Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis.

BACKGROUND: Due to the national dynamic zero-COVID strategy in China, there were no persistent local transmissions of SARS-CoV-2 in Beijing before December, 2022. However, imported cases have been frequently detected over the past 3 years. With soaring growth in the number of COVID-19 cases in China recently, there are concerns that there might be an emergence of novel SARS-CoV-2 variants. Routine surveillance of viral genomes has been carried out in Beijing over the last 3 years. Spatiotemporal analyses of recent viral genome sequences compared with that of global pooled and local data are crucial for the global response to the ongoing COVID-19 pandemic. METHODS: We routinely collected respiratory samples covering both imported and local cases in Beijing for the last 3 years (of which the present study pertains to samples collected between January and December, 2022), and then randomly selected samples for analysis. Next-generation sequencing was used to generate the SARS-CoV-2 genomes. Phylogenetic and population dynamic analyses were performed using high-quality complete sequences in this study. FINDINGS: We obtained a total of 2994 complete SARS-CoV-2 genome sequences in this study, among which 2881 were high quality and were used for further analysis. From Nov 14 to Dec 20, we sequenced 413 new samples, including 350 local cases and 63 imported cases. All of these genomes belong to the existing 123 Pango lineages, showing there are no persistently dominant variants or novel lineages. Nevertheless, BA.5.2 and BF.7 are currently dominant in Beijing, accounting for 90% of local cases since Nov 14 (315 of 350 local cases sequenced in this study). The effective population size for both BA.5.2 and BF.7 in Beijing increased after Nov 14, 2022. INTERPRETATION: The co-circulation of BF.7 and BA.5.2 has been present in the current outbreak since Nov 14, 2022 in Beijing, and there is no evidence that novel variants emerged. Although our data were only from Beijing, the results could be considered a snapshot of China, due to the frequent population exchange and the presence of circulating strains with high transmissibility. FUNDING: National Key Research and Development Program of China and Strategic Priority Research Program of the Chinese Academy of Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Simultaneous identification of DNA and RNA pathogens using metagenomic sequencing in cases of severe acute respiratory infection.

Metagenomic next-generation sequencing (mNGS) is a valuable technique for identifying pathogens. However, conventional mNGS requires the separate processing of DNA and RNA genomes, which can be resource- and time-intensive. To mitigate these impediments, we propose a novel method called DNA/RNA cosequencing that aims to enhance the efficiency of pathogen detection. DNA/RNA cosequencing uses reverse transcription of total nucleic acids extracted from samples by using random primers, without removing DNA, and then employs mNGS. We applied this method to 85 cases of severe acute respiratory infections (SARI). Influenza virus was identified in 13 cases (H1N1: seven cases, H3N2: three cases, unclassified influenza type: three cases) and was not detected in the remaining 72 samples. Bacteria were present in all samples. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii were detected in four influenza-positive samples, suggesting coinfections. The sensitivity and specificity for detecting influenza A virus were 73.33% and 95.92%, respectively. A κ value of 0.726 indicated a high level of concordance between the results of DNA/RNA cosequencing and SARI influenza virus monitoring. DNA/RNA cosequencing enhanced the efficiency of pathogen detection, providing a novel capability to strengthen surveillance and thereby prevent and control infectious disease outbreaks.

Major changes in prevalence and genotypes of rotavirus diarrhea in Beijing, China after RV5 rotavirus vaccine introduction.

To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test-negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011-2018, RVA-positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9-VIP[8]-III between 2019 and 2021 to G8-VP[8]-III in 2022, and P[8] sequences from G8-VP[8]-III strains formed a new branch called P[8]-IIIb. The complete genotype of G8-VP[8]-III was G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%-98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P[8], which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.

Increase of respiratory illnesses among children in Beijing, China, during the autumn and winter of 2023.

In 2023, through an ongoing respiratory pathogen surveillance system, we observed from mid-September onwards, an increase of respiratory illness among children aged ≤ 15 years presenting at hospital outpatient clinics in Beijing, China. Data indicated that illness was caused by multiple pathogens, predominantly Mycoplasma pneumoniae. Seasonality, periodicity and high prevalence of resistance to macrolide (30 of 30 strains sequenced with the A2063G mutation) were important characteristics of the M. pneumoniae epidemic, which resulted in a rise in consultations at specialised paediatric hospitals.

The role of absolute humidity in influenza transmission in Beijing, China: risk assessment and attributable fraction identification.

To assess the impact of absolute humidity on influenza transmission in Beijing from 2014 to 2019, we estimated the influenza transmissibility via the instantaneous reproduction number (Rt), and evaluated its nonlinear exposure-response association and delayed effects with absolute humidity by using the distributed lag nonlinear model (DLNM). Attributable fraction (AF) of Rt due to absolute humidity was calculated. The result showed a significant M-shaped relationship between Rt and absolute humidity. Compared with the effect of high absolute humidity, the low absolute humidity effect was more immediate with the most significant effect observed at lag 6 days. AFs were relatively high for the group aged 15-24 years, and was the lowest for the group aged 0-4 years with low absolute humidity. Therefore, we concluded that the component attributed to the low absolute humidity effect is greater. Young and middle-aged people are more sensitive to low absolute humidity than children and elderly.

Correction: RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.

[This corrects the article DOI: 10.1371/journal.ppat.1009401.].

RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.

The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the activity of cGAS must be tightly fine-tuned to maintain immune homeostasis in antiviral response. Here, we reported that neddylation modification was indispensable for appropriate cGAS-STING signaling activation. Blocking neddylation pathway using neddylation inhibitor MLN4924 substantially impaired the induction of type I interferon and proinflammatory cytokines, which was selectively dependent on Nedd8 E2 enzyme Ube2m. We further found that deficiency of the Nedd8 E3 ligase Rnf111 greatly attenuated DNA-triggered cGAS activation while not affecting cGAMP induced activation of STING, demonstrating that Rnf111 was the Nedd8 E3 ligase of cGAS. By performing mass spectrometry, we identified Lys231 and Lys421 as essential neddylation sites in human cGAS. Mechanistically, Rnf111 interacted with and polyneddylated cGAS, which in turn promoted its dimerization and enhanced the DNA-binding ability, leading to proper cGAS-STING pathway activation. In the same line, the Ube2m or Rnf111 deficiency mice exhibited severe defects in innate immune response and were susceptible to HSV-1 infection. Collectively, our study uncovered a vital role of the Ube2m-Rnf111 neddylation axis in promoting the activity of the cGAS-STING pathway and highlighted the importance of neddylation modification in antiviral defense.

Epidemiological features, genomic characteristics, and origin tracing of the COVID-19 outbreaks in Beijing from January to September 2022.

Different variants of severe acute respiratory syndrome coronavirus 2 have been discovered globally. At present, the Omicron variant has been extensively circulated worldwide. There have been several outbreaks of the Omicron variant in China. Here, we investigated the epidemiologic, genetic characteristics, and origin-tracing data of the outbreaks of COVID-19 in Beijing from January to September 2022. During this time, 19 outbreaks occurred in Beijing, with the infected cases ranging from 2 to 2230. Two concern variants were detected, with eight genotypes. Based on origin tracing analysis, two outbreaks were from the cold-chain transmission and three from items contaminated by humans. Imported cases have caused other outbreaks. Our study provided a detailed analysis of Beijing's outbreaks and valuable information to control the outbreak's spread.

Excess acute diarrhoea cases attributed to norovirus variants in Beijing, China between 2011 and 2018.

New norovirus (NoV) variants emerge often leading to increased acute gastroenteritis outbreaks and outpatient visits. However, these increases are rarely quantified. Between September 2011 and August 2018, we included a total of 133 131 acute diarrhoea cases in 11 enteric disease outpatient clinics which were open all year round in Beijing. Over the same period, the etiology surveillance for acute diarrhoea was conducted, a total of 13 139 specimens were collected and tested, and 16.84% (2213/13 139) of all specimens were NoV-positive. The partial VP1 genes were successfully sequenced in 965 NoV strains. GII.4 Sydney, GII.17, and GII.2 predominated in 2012-2013, 2014-2015, and 2016-2017, respectively. We estimated the excess NoV-associated acute diarrhoea cases using the adjusted Serfling regression model, and three excess periods were found, corresponding to the predominance periods of GII.4 Sydney, GII.17 and GII.2, respectively, represented increases of 180.5% (95% confidence interval [CI]: 115.0%-246.0%), 114.7% (95% CI: 66.4%-163.1%) and 152.6% (95% CI: 100.2%-205.0%), compared with the baseline level. New NoV variants often caused an excess in their first year of predominance, and the excess periods of NoV-associated acute diarrhoea cases coincided with the predominance periods of NoV variants.

Stability of SARS-CoV-2 and persistence of viral nucleic acids on common foods and widely used packaging material surfaces.

SARS-CoV-2 is still spreading globally. Studies have reported the stability of SARS-CoV-2 in aerosols and on surfaces under different conditions. However, studies on the stability of SARS-CoV-2 and viral nucleic acids on common food and packaging material surfaces are insufficient. The study evaluated the stability of SARS-CoV-2 using TCID50 assays and the persistence of SARS-CoV-2 nucleic acids using droplet digital polymerase chain reaction on various food and packaging material surfaces. Viral nucleic acids were stable on food and material surfaces under different conditions. The viability of SARS-CoV-2 varied among different surfaces. SARS-CoV-2 was inactivated on most food and packaging material surfaces within 1 day at room temperature but was more stable at lower temperatures. Viruses survived for at least 1 week on pork and plastic at 4°C, while no viable viruses were detected on hairtail, orange, or carton after 3 days. There were viable viruses and a slight titer decrease after 8 weeks on pork and plastic, but titers decreased rapidly on hairtail and carton at -20°C. These results highlight the need for targeted preventive and disinfection measures based on different types of foods, packaging materials, and environmental conditions, particularly in the cold-chain food trade, to combat the ongoing pandemic.

Phylogenetics and phylogeographic characteristics of coxsackievirus A16 in hand foot and mouth disease and herpangina cases collected in Beijing, China from 2019 to 2021.

Coxsackievirus A16 (CV-A16) is a significant pathogen responsible for causing hand foot and mouth disease (HFMD) and herpangina (HA). This study aimed to investigate the recent evolution and spread of CV-A16 by monitoring HFMD and HA cases in 29 hospitals across 16 districts in Beijing from 2019 to 2021. The first five cases of HFMD and the first five cases of HA each month in each hospital were included in the study. Real-time reverse transcription polymerase chain reaction was used to identify CV-A16, CV-A6, and EV-A71. From each district, two to four CV-A16 positive samples with a relatively long sampling time interval every month were selected for sequencing. A total of 3344 HFMD cases and 2704 HA cases were enrolled in this study, with 76.0% (2541/3344) of HFMD and 45.4% (1227/2704) of HA cases confirmed to be infected by enterovirus. Among the EV-positive samples, CV-A16 virus was detected in 33.61% (854/2541) of HFMD cases and 13.4% (165/1227) of HA cases, with the predominant cluster being B1a. Both B1a and B1b had a co-circulation of local and imported strains, with different origin time (1993 vs. 1995), different global distribution (14 countries vs. 10 countries), and different transmission centers but mainly distributed in the southern and eastern regions of Beijing. Strengthening surveillance of HFMD in southern and eastern regions will improve the prevention and control efficiency of enterovirus infections.

Stability of mpox virus on different commonly contacted surfaces.

Mpox is still spreading globally and is mostly reported to be transmitted by skin and mucosal contact. However, transmission through contact with fomites, contaminated objects, or surfaces has been reported in general population. Evaluation of the stability of mpox virus (MPXV) on different surfaces is important to minimize mpox transmission. In the study, the stability of MPXV on different kinds of commonly contacted surfaces was determined. MPXV was observed to have a surface-dependent stability pattern. Viable virus was detected on both glass and stainless steel for up to 5 days, and on plastic surfaces for up to 3 days. In contrast, no viable MPXV was detected on wooden board and cardboard, which are porous and water-absorbent surfaces, after 1 and 2 days of incubation, respectively. In addition, MPXV nucleic acids were more stable and showed better correlation with viral titers on stainless steel, plastic, and glass. The results indicate that fomite transmission of MPXV is plausible. Moreover, the stability of MPXV was highly surface-dependent and more stable on smooth surfaces, which could provide more information for minimizing the transmission of mpox and emphasize the significance of environmental disinfection in mpox prevention and control.

Transmissibility quantification of norovirus outbreaks in 2016-2021 in Beijing, China.

The transmissibility is a crucial feature for norovirus, yet its quantitative estimation has been limited. Our objective was to estimate the basic reproduction number (R0 ) of norovirus and investigate its variation characteristics. Norovirus outbreaks reported from September 2016 to August 2021 in Beijing were analyzed. The susceptible-infected-removed compartment model was established to estimate R0 . Linear regression models and logistic regression models were used to explore the factors affecting the transmissibility of norovirus. The overall median R0 of norovirus was estimated as 2.1 (interquartile range [IQR] 1.8-2.5), with 650 norovirus outbreaks. The transmissibility of norovirus varied by year, outbreak setting and genotype. The R0 of norovirus during September 2019 to August 2020 (median 2.1, IQR 1.8-2.4) and September 2020 to August 2021 (median 2.0, IQR 1.7-2.3) was lower than that of September 2016 to August 2017 (median 2.3, IQR 1.8-2.7) (ß = 0.94, p = 0.05; ß = 0.93, p = 0.008). The R0 of norovirus for all other settings was lower than that for kindergarten (median 2.4, IQR 2.0-2.9) (primary school: median 2.0, IQR 1.7-2.4, ß = 0.94, p = 0.001; secondary school: median 1.7, IQR 1.5-2.0, ß = 0.87, p < 0.001; college: median 1.7, IQR 1.5-1.8, ß = 0.89, p = 0.03; other closed settings: median 1.8, IQR 1.5-2.0, ß = 0.90, p = 0.004). GⅡ.2[P16] outbreaks had a median R0 of 2.2 (IQR 1.8-2.7), which was higher than that for GⅡ.6[P7] outbreaks (median 1.8, IQR: 1.8-2.0, odds ratio = 0.19, p = 0.03; GⅡ.2[P16] as reference) and mixed-genotype outbreaks (median 1.7, IQR: 1.5-1.8, ß = 0.92, p = 0.02; mixed-genotype as reference). In kindergartens and primary schools, norovirus shows increased transmissibility, emphasizing the vulnerable population and high-risk settings. Furthermore, the transmissibility of norovirus may change over time and with virus evolution, necessitating additional research to uncover the underlying mechanisms.

Characterisation of human astrovirus in a diarrhoea outbreak using nanopore and Sanger sequencing protocols.

Human astroviruses (HAstV) are etiologic agents of acute gastroenteritis that most often afflict young children and elderly adults. Most studies of HAstV have focused on epidemiology. In this study, we collected 10 stool samples from a diarrhea outbreak from a diarrhea sentinel surveillance hospital in Beijing. Samples were evaluated immediately using parallel multiplex RT-qPCR and nanopore sequencing, and were then amplified by designed primers and Sanger sequencing to obtain whole genome sequences. Six isolates were categorized as HAstV-5 and subjected to whole genome analysis to characterize their genetic variation and evolution. Full genome analysis revealed low genetic variation (99.38-100% identity) among isolates. Phylogenetic analysis showed that all isolates were closely related to domestic strains Yu/1-CHN and 2013/Fuzhou/85. The recombination breakpoint of the six isolates was located at 2741 bp in the overlap region of ORF1a and ORF1b, similar to those of Yu/1-CHN and 2013/Fuzhou/85. Overall, our study highlights the combined use of RT-qPCR and sequencing as an important tool in rapid diagnosis and acquisition of whole genome sequences of HAstV.

Molecular epidemiology and phylodynamic analysis of enterovirus 71 in Beijing, China, 2009-2019.

BACKGROUND: Enterovirus 71(EV71)-associated hand, foot and mouth disease (HFMD) decreased dramatically in Beijing from 2009 to 2019. This study was to investigate the epidemiological characteristics, evolutionary dynamics, geographic diffusion pathway, and other features of EV71 in Beijing, China. METHODS: We conducted a retrospective study of EV71-associated HFMD and its causative agent in Beijing, China, from 2009 to 2019. Phylogenetic and phylogeographic methods based on the EV71 genome were used to determine the evolution features, origin, and spatiotemporal dynamics. Positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. Bayesian birth-death skyline model was used to estimate the effective reproductive number (Re). RESULTS: EV71-associated HFMD decreased greatly in Beijing. From 2009 to 2019, EV71 strains prevalent in Beijing shared high homology in each gene segment and evolved with a rate of 4.99*10- 3 substitutions per site per year. The genetic diversity of EV71 first increased and peaked in 2012 and then decreased with fluctuations. The time to the most recent common ancestor (TMRCA) of EV71 in Beijing was estimated around 2003 when the EV71 strains were transmitted to Beijing from east China. Beijing played a crucial role in seeding EV71 to central China as well. Two residues (E145Q/G, A293S) under positive selection were detected from both the VP1 dataset and the P1 dataset. They were embedded within the loop of the VP1 capsid and were exposed externally. Mean Re estimate of EV71 in Beijing was about 1.007. CONCLUSION: In recent years, EV71 was not the primary causative agent of HFMD in Beijing. The low Re estimate of EV71 in Beijing implied that strategies for preventing and controlling HFMD were performed effectively. Beijing and east China played a crucial role in disseminating EV71 to other regions in China.

Norovirus outbreaks in China, 2000-2018: A systematic review.

To understand epidemiological characteristics of norovirus outbreaks in China from 2000 to 2018 the literature on norovirus outbreaks was identified by searching WANFANG, CNKI, PubMed, and Web of Science databases before 31 December 2018. Statistical analyses were performed using Statistical Product Service Solutions software. RStudio1.4.1717 and ArcGIS trial version were used for plotting bar graphs and maps. A total of 419 norovirus outbreaks were reported in the 394 included articles, which occurred between June 2000 and October 2018, showing an overall increasing trend. The majority of outbreaks occurred in schools (52.28%, 218/417) and kindergartens (55/417, 13.19%). Person-to-person transmission (41.64%, 137/329) was most common, followed by food-borne transmission (75/329, 22.80%) and water-borne transmission (72/329, 21.88%). GII was the most predominant norovirus genogroup, with GII.4, GII.17 and GII.2 being the dominant genotypes in 2007-2013, 2014-2015, 2016-2017, respectively. Increased outbreaks were associated with the prevalence of new variants. Most norovirus outbreaks were reported in the southeast of the country. The number of norovirus outbreaks was positively associated with the per capita gross domestic product and the year-end resident population. Norovirus outbreaks have become an important public health problem in China. It is necessary to establish surveillance in hospitals and nursing homes. Genotyping of noroviruses is important for monitoring the circulating strains and improving the vaccine design, so it should be carried out in more regions.

Spatio-temporal distribution and influencing factors of norovirus outbreaks in Beijing, China from 2016 to 2020.

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis (AGE) worldwide. The geographical characteristics of norovirus outbreaks in Beijing and their influencing factors remain unknown. This study aimed to explore the spatial distributions, geographical characteristics, and influencing factors of norovirus outbreaks in Beijing, China. METHODS: Epidemiological data and specimens were collected through the AGE outbreak surveillance system in all 16 districts of Beijing. Data on spatial distribution, geographical characteristics, and influencing factors of norovirus outbreaks were analyzed using descriptive statistics methods. We measured spatial, geographical clustering of high- or low-value deviance from random distribution using Z-scores and P-values as statistical significance measures with Global Moran's I statistics and Getis-Ord Gi in ArcGIS. Linear regression and correlation methods were used to explore influencing factors. RESULTS: Between September 2016 and August 2020, 1,193 norovirus outbreaks were laboratory-confirmed. The number of outbreaks varied seasonally, typically peaking in spring (March to May) or winter (October to December). Outbreaks primarily occurred around central districts at the town level, and spatial autocorrelation was evident in both the entire study period and in individual years. Hotspots of norovirus outbreaks in Beijing were primarily found in contiguous areas between three central districts (Chaoyang, Haidian, Fengtai) and four suburban districts (Changping, Daxing, Fangshan, Tongzhou). The average population numbers, mean number of all schools, and mean number of kindergartens and primary schools for towns in central districts and hotspot areas were higher than those in suburban districts and non-hotspot areas respectively. Additionally, population numbers and densities of kindergartens and primary schools were influencing factors at the town level. CONCLUSIONS: Hotspots of norovirus outbreaks in Beijing were in contiguous areas between central and suburban districts with high populations, and high kindergarten and primary school densities were the likely driving forces. Outbreak surveillance needs to focus on contiguous areas between central and suburban districts with increased monitoring, medical resources, and health education.

The First Human Infection Case of Macacine Alphaherpesvirus 1 Virus in China.

BACKGROUND: Macacine alphaherpesvirus 1 (BV) was first reported in the 1930s and only about 60 cases have been diagnosed since then. METHODS: A 53-year-old male who worked as a veterinary surgeon, developed a fever with nausea and vomiting in April 2021 in Beijing, China. Real-time polymerase chain reaction (PCR) and metagenomics Next Generation Sequencing (mNGS) were used for diagnosis. RESULTS: BV DNA was confirmed by mNGS and PCR. The case died 51 days after onset, due to the damage to the brain and spinal cord caused by a viral infection and hypoxic-ischemic encephalopathy. The typical BV inclusion bodies in the brain were found for the first time. CONCLUSIONS: Here we reported the first human infection case of BV in China. This fatal case highlights the potential threat of BV to occupational workers and the essential role of surveillance.

Using an influenza surveillance system to estimate the number of SARS-CoV-2 infections in Beijing, China, weeks 2 to 6 2023.

With COVID-19 public health control measures downgraded in China in January 2023, reported COVID-19 case numbers may underestimate the true numbers after the SARS-CoV-2 Omicron wave. Using a multiplier model based on our influenza surveillance system, we estimated that the overall incidence of SARS-CoV-2 infections was 392/100,000 population in Beijing during the 5 weeks following policy adjustment. No notable change occurred after the Spring Festival in early February. The multiplier model provides an opportunity for assessing the actual COVID-19 situation.

Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants.

BACKGROUND: The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. METHODS: We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China's current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. RESULTS: We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China's pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. CONCLUSIONS: As China's current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.