A Batch-Dependent Safety Signal Related to All-Cause Mortlity Associated with COVID-19 Vaccination

Background: Variation in suspected serious adverse events (SAEs) linked to different batches of COVID-19 vaccines has been reported in several countries, including the Czech Republic, Denmark, Sweden, and the USA. However, SAE data come from spontaneous reporting systems and are subject to under-reporting and other biases. We examined all-cause mortality (ACM) data to explore the temporal relationship between COVID-19 vaccine type and batch, and death, up to three months after vaccination. Methods: We analyzed nationwide data from the Czech Republic on vaccine type and batch, along with the corresponding three-month ACM data. Cluster analysis was used to assess differences in ACM across vaccine types and batches. Cluster-specific mortality rates were adjusted for age and sex and compared, with a focus on the timing of batch administration. We also investigated the relationship between ACM and SAEs for the same batches. Results: During a 21-month period (December 2020 to September 2022), vaccine batches were grouped according to three-month ACM rates for the four products administered (Comirnaty, SPIKEVAX, Vaxzevria, and Jcovden). For Comirnaty, SPIKEVAX, and Vaxzevria, a clear temporal pattern appeared, with earlier batches showing significantly higher ACM rates, even after adjusting for age and sex. A strong correlation was found between batches clustered by mortality and those previously identified to cluster by reported SAEs for all products except Jcovden. Conclusions: Data from the Czech Republic reveal a clear link between the most recently administered COVID-19 vaccine batch and short-term ACM rates. For three of the four vaccines, earlier batches were associated with notably higher ACM. The similar pattern observed between batch-associated mortality and SAE rates supports the existence of batch-related safety signals that warrant further investigation using individual-level patient data.