TOPLINE:

The first dose of the COVID vaccine AZD1222 was associated with an increased risk for thrombotic thrombocytopenia syndrome (TTS) within 28 days after vaccination; however, no significant association was observed after a second dose of AZD1222 or after either dose of BNT162b2.

METHODOLOGY:

• Researchers in England conducted a matched case-control study and a self-controlled case series analysis to assess whether COVID vaccination with AZD1222 or BNT162b2 was linked to the occurrence of TTS.
• An incident case of TTS was defined as the co-occurrence of thromboembolism and thrombocytopenia within ±7 days of each other during the study period.
• In the matched case-control analysis, cases of TTS (n = 666; mean age, 64.18 years; 55.4% men) were matched to control individuals without TTS, thromboembolism, or thrombocytopenia on the basis of age, sex, and GP.
• In the self-controlled case series analysis, 660 cases of TTS were followed up until the earliest of the end of data availability, death, disenrolment, a second TTS event, or the receipt of a third COVID vaccine dose/second dose not under study.
• The primary outcome was the first incident TTS event within 28 days after the first or second dose of AZD1222 or BNT162b2.

TAKEAWAY:

• Matched case-control analyses found no significant association between TTS and composite AZD1222 exposure, either the first or second dose (adjusted odds ratio [aOR], 1.45; P = .13). However, in the dose-specific analysis, the first dose of AZD1222 was associated with higher odds of TTS (aOR, 2.12; P = .02).
• The self-controlled case series analysis showed a significantly increased rate of TTS within 3-28 days after composite AZD1222 exposure (incidence rate ratio, 2.44; P < .001); a similar increase was observed after the first dose of AZD1222.
• No association was observed between TTS and the second dose of AZD1222 or BNT162b2 at any exposure level.

IN PRACTICE:

"Our findings are consistent with previous studies that demonstrated an increased association between TTS and the administration of the first dose of AZD1222," the authors wrote.

SOURCE:

This study was led by José M. Ordóñez-Mena and Xinchun Gu, University of Oxford, Oxford, England. It was published online on December 09, 2025, in the International Journal of Infectious Diseases.

LIMITATIONS:

No single clinical code or agreed case definition existed for TTS, which may have led to misclassification. The broad case definition could not separate the coincidental co-occurrence of thromboembolism and thrombocytopenia from vaccine-related cases, and because about 90% of TTS cases did not follow vaccination, this may have affected the findings. This study did not assess the risk for TTS after booster doses.

DISCLOSURES:

This study was funded by AstraZeneca. Two authors were former employees of AstraZeneca and may own stock or shares. Some authors reported receiving funding, serving on advisory boards, and having other ties with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.