What are the current incidence estimates of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral‑vector COVID‑19 vaccines by age and sex?

1. Incidence estimates by vaccine — headline numbers and ranges

Published syntheses and regulatory reviews place the incidence of TTS after the ChAdOx1‑S (AstraZeneca) vaccine across a wide band — commonly reported as about 3.2 to 16.1 cases per million doses in systematic reviews and expert summaries (Vaxzevria) ^[1], with some country‑level analyses and early signal investigations reporting higher or lower point estimates (for example preprint and national reports citing ~5 per million for certain datasets or as high as ≈30 per million in specific risk–benefit scenarios used early in Australia) ^{[4] [5]}. For Ad26.COV2.S (Janssen/J&J) the pooled literature typically reports lower overall rates — commonly in the range of ~1.7 to 3.7 per million doses in broad reviews, while targeted safety updates and regulatory fact sheets estimated about 7 cases per million doses in women aged 18–49 and about 0.9 per million in women older than 49 ^{[1] [2]}. Some case series and reviews report even broader numeric bounds for ChAdOx1 (e.g., incidence estimates spanning 1/26,500 to 1/518,181, which translate to roughly 38 to 1.9 per million), underlining heterogeneity across studies ^[3].

2. Age and sex patterns — who is at higher risk

Across multiple reviews and surveillance reports there is a consistent signal that younger adults — particularly women in reproductive age groups (roughly 18–49 years) — accounted for a disproportionate fraction of early identified TTS/VITT cases after adenoviral vaccines, and regulatory risk estimates reflect that (for example the U.S. J&J fact‑sheet estimates of ~7 cases per million in women 18–49 versus <1 per million in older women) ^{[6] [2] [1]}. That said, not all datasets show identical sex dominance: national surveillance in Canada reported a median age of 56 years and a slight male predominance (54% male) among reported TTS cases as of October 2022, illustrating that case demographics can differ by country, vaccine rollout populations and detection criteria ^[7]. Systematic reviews emphasize the age‑dependent risk gradient but also stress that heterogeneity in reporting and denominators complicates precise age‑sex stratification ^{[8] [3]}.

3. Why estimates vary — surveillance, definitions and denominators

Differences in incidence estimates are driven by several methodological and contextual factors: whether a study counts only cases meeting strict anti‑PF4‑positive VITT criteria versus broader TTS definitions; passive versus active surveillance; which dose (mostly first doses show the signal); the background rates used for comparison; and demographic structure of vaccinated cohorts ^{[9] [1] [4]}. Reviews and public health agencies repeatedly caution that direct comparisons across countries or across vaccine platforms are confounded by these factors, and some reviewers note that low‑level reporting of similar events after mRNA vaccines complicates absolute attribution, even if rates for adenoviral platforms remain higher in most analyses ^{[8] [10]}.

4. Bottom line — practical interpretation and uncertainty

The consensual conclusion across expert reviews is that TTS/VITT is very rare after adenoviral‑vector COVID‑19 vaccines: typical aggregated ranges are a few to at most several dozen cases per million doses depending on vaccine and subgroup, with higher observed rates in younger adult women in several datasets but not universally so ^{[1] [2] [3]}. Important caveats remain: estimates differ by study and surveillance system, some national reports show different age/sex patterns ^[7], and the quality of stratified denominators limits precision; readers should treat single point estimates as approximations within the published ranges and interpret risk in light of local vaccine availability and the substantially larger thrombotic risks posed by COVID‑19 infection itself ^{[9] [10]}.