Abstract
Introduction: COVID-19 vaccines were rapidly authorised, thus requiring intense post-marketing re-evaluation of their benefit-risk profile. A multi-national European collaboration was established with the aim to prospectively monitor safety of the COVID-19 vaccines through web-based survey of vaccinees. Methods: A prospective cohort event monitoring study was conducted with primary consented data collection in seven European countries. Through the web applications, participants received and completed baseline and up to six follow-up questionnaires on self-reported adverse reactions for at least 6 months following the first dose of COVID-19 vaccine (Netherlands, France, Belgium, UK, Italy) and baseline and up to ten follow-up questionnaires for one year in Germany and Croatia. Rates of adverse reactions have been described by type (solicited, non-solicited; serious/non-serious; and adverse events of special interest) and stratified by vaccine brand. We calculated the frequency of adverse reaction after dose 1 and prior to dose 2 among all vaccinees who completed at least one follow-up questionnaire. Results: Overall, 117,791 participants were included and completed the first questionnaire in addition to the baseline: 88,196 (74.9%) from Germany, 27,588 (23.4%) from Netherlands, 984 (0.8%) from France, 570 (0.5%) from Italy, 326 (0.3%) from Croatia, 89 (0.1%) from the UK and 38 (0.03%) from Belgium. There were 89,377 (75.9%) respondents who had received AstraZeneca vaccines, 14,658 (12.4%) BioNTech/Pfizer, 11,266 (9.6%) Moderna and 2490 (2.1%) Janssen vaccines as a first dose. Median age category was 40–49 years for all vaccines except for Pfizer where median age was 70–79 years. Most vaccinees were female with a female-to-male ratio of 1.34, 1.96 and 2.50 for AstraZeneca, Moderna and Janssen, respectively. BioNtech/Pfizer had slightly more men with a ratio of 0.82. Fatigue and headache were the most commonly reported solicited systemic adverse reactions and injection-site pain was the most common solicited local reaction. The rates of adverse events of special interest (AESIs) were 0.1–0.2% across all vaccine brands. Conclusion: This large-scale prospective study of COVID-19 vaccine recipients showed, for all the studied vaccines, a high frequency of systemic reactions, related to the immunogenic response, and local reactions at the injection site, while serious reactions or AESIs were uncommon, consistent with those reported on product labels. This study demonstrated the feasibility of setting up and conducting cohort event monitoring across multiple European countries to collect safety data on novel vaccines that are rolled out at scale in populations which may not have been included in pivotal trials.
| Original language | English |
|---|---|
| Pages (from-to) | 391-404 |
| Number of pages | 14 |
| Journal | Drug Safety |
| Volume | 46 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Funding
The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network, which is a public academic partnership coordinated by the Utrecht University, The Netherlands. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE. This document expresses the opinions of the authors of the paper, and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties. In Croatia, the study was funded partially by the Agency for Medicinal Products and Medical Devices of Croatia (HALMED). In Germany, the SafeVac 2.0 study was funded by the German ministry of Health and conducted by Paul-Ehrlich-Institut the national competed authority for vaccines and biomedicinal products in Germany. The French part of the study, named EVANESCO, was partially funded by the European Medicines Agency. In France, EVANESCO was identified as a National research priority (priorité nationale de recherche) by the CAPNET, and received a complementary funding from the Ministère de la Santé et des Solidarités and the Ministère de l’Enseignement supérieur, de la Recherche et de l’Innovation. The Dutch part of the study was funded by a grant from the Dutch Ministry of Health, Welfare and Sport. The Dutch Ministry of Health, Welfare and Sport had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. In the United Kingdom the project was funded by the European Medicines Agency through the cohort event monitoring project. The authors acknowledge: Leontine van Balveren, Loes Ruijs and Jasper Schmitz for their contribution to the Early COVID-19 Vaccine Monitor (ECVM) study conducted in the Netherlands; Stéphanie Lamarque, Estelle Guiard, Emmanuelle Bignon, Pauline Bosco-Levy, Patrick Blin et Cécile Droz-Perroteau for their contribution to the French part of the ECVM study, EVANESCO; Ugo Moretti, Chiara Bellitto, Francesco Ciccimarra, Laura Augusta Gonella, Giuliana Petrelli, Cristiano Chiamulera and Elena Arzenton (University of Verona, Department of Diagnostics and Public Health – Section of Pharmacology, Verona, Italy); Riccardo Lora, David Bellantuono and Alberto Sabaini (MedBrains); Alberto Firenze, Donatella Zodda, Fabrizia Guidotti, Maria Zappone and Bernardo Alagna (Struttura Commissariale per l’Emergenza COVID della città metropolitana di Messina/Messina Local Health Unit, Messina, Italy); Paola Maria Cutroneo and Claudia Minore (Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina, Messina, Italy); Claudio Costantino and Francesco Vitale (University of Palermo, Palermo, Italy – Department of Health Promotion, Mother and Child Care, Internal Medicine and MedicalSpecialties "G. D'Alessandro", Hygiene section); Ilaria Morreale – Sicilian Regional Center of Pharmacovigilance, Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Internal Medicine, Pharmacovigilance and Clinical Pharmacology Unit; Laura Marsala, Desirè Farinella and Silvana Bavetta (Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione (ARNAS) “Civico”, Palermo, Italy); Maria Pia Fantini, Chiara Reno, Emanuel Raschi and Elisabetta Poluzzi (Alma Mater Studiorum-University of Bologna, Italy – Department of Medical and Surgical Sciences); Ester Sapigni, Annamaria Potenza, Debora Podetti, Victoria Nikitina, Rita Ricciardelli, Nazanin Mogheiseh, Silvia Croce and Barbara Paltrinieri (Emilia-Romagna Pharmacovigilance Regional Centre, Bologna – Italy); Sofia Castellani, Elisa Sangiorgi, Margherita Selleri, Simona Lucchesi and Giuseppe Catucci (Ferrara Local Health Unit, Ferrara, Italy); Denis Savini, Chiara Sacripanti, Marco Faccioli, Maria Silvia Romio and Laura Rossi (Bologna Local Health Unit, Bologna, Italy); Simonetta Radici – Piacenza Local Health Unit, Piacenza, Italy; Giovanna Negri - Parma Local Health Unit, Parma, Italy; Lidia Fares – Reggio Emilia Local Health Unit, Reggio Emilia, Italy; Chiara Ajolfi – Modena Local Health Unit, Modena, Italy; Antonella Fadda, Antonella Chiarello – Imola Local Health Unit, Imola, Italy; Fabio Pieraccini, Barbara Gavioli, Simonetta Palazzi – Romagna Local Health Unit, Romagna, Italy; Marco Tuccori – Tuscany Region, Italy – Unit of Adverse Drug Reactions Monitoring, University Hospital of Pisa, Unit of Adverse Drug Reactions Monitoring, Pisa, Italy; Alfredo Vannacci, Roberto Bonaiuti, Claudia Ravaldi, Niccolò Lombardi, Giada Crescioli – PeaRL – Perinatal Research Laboratory, NEUROFARBA Department, University of Florence and CiaoLapo Foundation for Perinatal Health; Florence, Italy; Francesco Gori – Firenze Local Health Unit, Florence, Italy; Roberto Tessari (IRCCS Ospedale Sacro Cuore Don Calabria – Hospital Pharmacy, Negrar di Valpolicella, Italy); Emanuela Zandonà (University Hospital of Verona, Italy – Medical Coordination Unit); Maria Angiola Crivellaro – University Hospital of Padua, Padova, Italy – Occupational Health Unit and Allergology Unit, Department of Cardiac Thoracic Vascular and Public Health Sciences University of Padova; Mauro Cancian – University Hospital of Padua, Departmental Allergy Unit, Padua, Italy; Francesca Venturini – University Hospital of Padua, Pharmacy Department, Padua, Italy; Marina Ferri and Luca Leonardi (Trento Local Health Unit, Trento, Italy); Paolo Baldo, Sabrina Orzetti and Elisabetta Caccin (Centro di Riferimento Oncologico (CRO) di Aviano, IRCCS – Pharmacy Unit, National Cancer Institute, Aviano, Italy); Annalisa Capuano and Concetta Rafaniello (Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Naples, Italy); Claudia Pagliaro, Mariangela Mercaldo, Annalisa Di Giorgio, Sonia Manna, Giuseppina Farina, Cristina Di Mauro and Michele Tari (Caserta Local Health Unit, Caserta, Italy); Ilenia De Carlo (Abruzzo Region, Pharmacovigilance Regional Centre, Italy); Ilenia De Carlo, Ilenia Senesi – Abruzzo Region, Pharmacovigilance Regional Centre, Italy; Claudia Pileggi, Caterina Palleria, Luca Gallelli, Caterina De Sarro, Chiara Verduci, Rosa Papadopoli and Giovambattista De Sarro (Department of Health Sciences, University of Catanzaro "Magna Græcia"/Regional Centre for Pharmacovigilance of Calabria, Catanzaro, Italy); Mariagrazia Morgese, Stefania Schiavone, Paolo Tucci, Maria Bove and Luigia Trabace (University of Foggia, Foggia, Italy); Francesco Lapi and Claudio Cricelli - Italian Society of General Practitioners; Giorgio Racagni (Italian Society of Pharmacology); Silvia Tonolo (Association of Patients with Rheumatic diseases); Giusi Fava, Sandro Giuffrida and Vincenza Amato (Reggio Calabria Local Health Unit, Reggio Calabria, Italy); Marco Gambera and Valentina Montresor (Ospedale Pederzoli – Hospital Pharmacy, Peschiera del Garda, Italy); Dario Mastropasqua – Croce Verde Verona, Verona, Italy. For their contribution to the Italian part of the ECVM study, as the “ilmiovaccinoCOVID19 collaborating group”. Sandra Dujmović Blažok, Morana Pavičić, Željana Margan Koletić, Ivana Ljubičić, Lara Miletić, Eva Šintić and Mario Zubec (Agency for Medicinal Products and Medical Devices of Croatia) for their contribution to the Croatian part of the ECVM study. Kenny Kestens, Dieter Cenens, Katrien Bernaert, Jamila Hamdani and Thierry Roisin for their contribution to the Belgian part of the ECVM study.
| Funders | Funder number |
|---|---|
| Annalisa Capuano and Concetta Rafaniello | |
| Azienda Ospedaliera Universitaria Policlinico P. Giaccone | |
| Barbara Gavioli | |
| CAPNET | |
| Chiara Sacripanti | |
| CiaoLapo Foundation for Perinatal Health | |
| Denis Savini | |
| Department of Cardiac Thoracic Vascular | |
| Dep Biomolecular Health Sciences | |
| Department of Medical and Surgical Sciences | |
| Departmental Allergy Unit | |
| Emilia-Romagna Pharmacovigilance Regional Centre | |
| Fabio Pieraccini | |
| Ilaria Morreale – Sicilian Regional Center of Pharmacovigilance | |
| Ilenia De Carlo | |
| Ilenia Senesi – Abruzzo Region | |
| Italian Society of General Practitioners | |
| Marco Gambera and Valentina Montresor | |
| Marco Tuccori – Tuscany Region | |
| Maria Pia Fantini | |
| Mauro Cancian – University Hospital of Padua | |
| NEUROFARBA Department | |
| Perinatal Research Laboratory | |
| Tuscan Regional Centre of Pharmacovigilance | |
| Public Health Sciences University of Padova | |
| Simonetta Palazzi | |
| Simonetta Radici | |
| University of Catanzaro | |
| National Cancer Institute Thailand | |
| Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation | |
| Università degli Studi di Foggia | |
| Ministerie van Volksgezondheid, Welzijn en Sport | |
| Università degli Studi di Firenze | |
| Regione Abruzzo | |
| European Medicines Agency | EMA/2018/28/PE |
| Ministère des Solidarités et de la Santé |
