People on social media and even some mainstream channels are having their “we told you so” moment this week after the pharmaceutical company AstraZeneca “admitted” in court to the side effects of its Covid-19 vaccine, manufactured and marketed in India as Covishield.
This follows a story in The Telegraph of the UK on April 28 about a class action suit brought against the company. The report says, “AstraZeneca has admitted for the first time in court documents that its Covid vaccine can cause a rare side effect,” a condition called Thrombosis with Thrombocytopenia Syndrome (TTS), which translates to blood clots and low levels of platelets (a type of blood cell that prevents bleeding).
Risk, in perspective
The key words are “rare side effect”. What does that mean?
Australian Department of Health and Aged Care found TTS in people who had taken the AstraZeneca vaccine to be “very rare” — 2-3 per 1,00,000. In April 2021, the World Health Organisation’s Global Advisory Committee on Vaccine Safety computed this risk for the UK and EU to be one in 2,50,000 and one in 1,00,000, respectively. Such data is unfortunately not available for India, even after reportedly using 1.75 billion (or 175 crore) doses of Covishield. The risk is likely to be similar for Indians as well.
To put this in perspective, the global risk of dying in a traffic accident is 17.4 deaths per 1,00,000. For low-income countries, this risk is 24 deaths per 1,00,000, and for high-income countries, it is nine deaths per 1,00,000. So, the risk of TTS in those who took the AstraZeneca vaccine is about 5 to 12 times lower than the risk of dying in a road accident.
Medicine is all about risk versus benefit. If the benefits of a drug far outweigh the risks, we use it. The hugely successful oral polio vaccine, which has been instrumental in eradicating polio from most of the world, including India, has a one in 2.7 million risk of causing vaccine-associated paralysis. To that one child, the risk is very high but for public health, the benefits are extremely high. And therefore, we use it.
Could side effects be anticipated?
Can we test for these rare risks before a vaccine is approved? A risk of one in 1,00,000 will not show up in a clinical trial that has 30,000 volunteers — half getting the vaccine and the other half a placebo. This was typically the size of phase 3 trials for Covid-19 vaccines. Should we then have clinical trials with millions of volunteers (where would we get so many volunteers?), spread over many years, and at a huge cost to inform of a minuscule risk before a vaccine is approved? That makes little sense. Further, such a vaccine would be useless for a pandemic caused by a newly-emerged pathogen.
The rare events become visible only after a vaccine is rolled out and millions of doses are administered. A multi-country observational study on the Pfizer, Moderna and AstraZeneca vaccines was published in the journal Vaccine on April 2, 2024. It showed that these vaccines increase the incidence of Guillain-Barré syndrome, an autoimmune disorder that leads to neurological symptoms and brain clots within 42 days of receiving the vaccine. About 200 cases were found among 99 million people who were studied — a risk of one in 5,00,000. A separate study of 6.7 million people in Australia found a risk of one in 5,00,000 to one in 1.3 million for brain and spinal cord inflammation in people receiving these vaccines.
The value of such studies is two-fold. They establish the safety of these vaccines in very large populations and real-world conditions. They also alert scientists to potential (albeit low) risks associated with the RNA and viral vector platforms. Future research will focus on making these vaccine platforms even safer.
Don’t politicise the vaccine
In India’s election season, Covid-19 vaccines have once again attracted political attention. However, using vaccines for political one-upmanship can be detrimental to public health. In a study that evaluated over 5,00,000 deaths in the states of Florida and Ohio (in the US) during the pandemic, excess mortality was significantly higher for Republican voters than Democratic voters after Covid-19 vaccines were available to all adults, but not before. This was attributed to political rhetoric that reduced trust in science in general, and vaccines in particular. We should not repeat the same mistakes.
Vaccines remain the most effective of public health tools. A modelling study on Covid-19 transmission and vaccination from Imperial College, London, estimated that vaccines saved 14 to 20 million excess deaths in just the first year of use. A Working Paper from the US-Asia Technology Management Center at Stanford University estimated that India prevented around 3.4 million excess deaths due to its Covid-19 vaccination programme.
The bottom line is that these “new” disclosures by AstraZeneca are neither new nor worth worrying over. We should stay focused on improving public health everywhere and for everyone. Vaccines will remain central to those efforts.
The writer is a virologist, and currently a Fellow at OCIS and Green Templeton College, University of Oxford, UK
