Studies Detail Thrombosis Risks Associated with Different COVID-19 Vaccines

Gregory Weiss, MD

Vaccines for COVID-19 have become a routine part of life all over the world since the end of the first year of the global pandemic. The rapid production and authorization of several vaccines with activity against COVID-19 lead to widespread vaccination across the globe and are largely responsible for dramatic reductions in hospitalization and death as a result of the novel coronavirus.

Even before the rollout of the first batches of mRNA vaccines and then the more conventional vaccine types, reactions from the general public ranged from enthusiastic hope to frank skepticism and fear.

Despite significant trepidation about the speed with which the COVID-19 vaccines were produced, the first 2 were approved and distributed for use in December of 2020. While phase 3 clinical trials did not reveal any significant adverse events, anecdotal reports began to emerge from European centers that patients were suffering more thromboembolic events following COVID-19 vaccination.¹ Jacob Dag Berild, MD, and fellow researchers in Norway, Finland, and Denmark sought to determine the association if any between 3 COVID-19 vaccines and post-vaccination clotting problems.

The 3 vaccines examined in this project included the 2 mRNA vaccines, BnT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), as well as the ChAd0x1nCoV-19 (AZD1222 AstraZeneca) vaccine.¹ The authors used national patient registers to identify hospital visits and admissions secondary to thromboembolic and thrombocytopenic complications.¹ Primary outcomes included relative rates of coronary artery disease, coagulation disorders, and cerebrovascular disease while secondary outcomes included coagulation disorders and cerebrovascular disease (intracranial hemorrhage, cerebral thromboembolic events, and cerebral vein thrombosis).¹

By vaccine type the following results were obtained:

AZD1222 Vaccine

In the month following vaccination 305 events of coronary artery disease, 226 events of coagulation disorders and 231 events of cerebrovascular disease were observed.¹ Significant relative risk scores were seen for coagulation disorders including venous thrombosis, thrombocytopenia, and cerebral venous thrombosis.¹

BNT162b2 mRNA Vaccine

In the month following vaccination 3359 cases of coronary artery disease, 1674 cases of coagulation disorders, and 3228 cases of cerebrovascular diseases were observed.¹ The relative risk for coagulation disorders was 1.12, and for cerebrovascular diseases was 1.09.¹ No rate increases were observed for coronary artery disease and only small rate increases were seen for cerebrovascular thrombosis and coagulation disorders; however, these increases were only seen in the oldest birth cohorts.¹

mRNA-1273 Vaccine

In the month following vaccination 399 cases of coronary artery disease, 177 cases of coagulation disorders, and 358 cases of cerebrovascular disease were observed.¹ Relative risk scores over 1 were observed for all the main outcomes and rate increases were observed for most secondary outcomes with the exception of thrombocytopenia or purpura.¹ As with the Pfizer vaccine, the vast majority of outcomes occurred in the oldest cohort.¹

The authors performed post hoc absolute risk analyses and found that while the relative risk for adverse outcomes was significantly increased the absolute risk only amounts to 4.9 events per 100,000 doses of vaccine.1 This is a very important result. While any adverse events should be taken seriously these data mean that the vast majority of individuals receiving COVID-19 vaccination will be protected from hospitalization and death and not experience an adverse event.

In summary, the results Berild and colleagues obtained show that vaccination with AZD1222 (AstraZeneca) was associated with increased rates of hospital contacts for thromboembolic coagulation disorders, especially thrombocytopenia.1 In addition, an increased risk for cerebrovascular thrombosis was seen after vaccination with AZD1222 and was consistent and robust across all 3 countries studied.1 The authors also observed statistically significant increases in the risk of hospital contacts for thrombocytopenic and thromboembolic events after BNT162b2 and the mRNA-1273 vaccination.¹ However, the risk was small compared with those after AZD1222 vaccination. Finally, with the mRNA vaccines, the national estimates varied, with increased risk observed only in the oldest cohorts, with sensitivity analysis checking underlying assumptions of the analyses being inconsistent at best.¹

A pair of main takeaways can be garnered from these data. The AstraZeneca AZD122 COVID-19 vaccine increases the risk for thromboembolic events while the 2 mRNA vaccines studied only do so to a much smaller extent and with less consistency. With continued doubt from the general public these results should show skeptics that the benefits sharply outweigh the risk. More research is needed to define the risk with mRNA vaccines. This study serves as a good foundation for further investigation while reassuring clinicians that we should continue to recommend full COVID-19 vaccination, especially for high-risk individuals.

Reference:

1. Berild, J. D., Larsen, V. B., Hviid, A. et al. Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries. JAMA Network Open. 2022;5(6):e2217375. doi:10.1001/jamanetworkopen.2022.17375