Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials

Ahmadizar, F.; Luxi, N.; Raethke, M.; Schmikli, S.; Riefolo, F.; Saraswati, P. W.; Bucsa, C.; Osman, A.; Liddiard, M.; Maques, F. B.; Petrelli, G.; Sonderlichova, S.; Thurin, N. H.; Villalobos, F.; Trifiro, G.; Sturkenboom, M.; Moretti, U.; Bellitto, C.; Ciccimarra, F.; Gonella, L. A.; Arzenton, E.; Chiamulera, C.; Lora, R.; Bellantuono, D.; Sabaini, A.; Firenze, A.; Zodda, D.; Guidotti, F.; Zappone, M.; Alagna, B.; Cutroneo, P. M.; Minore, C.; Costantino, C.; Vitale, F.; D'Alessandro, G.; Morreale, I.; Marsala, L.; Farinella, D.; Bavetta, S.; Fantini, M. P.; Reno, C.; Raschi, E.; Poluzzi, E.; Sapigni, E.; Potenza, A. M.; Podetti, D.; Nikitina, V.; Ricciardelli, R.; Mogheiseh, N.; Croce, S.; Paltrinieri, B.; Castellani, S.; Sangiorgi, E.; Selleri, M.; Lucchesi, S.; Catucci, G.; Savini, D.; Sacripanti, C.; Faccioli, M.; Romio, M. S.; Rossi, L.; Radici, S.; Negri, G.; Fares, L.; Ajolfi, C.; Fadda, A.; Chiarello, A.; Pieraccini, F.; Gavioli, B.; Palazzi, S.; Tuccori, M.; Vannacci, A.; Bonaiuti, R.; Ravaldi, C.; Lombardi, N.; Crescioli, G.; Gori, F.; Tessari, R.; Zandona, E.; Zanoni, G.; Senna, G.; Crivellaro, M. A.; Cancian, M.; Venturini, F.; Ferri, M.; Leonardi, L.; Orzetti, S.; Caccin, E.; Baldo, P.; Capuano, A.; Rafaniello, C.; Ferrajolo, C.; Pagliaro, C.; Mercaldo, M.; di Giorgio, A.; Tari, M.; Manna, S.; Farina, G.; Di Mauro, C.; De Carlo, I.; Senesi, I.; Pileggi, C.; Palleria, C.; Gallelli, L.; De Sarro, G.; de Sarro, C.; Verduci, C.; Papadopoli, R.; Trabace, L.; Morgese, M.; Schiavone, S.; Tucci, P.; Bove, M.; Lapi, F.; Cricelli, C.; Racagni, G.; Tonolo, S.; Fava, G.; Giuffrida, S.; Amato, V.; Gambera, M.; Montresor, V.; Mastropasqua, D.

doi:10.1007/s40264-023-01304-5

Background and Objectives: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. Methods: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. Results: The CVM study enrolled 658 first-dose vaccinees (children aged 5–11 years; n = 250 and adolescents aged 12–17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. Conclusions: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data.

Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials / Ahmadizar F.; Luxi N.; Raethke M.; Schmikli S.; Riefolo F.; Saraswati P.W.; Bucsa C.; Osman A.; Liddiard M.; Maques F.B.; Petrelli G.; Sonderlichova S.; Thurin N.H.; Villalobos F.; Trifiro G.; Sturkenboom M.; Moretti U.; Bellitto C.; Ciccimarra F.; Gonella L.A.; Arzenton E.; Chiamulera C.; Lora R.; Bellantuono D.; Sabaini A.; Firenze A.; Zodda D.; Guidotti F.; Zappone M.; Alagna B.; Cutroneo P.M.; Minore C.; Costantino C.; Vitale F.; D'Alessandro G.; Morreale I.; Marsala L.; Farinella D.; Bavetta S.; Fantini M.P.; Reno C.; Raschi E.; Poluzzi E.; Sapigni E.; Potenza A.M.; Podetti D.; Nikitina V.; Ricciardelli R.; Mogheiseh N.; Croce S.; Paltrinieri B.; Castellani S.; Sangiorgi E.; Selleri M.; Lucchesi S.; Catucci G.; Savini D.; Sacripanti C.; Faccioli M.; Romio M.S.; Rossi L.; Radici S.; Negri G.; Fares L.; Ajolfi C.; Fadda A.; Chiarello A.; Pieraccini F.; Gavioli B.; Palazzi S.; Tuccori M.; Vannacci A.; Bonaiuti R.; Ravaldi C.; Lombardi N.; Crescioli G.; Gori F.; Tessari R.; Zandona E.; Zanoni G.; Senna G.; Crivellaro M.A.; Cancian M.; Venturini F.; Ferri M.; Leonardi L.; Orzetti S.; Caccin E.; Baldo P.; Capuano A.; Rafaniello C.; Ferrajolo C.; Pagliaro C.; Mercaldo M.; di Giorgio A.; Tari M.; Manna S.; Farina G.; Di Mauro C.; De Carlo I.; Senesi I.; Pileggi C.; Palleria C.; Gallelli L.; De Sarro G.; de Sarro C.; Verduci C.; Papadopoli R.; Trabace L.; Morgese M.; Schiavone S.; Tucci P.; Bove M.; Lapi F.; Cricelli C.; Racagni G.; Tonolo S.; Fava G.; Giuffrida S.; Amato V.; Gambera M.; Montresor V.; Mastropasqua D.. - In: DRUG SAFETY. - ISSN 0114-5916. - ELETTRONICO. - 46:6(2023), pp. 575-585. [10.1007/s40264-023-01304-5]