Assessing Case Fatality on Cases of Thrombosis with Thrombocytopenia (TTS) Following COVID-19 Vaccine AstraZeneca (Vaxzevria) in the United Kingdom: A Review of Spontaneously Reported Data

(Pre-peer reviewed publication)

The DSRU Global Pharmacovigilance Observatory recently completed a review of spontaneously reported adverse events data from the UK, to calculate the case fatality of reported cases of thrombosis with concurrent thrombocytopenia (Thrombotic Thrombocytopenia Syndrome; TTS) following COVID-19 Vaccine AstraZeneca (Vaxzevria).

We used publicly available reports of TTS to the UK’s Yellow Card spontaneous reporting system following Vaxzevria, which were extracted at weekly time points between 12 May 2021 and 19 January 2022. Cumulative numbers of TTS cases and deaths were recorded for each weekly interval, overall and stratified by age, sex, and vaccine dose. We calculated the proportion of events with a fatal outcome (case fatality) for cases of TTS which had been spontaneously reported in the UK.

Up to 6 April 2022, there had been 440 cases of thrombosis with concurrent thrombocytopenia reported to the Yellow Card scheme (Table 1). Of these, there were 79 fatal cases. Therefore, the overall, cumulative case fatality was estimated at 17.95% (95% CI 14.48-21.87%). There were no clear trends in case fatality according to age or sex. The majority of events had been reported following the first or unknown dose (n=391 of 440 reports, (88.89% [95% CI 85.54-91.65%)). Cumulative case fatality was higher for events reported following the first or unknown dose (18.67% [95% CI 14.93-22.89%]) than reports following a second dose of Vaxzeria (12.24% [95% CI 4.63-24.77%]).In the UK, Vaxzevria is not routinely used in the booster vaccination programme; only those for whom messenger RNA (mRNA) vaccines (COVID-19 Vaccine Pfizer/BioNTech [Comirnaty] or Moderna [Spikevax]) are clinically contraindicated should be offered Vaxzevria, provided they had received at least one dose of this vaccine previously (11). Due to this, usage of Vaxzevria as a third dose is small, however the vaccine is expected to remain the primary choice for COVID-19 vaccination programmes in other countries, particularly where health and logistical infrastructure limits cold storage of vaccines (12). Therefore, it remains important to report on case fatality of TTS events observed in the UK population where there was wide usage of the vaccine in the primary COVID-19 vaccination programme.

In summary, in the UK, case fatality of TTS following Vaxzevria has remained stable at approximately 17-18% since May 2021. There may be small differences in fatality based on age, but not sex. Reports are highest following a first vaccine dose. TTS is very rare, and benefits of vaccination continue to outweigh the risks.

The full-text of the pre-peer reviewed manuscript is available here.