Review: What Did the ICMR Study on Factors Associated With Unexplained Sudden Deaths Among Adults in India Find?

In the post COVID-19 times, speculation has arisen about potential links between COVID-19 and an increased risk of heart attacks in young adults. The matter was raised on multiple occasions in both the houses of the Indian Parliament. According to Health Ministry’s statement, ICMR was conducting three different studies to determine the facts regarding the apprehension of rising cases of cardiac arrest after COVID-19. Here is a review of the first one.

Gujarat’s Navratri celebrations are renowned worldwide for their energetic Garba dance. However, this year, the celebrations took a tragic turn as multiple incidents of sudden death from heart attacks were reported during garba. The victims were mostly teenagers and young adults, according to reports. Not just during the Navratri season, even otherwise, a sudden surge in cases of myocardial infarctions in youth and seemingly healthy persons has been a cause of concern in the post COVID-19 times. The concern is not restricted to India. Globally many countries have observed similar trends including UAE, USA, and Australia.

Often, heart attacks are linked to lifestyle-related risk factors. Consumption of foods high in saturated fats and sodium, like fast foods or processed meals, leading a sedentary lifestyle, smoking, alcohol, and drugs are some lifestyle choices that affect cardiovascular health. Additionally, health conditions like high blood pressure, high cholesterol, and diabetes also heighten the risk, as does the experience of chronic stress. Genetic factors also likely play some role in high blood pressure, heart disease, and other related conditions, as per the CDC. However, in the post COVID-19 times, speculation has arisen about potential links between COVID-19 and an increased risk of heart attacks.

Increase in heart attacks among young adults is being studied by ICMR

Governments and health authorities have acknowledged the concerns. The matter was raised on multiple occasions in both the Houses of the Indian Parliament. According to the Health Ministry’s statement, ICMR was conducting three different studies to determine the facts regarding the apprehension of rising cases of cardiac arrest after COVID-19. One of the studies, titled ‘Factors associated with sudden deaths among adults aged 18 – 45 years, India: multicentric matched case control study’ was published recently in the Indian Journal of Medical Research. Two more studies, one on the effect of COVID-19 vaccine and another study that seeks to explain the cause of deaths through physical and virtual autopsies are underway. The studies are reviewed and monitored by a committee of experts including epidemiologists, clinicians, pathologists, forensic medicine experts, and public health specialists.

729 cases and 2916 control subjects were covered in the ICMR study

The ICMR study that was recently published was conducted through the participation of 47 tertiary care hospitals across India. It focused on apparently healthy individuals aged 18 to 45 years, free from any known underlying health issues, who experienced sudden and unexplained deaths between 01 October 2021 and 31 March 2023. The criteria for selecting cases involved individuals who had been seemingly healthy, without any known chronic health conditions, and who suddenly died within 24 hours of hospitalization or were observed to be healthy 24 hours before their unexpected death.

A total of 29,171 sudden deaths were identified out of which the records of 729 cases as well as 2,916 control subjects were included in the analysis. That is, for every case, there were four other individuals selected specifically to closely resemble the case based on similar characteristics such as age, gender, and living in the same or similar neighbourhood. Details of medical history, smoking, alcohol use, intense physical activity, hospitalization due to COVID-19, and vaccination status were collected.

Hospitalization due to COVID-19, poor lifestyle, and family history have been positively associated to unexpected deaths

The key findings of the study are as follows:

• COVID-19 vaccination did not increase the risk of unexplained sudden deaths among young adults in India. Nonetheless, the odds of unexplained sudden death were lower for those who had taken two doses of the vaccine.
• Binge drinking 48 hours before death/interview was associated with unexplained sudden deaths. Further, a higher frequency of alcohol use correlated with increased odds of unexplained sudden death compared to never users. The use of recreational drugs also increased the odds.
• Past COVID-19 hospitalization and family history of sudden death were positively associated with unexplained sudden death among young Indians. Patients with unexplained sudden death were found to be four times more likely to have been hospitalized for COVID-19 while family history of sudden death was almost three times more likely to be associated with unexplained sudden death.
• Individuals who participated in vigorous physical activities within the 48 hours leading up to their sudden unexplained death, were more likely to experience this event compared to those who did not engage in such activities.

It should be noted that the ICMR study has its own limitations. Some of them are:

• Potential Misclassification: There’s a possibility that some cases or controls might have been misclassified due to incomplete information about the cause of death or lack of documentation regarding medications.
• Documentation of Cases: Most of the cases involved witnessed deaths, which likely had better documentation of medical history or diagnosis, making them more reliable for analysis. For unwitnessed deaths, verbal autopsies were conducted by trained investigators followed by medical cause assignment by clinicians.
• Selection of Controls: There could have been bias in selecting controls if some potential interviewees were unavailable.
• Information Bias: Data collection might have suffered from information bias, especially regarding vaccination status and lifestyle risk factors like alcohol or substance use.

Other research studies have also highlighted the heightened risk of cardiovascular conditions in those infected with COVID-19

Even before the ICMR study was published, many other international studies corelated COVID-19 infection with cardiovascular diseases.

A large Lancet study conducted in the USA analysed the medical records of over 6.91 lakh persons who tested positive for COVID-19. The mean age of the group was 43 years. Those who were vaccinated were excluded from the study. The study found that the COVID-19 survivors have higher risks of cardiovascular complications, including cerebrovascular complications, arrhythmia, inflammatory or ischemic heart disease, and thromboembolic disorders than those who did not test positive or exhibit symptoms. An analysis of different sub-groups in the study showed that the risks of myocarditis (inflammation of the heart) and ischemic cardiomyopathy (weakened heart muscle) were the top two risks in younger COVID-19 survivors aged 20−44 years.

Another study published in 2022 noted that prior to the pandemic, deaths due to Acute Myocardial Infarction (AMI) had reduced. However, the trends were reversed since the pandemic outbreak. Excess deaths, or the difference between the observed and the predicted mortality rates, were most pronounced for the 25- to 44-year-old age group. One reason for this has been cited as the possibility that COVID-19 infection may have exacerbated the development of pre-existing heart conditions. It also added that psychological stressors associated with the pandemic such as job loss and other financial pressures may have also contributed to this.

While the ICMR study did not find any positive association of vaccines with sudden deaths, a study published in the British Medical Journal found that adolescent and young adult men are at the highest risk of myocarditis after mRNA vaccination for COVID-19. However, the incidence of myocarditis after mRNA vaccination among males was 50-139 cases per million in 12- to 17-year-olds and 28-147 cases per million in 18- to 29-year-olds. The mRNA vaccines considered in the study were that of Moderna and Pfizer. These vaccines were not bought by the Indian Government.

Heart diseases have been a concern in India even prior to the pandemic

Even before COVID-19, heart diseases contributed 28.1% of the total deaths in India in 2016 compared to 15.2% in 1990 for the 18 to 69 year-old age group, according to a 2017 ICMR study report indicating an increasing trend in cardiovascular diseases. It associated tobacco use, alcohol use, insufficient physical activity, and unhealthy diet with the prevalence of non-communicable diseases. The impact of such behavioural risk factors can reflect raised blood pressure, diabetes, cholesterol, overweight, and obesity.  During the pandemic too, the unforeseen restrictions have brought significant changes to lifestyle and mental health which may have added to the increased prevalence of non-communicable diseases.

Considering the increasing cases and growing concerns, research should be promoted by the government to understand the issue in detail. Currently, as highlighted by a standing committee report, ‘grossly insufficient funds’ are allocated to research councils in India.