Covid-19 Vaccine Monitor: Interim Study Report for Cohort Event Monitoring of vaccinated persons

Rationale and background For the marketed COVID-19 vaccines, a pan-European cohort event monitoring system is an important addition to existing spontaneous reporting systems for signal detection. This enables the collection of patient-reported safety data in near real-time and generates incidence rates of vaccine-related adverse reactions. Research question and objectives Primary aim To collect data on patient-reported adverse reactions of different COVID-19 vaccines, estimate the frequency, compare incidence rates across the participating countries in general and special populations (pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy, and people with prior SARS-CoV-2 infection) in near-real-time. Secondary aim To identify and generate incidence rates and potential predictors of the most frequently reported adverse reactions related to different COVID-19 vaccines after first/second dose(s) of the first vaccination cycle as well as booster doses within the general population and special cohorts of vaccinees. Study design Prospective cohort study in general and special populations (pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy and people with prior SARS- CoV-2 infection). Data are prospectively collected, directly from vaccine recipients in 11 countries. The common core data from different countries were pooled, stratified by special cohort and analysed at the European level. The study is set up as a cohort monitoring for a duration of up until 6 months from the first dose vaccination date (except for pregnant women who are followed up until 1.5 month after the pregnancy end). Data were collected using the Lareb Intensive Monitoring (LIM) system (general population first dose), the Research Online (RO) tool (booster and special populations), the Croat OpeN data collection system and the German SafeVac2.0 data collection system. Setting Participants to be included should be vaccinated in one of the participating countries in the period ranging from December 2020 (in Countries already starting prospective monitoring in ECVM) until August 2022. This interim report includes LIM and RO data updated until the 9th of February 2022, and Croat OPeN data until the 15th of February 2022. German SafeVac 2.0 datasets are included in batches, with Moderna data updated until May 2021, AstraZeneca until September 2021, and the new BioNTech/Pfizer data until March 2022. Subjects and study size General and special population vaccinees (pregnant and lactating women, children, adolescents, immunocompromised, people with a history of allergy, and people with prior SARS-CoV-2 infection) who were recruited at multiple vaccination centers within 48 hours from either the first or booster COVID-19 vaccine dose administration. The aim was the inclusion of up to 60,000 vaccine recipients belonging to both general and special cohorts from 12 European countries which would exceed the numbers of vaccinated in clinical trials. Variables Vaccine brand and batch number, adverse drug reactions (ADRs), age, sex, height and weight, geographical area, medical history including information on comorbidities and concomitant diseases, and concomitant medications. Results The populations that adhere to this observational study are described in this report by the number of patients included in the cohort for each participating country, gender distribution, age categories, and vaccine brands. First vaccination cycle data in general population For both general and special populations, dedicated cumulative structured overviews of numbers and incidences of all adverse reactions are provided. Reported adverse events are stratified in solicited, unsolicited, serious adverse events, adverse events of special interest, vaccine brand, country, gender, and age groups when all these informative details can be extrapolated from the data. For the first vaccination cycle, in this report we included 30,108 participants in Belgium, Croatia, France, Italy, the Netherlands, and the United Kingdom, and 520,076 general population participants from Germany. Across the sites 0.2-0.3% % reported at least one serious adverse reaction after receiving the first and/or the second dose. The majority of all reports of an AESI were from females, across all vaccine brands. Special populations first vaccination Among the 7,057 vaccinees in the special populations who reported at least one ADR following the first vaccination dose, 17 (0.2%) reported at least one serious ADR. In 3,793 vaccinees who reported at least one ADR following the second vaccination dose, 9 (0.2%) reported at least one serious ADR. Out of the total number of vaccinees who reported at least one ADR following the first (N= 7,057) and second (N= 3,793) vaccination dose, 25 (0.4%) and 15 (0.4%) vaccinees reported at least one AESI following the first and second vaccination dose, respectively. The most reported solicited local adverse reaction among all the COVID-19 vaccine brands, special cohorts, and between 1st and 2nd dose is injection site pain. This is in line with the general population observations (and with previously published works). Among the solicited systemic adverse reactions, fatigue, headache, malaise, and myalgia, were the most frequently reported events, which is consistent with total populations. Serious adverse reactions and AESI were uncommon among each of the special cohorts, although sample size and power to detect differs. This is also in line with the general populations' pivotal clinical trials and this study's results in general populations. Caution should be taken in interpreting the data as analysis considering participants’ baseline characteristics and the adverse reaction they reported has not yet been conducted. On the basis of the Research Online app that was used in Italy, Romania, Slovakia, Spain and Switzerland, 377 first dose vaccinees with one of the special conditions were included mostly children and persons with prior Sars-Cov-2 infection. The rate of serious reactions could not yet be validly estimated. Pregnant women: 8 cases of spontaneous abortion events were observed among both general and special population data, but only 1 case was recorded as pregnant women at baseline. No other AESI were yet observed. Children/adolescents: Serious ADRs following COVID-19 vaccination are uncommon. No AESI were observed. Immunocompromised, people with history of allergy, people with prior COVID-19: Serious ADRs and AESI after COVID-19 vaccinations are uncommon. Among the observed AESI, COVID-19 infection, hypersensitivity, and arrhythmia, have been the most frequently reported. Booster dose A total of 11.100 subjects who received a booster dose were included in this study, all use the RO application for enrolment. Most of the persons were not part of a special population (8493), 419 pregnant or lactating women were included. BioNTech/Pfizer and Moderna are the most commonly administered COVID-19 vaccines in our observational study. Children/adolescents reported the lowest rate of ADRs among the cohorts involved in this booster vaccination study. Lactating women reported the highest numbers of ADRs. Informative details about the type of the reported ADRs are not yet reported for these booster dose data. Conclusion This interim report summarises the safety evidence of covid-19 vaccines in more than 550,000 persons from both the general and special populations that were included after first dose, and booster doses. We combined data originating from a total of eleven countries and four different data capture systems. Solicited reactions were comparable to those observed in trials. Across the sites 0.2-0.3% % reported at least one serious adverse reaction after receiving the first and/or the second dose, this was similar after the first booster.
The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network (led by Utrecht University) with collaboration from the Vaccine Monitoring Collaboration for Europe network (VAC4EU). The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/23/PE. This report expresses the opinion of the authors 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. The work in this report is based on: EU PAS Register No: WP1: EUPAS42504 WP2: EUPAS39798