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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

See all articles by Sreemanee Raaj Dorajoo

Sreemanee Raaj Dorajoo

Health Sciences Authority - Vigilance & Compliance Branch

Hui Xing Tan

Health Sciences Authority - Vigilance & Compliance Branch

Teo Chun Hwee Desmond

Health Sciences Authority - Vigilance & Compliance Branch

Neo Jing Wei

Health Sciences Authority - Vigilance & Compliance Branch

Koon Yen Ling

Health Sciences Authority - Vigilance & Compliance Branch

Ng Jing Jing Amelia

Health Sciences Authority - Vigilance & Compliance Branch

Tham Mun Yee

Health Sciences Authority - Vigilance & Compliance Branch

Foo Pei Qin Belinda

Health Sciences Authority - Vigilance & Compliance Branch

Peck Li Fung

Health Sciences Authority - Vigilance & Compliance Branch

Ang Pei San

Health Sciences Authority - Vigilance & Compliance Branch

Lim Theen Adena

Health Sciences Authority - Vigilance & Compliance Branch

Jalene Poh

Health Sciences Authority - Vigilance & Compliance Branch

Toh Su Lin Dorothy

Health Sciences Authority - Health Products Regulation Group

Chan Cheng Leng

Health Sciences Authority - Health Products Regulation Group

Douglas Ian

London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health

Soh Bee Leng Sally

Health Sciences Authority - Vigilance & Compliance Branch

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

Dorajoo, Sreemanee Raaj and Tan, Hui Xing and Desmond, Teo Chun Hwee and Wei, Neo Jing and Ling, Koon Yen and Amelia, Ng Jing Jing and Yee, Tham Mun and Belinda, Foo Pei Qin and Fung, Peck Li and San, Ang Pei and Adena, Lim Theen and Poh, Jalene and Dorothy, Toh Su Lin and Leng, Chan Cheng and Ian, Douglas and Sally, Soh Bee Leng, Nationwide Safety Surveillance of COVID-19 mRNA Vaccines Following Primary Series and First Booster Vaccination in Singapore. Available at SSRN: https://ssrn.com/abstract=4357996 or http://dx.doi.org/10.2139/ssrn.4357996

Sreemanee Raaj Dorajoo

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Hui Xing Tan

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Teo Chun Hwee Desmond

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Neo Jing Wei

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Koon Yen Ling

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Ng Jing Jing Amelia

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Tham Mun Yee

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Foo Pei Qin Belinda

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Peck Li Fung

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Ang Pei San

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Lim Theen Adena

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Jalene Poh

Health Sciences Authority - Vigilance & Compliance Branch ( email )

Toh Su Lin Dorothy

Health Sciences Authority - Health Products Regulation Group ( email )

Chan Cheng Leng

Health Sciences Authority - Health Products Regulation Group ( email )

Douglas Ian

London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health ( email )

London, WC1E 7HT
United Kingdom

Soh Bee Leng Sally (Contact Author)

Health Sciences Authority - Vigilance & Compliance Branch ( email )

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