Safety of BNT162b2 mRNA COVID-19 vaccine batches: A nationwide cohort study (preprint)

Background: The safety of the BNT162b2 mRNA COVID-19 vaccine has been extensively evaluated since the global rollout began. While serious adverse events are rare, safety issues continue to arise. This study evaluates the claim that earlier small vaccine batches were associated with higher rates of serious adverse events compared to later batches. Methods: A nationwide cohort study was conducted in Denmark, comprising individuals vaccinated with the BNT162b2 vaccine from 52 pre-defined batches classified into three pre-defined groups. Vaccinated individuals were matched 1:1 between batch groups on age, sex, and vaccination priority group. The study outcomes, included 27 serious adverse events, 2 negative control outcomes and all-cause mortality. Cox regression was used to estimate hazard ratios (HRs) comparing rates between batch groups in the 28-days following vaccination. We conducted two comparisons of the early small batches to two groups of larger batches used later in the pandemic. Results: In the study period, 9,983,448 vaccinations were administered from batches in the three pre-defined groups. Slightly increased rates of arrhythmia were observed in both study comparisons, HRs 1.25 (95% CI,1.05-1.50) and 1.15 (1.00-1.31), respectively, but sensitivity analyses did not robustly support these associations. For the remaining outcomes, increased rates in both study comparisons were not observed. Conclusion: This nationwide cohort study provides reassurance regarding the safety of the BNT162b2 vaccine across different batches used in Denmark. The findings support the overall safety of the vaccine, with no clinically relevant variations in serious adverse event rates between batches.

A standardised protocol for assessment of relative SARS-CoV-2 variant severity, with application to severity risk for COVID-19 cases infected with Omicron BA.1 compared to Delta variants in six European countries (preprint)

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased SARS-CoV-2 testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of newly emerged variants. The Joint WHO Regional Office for Europe and ECDC Infection Severity Working Group was formed to produce and pilot a standardised study protocol to estimate relative variant case-severity in settings with individual-level SARS-CoV-2 testing and COVID-19 outcome data during periods when two variants were co-circulating. To assess feasibility, the study protocol and its associated statistical analysis code was applied by local investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the case-severity of Omicron BA.1 relative to Delta cases. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio [aHR]=0.41, 95% CI 0.31-0.54), ICU admission (aHR=0.12, 95% CI 0.05-0.27), and death (aHR=0.31, 95% CI 0.28-0.35) was lower for Omicron BA.1 compared to Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study has demonstrated the feasibility of conducting variant severity analyses in a multinational collaborative framework. The results add further evidence for the reduced severity of the Omicron BA.1 variant.