Spontaneously reported adverse events following COVID-19 basic and booster immunizations in the Netherlands

Abstract

Introduction: The rapid roll-out of novel COVID-19 vaccines made near real-time post-marketing safety surveillance essential to identify rare and long-term adverse events following immunization (AEFIs). In light of the ongoing booster vaccination campaigns, it is key to monitor changes in observed safety patterns post-vaccination. The effect of sequential COVID-19 vaccinations, as well as heterologous vaccination sequences, on the observed post-vaccination safety pattern, remains largely unknown.

Methods: The primary objective of this study was to describe the profile of spontaneously reported AEFIs following COVID-19 vaccination in the Netherlands, including the primary and booster series. Reports from consumers and healthcare professionals were collected via a COVID-19 vaccine-tailored online reporting form by the National Pharmacovigilance Centre Lareb (Lareb) between 6 January 2021 and 31 August 2022. The data were used to describe the most frequently reported AEFIs per vaccination moment, the consumer experienced burden per AEFI, and differences in AEFIs reported for homologous and heterologous vaccination sequences.

Results: Lareb received 227,884 spontaneous reports over a period of twenty months. Overall, a high degree of similarity in local and systemic AEFIs per vaccination moment was observed, with no apparent change in the number of reports of serious adverse events after multiple COVID-19 vaccinations. No differences in the pattern of reported AEFIs per vaccination sequence was observed.

Conclusion: Spontaneous reported AEFIs demonstrated a similar reporting pattern for homologous and heterologous primary and booster series of COVID-19 vaccination in the Netherlands.

Keywords: Adverse events following immunization; Booster vaccine; COVID-19 basic series; COVID-19 vaccine; Post-marketing monitoring; Spontaneous reporting.

Fig. 1

Vaccination strategy in the Netherlands from January 2021 to September 2022. The vaccination campaign commenced on 6 January 2021 with two immunizations with Pfizer-BioNTech, Moderna, AstraZeneca, Nuvaxovid (from December 2021) or one immunization with Janssen (or Pfizer-BioNTech, Moderna, or AstraZeneca in case of COVID-19 in the medical history). For immunocompromised patients, a third vaccination was available following the initial series. The booster vaccination campaign commenced in November 2021, followed by a second booster available as of February 2022. In the Netherlands, these were both performed with same dose Pfizer-BioNTech or half-dose Moderna.

Fig. 2

Cumulative number of spontaneous ICSRs and total number of vaccinations administered over time. Each bar represents the cumulative number of ICSRs received by Lareb over time (left y-axis), each colour represents the cumulative number of ICSRs per vaccine moment. The black line represents the cumulative number of vaccines administered to the Dutch population (right y-axis). ICSR: individual case safety report.

Fig. 3

Time interval between successive vaccinations. From top to bottom, the percentage of ICSRs per number of days between consecutive vaccinations is shown. ICSRs in which the date of vaccination was unknown were excluded. For an ICSRs where multiple vaccinations had the same date of administration, only one vaccination was used. The maximum time-interval between vaccination allowed was 602 days, all ICSRs with greater time intervals were excluded. When the time interval was zero, the vaccination was excluded. ICSR: individual case safety report.

Fig. 4

Twenty most reported solicited and unsolicited AEFIs per vaccination moment. The most common solicited (A) and unsolicited (B) AEFIs are shown. Solicited adverse events were injection site reactions, fever, chills, headache, nausea, myalgia, arthralgia, malaise, fatigue, and as of 8 March 2022 also heavy menstrual bleeding, polymenorrhea, menstruation delayed, amenorrhea, intermenstrual bleeding, vaginal haemorrhage, postmenopausal haemorrhage, and lymphadenopathy. Unsolicited adverse events were all other reported events. Data is shown as the percentage of the total AEFIs reported for a specific vaccination moment (including all solicited and unsolicited AEFIs). AEFI: adverse event following immunization.

Fig. 5

Percentage of reported ICSRs per burden level. Reporters were asked to score the burden of each AEFI on their daily life. If a person reported more than one (solicited/unsolicited) AEFI per ICSR, the highest score was used. AEFI: Adverse event following immunization. ICSR: individual case safety report.