(333) Case Series Analysis of Immune-Mediated Neurological Events in Vaccinees following AZD1222 (ChAdOx1 nCoV-19): Results from a UK Post-authorisation Active Surveillance Study

Background: Due to the rapid development of COVID-19 vaccines to meet the urgent public health need, robust methods of collecting post-authorisation safety data to facilitate the ongoing evaluation of the product’s safety profile were required. Although rare, there have been reports of neurological events following COVID-19 vaccination in both the pre- and post-marketing setting.

Objectives: To examine the safety of AZD1222 (ChAdOx1 nCoV-19) through active surveillance of vaccinee reported adverse events (AEs) including quantification and characterization of AEs of special interest (AESI), which included a focus on immune mediated neurological AEs.

Methods: Vaccinees taking part in the study were contacted at 1, 4 and 14 weeks followed by 6, 9, 12 and 18 months via electronic data capture forms to report any symptoms/conditions following first dose vaccination with AZD1222. Following medical review, AEs were assessed with regard to seriousness and causality. Complete case level data was used to support the classification of an AESI. Incident AE data were presented for each AESI (where ≥ 10 AEs) reported on or after the first dose vaccination up until the end of the observation period for each vaccinee.

Results: From March 2021-April 2023, 17945 vaccinees were eligible and provided consent. The majority were female (n=10845; 60.4%) with median (interquartile range, IQR) age of 50 (43, 62) years; most vaccinees were from white ethnic groups (n=14220; 79.2%). A total of 22529 AEs were reported in 6911 vaccinees, inclusive of 507 serious AEs and 388 AESIs. Thirty-nine vaccinees reported an immune mediated neurological event; most occurred in women (n=31) and the majority were reported within vaccinees aged between 40-49 years, (median age (IQR) 48 years (43, 54). Median time to onset was 4 days (IQR 1, 16) following first dose. Roughly half of the AEs were assessed as serious (n=20). The outcome of ‘Not recovered/not resolved’ was reported in 20 cases. The majority of neurological AEs were considered to have a potential causal relationship to at least one dose of AZD1222 (n=37); of these, 25 vaccinees were reported to have at least one past medical history condition (the most commonly reported were hypersensitivity (n=9), asthma (n=8) and drug hypersensitivity (n=7)). Amongst cases considered to be serious, the following events were each reported in counts of < 5: transverse myelitis, relapsing remitting multiple sclerosis, Bell’s palsy, Guillain-Barré syndrome, Parsonage Turner syndrome, facial paresis, facial paralysis and paresis of the fourth cranial nerve.

Conclusions: The severity of events included in the AESI category of immune mediated neurological AEs in this study varied, which was reflected in the assessment of roughly half of cases (n=20) classified as serious.