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

Background: Variation in suspected adverse drug reactions (SAR) linked to different batches of COVID-19 vaccines has been reported in several countries, including the Czech Republic, Denmark, Sweden, and the USA. However, SAR data come from spontaneous reporting systems and are subject to under-reporting and other biases. To investigate the potential association between vaccine batches and adverse reactions using an unequivocal endpoint, we examined the temporal relationship between all-cause mortality (ACM) and COVID-19 vaccine type and batch, up to three months after vaccination.Methods: We analyzed nationwide data from the Czech Republic on vaccine type and batch, along with corresponding three-month ACM data. Cluster analysis was used to assess age- and sex-specific ACM differences between individual vaccine batches and across vaccine types. We also investigated the relationship between ACM and SAR rates for the same batches.Results: During a 21-month period (December 2020 to September 2022), vaccine batches clustered according to their three-month age- and sex-adjusted ACM rates for the four products administered (Comirnaty, Spikevax, Vaxzevria, and Jcovden). For Comirnaty, Spikevax, and Vaxzevria, a clear temporal pattern was observed, with earlier batches showing significantly higher ACM rates. A strong correlation was found between batches that clustered by ACM and those previously identified to cluster by SARs, for all vaccine products except Jcovden.Conclusions: Data from the Czech Republic show a clear relationship between administered COVID-19 vaccine batches and 3-month ACM rates for Comirnaty, Spikevax, and Vaxzevria, with earlier batches associated with notably higher ACM. A high correlation between batch-associated ACM and SAR rates for Comirnaty and Spikevax supports the validity of these batch-related safety signals and warrants further investigation using individual-level patient data.