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Nationwide Safety Surveillance of COVID-19 mRNA Vaccines Following Primary Series and First Booster Vaccination in Singapore
21 Pages Posted: 16 Feb 2023
More...Abstract
Background: The real-world safety profile of COVID-19 mRNA vaccines remains incompletely understood. We sought to identify and validate potential safety signals associated with COVID-19 mRNA vaccines.
Methods: We performed a nationwide post-market safety surveillance analysis in vacinees aged 5 years and above, up till 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 via 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 [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. On stratified analyses, males aged 12 to 17 exhibited the 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 series vaccination. CVT was also predominantly observed in males aged 50 years accounting for 11 out of 16 cases occurring within 42-days of vaccination.
Interpretation: Our surveillance programme applying O/E and SCCS analyses has corroboratively identified three salient safety signals of myocarditis/pericarditis, appendicitis and CVT associated with COVID-19 mRNA vaccines, when used as primary series vaccination in a setting with very few COVID-19 infections. Of these, the risk of myocarditis/pericarditis continues to be elevated after booster dose 1. The other AESIs such as acute myocardial infarction, strokes and pulmonary embolism were not associated with an elevated risk. Males at various ages appear to exhibit a higher risk of all three AEs identified.
Funding: Nil.
Declaration of Interest: All authors declare no conflicts of interest.
Keywords: Pharmacovigilance, active surveillance, vaccine safety, COVID-19 mRNA vaccines, signal detection, signal validation
Suggested Citation: Suggested Citation