Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study

SPS commentary:

In the study, increased risk of thrombocytopenia occurred after ChAdOx1 nCoV-19 (Astra Zeneca) vaccination (incidence rate ratio 1.33, 95% CI 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA (Pfizer) vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days).

According to an editorial, one interesting feature of the study is the analysis of adverse events after SARS-CoV-2 infection, confirming substantially higher and more prolonged risks after infection than after vaccination. This analysis included only vaccinated participants, and rates of these events would likely be higher in unvaccinated people with SARS-CoV-2 infection, again suggesting a net positive benefit

It notes that continuous monitoring of vaccine safety using both passive and active surveillance, combined eventually with controlled observational studies, is critical to ensure the best, safest, and most rational use of covid-19 vaccines. The accelerated development and regulatory assessment as well as rapid deployment of vaccines have exposed both the strengths and the limitations of current safety monitoring systems. Rare adverse events such as thrombotic thrombocytopenia, cerebral venous sinus thrombosis, and myocarditis were initially detected by passive surveillance based on spontaneous reporting to regulatory agencies. Spontaneous reporting systems, however, are prone to underreporting and cannot be used to estimate rates of adverse events. Analyses of large routine healthcare databases complement passive surveillance, allowing estimation of risk among vaccinated people and comparison with unvaccinated groups.

It adds that to strengthen pharmacovigilance activities to inform and accelerate regulatory decision making, the many barriers to timely investigation of emerging concerns about drug safety must be overcome, including lags in data availability, delays in access to that data for researchers, and barriers to sharing data across countries. The EMA recently pledged to improve this situation in Europe through its Data Analysis and Real World Interrogation Network (Darwin EU) initiative, which aims to be fully operational by 2024. This mirrors the US Food and Drug Administration’s sentinel system.