Table 1.
Clinical and genetic characteristics of Thai cases with SUD within 7 d of COVID-19 vaccinations
| No | Gender | Age (y) | Ethnic | Underlying disease | Type of vaccine∗ | Self-reported side effects | Days of death after vaccination | Forensic impression and autopsy findings | Gene† | DNA changes | Amino acid changes | Type of mutation | Zygosity | gnomAD |
Thai exomes (6462 alleles) | Reported in patients in PubMed or ClinVar | PubMed or ClinVar no. | ACMG (A) | SIFT (S) | Polyphen (P) | mCAP (m) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (alleles) | |||||||||||||||||||||
| I. Cases with variants in SCN5A (n = 5)‡ | |||||||||||||||||||||
| 1 | M | 23 | Thai | None | SV-AZ | Fever, headache, fatigue | 1 | Unexplained | SCN5A | c.3269C>T | p.Pro1090Leu | Missense | Hetero- | 411/245980 | 84 | BrS | 16344400, 15996170 | Y | |||
| SCN10A | c.1157T>G | p.Phe386Cys | Missense | Hetero- | 129/251388 | 16 | BrS, LQTS | 28407228, 24998131 | Y | Y | Y | ||||||||||
| 2 | M | 33 | Thai | Schizophrenia with clonazepam, diazepam, fluoxetine | SV-AZ | None | 1 | Unexplained | SCN5A | c.3578G>A | p.Arg1193Gln | Missense | Hetero- | 1414/272838 | 323 | BrS, atrioventricular block, and DCM | 16344400, 19808398 | ||||
| 3 | M | 43 | Thai | Asthma, gout | SV-SV-PZ | Fever, myalgia | 1 | DCM | SCN5A | c.833A>G | p.His278Arg | Missense | Hetero- | 1/152256 | 0 | BrS | 29202755 | Y | Y | Y | |
| 4 | M | 46 | Thai | Hyperthyroidism | SV | None | 3 | Unexplained | SCN5A | c.3578G>A | p.Arg1193Gln | Missense | Hetero- | 1414/272838 | 323 | BrS, atrioventricular block, and DCM | 16344400, 19808398 | ||||
| 5 | F | 28 | Thai | None | SV | None | 7 | Arrhythmogenic right ventricular dysplasia | SCN5A | c.3068G>A | p.Arg1023His | Missense | Hetero- | 72/279064 | 2 | BrS, LQTS | 16344400, 25935074 | Y | |||
| II. Cases with variants in non-SCN5A genes (n = 6) | |||||||||||||||||||||
| 6 | M | 35 | Thai | None | SP | Fever, pain in both knees | 1 | Unexplained | SCN3B | c.328G>A | p.Val110Ile | Missense | Hetero- | 77/251476 | 13 | BrS, sudden death of the young | 23257389, 27435932, 30662450 | Y | Y | ||
| 7 | M | 36 | Thai | Alcoholic hepatitis | SV-AZ | None | 1 | Unexplained | MYBPC3 | c.2807C>T | p.Thr936Met | Missense | Hetero- | 10/247610 | 0 | LVHT | 28798025 | Y | Y | Y | |
| Thai | Hetero- | ||||||||||||||||||||
| 8 | M | 38 | Thai | None | SP-SP | None | 1 | Coronary atherosclerosis | SLC22A5 | c.865C>T | p.Arg289Ter | Null | Hetero- | 4/251492 | 0 | PCD and SCD | 30863740, 26828774 | Y | |||
| SLC22A5 | c.1022G>A | p.Arg341Gln | Missense | Hetero- | 6/251448 | 2 | PCD and HCM | ClinVar:VCV000650541.1 | Y | Y | Y | ||||||||||
| 9 | M | 72 | Thai | None | AZ | Chest pain | 1 | Coronary atherosclerosis | TTN | c.20165-1G>A | N/A | Null | Hetero- | 6/244112 | 0 | DCM | ClinVar:VCV001053732.1 | ||||
| DNMT3A | c.939G>A | p.Trp313Ter | Null | Hetero- | 0 | 2 | DCM in Tatton-Brown-Rahman syndrome | 32435502 | |||||||||||||
| 10 | F | 53 | Thai | B-thalassemia§ | AZ | None | 1 | Thalassemia with liver cirrhosis | TTN | c.6668A>T | p.His2223Leu | Missense | Hetero- | 17/251140 | 48 | CM | 23861362 | Y | |||
| 11 | F | 59 | Thai | None | AZ | None | 1 | Coronary atherosclerosis | TTN | c.18530T>G | p.Leu6177Arg | Missense | Homo- | 26/273246 | 12 | SCD | 28704380 | ||||
| III. Cases with no candidate variants (n = 2) | |||||||||||||||||||||
| 12 | M | 34 | Thai | None | AZ | None | 1 | Unexplained | |||||||||||||
| 13 | M | 56 | Australian | None | MD | None | 4 | Coronary atherosclerosis | |||||||||||||
ACMG = The American College of Medical Genetics and Genomics; BrS = Brugada syndrome; CM = cardiomyopathy; COVID-19 = coronavirus disease 2019; DCM = dilated cardiomyopathy; F = female; HCM = hypertrophic cardiomyopathy; LQTS = long QT syndrome; LVHT = left ventricular hypertrabeculation; M = male; PCD = primary carnitine deficiency; SCD = sudden cardiac death; SUD = sudden unexplained death; Y = yes.
Vaccines: AZ: ChAdOx1 nCoV-19 (AstraZeneca); MD: mRNA-1273 (Moderna); PZ: BNT162b2 (Pfizer/BioNTech); SP: BBIBP-CorV (Vero Cells) (Sinopharm [Beijing]); SV: CoronaVac (Sinovac).
Transcripts used: SCN5A (NM_001099404.2), SCN10A (NM_006514.3), SCN3B (NM_018400.4), MYBPC3 (NM_000256.3), SLC22A5 (NM_003060.4), TTN (NM_001256850.1), DNMT3A (NM_022552.5).
In the last 4 columns, (A): pathogenic; (S) deleterious; (P): damaging; (m): pathogenic.
Compound heterozygous for p.Glu27Lys and p.Phe42Leufs∗19 in the HBB gene.