Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

ABSTRACT

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.