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

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.

Fig. 1

Observed/Expected analyses for selected AESIs with mRNA vaccination Primary series for vaccines aged 12 years and above with two distinct risk period definitions. All cases in the ‘Day 0 to Day 21′ analyses are also included in the ‘Day 0 to Day 42′ analyses.

Fig. 2

Observed/Expected analyses for selected AESIs with mRNA vaccination Booster Dose 1 through 31 July 2022 for vaccinees aged 12 years and above with two distinct risk period definitions. All cases in the ‘Day 0 to Day 21′ analyses are also included in the ‘Day 0 to Day 42′ analyses.

Fig. 3

Observed/Expected analyses for selected AESIs with mRNA vaccination through July 31, 2022, in children aged five to 11 years of age with two distinct risk period definitions. All cases in the ‘Day 0 to Day 21′ analyses are also included in the ‘Day 0 to Day 42′ analyses.