Nicoletta Luxi ¹ Chiara Bellitto ² Francesco Ciccimarra ² Emiliano Cappello ³ Luca L'abbate ² Marco Bonaso ³ Chiara Ajolfi ⁴ Paolo Baldo ⁵ Roberto Bonaiuti ⁶ Claudio Costantino ⁷ Giovambattista De Sarro ⁸ Di M. Cristina ⁹ Giuseppina Fava ¹⁰ Marina Ferri ¹¹ ALBERTO FIRENZE ¹² Fabiana Furci ¹³ Luca Gallelli ⁸ Luca Leonardi ¹¹ Giovanna Negri ¹⁴ Fabio Pieraccini ¹⁵ Elisabetta Poluzzi ¹⁶ Chiara Sacripanti ¹⁷ Elisa Sangiorgi ¹⁸ Ester Sapigni ¹⁹ Ilenia Senesi ²⁰ Roberto Tessari ²¹ Luigia Trabace ²² Alfredo Vannacci ⁶ Francesca Venturini ²³ Francesco Vitale ²⁴ Donatella Zodda ²⁵ Marco Tuccori ³ Gianluca Trifirò ^2*

• ¹ Department of Medicine, University of Verona, Verona, Italy
• ² Department of Diagnostics and Public Health, University of Verona, Verona, Veneto, Italy
• ³ Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Tuscany, Italy
• ⁴ Local Health Unit of Modena, Modena, Emilia-Romagna, Italy
• ⁵ Aviano Oncology Reference Center (IRCCS), Aviano, Friuli-Venezia Giulia, Italy
• ⁶ PeaRL-Perinatal Research Laboratory, CiaoLapo Foundation, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Tuscany, Italy
• ⁷ Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Excellence Specialties "G. D’Alessandro" - University of Palermo, Palermo, Italy
• ⁸ Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Calabria, Italy
• ⁹ Azienda Sanitaria Locale Caserta, Caserta, Campania, Italy
• ¹⁰ Reggio Calabria Local Health Unit, Reggio Calabria, Italy
• ¹¹ Autonomous Province of Trento, Pharmacovigilance Centre, Trento, Italy
• ¹² Struttura Commissariale dell’Azienda Ospedaliera Papardo, Messina, Italy
• ¹³ Provincial Healthcare Unit, Section of Allergy, Vibo Valentia, Italy
• ¹⁴ Parma Local Health Unit, Parma, Italy
• ¹⁵ Romagna Local Health Unit, Romagna, Italy
• ¹⁶ Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
• ¹⁷ Bologna Local Health Unit, Bologna, Italy
• ¹⁸ Emilia-Romagna Region, Bologna, Italy
• ¹⁹ Emilia-Romagna Pharmacovigilance Regional Centre, Bologna, Italy
• ²⁰ Abruzzo Region, Pharmacovigilance Regional Centre, Teramo, Italy
• ²¹ IRCCS Ospedale Sacro Cuore Don Calabria—Hospital Pharmacy, Negrar di Valpolicella, Italy
• ²² Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Apulia, Italy
• ²³ University Hospital of Padua, Pharmacy Department, Padua, Italy
• ²⁴ Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Excellence Specialties 'G. D’Alessandro' - University of Palermo, Palermo, Sicily, Italy
• ²⁵ Messina Local Health Unit, Messina, Italy

In 2021, the European Medicines Agency supported the "Covid Vaccine Monitor (CVM)," an active surveillance project spanning 13 European countries, aimed at monitoring the safety of COVID-19 vaccines in general and special populations (i.e., pregnant/breastfeeding women, children/adolescents, immunocompromised, people with a history of allergies or previous SARS-CoV-2 infection). Italy participated to this project as a large multidisciplinary network called "ilmiovaccinoCOVID19 collaborating group" Methods: The study aimed to describe the experience of the Italian network "ilmiovaccinoCOVID19 collaborating group" in the CVM context from June 2021 to February 2023. Comprising about 30 partners, the network aimed to facilitate vaccinees' recruitment. Participants completed baseline and follow-up questionnaires within 48 hours from vaccination over a 6-month period. Analyses focused on those who completed both baseline and the first follow-up questionnaire (Q1), exploring temporal trends, vaccination campaign correlation, and loss to follow-up. Characteristics of recruited vaccinees and vaccinee-reported adverse drug reactions (ADRs) were compared with passive surveillance data in Italy. Results: From June 2021 to November 2022, 22,384,663 first doses and 38,207,452 booster doses of COVID-19 vaccines were administered in Italy. Simultaneously, the study enrolled 1,229 and 2,707 participants for the first and booster doses, respectively. Of these, 829 and 1,879 vaccinees respectively completed both baseline and at least the Q1 and were included in the analyses with a significant proportion of them (57.8%/34.3%) belonging to special cohorts. Most vaccinees included in the analyses were females. Comirnaty® (69%) and Spikevax® (29%) were the most frequently administered vaccines. ADR rates following Comirnaty® and Spikevax® were higher after the second dose, particularly following Spikevax®. Serious ADRs were infrequent. Differences were observed in ADR characteristics between CVM and Italian passive surveillance.Conclusions: This study confirmed the favorable safety profile of COVID-19 vaccines, with findings consistent with pivotal clinical trials of COVID-19 vaccines, although different proportions of serious ADRs as compared to spontaneous reporting were observed. Continuous evaluation through cohort event monitoring studies provides real-time insights crucial for regulatory responses. Strengthening infrastructure and implementing early monitoring strategies are essential to enhance vaccine safety assessment and prepare for future pandemics.