Factors associated with unexplained sudden deaths among adults aged 18-45 years in India – A multicentric matched case–control study
Authors: Ponnaiah Manickam , Bhatnagar Tarun , Abdulkader Rizwan Suliankachi , Elumalai Rajalakshmi , Surya Janani , Jeyashree Kathiresan , Kumar Muthusamy Santhosh , Govindaraju Ranjithkumar , Thangaraj Jeromie Wesley Vivian , Aggarwal Hari Krishan , Balan Suresh , Baruah Tridip Dutta , Basu Ayan , Bavaskar Yogita , Bhadoria Ajeet Singh , Bhalla Ashish , Bhardwaj Pankaj , Bhat Rachana , Chakravarty Jaya , Chandy Gina Maryann , Gupta Bal Kishan , Kakkar Rakesh , Karnam Ali Hasan Faiz , Kataria Sushila , Khambholja Janakkumar , Kumar Dewesh , Kumar Nithin , Lyngdoh Monaliza , Meena M. Selva , Mehta Kedar , Sheethal M. P. , Mukherjee Subhasis , Mundra Anuj , Murugan Arun , Narayanan Seetharaman , Nathan Balamurugan , Ojah Jutika , Patil Pushpa , Pawar Sunita , Ruban A. Charles Pon , Vadivelu R. , Rana Rishabh Kumar , Boopathy S. Nagendra , Priya S. , Sahoo Saroj Kumar , Shah Arti , Shameem Mohammad , Shanmugam Karthikeyan , Shivnitwar Sachin K. , Singhai Abhishek , Srivastava Saurabh , Sulgante Sudheera , Talukdar Arunansu , Verma Alka , Vohra Rajaat , Wani Rabbanie Tariq , Bathula Bhargavi , Kumari Gayathri , Kumar Divya Saravana , Narasimhan Aishwariya , Krupa N. C. , Senguttuvan Thirumaran , Surendran Parvathi , Tamilmani Dharsikaa , Turuk Alka , Kumar Gunjan , Murkherjee Aparna , Aggarwal Rakesh , Murhekar Manoj Vasant ,   Sudden Adult Deaths Study Group
Published: November 2023

Background & objectives:
In view of anecdotal reports of sudden unexplained deaths in India’s apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case–control study.

Methods:
This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1st October 2021-31st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI).

Results:
Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not.

Interpretation & conclusions:
COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.