A comprehensive territory-wide cohort study in Hong Kong has provided crucial comparative safety data between two major COVID-19 vaccine platforms, revealing reassuringly low rates of serious adverse events for both the inactivated CoronaVac vaccine and the mRNA BNT162b2 vaccine.
The study, published in PLOS Medicine, analyzed data from over 2.2 million vaccine recipients between February and September 2021, representing one of the largest head-to-head comparisons of these vaccine platforms. Researchers found cumulative incidence rates of adverse events of special interest (AESIs) ranging from 0.06% to 0.09% for both vaccines, with all-cause mortality rates remaining very low.
Key Safety Findings
The analysis revealed generally comparable safety profiles between the two vaccines after adjusting for baseline patient characteristics. However, several notable differences emerged for first-dose recipients. CoronaVac recipients showed a significantly higher incidence rate of Bell's palsy compared to BNT162b2 recipients, while BNT162b2 recipients experienced higher rates of anaphylaxis and sleeping disturbances or disorders.
"Despite the slightly higher crude incidence rates of overall AESIs among CoronaVac recipients than among BNT162b2 recipients, the incidence rates of overall AESIs and all-cause mortality were comparable between the 2 vaccines after weighting," the researchers noted.
Importantly, these significant associations did not persist during the follow-up period after second-dose vaccination, suggesting the differences were primarily related to initial immune responses.
Anaphylaxis and Allergic Reactions
The study confirmed previous observations regarding anaphylaxis rates. BNT162b2 vaccination was associated with higher rates of anaphylaxis, ranging from 4.7 to 13.7 per million doses in previous studies, compared to an estimated rate of 2.2 per million doses for CoronaVac. The researchers attributed this difference to potential allergens in each vaccine platform - polyethylene glycol (PEG) excipient in BNT162b2 versus inactivated virus fragments and aluminum hydroxide adjuvant in CoronaVac.
Neurological Events
Bell's palsy emerged as a significant finding, with CoronaVac recipients showing higher incidence rates, particularly after the first dose. The researchers noted that "autoimmunity might play a role in the development of Bell palsy, hence calling for an investigation into the immunomodulatory effects of viral antigens and adjuvants of different vaccine platforms."
The study was unable to perform statistical analysis for other neurological conditions like Guillain-Barré syndrome and transverse myelitis due to very few recorded cases, which the researchers noted as reassuring given the rarity of these serious conditions.
Cardiovascular Safety Profile
While the study recorded higher crude incidence rates of carditis among BNT162b2 recipients, particularly after the second dose, the small number of cases prevented detailed statistical analysis. The researchers attributed this partly to their exclusion of individuals under 18 years old, as significantly increased risks of acute myocarditis or pericarditis have been identified among male adolescents following BNT162b2 vaccination in local studies.
For other cardiac events including arrhythmia, coronary artery disease, and myocardial infarction, no significant differences were identified between the two vaccine platforms.
Thrombotic Events
The analysis found no statistically significant differences in thrombotic and hemorrhagic events between CoronaVac and BNT162b2 recipients. This finding contrasts with adenoviral vector vaccines, which have been associated with rare thrombotic events. The researchers noted that "BNT162b2 vaccination does not seem to favor these outcomes, nor does the inactivated vaccine CoronaVac."
Study Strengths and Limitations
The research leveraged Hong Kong's unique position as one of the few regions offering both vaccine platforms simultaneously, allowing for direct comparison. The large sample size and population-based design provided substantial statistical power to detect rare adverse events.
However, the researchers acknowledged several limitations, including potential residual confounding despite propensity score weighting, possible underreporting of events managed in private healthcare settings, and insufficient power to draw definitive conclusions about very rare adverse events.
Global Implications
The findings have particular relevance for low- and middle-income countries where inactivated COVID-19 vaccines like CoronaVac are predominantly used. The study provides reassurance about the safety profile of inactivated vaccines compared to the extensively studied mRNA platforms.
The researchers emphasized the importance of continued pharmacovigilance, stating that "clinical data and observational reports of COVID-19 vaccines should continue to be made publicly available for all vaccine platforms in a timely manner, as a means of facilitating the continuous monitoring of vaccine safety."
This comprehensive safety comparison reinforces that both vaccine platforms maintain excellent safety profiles, with the benefits of vaccination clearly outweighing the risks of rare adverse events. The study's findings support continued confidence in both vaccine technologies while highlighting the need for ongoing safety monitoring as vaccination programs evolve globally.
