Covishield and TTS
A rare life-threatening post-vaccination complication named ‘thrombosis with thrombocytopenia syndrome’ (TTS), was the topic of well-circulated disinformation on social media.
The trigger for this was a court submission by Astra Zeneca that its COVID vaccine, ChAdOx1-nCoV19, manufactured as Covishield by Serum Institute in India, can in rare cases cause clots due to TTS.
Many people mistakenly saw this as new information that to their mind explained the recent increase in heart attacks and strokes, among the youth, when this is old information about a rare side-effect that occurs in just a few people out of every million recipients.
As far back as March 2021, after tens of millions of doses had been administered, countries in Europe and UK reported cases of TTS, a week to a month after receiving ChAdOx1-nCoV-19, with remarkably extensive thrombosis.
Risk vs Benefit
First, risk. TTS was found to occur most commonly in fit, healthy, young women around thirty years of age at a very low frequency of around one to two per lakh
At a general population level, it was estimated to occur at only about two to three cases per million people vaccinated.
To put these numbers in perspective, the Ministry of Road Transport and Highways estimates annual deaths in road accidents at about ten per lakh.
Thus, the highest estimated risk of TTS is still much lower than the annual risk of dying in a road accident.
While we should strive to improve on both numbers, since every death that can be avoided matters, there is absolutely no reason for fear; not then, not now a couple of years after.
Second, benefit. Covishield was associated with over 80% protection against severe COVID-19 and over 90% protection against death in multiple studies, including during the severe Delta wave.
For a 50% chance of contracting COVID-19 and 0.1% risk of death, this corresponds to a mortality benefit of around 40 in 100,000 - that outweighs the risk by far.
The true benefit is much more than this, however.
Reducing disease severity is important for minimising immediate suffering and stress on healthcare systems, as well as minimising long-term disability and risk of premature heart attacks and strokes.
While we do not have sufficient Indian data for Covishield, it is clear from global data that COVID-19 increased the risk of subsequent thrombotic events, including heart attacks and strokes by three-four fold, even after the infection was fully resolved.
This risk was observed very early in the pandemic, even before vaccines were developed, and was found to be reduced by vaccination.
The current disinformation about vaccines and young heart attacks ignores this important data from large studies.
Importance of vaccines
European nations, UK, USA, and Australia stopped the use of ChAdOx1-nCoV19 / Covishield after TTS reports, despite benefits outweighing risks.
They had sufficient doses of mRNA vaccines that were more immunogenic and not associated with TTS although cases of non-fatal myocarditis had been observed.
Given this alternative, it was a sensible decision.
For India, given the extremely large number of doses required and slow production of Covaxin, which requires culture and inactivation of the virus, it made more sense to continue
It seems that this is a rare side effect of the current recombinant DNA platform technology, since a similar vaccine used in America, developed by Johnson and Johnson, also increased TTS risk.
Antibodies to platelet activating factor (PF4) are seen in most patients, similar to another drug-induced TTS – heparin-induced thrombosis and thrombocytopenia.
Overall, it seems that the same powerful induction of immune response that makes DNA vaccines effective also carries a small risk of inducing auto-immune responses that lead to side effects.
People who benefit the most from vaccines – older people and those with diabetes – seem to also be least likely to develop such aberrant responses.
A similar pattern has been seen with mRNA vaccines and autoimmune myocarditis, where young healthy males were most at risk.
Killed virus vaccines appear to be safer but induce lower levels of immune response, conferring lower levels of protection against severe disease and death.
This was importantly seen in elderly deaths during the 2022 Omicron wave in Hong Kong.
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