Introduction

SARS-CoV-2 Omicron variants dominated the COVID-19 pandemic in 2022. They were found with increased transmissibility1,2, and resistance from both naturally acquired and vaccine-elicited antibodies3,4, which was considered to be one of the major challenges for disease control. The Omicron variants continuously evolved with epidemiologic and virological characteristics for adaptation in the human population. As of 8 January 2023, the Omicron BA.5 subvariants are the dominating strain amidst the pandemic, accounting for 85.9% of viral sequences of human SARS-CoV-2 submitted to the Global Initiative on Sharing Avian Influenza Data (GISAID) from 9 December 2022 to 9 January 20235.

The increasing numbers of Omicron infections raised concerns, particularly for vulnerable populations including children and adolescents, who are often featured with higher contact rates (e.g., in school or household settings), and lower vaccine coverage than other age groups6. Although literature presented evidence suggesting that pediatric COVID-19 was rarely severe7,8,9, critical symptoms including the Multisystem Inflammatory Syndrome in Children (MIS-C)8,10 and long-COVID-19 may occur11. Besides, children and adolescents were found more susceptible to COVID-19 infection than adults, especially during an Omicron predominance phase12,13. Real-world observational studies demonstrated moderate effectiveness of mRNA COVID-19 vaccine (BNT162b2) against Omicron infection among children and adolescents14,15, and high vaccine effectiveness (VE) against hospitalization, death, and ICU admission16,17,18, though the protective effects waned quickly over time. To date, only a small number of studies have examined the VE of inactivated COVID-19 vaccines among children and adolescents19,20,21,22,23,24. Yet, none of these studies evaluated the VE against the Omicron subvariants (BA.5), which could provide additional insights into the protection of inactivated vaccines against the novel circulating SARS-CoV-2 variants.

From the standpoint of outbreak control, cutting off the transmission chain is one of the most effective measures apart from vaccination. Children and adolescents played an essential role in transmissions that occurred in household and school settings25,26. Despite early studies suggesting a lower transmission risk, as indicated by a lower secondary attack ratio (SAR) of children index cases than that of adult index cases for the ancestral SARS-CoV-2 strains27, children infected by the early Omicron variants were found more transmissible than adults28. Monitoring the transmission risks of children and adolescents infected by the emerging Omicron subvariants was urgently needed across different strata of risk factors and settings, given the rapid expansion of Omicron infections. Furthermore, the data regarding the VE against transmission among children and adolescents remains scarce29,30, which can shed light on the protection of vaccines against the risks of onward transmission seeded by children and adolescents.

From 1 August to 7 September 2022, Urumqi city, China experienced an outbreak seeded by the Omicron BA.5 variants. A series of stringent public health and social measures (PHSMs) have been implemented in response to the epidemics, including the city-wide lockdown, mass testing, contact tracing, and case isolation. Since August 3, 2021, China has recommended the inactivated vaccine rollout for children and adolescents aged 3–17 years, and Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac) were the only two types of COVID-19 vaccine approved to be used in Urumqi city, where Sinopharm was the majority with >85% among vaccinated population (internal data from Urumqi CDC).

In this study, by leveraging detailed contact tracing data, we aim to assess the transmission characteristics of Omicron BA.5 among children and adolescents and the protective effectiveness of inactivated vaccines against the infection and transmission of the BA.5 variants. We estimate that the BA.5 variant has a relatively high risk of transmission among children and adolescents contacts in household while with considerable superspreading potential in non-household settings. We show that a second dose of inactivated vaccine within a year was associated with a substantial reduction in transmission risk in children and adolescents, as compared to a one-dose or dated second-dose vaccine. These findings underscore the need for monitoring the effectiveness of COVID-19 vaccines and the transmission potential among younger populations infected with emerging SARS-CoV-2 variants.

Methods

Study design and participants

This was a retrospective cohort analysis for SARS-CoV-2 infections and close contacts aged 0–17 years during an Omicron BA.5 outbreak in Urumqi, China. Children and adolescent close contacts and infected, and their close contacts were included in the screening. Owning to the zero-COVID policy (implemented before November 2022) in mainland China, no large-scale COVID-19 outbreak occurred in Urumqi before August 2022, which means that the 3.8 million population was largely infection-naïve, and thereby the likelihood of re-infection was negligible. The COVID-19 vaccines received by almost all vaccinees in mainland China were Sinopharm and Sinovac vaccines, which were recommended and administered under the supervision of Chinese authorities for those aged over 3 years.

De-identified individual-level line-list surveillance data was obtained from the ** marts, restaurants, and entertainment settings) were conducted. Thus, the number of exposure or contact was generally lower in the population, which gave rise to a lower risk of infection and transmission. A study has shown that the protection conferred by the COVID-19 vaccine is dependent on the rate of exposure, with a higher level of exposure diminishing the effectiveness of vaccine against the Omicron infection47. Our VE estimates were also higher than that from a Hong Kong study, which indicated that the effectiveness of a two-dose CoronaVac vaccine was 55% against infection among 12–18 years old20. Since the beginning of the Omicron epidemic, Hong Kong has implemented a Vaccine Pass policy for individuals over 12 years old, whereby at least one dose of vaccine was required for entering public facilities. As such, vaccinated adolescents likely had a higher risk of infection because of being involved in various exposure settings as compared to an unvaccinated one, which may drive the VE downward. Moreover, previous data demonstrated that the Sinopharm vaccine had a higher relative effectiveness against SARS-CoV-2 infection than the Sinovac-CoronaVac vaccine48, which may also contribute to explaining the difference in VE of the present study and that of the Brazilian and Chilean studies, given that the majority of the participants (>85%) received the Sinopharm vaccine. Additionally, a comparative study among adolescents aged 12–17 years old showed the effectiveness of a two-dose BNT162b2 vaccine against infection was much higher in Scotland (80.7%) than in Brazil (64.7%), and the VE waned at a much lower rate in Scotland compared to Brazil49. Therefore, the heterogeneity of the underlying population could also play an important role in determining the VE estimates. Our analysis for VE against the Omicron BA.5 infection showed that among children and adolescents, the risk of infection by the BA.5 variants for individuals who received a two-dose inactivated vaccine reduced by 92.4% within six months (75.4% for those who have received a two-dose inactivated vaccine for 181–365 days) (Supplementary Data 1), as compared to those who only received a one-dose inactivated vaccine and those who received the two-dose regimen for more than a year. Considering a one-dose vaccine only provided a weak immune response and protection against SARS-CoV-2 infection, and the immunity level would wane to a considerably lower level a year after receiving the second dose of the inactivated vaccine19,32,33,50, our reference group might represent the group of children and adolescents who have a relatively lower internal immunity induced by the vaccine. Furthermore, the estimated risk reduction not only reflected the additional protection conferred by a second dose of vaccine compared to a one-dose vaccine but also a waned VE. Given that the effectiveness of the inactivated vaccine against the Omicron variant tends to wane rapidly within months after the inoculation among children and adolescents23, along with the compromised immune response induced by the vaccine51, a booster dose of COVID-19 vaccine should be considered for the pediatric population in China. To our knowledge, only a few studies evaluated the VE of mRNA vaccines against the transmission during the period when SARS-CoV-2 Alpha or Delta variants dominated29,30,52, and the investigation of VE of inactivated vaccines against transmission of Omicron subvariants was generally lacking53. Notably, our findings suggested an effective protection against BA.5 transmission within a year conferred by a second dose of inactivated vaccine in children and adolescents, consistent with another finding of lower values of R and SAR estimates for children and adolescents index cases with two-dose vaccine within a year. Furthermore, it appeared that the level of VE against transmission sustained within a year post-vaccination, partly consistent with the finding from large-scale cohort studies suggesting that the protection provided by the vaccine against individual infectiousness was less affected by time54.

Our study had several limitations. First, our estimations of the transmission risk and VE relied heavily on contact tracing data. Thus, any recall bias from the traced cases during the contact tracing process, and the under-ascertainment of case issues would deviate our estimates. Nonetheless, since lockdown and door-to-door mass testing have been rapidly conducted since the very beginning of the local outbreak, the proportion of under-ascertainment cases was assumed to be low. Second, selection bias may affect the VE estimates if there were systematic differences between the two-dose vaccine and reference groups. We partially accounted for this issue by adjusting the estimates with several observable confounders. Nevertheless, limited access to the data restricted us from testing whether children and adolescent or their caregivers in these groups contrast in some unobservable characteristics such as risk perception to infection and compliance to COVID-19 prevention behaviors. The sample size for the analyses of VE was small and may not be representative of the general pediatric population in China and thereby our VE estimates should be interpreted with caution. Our study sample contained all pediatric cases and close contacts identified during the whole course of an Omicron outbreak and we believed that our finding would be especially helpful for the local government and other settings with similar public health capacity. In addition, as we lack data regarding the vaccine brand (Sinopharm or Sinovac) each participant received, we considered two inactivated vaccine brands together in the analysis. Our VE estimates were mostly driven by the Sinopharm vaccine, given that majority of the vaccinees received the Sinopharm vaccine during the study period. Third, since no children and adolescents in our study cohort received a third dose of vaccine, we cannot assess the effectiveness of a booster dose of inactivated vaccine. Furthermore, since we did not have unbiased unvaccinated children and adolescents, we cannot estimate the absolute effectiveness of a two-dose inactivated vaccine. Finally, as the majority of children and adolescent cases included in our study were asymptomatic (89%, 109/122), the estimated VE may be more generalizable to asymptomatic cases. Likewise, as the most of subjects in the 0–12 age group were over 3 years old, our findings for this age group should be interpreted towards those aged 4–12 years.

Conclusions

Our findings demonstrated a moderate transmission risk of children and adolescent cases with the Omicron BA.5 infection, with a higher risk in household settings in the context of stringent PHSMs. Two-dose inactivated vaccine may potentially reduce the risk of transmission. The protective effect of a two-dose inactivated vaccine against all infection and transmission of Omicron BA.5 was high among children and adolescents within a year compared to a one-dose or a two-dose vaccine after a year. These results provide additional evidence concerning the inactivated vaccine to prevent the Omicron BA.5 infection and transmission. Considering the persistently emerging Omicron variants, monitoring the effectiveness of COVID-19 vaccines is important to inform vaccine rollout among children and adolescents.