(349) Observed versus Expected Analysis of Adverse Events of Special Interest after AZD1222 (ChAdOx1 nCoV-19) Vaccination: Results from a UK Post-authorisation Active Surveillance Study

Background: In cases of urgent public health need, such as the COVID-19 pandemic, the timeframe for developing a vaccine was dramatically shortened. Phase II and III clinical trials were fast-tracked, and the vaccines authorised for emergency use. Post-marketing surveillance studies were required to monitor the safety and effectiveness in a real-world setting.

Objectives: To monitor the safety and utilisation of AZD1222 (ChAdOx1 nCoV-19) administered to vaccinees under real-world use in the UK which included a comparison of observed versus expected (O:E) rates of adverse events of special interest (AESI).

Methods: Vaccinees were recruited via vaccination sites and social media/advertisements within the UK, supported by the National Institute for Health Research Clinical Research Networks. Vaccinees were contacted to report any symptoms/conditions experienced following vaccination at weeks 1, 4, and 14 and then months 6, 9, 12, and 18 post first AZD1222 (ChAdOx1 nCoV-19) dose, via electronic data capture forms. O:E analyses with 95% Poisson exact confidence intervals (CI) was conducted for selected AESI. Background incidence rates for the 2019 calendar year were obtained from Clinical Practice Research Datalink (CPRD) GOLD through the ACCESS (vACCine covid-19 monitoring readinESS) project and were used (alongside person time contributions to the study) to calculate the estimated counts.

Results: Between 1st March 2021 and 6th April 2023, a total of 17945 vaccinees were eligible and provided consent. The majority of vaccinees were female (n=10845; 60.4%) and the median age (interquartile range) was 50 (43, 62) years. Most vaccinees were from White ethnic groups (n=14220; 79.2%). An increased O:E ratio was observed for anaphylaxis (O:E 7.38 [95% CI; 2.80-11.95]; based on 10 observed cases [expected cases: 1.36]) and anosmia (loss of smell) and/or ageusia (loss of taste) (O:E 39.23 [95% CI; 29.13-49.32]; based on 58 observed cases [expected cases: 1.48]). A decreased O:E ratio was observed for arrhythmia (O:E 0.35 [95% CI; 0.15-0.55]; based on 12 observed cases [expected cases: 34.25]), coronary artery disease (O:E 0.52 [95% CI; 0.10-0.93]; based on 6 observed cases [expected cases: 11.62]), and death (O:E 0.13 [95% CI; 0.04-0.22]; based on 8 observed cases [expected cases: 61.74]).

Conclusions: An increased O:E ratio (compared to pre-COVID-19 pandemic rates) was seen for the adverse events of anosmia and/or ageusia and anaphylaxis. Anosmia and/or ageusia were likely a proxy for COVID-19 infection. Hypersensitivity reactions including anaphylaxis are listed in the SmPC for AZD1222 (ChAdOx1 nCoV-19). There were no emerging safety issues identified in this study.