<span class="word">A <span class="word"><span class="changedDisabled">Batch-<span class="word"><span class="changedDisabled">Dependent <span class="word"><span class="changedDisabled">Safety <span class="word"><span class="changedDisabled">Signal <span class="word"><span class="changedDisabled">Related <span class="word">to <span class="word"><span class="changedDisabled">All-<span class="word"><span class="changedDisabled">Cause <span class="word"><span class="changedDisabled">Mortlity <span class="word"><span class="changedDisabled">Associated <span class="word">with <span class="word allCaps">COVID-<span class="word">19 <span class="word"><span class="changedDisabled">Vaccination

Background: Variation in suspected adverse drug reactions (SARs) 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 from spontaneous reporting systems 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 analysed nationwide data from the Czech Republic on vaccine type and batch, together with corresponding three-month ACM data. Cluster analysis was used to assess age- and sex-specific differences in ACM within and across vaccine batches and 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 as clustering by SARs, across all vaccine products except Jcovden.Conclusions: Data from the Czech Republic show a clear association between administered COVID-19 vaccine batches and 3-month ACM rates for Comirnaty, Spikevax, and Vaxzevria, with earlier batches linked to notably higher ACM. A strong 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.