Sudden Death in the Young in India in the Postpandemic Period: Time for Action

Sudden unexplained death in young (SUDY) individuals is a tragic event reported from various parts of the country, causing concern among the public and the medical community. There is a growing concern that the incidence has increased over the past few years, particularly following the coronavirus disease 2019 (COVID-19) pandemic. It is a devastating event not only for the affected families but also for society, as it has significant psychosocial impacts. Many prominent figures, including actors and sports personalities, have died suddenly, leading to public outcry, fear, and excessive caution.[1] Reports of young people dying suddenly in schools, playgrounds, and dance floors have been documented from various locations, including rural areas. Terms such as Sudden Death (SD), Sudden Cardiac Death (SCD), and Sudden Out-of-Hospital Cardiac Arrest are used to describe these events; therefore, their definitions may vary depending on the criteria applied. SCD is defined as death occurring within an hour of symptom onset due to underlying cardiac disease.[2] Following reports of increased cases during the immediate post-COVID-19 period and after large-scale vaccinations, concerns were raised in the media that COVID vaccines or COVID-19 itself could trigger SUDY incidents. To investigate this, the Indian Council of Medical Research (ICMR) conducted a multicenter case–control study from 2021 to 2023, involving 47 tertiary care centers across 19 states and Union Territories, analyzing 721 cases of sudden, unexplained death in individuals aged 18–45 years. The study found no link between COVID vaccination and SUDY. It identified the associations such as prior COVID-19 hospitalization, family history of SD, binge drinking within 48 h before the event, recreational drug use, and vigorous physical activity within 48 h before the event, which increased the risk of SD.[3] To date, this remains the only published evidence on factors influencing SUDY in India during the postpandemic period. India, with over 4.5 million reported COVID-19 cases and approximately 0.53 million deaths, has undertaken an extensive vaccination campaign, administering nearly 2.2 billion doses, which has covered more than 60% of its population with two doses. Although the study results should have dispelled doubts about SDs related to vaccines, some methodological concerns about the study process were raised. The high vaccination figures made it challenging to design a study to evaluate the relationship between COVID-19 vaccines and SUDY cases. Questions also arose about the appropriateness of the case–control design, with some experts suggesting that the study adds limited understanding of the recent surge in SDs. They propose a multidisciplinary approach involving pathologists, geneticists, and prospective study designs to improve robustness.[4] A few months ago, in Karnataka, following reports of an increase in SUDY cases, the Chief Minister appointed an expert committee to examine the rising incidents and investigate any potential link with COVID-19 vaccines.[5] The Government of India, however, strongly dismissed such concerns, reaffirming the findings of the ICMR study. It also referenced an interim analysis of 2214 deaths by the All-India Institute of Medical Sciences, New Delhi, which found that SUDY accounted for 8.1% (180 cases), with cardiovascular and respiratory causes being the predominant causes, and stated that there was no association with vaccination.[6-9] The Karnataka expert committee analyzed 251 patients under 45 years, admitted with acute coronary syndrome (ACS) at Sri Jayadeva Institute of Cardiology, Bangalore. They reported that traditional risk factors such as diabetes, hypertension, and smoking were the major causes of heart attacks in young individuals. However, since the committee studied patients with ACS and not SDs, they could not establish a causal link with COVID-19 or vaccination. Interestingly, 28.2% of these patients had no conventional cardiovascular risk factors. The committee recommended large prospective studies and autopsy procedures for SUDY cases; subsequently, SUDY was made a notifiable disease in Karnataka, and autopsies were mandated.[10,11] PAUCITY OF HARD DATA Despite ongoing debates in the media, hard data confirming or refuting trends of higher rates of SUDY in the postpandemic period are unavailable. Even before the pandemic, India had a high prevalence of cardiovascular disease (CVD) compared to Western populations, especially among the young. India accounts for one-fifth of global cardiovascular mortality, with age-standardized CVD death rates of 272 per 100,000 people, compared to the global average of 235.[12] The prevalence of coronary artery disease (CAD) in India is 21.4% among diabetics and 11% among nondiabetics. In rural areas, CAD prevalence is nearly half that of urban regions.[12] CAD affects 12%–16% of young people in India, particularly those aged 35–65 years, at a rate higher than other ethnic groups. About half of CVD deaths occur in India before the age of 50 years and 25% of acute myocardial infarction (MI) cases happen in individuals under 40 years. CAD tends to develop in Indians 5 to 10 years earlier than in other populations. Notably, younger Asian women have worse 28-day survival rates after acute MI.[13] These factors suggest that Indians already face a higher baseline risk of increased CVD. However, whether there is a trigger in the postpandemic period remains unconfirmed due to a lack of data. No reliable data exist on age-standardized mortality figures and cause-specific mortality for young people in the postpandemic period. Available data from the National Crime Records Bureau (NCRB) show a consistent increase in SDs due to heart attacks from 2021 to 2023. In 2023, 63,643 SDs were reported to the NCRB, compared to 56,450 in 2022 – a 12.7% increase. SDs due to heart attacks numbered 35,715 in 2023, up from 32,457 in 2022 – a 10% rise.[14] For comparison, total SDs in 2019 numbered 47,295, with 28,579 caused by heart attacks, indicating a 34.7% increase in overall SDs and a 25% increase in heart attack-related deaths between 2019 and 2023. Although these numbers included all age groups, individuals under 45 constituted 43% to 46% of total SDs in 2019 and 2023, respectively. In 2023, 29,147 people under 45 experienced SD, compared to 20,179 in 2019 – a 44% rise. The age group 45–60 years had the highest percentage of SDs at 34%, while those under 45 years contributed nearly 46% of all SDs. A graphical analysis of data from 2015 to 2023 shows a steady increase with a marked upward trend from 2021 onward [Figure 1]. The age-wise SDs show a steady rise in numbers in the 18–30 and 30–45 years’ age groups, with a noticeable upward trend from 2021 [Figure 2]. In the absence of other nationally representative data, these figures suggest shifting trends in the postpandemic period, although some limitations in generalizability exist. These trends underscore the need for further investigation using more comprehensive national datasets. Analyzing quarterly age-standardized mortality trends over the past decade, with P-charts for SDs as a proportion of total mortality, could help determine whether there has been a real increase in SDs among young people in India.Figure 1: Trends in sudden deaths (SDs), heart attacks and SD due to other causes from 2015 to 2023 (created with data from National Crime Records Bureau)[ 14 ]Figure 2: Trends in sudden death in different age groups of young (created with data from National Crime Records Bureau)[ 14 ]CORONAVIRUS DISEASE 2019 AND THE EFFECTS ON CARDIOVASCULAR DISEASE It has been well-known that COVID-19 was associated with an increase in cardiovascular complications throughout the pandemic. A study involving a large dataset from the US Department of Veteran Affairs, involving 153,760 individuals with COVID-19 and a control population of around 5 lakh contemporary controls and 5.8 lakh historic controls, showed that beyond 30 days of infection, individuals with COVID-19 had higher risks of cardiovascular events, cerebrovascular events, dysrhythmias, pericarditis, myocarditis, heart failure, and thromboembolic episodes, and this risk was evident even in those who were not hospitalized. The risk increased in a graded fashion with the severity of illness and care settings.[15] During the pandemic, there were the reports of increased incidence of SCD and out-of-hospital cardiac arrest. Arrhythmias, thromboembolic episodes, and ACSs were some of the reasons attributed to SCD.[16] COVID-19 can cause microthrombi, resulting in cardiovascular and cerebrovascular complications. India had the second highest number of COVID-19 infections in the world, and therefore, the impact of long COVID-19 on incident CVD in the postpandemic period needs to be explored CORONAVIRUS DISEASE 2019 VACCINES AND CARDIOVASCULAR EVENTS COVID-19 vaccines have been widely administered in India, with about 2.2 billion doses given so far. The reported rate of adverse events following immunisation (AEFI) is 0.007%.[17] Although this percentage is very low, the total number remains significant given the large vaccinated population. Myocarditis was the most common cardiovascular event after mRNA vaccines, while adenovirus vector vaccines were very rarely linked to thrombocytopenia with thrombosis, especially in young women. In a systematic review, autopsy findings were assessed to determine the causal relationship between death and COVID-19 vaccines. The authors analyzed 38 cases from 17 papers and found that 22 cases were related to ChAdOx1 nCoV-19 vaccines, while 14 cases involved mRNA vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) was associated with the ChAdOx1 nCoV-19 vaccine, while myocarditis was linked to mRNA vaccines.[18] Autopsies revealed cerebral venous thrombosis, microthrombi, cerebral infarction, and hemorrhages. Infarcts and hemorrhagic areas were observed in individuals who died after receiving ChAdOx1 nCoV-19 vaccines. In another study from Italy, autopsy examinations in adults under 40 years with SCD showed no change in patterns compared to the prepandemic period. Analysis of SCD rates from 2018 to 2022 revealed no increase during the pandemic or after vaccination, and these rates remained consistent with prepandemic levels. No increased incidence of myocarditis was observed.[19] Another autopsy study from Thailand examining 34 deaths within 30 days of vaccination identified ischemic heart disease (IHD) as the most common cause of death and found no causal link between vaccines and death.[20] Therefore, while vaccine-related myocarditis and VITT are likely responsible for some immediate postvaccination deaths, these adverse effects are unlikely to explain the current surge in SCD. SUDDEN UNEXPLAINED DEATH IN YOUNG: NEED FOR A BROADER OUTLOOK The discussion surrounding SUDY has always focused on vaccines. Even the ICMR study and the expert group in Karnataka primarily focused on this question to explore any possible link with COVID-19 vaccines. This issue is complex and requires a multifaceted approach, with multidisciplinary studies being crucial. Since India already had a high baseline rate of IHD-related deaths before the pandemic, it is essential to determine whether the pandemic altered this trend, which must be clarified through well-designed epidemiological research. India experienced a heavy burden of COVID-19 cases; thus, examining the disease’s impact on the country’s existing CVD burden is necessary. Phase 4 postmarketing studies of COVID-19 vaccines, long-term follow-up of AEFI cases, and data sharing about major AEFIs will promote transparency and foster public trust. The influence of traditional risk factors, such as diabetes control, blood pressure management, physical activity, smoking, binge drinking, mental stress, and the use of anabolic steroids among young people for bodybuilding, should also be evaluated. Otherwise, we might miss the forest for the trees. The potential emergence of new risk factors and genetic susceptibilities must be investigated. Leading research institutions in India should undertake long-term prospective studies to address this urgent issue of SUDY and identify strategies to prevent these tragic events. Having reliable, nationwide data stratified by age and sex is critically important, and every effort should be made to ensure prompt notification. The death of every young person causes significant social, economic, and psychological suffering for families, and it is our collective responsibility as the scientific community to take this issue seriously and work toward prevention. The scientific community, government, and citizen groups must collaborate to develop the evidence-based solutions, rather than relying on assumptions or denials.