Andaur Navarro CL, de Luise C, Cid Royo A, Mildiner Moraga S, Ryan O, Hoxhaj V, Vila Guilera J, Garcia de Albeniz Martinez X, Carsin AE, Weinrib R, Bertran Melines S, Aguado J, Pala E, Pazos I, Haugh M, Poblador-Plou B, Gimeno-Miguel A, Santos-Mejias A, Barbieri E, Stona L, Lysen T, Gaspersz J, Overbeek J, Roy D, Lane S, Fry C, Morris D, Aurelius T, Desalegn A, Lupattelli A, Villalobos Martinez F, Bissacco CA, Far M, Sturkenboom M, Arana A. Interim results from post-authorisation safety study (PASS) for the Pfizer-BioNTech COVID-19 vaccine(Comirnaty) bivalent/omicron BA.1 and BA.4-5 in Europe: a study in the VAC4EU network. Presented at the ISPE 42nd Annual Meeting; September 1, 2026. Milan, Italy.

BACKGROUND: In late 2021, the SARS-CoV-2 subvariant Omicron emerged which required broader protection from the mRNA vaccine. Bivalent vaccines (Comirnaty Original/Omicron BA.1 and BA.4-5) were authorised in the EU and UK in late 2022, necessitating post-authorisation safety monitoring.

OBJECTIVES: To determine the risk of pre-specified adverse events of special interest (AESIs) following bivalent BA.1 or BA.4-5 vaccination compared with unvaccinated individuals with similar vaccination history.

METHODS: We conducted a matched cohort using electronic healthcare records from Pedianet (IT), NHR (NO), and SIDIAP (ES) from September 2022 to June 2024. Bivalent-vaccinated individuals were matched 1:1 to unvaccinated individuals based on vaccination history, age, sex, and other demographic and clinical factors. Thirty-eight AESIs were analysed under a common protocol (EUPAS108847), and a common data model and analytical programs. Propensity score-adjusted hazard ratios (aHRs) with 95% CI were estimated for eventspecific risk windows.

RESULTS: Overall, 855,178 exposed individuals were matched (Pedianet: 31, NHR: 155,033, SIDIAP: 700,114). Median age in years was 13 in Pedianet, 69 in NHR, and 71 in SIDIAP. No AESIs occurred in Pedianet. Event rates for AESIs were low with wide 95% CIs in NHR and SIDIAP. Arrhythmia was the most frequently observed AESI: the aHR was 0.94 (95% CI: 0.86–1.03) in NHR and 1.02 (95% CI: 0.99–1.06) in SIDIAP. Guillain–Barré syndrome was rare but observed in NHR, with an aHR of 4.25 (95% CI: 0.47–38.30) and 1.33 (95% CI: 0.37–4.86) in SIDIAP. Acute respiratory distress syndrome showed an aHR of 2.73 (95% CI: 0.53–14.05) in NHR and 1.56 (95% CI: 0.95–2.57) in SIDIAP. Other AESIs with aHR > 2 included myositis and myocarditis or pericarditis (1– 21 days risk window). All AESIs were based on diagnostic codes and were not validated.

CONCLUSIONS: The interim analysis did not show an increased risk for any AESIs. Short follow-up in NHR (< 4 months) restricted AESIs estimates with longer risk window. Results from the final study report will include additional data from Pedianet, NHR, SIDIAP and three other databases (PHARMO [NL], EpiChron [ES], and CPRD Aurum [UK]), analyses of the pregnancy cohort and other subpopulations, SCRI, sensitivity analyses, pooled estimates, and validated AESIs, thus providing more comprehensive evidence for the safety of bivalent vaccines.