In a recent study posted to the Preprints with The Lancet* server, researchers determined the association between adverse events of special interest (AESIs) following BNT162b2 vaccination, a coronavirus disease 2019 (COVID-19) vaccine based on the messenger ribonucleic acid (mRNA) technology.
New Zealand used a passive reporting system developed by Medsafe, their Medicines and Medical Devices Safety Authority, to monitor the safety of the BNT162b2 COVID-19 vaccine in which healthcare professionals and the public voluntarily participated. Though it detected signals adequately, underreporting or reporting biases must have hindered the efficacy of this system. So, later, the government adopted an active system that used electronic health records (EHRs) to assess the risk of AESIs after BNT162b2 vaccination.
Since approximately 95% of the eligible New Zealand population have received at least one dose of BNT162b2, the real-world setting for evaluating its safety profile was unique and ideal, representing a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) naïve population.
Additionally, New Zealand's demographics are unique because it mainly has three minority ethnic groups, Māori (indigenous New Zealanders), Pacific islanders, and Asians. It makes it crucial to assess the safety profile of BNT162b2 in a New Zealand-specific context, which clinical trials could not have deciphered.
The mass COVID-19 vaccine rollout using the BNT162b2 vaccine began in New Zealand in February 2021. Though clinical trials have shown a good efficacy and safety profile for BNT162b2, they yielded limited results. They often failed to detect rare adverse events following immunization (AEFI) due to their small sample size, inadequate patient selection criteria, and shorter follow-up or study duration. Also, vaccine responses concerning a particular AEFI could differ among population subsets depending on their age, gender, and representation of minority groups.
About the study
In the current retrospective cohort study, researchers compared the incidence rates of each prespecified AESI within zero to 21 days following BNT162b2 vaccination to the expected rate based on historical incidence rates between 2014 and 2019. The study monitoring period began on 19 February 2021 with the vaccine rollout and ended on 10 February 2022.
The study population comprised New Zealanders aged five or above who received a primary dose of the adult and pediatric BNT162b2 formulation. This study estimated the incidence per 100,000 persons, per year, of 12 predefined AESI associated with COVID-19 vaccines, stratified by year, age group, gender, ethnicity, et cetera.
The risk of myocarditis and pericarditis was low in those under 19 years old, with more than five and two events per 100,000 persons after the second and first vaccine dose(s), respectively. Since studies have shown that the risk of myocarditis following COVID-19 is much greater than after vaccination with an mRNA vaccine, its benefits continue to offset the risk of the disease.
Further, the researchers noted a statistically marked increase in the incidence of acute kidney injury (AKI) following first and second doses of BNT1262b in all age bands except five to 19-year-olds. Most patients who reported AKI were >65 years, and over 50% of them had pre-existing diseases that could have contributed to AKI (e.g., diabetes). Thus, more research alone could justify the observed association, if there is any.
Among the second dose recipients, the researchers noted 1.3 and 1.2 events of thrombocytopenia and venous thromboembolism (VTE). Though the observed events were more than expected, the rate upsurges were small, and the confidence intervals (CIs) were near one, suggesting a minimal difference between the two events. While VTE increased slightly following the first BNT1262b dose in the 40–59-year-olds, there was no substantial increase in thrombocytopenia events in any subgroup. Other studies have reported cases of these AESIs after BNT162b2 vaccination; however, large-scale real-world studies have not confirmed a higher possibility of thrombocytopenia or VTE after BNT162b2 vaccination.
The researchers also observed more risk of single-organ cutaneous vasculitis after the first dose of BNT162b2 in the 20–39-year-olds. However, the observed and expected events remained under six, leading to wider CIs. Due to a lack of scientific data, there is a need for more research to establish an association between single-organ cutaneous vasculitis and the BNT162b2 vaccine. Finally, the researchers found no significant associations between the BNT162b2 vaccine and any other outcome of interest or AESIs.
This nationwide cohort study covered over four million vaccinated New Zealanders representing all ethnic groups. The results of this post-marketing vaccine safety study provided reassurance on the overall safety profile of the BNT162b2 vaccine. Except for the increased risk of myo/pericarditis following BNT162b2 vaccination, there was no association between BNT162b2 vaccination and most other AESIs. For myo-/pericarditis, the association was highest in the under 39 years old recipients. In general, the risk was highest following the second dose and in the youngest age groups. To conclude, the study results confirmed the safety profile of BNT1262b from a New Zealand-specific context.
Preprints with The Lancet publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Walton, Muireann, and Pletzer, Vadim and Teunissen, Thomas and Lumley, Thomas and Hanlon, Timothy. (2023). Adverse Events Following the BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNtech) in Aotearoa New Zealand. SSRN. https://ssrn.com/abstract=4329970