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

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.

Cohort Event Monitoring of Adverse Reactions to COVID-19 Vaccines in Seven European Countries: Pooled Results on First Dose.

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.

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature.

Background: Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature. Methods: Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of 'any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination. Results: The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females. Discussion: The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature

Background Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature. Methods Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of ‘any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination. Results The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females. Discussion The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.