Case Series Analysis of Thromboembolic Events (Arterial and Venous) in Vaccinees Following AZD1222 (ChAdOx1 nCoV-19): Results from a UK Post-authorisation Active Surveillance Study

Background: COVID-19 vaccines underwent rapid development in response to the COVID-19 pandemic and therefore active post-marketing surveillance studies were required to further define the safety profile.

Objectives: To examine the safety of AZD1222 (ChAdOx1 nCoV-19) through active surveillance of vaccinee reported adverse events (AEs) including quantification and characterization of adverse events of special interest (AESI), such as arterial and venous thromboembolic (TE) events.

Methods: Consented vaccinees included 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 experienced following first AZD1222 (ChAdOx1 nCoV-19) vaccination dose. All reported AEs were medically reviewed and classified as an AESI where there was sufficient case level data to support this, including AESI categories of ‘arterial thromboembolism’ [ATE], ‘venous thromboembolism’ [VTE] and [ATE + VTE]. Incident event data were presented for each AESI (where ≥ 10 events) 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 a total of 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. Amongst the thromboembolic events, none were reported to have been associated with thrombocytopenia. Thirty-six vaccinees had an ATE or VTE event (n=17 ATE, n=14 VTE, n=1 ATE+VTE, n=4 type not known). Most were female (n=24), with a median age (IQR) of 57.5 years (51, 67), and a median time to onset (IQR) of 72 days (10, 209) following first dose. Almost all events were classified as serious (n=35) with one fatal outcome; this was reported in a vaccinee as a condition which led to the primary cause of death. Of the 36 vaccinees that reported ATE or VTE, 30 cases were considered to be potentially related to at least one dose of AZD1222 (ChAdOx1 nCoV-19); amongst the 30 cases, the median time to onset was 47 days (IQR 10, 136); nine vaccinees received other medications during the study observation period, including medicines known to affect thrombolysis; platelet aggregation inhibitors excl. heparin, direct factor Xa inhibitors and salicylic acid and derivatives (all counts < 5).

Conclusions: The majority of thromboembolic events identified were serious and considered to be potentially related to at least one dose of AZD1222 (ChAdOx1 nCoV-19).