(AP) Cohort Monitoring of 29 Adverse Events of Special Interest Prior to and After COVID-19 Vaccination in Four Large European Data Sources

Publication Number: 1040

Background: The global spread of COVID-19 triggered the development of vaccines.

Objectives: To monitor use of COVID-19 vaccines and incidence rates (IR) of pre-specified adverse events of special interest (AESI) of COVID-19 vaccines prior to and after vaccination

Methods: A retrospective cohort study was designed, including subjects from January 1, 2020 to October 31st, 2021. Data were obtained from administrative and surveillance data banks in an Italian region (ARS) and from primary care medical records (PCMR) in the UK (CPRD Aurum), and in the Netherlands (PHARMO Institute - PHARMO). In Spain, PMCR could be linked to Covid registry and, in some regions, to hospital administrative records (BIFAP). All sites used the ConcePTION common data model and the same data analysis scripts. Follow-up started at January 1, 2020 and ended at death, occurrence of the specific AESI, leaving the data source, or last extraction date, whichever was earliest.
IR of 29 AESI were calculated in 2020 (BGR) and within 28 days post-vaccination of both dose 1 and 2. Age-standardized rate differences (ASRD) were calculated, and Poisson regression was used to compare IR post-vaccination with BGR, while adjusting for factors age, any risk factor for severe COVID-19 disease, history of SARS-CoV-2 infection, gender. Incidence rate ratios (IRR) were pooled using both fixed and random effects and were considered relevantly elevated if >2.0 and the lower level of the 95%CI was above 1.0.

Results: This study included 25,720,158 individuals from four European countries, 12,117,458 received at least a dose of vaccine: 54% with Comirnaty (PFI), 38% Vaxzevria (AZ), 6% Spikevax (MOD), and 2% Janssen Covid-19 vaccine (J&J). BGR of AESI were very rare < 10/100,000 PY, except thrombotic and cardiac events. Following vaccination, 24 statistically significant ASRD and 10 elevated pooled IRR were observed. These comprised anaphylaxis after AZ vaccine, thrombotic thrombocytopenia syndrome (TTS) after both AZ and J&J vaccine, erythema multiforme after MOD, Guillain Barré after J&J, single organ cutaneous vasculitis (SOCV) after J&J, thrombocytopenia (TP) after J&J and MOD and venous thromboembolism after MOD and PFI. The pooled partially adjusted IRR was more than two-fold increased for TTS, SOCV and TP.

Conclusions: Several associations were observed, most of which have been topic of regulatory discussions. Our results confirm that adjustment for vaccine roll out determinants is needed to avoid spurious signals. Causal inference studies are required to establish causality.