Ittiwut C.Mahasirimongkol S.Srisont S.Ittiwut R.Chockjamsai M.Durongkadech P.Sawaengdee W.Khunphon A.Larpadisorn K.Wattanapokayakit S.Wetchaphanphesat S.Arunotong S.Srimahachota S.Pittayawonganon C.Thammawijaya P.Sutdan D.Doungngern P.Khongphatthanayothin A.Kerr S.J.Shotelersuk V.Mahidol University2023-06-182023-06-182022-11-01Heart Rhythm Vol.19 No.11 (2022) , 1874-187915475271https://repository.li.mahidol.ac.th/handle/20.500.14594/85420Background: Severe acute respiratory syndrome coronavirus 2 vaccination reduces morbidity and mortality associated with coronavirus disease 2019 (COVID-19); unfortunately, it is associated with serious adverse events, including sudden unexplained death (SUD). Objective: We aimed to study the genetic basis of SUD after COVID-19 vaccination in Thailand. Methods: From April to December 2021, cases with natural but unexplained death within 7 days of COVID-19 vaccination were enrolled for whole exome sequencing. Results: Thirteen were recruited, aged between 23 and 72 years; 10 (77%) were men, 12 were Thai; and 1 was Australian. Eight (61%) died after receiving the first dose of vaccine, and 7 (54%) died after receiving ChAdOx1 nCoV-19; however, there were no significant correlations between SUD and either the number or the type of vaccine. Fever was self-reported in 3 cases. Ten (77%) and 11 (85%) died within 24 hours and 3 days of vaccination, respectively. Whole exome sequencing analysis revealed that 5 cases harbored SCN5A variants that had previously been identified in patients with Brugada syndrome, giving an SCN5A variant frequency of 38% (5 of 13). This is a significantly higher rate than that observed in Thai SUD cases occurring 8–30 days after COVID-19 vaccination during the same period (10% [1 of 10]), in a Thai SUD cohort studied before the COVID-19 pandemic (12% [3 of 25]), and in our in-house exome database (12% [386 of 3231]). Conclusion: These findings suggest that SCN5A variants may be associated with SUD within 7 days of COVID-19 vaccination, regardless of vaccine type, number of vaccine dose, and presence of underlying diseases or postvaccine fever.MedicineArticleSCOPUS10.1016/j.hrthm.2022.07.0192-s2.0-851392374791556387135934244