Nationwide safety surveillance of COVID-19 mRNA vaccines following primary series and first booster vaccination in Singapore

Sreemanee Raaj Dorajoo; Hui Xing Tan; Chun Hwee Desmond Teo; Jing Wei Neo; Yen Ling Koon; Jing Jing Amelia Ng; Mun Yee Tham; Pei Qin Belinda Foo; Li Fung Peck; Pei San Ang; Theen Adena Lim; Wang Woon Jalene Poh; Su Lin Dorothy Toh; Cheng Leng Chan; Ian Douglas; Bee Leng Sally Soh

doi:10.1016/j.jvacx.2023.100419

Nationwide safety surveillance of COVID-19 mRNA vaccines following primary series and first booster vaccination in Singapore

Vaccine X. 2023 Dec 2:15:100419. doi: 10.1016/j.jvacx.2023.100419. eCollection 2023 Dec.

Authors

Sreemanee Raaj Dorajoo¹, Hui Xing Tan¹, Chun Hwee Desmond Teo¹, Jing Wei Neo¹, Yen Ling Koon¹, Jing Jing Amelia Ng¹, Mun Yee Tham¹, Pei Qin Belinda Foo¹, Li Fung Peck¹, Pei San Ang¹, Theen Adena Lim¹, Wang Woon Jalene Poh¹, Su Lin Dorothy Toh², Cheng Leng Chan², Ian Douglas³, Bee Leng Sally Soh¹

Affiliations

¹ Vigilance & Compliance Branch, Health Products Regulation Group, Health Sciences Authority, Singapore.
² Health Products Regulation Group, Health Sciences Authority, Singapore.
³ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical, Medicine, London, United Kingdom.

Abstract

Background: The real-world safety profile of COVID-19 mRNA vaccines remains incompletely elucidated.

Methods: We performed a nationwide post-market safety surveillance analysis in Singapore, on vacinees aged 5 years and older, through mid-September 2022. Observed-over-expected (O/E) analyses were performed to identify potential safety signals among eight shortlisted adverse events of special interest (AESIs): strokes, cerebral venous thrombosis (CVT), acute myocardial infarction, myocarditis/pericarditis, pulmonary embolism, immune thrombocytopenia, convulsions and appendicitis. Self-controlled case series analyses (SCCS) were performed to validate signals of concern, occurring within 42 days of vaccination.

Findings: Elevated risks were observed on O/E analyses for the following AESIs: myocarditis/pericarditis, [rate ratio (RR): 3.66, 95 % confidence interval (95 % CI): 2.71 to 4.94], appendicitis [RR: 1.14 (1.02 to 1.27)] and CVT [RR: 2.11 (1.18 to 3.77)]. SCCS analyses generated corroborative findings: myocarditis/pericarditis, [relative incidence (RI): 6.96 (3.95 to 12.27) at 1 to 7 days post-dose 2], CVT [RI: 4.30 (1.30 to 14.20) at 22 to 42 days post-dose 1] and appendicitis [RI: 1.31 (1.03 to 1.67) at 1 to 7 days post-dose 1]. Booster dose 1 continued to be associated with higher rates of myocarditis/pericarditis on O/E analysis [RR: 2.30, (1.39 to 3.80) and 1.69, (1.11 to 2.59)] at 21- and 42-days post-booster dose 1, respectively. Males aged 12 to 17 exhibited highest risks of both myocarditis/pericarditis [RI: 6.31 (1.36 to 29.3)] and appendicitis [RI: 2.01 (1.12 to 3.64)] after primary vaccination. Similarly, CVT was also predominantly observed in males aged above 50 (11 out of 16 cases), within 42-days of vaccination.

Interpretation: Our data suggest that myocarditis/pericarditis, appendicitis and CVT are associated with primary vaccination using COVID-19 mRNA vaccines. Males at specific ages exhibit higher risks for all three AEs identified. The risk of myocarditis/pericarditis continues to be elevated after booster dose 1.

Keywords: Active surveillance; Covid-19 mRNA vaccines; Pharmacovigilance; Signal detection; Signal validation; Vaccine safety.