The strengths of this study include the low dropout rate, reflecting the good tolerability of the vaccine. Additionally, the participants were from different risk groups and occupations, rendering the results of the study more generalisable to the real-world context. Additionally, active symptom surveillance was pursued to detect COVID-19 cases.
This study also has several limitations. First, the median follow-up period after randomisation to the date of unmasking was 43 days (IQR 36–48), which is a very short duration of follow-up. It is not possible to comment on the long-term protective effects of the two-dose immunisation schedule with this interim analysis.
Second, one should bear in mind that the study population consisted of relatively young (median age 45 years [37–51]) and healthy individuals with a low prevalence of chronic diseases, and the overall event rate was very low. Therefore, the generalisability of the findings of this interim analysis needs to be evaluated cautiously. In particular, the number of patients hospitalised with COVID-19 was quite low and the study population consisted of individuals at relatively low risk of severe or critical COVID-19, restricting our ability to make generalised conclusions about severe disease.
Third, the study used a 14-day interval immunisation scheme, whereas the community immunisation was with a 28-day interval. It has been claimed that, although 28-day immunisation schemes elucidated better immunogenicity after the second dose, longer intervals between the two doses are correlated with a higher probability of contracting COVID-19 before getting fully immunised and a great chance of emergence of mutant variants that can replicate in the setting of suboptimal levels of neutralising antibodies.29 As our results pertain to the data before the emergence of variants of concern, we cannot comment on the efficacy of CoronaVac on the prevention of infection with mutant viruses. Although one of the prespecified outcomes was seroconversion, we have avoided using this term in our reporting of the results because the immunoassay we used was a semiquantitative assay. In fact, all of the participants were seronegative at the time of screening; therefore, the seropositivity 14 days after the second dose of vaccine would indicate seroconversion. However, we could not exclude the possibility that some samples with antibody levels below a sample-to-cutoff ratio of 1 might have very low concentrations of established antibodies. The current report neither involves data on the sequential serum neutralising antibody titres nor the magnitude of T-cell responses or the duration of protectivity. However, a study setting has been established to analyse the proliferation and functional capacity of CD4+ and CD8+ T cells, and the results of an initial study in a group of COVID-19 survivors have been reported by Tavukcuoglu and colleagues.30 This setting is now being used to analyse the samples from selected participants of this trial to show the functional capacity of T cells induced by CoronaVac to reinvigorate antiviral immunity against SARS-CoV-2.
In summary, our results show that CoronaVac has good efficacy against symptomatic SARS-CoV-2 infection and severe COVID-19 (ie, that requiring hospitalisation), along with a very good safety profile in a population aged 18–59 years. Because this analysis included a very short follow-up period before the emergence of viral variants and included a young and low-risk population, further data are needed on the performance of CoronaVac to demonstrate the efficacy of the vaccine against the variants of concern and the duration of protection, and to assess the safety and efficacy in older adult populations, adolescents, and children, and individuals with specific chronic diseases.