Questions have been raised across the world about the safety of the COVID-19 vaccines. Many scientists previously raised concerns about the Sputnik vaccine but now the spotlight has turned on our very own “British” vaccine manufactured by Oxford / Astra Zeneca. The WHO has urged European countries to keep using the Astra Zeneca vaccine to save lives, and this is even more important for low income countries which cannot afford the expensive Pfizer vaccine.
However, recent evidence of a rare, but life-threatening, clotting disorder affecting younger patients has given rise to a complex ethical and scientific debate in the UK. I’m a blood specialist, I have degrees in law and medicine and a science PhD, but I certainly don’t know the answers to the predicament we find ourselves in. What I do know is that most of us aren’t asking the right questions. 'Evidence of a rare but life-threatening clotting disorder associated with the Astra Zeneca vaccine has given rise to a complex ethical and scientific debate. The answers will be difficult, but we need to start by asking the right questions.' Click To Tweet
Vaccine-Induced Thrombosis and Thrombocytopenia – what do we know?
Thrombosis is the formation of a clot in a blood vessel. This can either be arterial (blood flowing from the heart to your organs) or it can be venous (blood flowing back from your body to your heart). When the clot blocks the blood supply to vital organs such as the brain or lungs, then the consequences can be life-threatening. Even in other cases, a blockage in blood flow can be life-changing. For instance an arterial thrombus in the leg can require amputation.
Some of the most common clots involve the deep veins of the lower legs (a DVT) and the lungs (a pulmonary embolism). Specific risk factors (cancer, surgery, immobility, the combined oral contraceptive) are associated with these clots.
However, other types of clots can be much rarer and have different provoking factors, for instance CVST (a blood clot which forms in the brain’s venous sinuses) can be associated with inflammation, and splenic vein thrombosis prompts blood specialists to look for a mutation in a gene called JAK2.
The British Society of Haematology have recently issued a guideline about a new syndrome which seems to be associated with the Astra Zeneca vaccine. They call it “Vaccine-Induced Thrombosis and Thrombocytopenia” (VITT), although the President of the BSH has cautiously stated that “any link with the Coronavirus vaccine is not for us to determine”. It’s important to note that our understanding of this syndrome is rapidly evolving, and as of yet there is no conclusive proof that Astra Zeneca or any other COVID-19 vaccine causes blood clots.
The mechanism for VITT remains poorly understood, but many of these patients seems to demonstrate platelet factor 4 antibodies, platelet aggregation, thrombocytopenia (decrease in the number of platelets) and clots. 'Healthcare professionals are troubled because these vaccine-induced clots – although very rare – affect young patients who otherwise would not die if they were infected with COVID-19'. Click To Tweet
Vaccine-Induced Thrombosis remains very rare, but there are two features which are troubling healthcare professionals. Firstly, the syndrome is characterised by unusual and particularly devastating clots, for instance CVST in the brain. Secondly, it seems to be affecting young patients who otherwise would not die if they became infected with COVID-19.
Are we asking the right questions?
There remain powerful ethical and scientific arguments for continuing to roll out the Oxford vaccine despite the reports of thrombosis. Overall, it’s saving many lives throughout the UK and abroad. However, in the 21st century we need to treat patients like adults and provide them candid information, and it’s not clear that we’re doing this. To some extent this reflects our incomplete understanding of VITT, for instance some of the UK’s most respected experts on blood clots have taken the unusual step of publishing a formal letter to express concerns about MHRA advice.
The MHRA obviously has longstanding expertise in evaluating the safety of medicinal products used in the UK, and it’s clear that the Astra Zeneca vaccine has saved many lives, but both clinicians and the general public need to consider the data very carefully.
Firstly, it’s been repeatedly stated that the benefits of the Astra Zeneca vaccine outweigh the risks – Well, yes, that’s true, if you look at the population as a whole. However, if you look at the data for younger patients, then it’s not clear that the benefits outweigh the risks. In patients under the age of 40, the mortality from COVID-19 infection is well below 0.5%.
In addition, we cannot accurately evaluate risks versus benefits for younger patients at the current timepoint because the vast majority of vaccinated patients are elderly, and we cannot reliably extrapolate conclusions about the rest of the population from this data set.
Furthermore, we may not be accurately evaluating the risk versus benefit ratio because our systems for reporting COVID-related deaths are more robust than our systems for reporting vaccine side effects. This uncertainty in risk:benefit ratio is unlikely to affect decisions in older patients where COVID-associated mortality is very high, but it needs to be taken into account when vaccinating patients who are aged below 40.
CVST clots are notoriously difficult to diagnose clinically and the non-specific nature of symptoms means that usually these patients are investigated with a non-contrast CT scan which can miss a significant proportion of cases (CT venograms and MR venograms increase diagnostic yield). This means that statistical uncertainty exists about the incidence of CVST clots in both the unvaccinated population and in patients who have been vaccinated.
In addition, some serious clots, such as pulmonary embolism, may have been missed because they’re so common, and until recently most clinicians who have diagnosed these common clots have not automatically asked the question: “Were you vaccinated recently?”
Secondly, the MHRA has stated that your global risk of a blood clot does not increase if you have the Astra Zeneca vaccine. Such statements are true, but again potentially misleading. Clots are incredibly common, and so it’s possible that a vaccine “signal” is obscured if we look at the effect of a specific vaccine on all clots as a whole.
If we’re going to address this question scientifically, we should be comparing like with like. There’s an argument for removing superficial clots and even deep venous clots of the lower legs from our statistical analysis because these are common and also cause less mortality and disease burden than Vaccine-Induced Thrombosis.
We also need to age stratify vaccine risk in just the same way that we’re age stratifying vaccine benefit. We’re prioritising older patients for vaccination because older patients have the highest risk of mortality from COVID-19, and we should evaluate thrombosis risk in the same way.
It’s not good science to evaluate risk to younger patients by looking at thrombosis statistics for the entire population, when we know that the vast majority of “normal” clots form in patients over the age of 60.'It's not good science to evaluate risk to younger patients by looking at thrombosis statistics for the entire population, when we know that the majority of 'normal' clots form in patients over the age of 50'. Click To Tweet
Thirdly, we should adjust for data from confounding factors such as cancer or orthopedic surgery, because most younger people don’t have cancer or orthopedic surgery. Using the correct comparators will help us to properly assess the risk of the vaccine for each individual patient.
Don’t all medications have side effects?
Of course, all medications have side effects, and vaccines are no different. However, people have a choice about medications – for instance, nobody is asked if they’ve taken their metformin before boarding a flight or attending a football match. Vaccine passports are on the horizon. When a Government effectively makes a vaccine mandatory, then this increases the burden of proof for demonstrating that benefits outweigh risks for the individual patient.
Furthermore, the strongest argument for vaccinating younger age groups is to protect the elderly and vulnerable patients with poor immunity. We may need to vaccinate 75% to 90% of the population to safely open up society. Again, consenting to the COVID-19 vaccine raises much more complex ethical issues than consenting to medications – we take medicines to benefit ourselves, not to benefit others.
In fact, informed consent requires us to provide honest information about benefits and risks, and it’s not clear that younger patients are being informed that the benefits of vaccination may accrue to society rather than to the patient. The vaccination of children needs to be in their best interests if they lack capacity, which raises even trickier ethical issues.
Political leaders and public health experts are very rightly focused on the health of the entire UK population, but healthcare staff have a duty of care to each patient they treat. We cannot say, “Take this vaccine for the sake of your grandparents or for the sake of elderly people or for the sake of the community”. We are legally liable to give advice in the best interests of our patients, and it’s not clear that the Astra Zeneca vaccine is in the best interests of a younger patient. 'Healthcare professionals are legally liable to give advice in the best interests of individual patients, and it's not clear that the Astra Zeneca vaccine is in the best interests of a younger patient.' Click To Tweet
In the end, all these complex ethical and scientific debates may turn out to be irrelevant, as people take their health into their own hands. If the British public start to refuse to take the Astra Zeneca vaccine, then we may be left with a hard choice of either leaving people unvaccinated, with potentially devastating consequences for public health, or moving from Astra Zeneca to other vaccine options.
The behavioural scientists in SAGE are going to have their work cut out. Public health is as much about reality “out on the street” as it is about ethics and science. We’re starting to see British people express concerns about the Astra Zeneca vaccine, and it’s important to take those concerns seriously.
In the small hospital where I work, twenty to thirty patients are presenting every day to Accident & Emergency with headaches after taking the Astra Zeneca vaccine, and vaccine anxiety is turning into a national problem.
Very few of these patients will have a clot in their brain. However, each of these patients requires medical review, neurological examination, blood tests (hospitals are going to have to urgently stock up on fibrinogen assays), and possibly a CT venogram of their brain or other imaging as appropriate.
Bearing in mind that we’re planning to vaccinate millions more patients across the UK, the NHS might be on the brink of facing a significant post-vaccination burden.
The NHS is successfully rolling out the most ambitious and successful vaccination programme in British history, and this may help us avoid the third pandemic wave which is seizing other European nations. The British government deserves to be congratulated for this historic achievement.
However, only last week, we received a communication from Public Health England refusing to disclose even the number of pandemic exercises it conducted between 2015 and 2019 on the grounds that this information would threaten national security. PHE’s decision reflects a systemic lack of transparency which has to be reversed, or it will damage public confidence in UK public healthcare policy including our vaccination programme with potentially disastrous consequences. You can find out more about our campaign for UK pandemic transparency in our campaign timeline – we’re taking legal action against five British public authorities.
Public health strategy can’t work unless it takes into account the thoughts, feelings, values and behaviours of individuals in society, as well as biological evolutionary traits such as selfishness and altruism. We ask: Given the choice, which vaccine would you take? 'Public health strategy can't work unless it takes into account the behaviours of individuals in society, and evolutionary traits such as selfishness and altruism. Given the choice, which vaccine would you take?' Click To Tweet