Thrombotic adverse events reported for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines: comparison of occurrence and clinical outcomes in the EudraVigilance database (preprint)

ABSTRACT

Summary Background Vaccination against COVID-19 is the cornerstone to control and mitigate the ongoing pandemic. Thrombotic adverse events linked to Moderna, Pfizer and the Oxford-AstraZeneca vaccine have been documented and described as extremely rare. While the Oxford-AstraZeneca vaccine has received much of the attention, the other vaccines should not go unchallenged. This study aimed to determine the frequency of reported thrombotic adverse events and clinical outcomes for these three COVID-19 vaccines, namely, Moderna, Pfizer and Oxford-AstraZeneca Methods A retrospective descriptive analysis was conducted of spontaneous reports for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines submitted to the EudraVigilance database in the period from 17 February to 14 June 2021. Findings There were 729,496 adverse events for the three vaccines, of which 3,420 were thrombotic, mainly Oxford-AstraZeneca (n=1,988, 58·1%) followed by Pfizer (n=1,096, 32·0%) and Moderna (n=336, 9·8%). As serious adverse events, there were 705 reports of pulmonary embolism for the three vaccines, of which 130 reports (18·4%) were for Moderna, 226 reports (32·1%) for Pfizer and 349 (49·5%) for Oxford-AstraZeneca vaccines. The occurrence of pulmonary embolism is significantly associated with a fatal outcome (P=<0·001). Sixty-three fatalities were recorded (63/3420, 1.8%), of which Moderna (n=6), Pfizer (n=25) and Oxford-AstraZeneca (n=32). Interpretation Thrombotic adverse events reported for the three vaccines remains extremely rare with multiple causative factors reported elsewhere as precipitating these events. Practicing vigilance and proper clinical management for the affected vaccines, as well as continuing to report adverse events, are essential. Funding No funding was sought for this study. Research in context Evidence before this study During the first quarter of 2021, several European countries suspended the use of the Oxford–AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person. This was followed by several reports of fatalities related to pulmonary embolism and other thrombotic events including thrombocytopenia which has been referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). The European Medicines Agency on 18 March 2021 concluded that the Oxford– AstraZeneca vaccine was safe, effective and the benefits outweighed the risks. Added value of this study This study investigated the occurrence of thrombotic adverse events and their clinical outcomes of the three approved and most used COVID-19 vaccines namely Moderna, Pfizer and Oxford-AstraZeneca, using one of the largest spontaneous adverse events databases, namely EudraVigilance. Out of 729,496 adverse events reported for the three vaccines in the study period, only 3420 (0.47%) potential thrombotic adverse events were reported, the majority associated with Oxford-AstraZeneca (n=1,988, 58.1%). Implications of all the available evidence More than 4·89 billion doses of different COVID-19 vaccines have been administered across the globe. Despite thrombotic adverse events reported for the three vaccines in focus for this study - Moderna, Pfizer and Oxford-AstraZeneca - being extremely rare, so continuing to report adverse events is essential. On the basis of scientific evidence showing that benefit outweighs risk, people continue to be urged to accept the vaccination when offered.