Unexplained sudden deaths occurring among apparently healthy young adults have been a subject of considerable interest on social media recently. Some concerned individuals have claimed that these are the effects of COVID vaccination.

When the same story is heard from different sources, the human mind tends to believe it. This is how hoaxes are born, as detailed in my earlier article. A hoax is a false yet convincing belief that is held and propagated by many people. History tells us that deep-rooted false beliefs can be difficult to change, despite scientific proof to the contrary.
Is there really a connection between COVID vaccination and these sudden deaths, or is it a hoax? This has been a question on many peoples’ minds.

The only way to answer this question is through rigorous scientific investigation. Indian Council of Medical Research (ICMR) recently performed one of the largest studies addressing the topic of sudden deaths among young adults. The research was published in the October 2023 issue of Indian Journal of Public Health.

This article describes research methodology from a layperson’s standpoint, followed by a detailed analysis of the ICMR study, also discussing its implications.

How a research question is born

All scientific studies begin with a research question. The question can be as simple as determining the exact weight of an apple. Examples of more complex questions include comparing the effects of two painkillers or examining the link between helmet use and risk of head injury. Researchers use various types of studies to obtain answers to these questions. To better understand the ICMR study and its context, consider the following easy example.

Hypothetical example, for illustration purposes only

Consider the hypothetical case of a young woman who suffers her first spontaneous abortion. She is devastated, and starts searching for reasons. A neighbour tells her that she suffered an abortion because she ate pineapple. Surprised, she takes to social media and finds that other people have made the same claim. She checks with her class WhatsApp group, and some of her classmates give the same opinion. A Google search strengthens her confirmation bias. The woman now firmly believes that her abortion was caused by eating pineapple. How do we find out if this theory is true?

The only way to find the truth is to do a case control study. This research method compares two large groups of individuals, called cases and controls. Cases refer to people who have experienced a disease outcome (e.g., abortion), while controls are those who did not suffer such an outcome. The researchers investigate potential risk factors in both groups and then examine whether individuals who experienced an abortion were disproportionately exposed to any of these. While conducting the study, it is helpful to not only look for any link with pineapple, but also other established risk factors for abortion such as smoking, alcohol use and injury.

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In a case control study, the observed risk is expressed as adjusted odds ratio (aOR). If the aOR is greater than one and the 95% confidence interval (CI) does not include 1, then a statistically significant association is said to exist between the two factors, that is pineapple consumption and spontaneous abortion. The reason for preferring adjusted odds ratio (aOR) over odds ratio (OR) is that other factors that could potentially influence the association have been eliminated by a multivariate analysis.
The higher the aOR, the stronger the association or connection between the two factors. A value of 1 indicates no effect. A value below 1 indicates a negative or protective effect.

Three scenarios are possible:
1. If the study finds a significantly higher rate of pineapple consumption among women who had abortions, the belief is confirmed. For example, aOR = 3.1 (95% CI 2.5-4.2)
2. If they find that women who suffered spontaneous abortion had consumed pineapple at the same rate as women who did not suffer an abortion, then there is no link between the two. For example, aOR = 1 (95% CI 0.4-1.2) Such a negative result might not be enough to convince those who hold a deep-rooted belief, however.
3. On the other hand, if the study finds that healthy women ate more pineapple, then it indicates that eating pineapple protects against abortions. For example, aOR 0.5 (95% CI 0.2-0.6)

Technically speaking, this type of study is about a rare outcome of a common exposure. In other words, there are many people who eat pineapple (common exposure), but very few people who suffer an abortion (rare outcome). Therefore, asking a single individual who suffered an abortion will be of no value, because it could simply be coincidence. Besides, that person’s perception could be affected by public opinion. In such situations, large case control studies are required to reveal the truth.
The pineapple story was included as it is a common myth which people could relate to. By the way, there is no evidence that eating pineapple causes abortions.

The ICMR study in detail
The research question used by ICMR was to identify whether there are any risk factors that could have led to sudden unexplained deaths in apparently healthy adults. Among these, they highlighted COVID vaccination because that was a commonly discussed topic on social media. Specifically, they enquired whether COVID vaccination had a link with sudden deaths.

The researchers coordinated with 48 hospitals across the country, enlisting the help of multiple experts at each centre. They collected the case details of 729 young adults between the age of 18 and 45 who died suddenly and unexpectedly, without an apparent cause. In other words, these individuals did not die as a result of obvious reasons such as suicide, road accident or pneumonia. The group included both vaccinated and unvaccinated people.

The 729 cases were compared with a much larger group of 2916 healthy controls. The investigators looked at several potential risk factors for sudden deaths, that were previously known and otherwise. The aim was to see if any factor occurred more commonly among people who died suddenly.

They found that people who had COVID vaccination were less likely to suffer sudden deaths compared to those who did not. The adjusted odds ratio was below one. aOR = 0.51 (0.28-0.91)
In other words, vaccination was not associated with sudden deaths.

The following risk factors were associated with sudden deaths
1. Severe bout of COVID requiring hospitalisation, aOR = 2.24
2. Smoking, aOR = 1.38
3. Recreational drug use, aOR = 2.91
4. Family history of sudden death, aOR = 2.11
5. Heavy consumption of alcohol within 48 hours prior to event, aOR = 5.56
6. Vigorous intensity physical activity within 48 hours prior to event, aOR = 3.82

Interpretation of the findings
The higher the aOR, the stronger the link between each risk factor and sudden death. Binge drinking with an aOR of 5.56 has thus emerged as a strong risk factor.
When the aOR is below 1, then it is protective. Thus, an aOR of 0.51 means that those who were vaccinated were less likely to die suddenly.
Identifying risk factors does not imply that everyone with that factor will die. It simply means that they are more likely to experience such an event and should, therefore, be more watchful.

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The study adds new knowledge for those who have recovered from a severe bout of COVID. They must avoid strenuous exercises immediately following recovery. It is safer to wait for the body to fully recover before planning exercises. There is no restriction for resuming activities of daily living as tolerated.
People who had a mild bout of COVID can slowly restart their exercises depending on how their body responds.
For people experiencing persistent symptoms, it is better to check with their doctor regarding when and how to resume exercises.

Summary
In summary, the study found that COVID vaccination did not increase the risk of unexplained sudden deaths among young adults in India.

COVID is not the common cold
It is true that the initial symptoms of COVID are upper respiratory in nature and mild in most cases. However, COVID is not a common cold. The SARS-CoV2 virus affects the inner lining of blood vessels called endothelium. This is a delicate layer of cells that works like a sensor for our cardiovascular system. Abnormal functioning of these sensors could potentially result in cardiovascular events.

Studies from countries including India have shown that people who have recovered from COVID continue to experience higher rates of chronic health issues, cardiovascular events and death over an extended period of one year or longer. Common cold viruses do not pose such risks.
Authors believe that vaccination might have reduced the severity of COVID in these individuals, and therefore sudden deaths occurring afterwards were fewer among the vaccinated.

An additional concern is the ability of the virus to repeatedly infect the same individual, in spite of vaccination or natural immunity from past infection or both. The incremental damage caused by repeated infections is only beginning to be studied.

High death rate following COVID recovery occurred even before vaccine rollout
A large UK Biobank study showed that those who survived COVID in the pre-vaccine era also experienced a substantial five-fold increased risk of death over a prolonged period of time, after recovering from the infection. This negates the popular theory that deaths only started after vaccines were rolled out. This study was published in Cardiovascular Research, June 2023.

Sudden deaths occurred even before the pandemic
Social media discussions may have started only recently, but sudden deaths among younger adults have been occurring persistently in the past. This was detailed in my prior article.

In a study published in Asia Pacific Journal of Public Health in 2011, the yearly risk of heart-related deaths among young men aged 35-45 in Kerala was reported as 59 per 100,000. This equates to an annual risk of 1 in 1,700 for men, the rates among women being one-third of this.

In South Asian countries, the average age of suffering a heart attack is only 53, which means that half of those who get a heart attack are below the age of 53. The INTERHEART study published in The Lancet in 2007 points out that risk factors such as hypertension, diabetes, abdominal obesity, lack of exercise and sedentary lifestyle, heavy alcohol use, high LDL cholesterol are common among people in the subcontinent.

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What can be done to reduce the risk of sudden deaths?
1. Avoid smoking and excessive alcohol use.
2. Avoid a sedentary lifestyle, engage in regular exercise.
3 Eat a balanced diet, reducing the intake of trans fats.
4. Individuals with obesity, diabetes, hypertension, or hyperlipidemia need to know their numbers and take control of these modifiable risk factors.
5.Those experiencing symptoms such as chest pain, fatigue, palpitations, and shortness of breath must consult with their doctor.
6. Individuals with a family history of sudden deaths should inquire about the need for additional preventive measures.
7. Those who have had a severe bout of COVID should not rush to resume exercises, especially of the strenuous type.
(Dr Rajeev Jayadevan is past President, IMA Cochin, Public Health Advisory Panel, Kerala State IMA)

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