We have explored the general medical theme behind many of the COVID-19 headlines over the past year. The latest hot topic is the apparent risk of blood clots as a side effect of some COVID vaccines. So what are the risks, and what can this teach us about medicine?
All medicines carry the risk of side effects or severe adverse reactions. Medical treatments are designed to change something within our bodies, and our bodies can all react slightly differently. The immune system can also sometimes respond unpredictably.
Some examples of side effects include: antibiotics that cause diarrhoea, or vaccine injections that cause flu-like symptoms and sore arms. These do not affect everyone, and those that do get these side effects can experience them very differently.
A ‘cytokine storm’ is a bad immune response that can be caused by immunotherapies (such as vaccines). This causes excessive inflammation. In this case, the risk of not receiving the treatment is far greater than the risk posed by this immune response.
Vaccines: how do we decide which risks are worth taking?
The frequency and severity of the adverse outcomes from both the original illness and the treatment are important factors. For example, when balancing the risks and benefits of the AstraZeneca (AZ) COVID-19 vaccine, you would consider:
- Your risk of contracting COVID-19, and the risk of becoming seriously ill and/or dying from it if you do. Both are very low in most people, particularly now that vulnerable groups have been vaccinated.
- Your risk of having an adverse reaction to the vaccine, and the risk of becoming seriously ill and/or dying from it if you do.
- Other factors such as the risk posed to society if a large proportion of people remain unvaccinated.
The final point includes not just the risk to life of those who are immunocompromised and/or cannot receive the vaccine. It also includes the risk that a new variant could arise in, or be spread by, those who are unvaccinated.
The graphic below shows the harms associated with the vaccine on the right-hand side. That is, the number of people in each age range you would expect to develop a blood clot out of every 100,000 people who receive the vaccine. On the left it shows the benefit of the vaccine in terms of the number of ICU admissions (due to COVID-19) prevented per 100,00 people who receive the vaccine. This doesn’t even include prevention of milder cases and the reduction in transmission.
You can see more graphics like this, including the data for very low, low, and high exposure risk groups.
Vaccines data and expert opinions
There are various organisations responsible for deciding which medicines are safe and beneficial, and if there are any exceptions. Here’s what some of them have to say about the risk of blood clots in people who have received the AZ vaccine.
The European Medicines Agency (EMA) recommends that unusual blood clots with low blood platelet levels are listed as very rare side effects. While a prominent gender split has not been seen in the UK (see next section), it reports that women are most likely to experience this side effect. The EMA reviewed 86 blood clot cases from the UK and the European Economic Area and found that 18 resulted in death. This is out of a total of 25 million doses of the AZ vaccine. The EMA therefore recommends that the overall benefits (preventing COVID-19 and reducing hospitalisation and death) outweigh the risk of these side effects.
The Joint Committee on Vaccination and Immunisation (JCVI) reviewed evidence from the Medicines and Healthcare Products Regulatory Agency. Some of the key data is as follows:
- Nearly 50 million vaccine doses have been given in England (not all are AZ).
- This is predicted to have prevented more than 10,000 deaths (up to March 2021).
- Eight in every 1 million people experience the clotting condition, and it is not always fatal.
After considering the evidence, the JCVI gives the following evidence to the Government:
“Real-world vaccine effectiveness studies conducted in the UK confirm that the AstraZeneca vaccine works well in adults of all ages, providing high levels of protection from severe illness or death caused by a COVID-19 infection. The benefits of vaccination with the AstraZeneca vaccine still far outweigh the risks for the majority of the population.”
Why is it so difficult to work out the overall risk/benefit?
The maths is very complicated due to all of the different variables. For example, the 50 million doses were given to older and more vulnerable groups first. That means they are over-represented in the study. Additionally, not all of the vaccines (in some of the studies) were AZ. The clotting condition affects young people more frequently, whereas hospitalisation from COVID-19 occurs more often in older people. You must also account for those people that would have had the clotting condition even without the vaccine.
This is why researchers are often heard talking about ‘models’. Mathematical models try to account for the impact of a great many factors like these. This article by BBC News attempts to simplify the maths by working through the risk factors for 10 million imaginary people (a mathematical model).
What does this have to do with drug-resistant bacterial infections?
Resistant infections might cause the next pandemic. We already see people with multi-drug resistant infections that do not respond to a wide number of medicines. In those cases, we use older, more powerful antibiotics. These ‘last resort’ treatments are often relatively toxic and carry an increased burden of side effects.
As Professor Colin Garner, CEO of Antibiotic Research UK, explains: “The more we all understand how to balance the risks and benefits of taking treatments such as antibiotics and vaccines, the better prepared we will be to make those decisions.
“We work hard to try to halt drug-resistant infections in their tracks. But we also believe in educating people about healthcare and medical issues. Who knows what the future holds? We might soon be called on to receive another vaccine, but this time for a bacterial infection.”
Find out more
- Read what public health organisations have to say about the risks/benefits of the AZ vaccine: European Medicines Agency, Joint Committee on Vaccination and Immunisation and The World Health Organisation.
- Latest data from the MHRA on blood clots associated with the Astra Zeneca COVID-19 vaccine (Winton Centre for Risk and Evidence Communication, Cambridge University).
- The Centre for Disease Control and Prevention (CDC) has also released a statement on the Janssen vaccine and the potential risk of blood clots in women under 50.