Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: A retrospective study

Abstract

Background Safety monitoring of coronavirus disease 2019 (COVID-19) vaccines is crucial during mass vaccination rollout to inform the choice of vaccines and reduce vaccine hesitancy. Considering the scant evidence directly comparing the safety profiles of mRNA and inactivated SARS-CoV-2 vaccines, this territory-wide cohort study aims to compare the incidence of various adverse events of special interest (AESIs) and all-cause mortality between CoronaVac (inactivated vaccine) and BNT162b2 (mRNA-based vaccine). Our results can help vaccine recipients make an informed choice. Methods and findings A retrospective, population-based cohort of individuals who had received at least 1 dose of BNT162b2 or CoronaVac from 23 February to 9 September 2021 in Hong Kong, and had data linkage to the electronic medical records of the Hong Kong Hospital Authority, were included. Those who had received mixed doses were excluded. Individuals were observed from the date of vaccination (first or second dose) until mortality, second dose vaccination (for first dose analysis), 21 days after vaccination, or 30 September 2021, whichever came first. Baseline characteristics of vaccinated individuals were balanced between groups using propensity score weighting. Outcome events were AESIs and all-cause mortality recorded during 21 days of post-vaccination follow-up after each dose, except anaphylaxis, for which the observation period was restricted to 2 days after each dose. Incidence rate ratios (IRRs) of AESIs and mortality comparing between CoronaVac and BNT162b2 recipients were estimated after each dose using Poisson regression models. Among 2,333,379 vaccinated individuals aged 18 years or above, the first dose analysis included 1,308,820 BNT162b2 and 955,859 CoronaVac recipients, while the second dose analysis included 1,116,677 and 821,560 individuals, respectively. The most frequently reported AESI among CoronaVac and BNT162b2 recipients was thromboembolism (first dose: 431 and 290 per 100,000 person-years; second dose: 385 and 266 per 100,000 person-years). After the first dose, incidence rates of overall AESIs (IRR = 0.98, 95% CI 0.89–1.08, p = 0.703) and mortality (IRR = 0.96, 95% CI 0.63–1.48, p = 0.868) associated with CoronaVac were generally comparable to those for BNT162b2, except for Bell palsy (IRR = 1.95, 95% CI 1.12–3.41, p = 0.018), anaphylaxis (IRR = 0.34, 95% CI 0.14–0.79, p = 0.012), and sleeping disturbance or disorder (IRR = 0.66, 95% CI 0.49–0.89, p = 0.006). After the second dose, incidence rates of overall AESIs (IRR = 0.97, 95% CI 0.87–1.08, p = 0.545) and mortality (IRR = 0.85, 95% CI 0.51–1.40, p = 0.516) were comparable between CoronaVac and BNT162b2 recipients, with no significant differences observed for specific AESIs. The main limitations of this study include residual confounding due to its observational nature, and the possibility of its being underpowered for some AESIs with very low observed incidences. Conclusions In this study, we observed that the incidences of AESIs (cumulative incidence rate of 0.06%–0.09%) and mortality following the first and second doses of CoronaVac and BNT162b2 vaccination were very low. The safety profiles of the vaccines were generally comparable, except for a significantly higher incidence rate of Bell palsy, but lower incidence rates of anaphylaxis and sleeping disturbance or disorder, following first dose CoronaVac versus BNT162b2 vaccination. Our results could help inform the choice of inactivated COVID-19 vaccines, mainly administered in low- and middle-income countries with large populations, in comparison to the safety of mRNA vaccines. Long-term surveillance on the safety profile of COVID-19 vaccines should continue. In a retrospective study, Carlos King Ho Wong, Kristy Tsz Kwan Lau, and colleagues study adverse events reported following COVID-19 vaccination in Hong Kong. Author summary Why was this study done? Various SARS-CoV-2 vaccines have been developed for coronavirus disease 2019 (COVID-19) prevention to reduce the risks of severe disease and death; however, vaccine hesitancy due to fear of adverse reactions remains a barrier to mass uptake. Continuous post-marketing surveillance of vaccine safety is crucial to guide informed decision-making and promote vaccine uptake in the community. There is very limited evidence directly comparing the safety profiles of mRNA-based and inactivated SARS-CoV-2 vaccines. What did the researchers do and find? A territory-wide retrospective cohort study of individuals who had received at least 1 dose of BNT162b2 (mRNA-based vaccine, Comirnaty) or CoronaVac (inactivated SARS-CoV-2 vaccine) from 23 February to 9 September 2021 in Hong Kong was conducted to compare the occurrence of selected adverse events of special interest (AESIs) and all-cause death between recipients of the 2 vaccines during 21 days of follow-up after the first and second doses. The incidence of overall AESIs was very low for both vaccines (cumulative incidence rate of 0.06%–0.09%), and the most frequently reported AESI among CoronaVac and BNT162b2 recipients was thromboembolism (first dose: 431 and 290 per 100,000 person-years; second dose: 385 and 266 per 100,000 person-years). The incidence rates of overall AESIs and all-cause death were comparable between CoronaVac and BNT162b2 recipients after the first and second doses, except for a higher incidence rate of Bell palsy, and lower incidence rates of anaphylaxis and sleeping disturbance or disorder, following first dose CoronaVac versus BNT162b2 vaccination. What do these findings mean? Both vaccines had similarly acceptable safety profiles, and the risks of AESIs and all-cause death following CoronaVac or BNT162b2 vaccination were very low, which adds to the real-world evidence on the safety of both COVID-19 vaccines, and may help reduce vaccine hesitancy by addressing safety concerns. Our results may inform the public about the choice of COVID-19 vaccines, and governments about the allocation of healthcare resources for monitoring specific AESIs during vaccine rollout (especially for Bell palsy among first dose CoronaVac recipients, and anaphylaxis and sleeping disturbance or disorder among first dose BNT162b2 recipients). As currently done for mRNA vaccines, clinical data and observational reports of all COVID-19 vaccines should be made publicly available in a timely manner, and long-term monitoring of their safety profiles should continue.