Self-reported adverse reactions less likely after inactivated CZ02 vs mRNA-based BNT162b2

A prospective cohort study by the University of Hong Kong comparing the reactogenicity of coronavirus disease 2019 (COVID-19) vaccines reports a lower risk of self-reported adverse reactions following vaccination with inactivated CZ02 compared with mRNA-based BNT162b2.

“No research has compared CZ02’s reactogenicity with mRNA vaccines, which are developed on a different technological platform and typically more widely used in Western countries. A prolonged absence of this important information may worsen the problem of vaccine hesitancy and hamper our efforts in the fight against the pandemic,” wrote the researchers. [Vaccines 2021;doi:10.1038/s41541-021-00336-1; Clin Infect Dis 2021;doi:10.1093/cid/ciab438; Brain Behav Immun 2021;94:41-50]

As of 5 July 2021, 1,129 participants receiving CZ02 and 969 receiving BNT162b2 were recruited and scheduled to complete the 14th-day follow-up survey for the second dose. Both groups had response rates exceeding 80 percent throughout the follow-up period. [Vaccine 2022;40:1390-1396]

Throughout the follow-up period, 48.1 percent of CZ02 recipients and 82.7 percent of BNT162b2 recipients reported adverse reactions of any type. The random-intercept logistic regression model used by the researchers suggested that, compared with BNT162b2, receiving CZ02 was associated with 83 percent reduced odds of any adverse reactions (adjusted odds ratio [aOR], 0.17; 95 percent confidence interval [CI], 0.15 to 0.20), 92 percent reduced odds of local adverse reactions (aOR, 0.08; 95 percent CI, 0.06 to 0.09), and 76 percent reduced odds of systemic adverse reactions (aOR, 0.24; 95 percent CI, 0.16 to 0.28). For all three subtypes of adverse reactions (local, systemic, and severe allergic), significantly increased odds were observed in the BNT162b2 group.

“It is possible that the general immune response induced by vaccination was weaker among those receiving CZ02 vs those receiving BNT162b2, potentially explaining the lower risk of adverse reactions following vaccination. However, further immunoepidemiologic studies are needed to test this hypothesis, because there is no direct relationship between side effects and protection,” stressed the researchers. [Lancet 2021;398:213-222; N Engl J Med 2020;383:2603-2615; The Lancet Microbe 2021;doi:10.1016/S2666-5247(21)00177-4; Human Vaccines & Immunotherapeutics 2021;17:2969-2971]

For both doses of both vaccines, pain at the injection site, tiredness, muscle pain, headache, and swelling at the injection site were the five most frequently reported adverse reactions.

Among study participants reporting any adverse reactions at any time point following the first dose of either vaccine, 65.6 percent reported adverse reactions at some point following the second dose. However, among those who did not have adverse reactions at any time point following the first dose, only 25.8 percent reported adverse reactions at some point following the second dose. For adverse reactions of any type, the odds were increased by 18 percent (aOR, 1.18; 95 percent CI, 1.01 to 1.37) for the second dose vs the first dose among CZ02 recipients, and by 106 percent (aOR, 2.06; 95 percent CI, 1.81 to 2.35) among BNT162b2 recipients.

“This first postmarketing study comparing the reactogenicity of the two vaccines in the same population should help shape the public’s expectation of the likelihood of adverse reactions with CZ02 as compared with the more widely investigated BNT162b2, and could be used for formulating vaccination or medical leave policies,” concluded the researchers. [Eurosurveillance 2021;doi:10.2807/1560-7917.ES.2021.26.17.2100420]