Is the incidence of vaccine-induced immune thrombotic thrombocytopenia (VITT) different long-term between J&J and AstraZeneca compared to mRNA vaccines?
Executive summary
Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been repeatedly and robustly linked to adenoviral‑vector COVID‑19 vaccines—principally AstraZeneca’s ChAdOx1 and, to a lesser extent, Johnson & Johnson’s Ad26.COV2.S—while mRNA vaccines show an extremely low to negligible VITT signal in large surveillance cohorts (adenoviral >> mRNA) [1] [2] [3]. The excess risk is concentrated in the weeks after vaccination and appears much higher after first doses of ChAdOx1 than after Ad26.COV2.S, with regulatory pauses and age‑based guidance reflecting that differential risk rather than evidence of a persistent long‑term divergence beyond the acute post‑vaccine window [4] [1] [2].
1. Adenoviral vectors carry the VITT signature; mRNA vaccines do not — repeatedly observed in surveillance
Multiple epidemiologic and mechanistic reports identify VITT as a syndrome tied to adenovirus‑vector platforms: ChAdOx1 (AstraZeneca) shows the highest reported incidence, Ad26.COV2.S (J&J) a lower but nonzero incidence, and mRNA vaccines (Pfizer, Moderna) show either no confirmed VITT cases or only extremely rare, likely background events in large databases [1] [2] [3] [5].
2. Measured incidence varies by vaccine, age, and jurisdiction — estimates are imprecise but directionally consistent
Published incidence estimates span wide ranges because of case ascertainment and denominator differences: examples include ChAdOx1 rates as frequent as ~1 per 26,500 in Norway and as rare as 1 per 127,300 in Australia, and Ad26.COV2.S estimates such as ~1 per 263,000 doses in a U.S. ACIP analysis; U.K. data put ChAdOx1 risk at roughly tens of cases per million in younger adults versus fewer in older cohorts [6] [1] [4]. These disparate numbers nevertheless converge on a consistent ordering: ChAdOx1 > Ad26.COV2.S >> mRNA [2] [1].
3. Timing matters: the risk is acute, not a slowly accumulating long‑term hazard
VITT presents characteristically between about 4 and 42 days after vaccination, and most surveillance and clinical series evaluate that defined window; guidance and regulatory actions were therefore based on short‑term risk, not long‑term signal accrual [6] [5]. Analyses showing reduced VITT after second doses of ChAdOx1 underline that the phenomenon is an early post‑vaccination immunologic event rather than a progressive chronic risk [1].
4. Mechanistic work supports a platform effect, which helps explain the persistent difference
Laboratory and simulation studies point to platelet factor 4 (PF4) interactions with adenoviral capsids—BD simulations and biochemical data suggest PF4 binds ChAdOx1 more readily than Ad26, offering a plausible biological basis for why ChAdOx1 produces more VITT cases than Ad26 and why mRNA vaccines (lacking an adenoviral capsid) show far fewer cases [2] [7]. Importantly, anti‑PF4 antibodies in VITT do not target the spike protein, implying the causal feature is vector‑related rather than spike‑related [7].
5. Regulatory responses reflect comparative short‑term risk, not new long‑term evidence
Regulators paused or narrowed use of adenoviral vaccines when acute VITT signals emerged: U.S. FDA/CDC paused Ad26.COV2.S in April 2021 and later modified EUAs and guidance reflecting risk thresholds and mortality concerns, actions based on acute incidence and severity in surveillance data rather than evidence of delayed chronic risk [4]. Where jurisdictions continued adenoviral use, they often applied age or risk stratification to balance benefits and the noted short‑term VITT risk [8].
6. Limits of the record: under‑ascertainment, varying definitions, and background thrombosis complicate long‑term comparisons
Published incidence ranges reflect differences in case definitions, surveillance intensity, and possible underreporting; some authorities argue background rates of cerebral venous thrombosis complicate attribution, and rare thromboses occurred after many vaccine types though confirmed VITT cases are concentrated in adenoviral vaccines [5] [8] [9]. Long‑term comparisons beyond the acute 4–42 day window are sparse in the literature provided; available evidence and mechanistic plausibility nonetheless indicate the platform‑specific disparity persists as a factual assessment of risk during the risk window [1] [2].
Conclusion: short‑ and medium‑term evidence consistently show higher VITT incidence after AstraZeneca than after J&J, and both adenoviral vaccines have materially greater VITT risk than mRNA vaccines; the syndrome is an acute, immunologic event occurring within weeks of dosing, and there is no robust evidence in the cited literature of a divergent long‑term (months‑to‑years) VITT incidence developing after that acute period—surveillance, mechanistic data, and regulatory actions all support an adenoviral‑platform signal that is concentrated early and remains much higher than for mRNA vaccines [1] [2] [4].