. Human vaccines & immunotherapeutics. 2019;15(11):2508-26.
27. McMurtry CM. Managing immunization stress-related response: A contributor to sustaining trust in vaccines. Can Commun Dis Rep. 2020;46(6):210-8.
28. World Health Organization. Immunization stress-related response: a manual for program managers and health professionals to prevent, identify and respond to stress-related responses following immunization. Geneva: World Health Organization; 2019 2019.
29. Harron K, Dibben C, Boyd J, Hjern A, Azimaee M, Barreto ML, et al. Challenges in administrative data linkage for research. Big Data Soc. 2017;4(2):2053951717745678.

Most read articles by the same author(s)

1 2 3 4 5 6 7 > >>