Michela Mazzon: The Molecular Trigger Behind the COVID19 Vaccines-Associated ITT
Michela Mazzon, Virologist and Founder of Virology Research Services Ltd, shared on LinkedIn:
”This week a new paper in The New England Journal of Medicine dissects the molecular trigger behind the most severe adverse event linked to some adenoviral COVID19 vaccines, such as those from AstraZeneca and Johnson and Johnson: vaccine-induced immune thrombocytopenia and thrombosis (VITT).
Back in 2021 we learned that patients with VITT produce antibodies that attack platelet factor 4 (PF4), causing clotting with low platelet counts.
This new study investigates the upstream mechanism.
Around 60% of people generate antibodies to the adenoviral protein pVII, but in a very small subset a mutation allows those antibodies to cross-react with PF4 and start the clotting cascade.
All 21 VITT cases examined carried this feature, and when researchers reversed it in a mouse model, clot formation significantly dropped.
The article presents this largely as an unfortunate chain of immune events, and individual biology is clearly central. Yet, vaccination was also the stimulus bringing the Immune System onto this path.
Recognising this does not diminish the benefit of these vaccines, but it’s a point worth stating plainly.
One lesson is that expecting a new medical technology to be harmless in 100% of recipients is unrealistic.
Vaccines reach huge populations and intentionally engage immunity, the most variable system we have.
Risk-benefit analysis, as seen during COVID, tells us whether the greater danger lies in the intervention or in the disease it aims to prevent.
Assumptions of safety, even after clinical trials, will always meet the unexpected once scale increases.
The other lesson is about resolution. If rare adverse outcomes are explained by defined molecular or genetic contexts, they become processes that can theoretically be anticipated.
Last week I shared hypotheses linking interferon-response deficiencies to reactions observed with live attenuated Chikungunya vaccination; now we have another case where understanding mechanisms turns unexplained adverse events into something potentially actionable.
This raises the question: are we starting to open a diagnostic space before vaccination, where individual immune traits might inform personalised risk profiling?
And if the science points in that direction, will the limiting factor be the complexity and variability of biology, or will it be whether screening strategies are strategically viable and commercially attractive compared with improving or discontinuing a product?
What is your view?
I’m Michela, virologist and co-founder of VRS, where we help teams transform antiviral ideas into actionable data.
Curious about virology? Follow along. Need expert study support? Get in touch.”
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