The risk of mpox importation and subsequent outbreak potential in Chinese mainland: a retrospective statistical modelling study.

BACKGROUND: The 2022-2023 mpox (monkeypox) outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM). In this study, we aimed to evaluate mpox's importation risk, border screening effectiveness and the risk of local outbreak in Chinese mainland. METHODS: We estimated the risk of mpox importation in Chinese mainland from April 14 to September 11, 2022 using the number of reported mpox cases during this multi-country outbreak from Global.health and the international air-travel data from Official Aviation Guide. We constructed a probabilistic model to simulate the effectiveness of a border screening scenario during the mpox outbreak and a hypothetical scenario with less stringent quarantine requirement. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. RESULTS: We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Under the quarantine policy, 15-19% of imported infections would remain undetected. Once a case of mpox is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to > 95% with over six cases. CONCLUSIONS: Our study demonstrates that the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic reduced mpox importations prominently. However, the risk could be substantially higher with the recovery of air-travel volume to pre-pandemic level. Mpox could emerge as a public health threat for Chinese mainland given its large MSM community.

Counterfactual analysis of the 2023 Omicron XBB wave in China.

Background: China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023. Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenarios that combine the use of vaccines, antiviral drugs, and nonpharmaceutical interventions. Methods: We developed a mathematical model of XBB transmission in China, which has been calibrated using SARS-CoV-2 positive rates per week. Intrinsic age-specific infection-hospitalization risk, infection-ICU risk, and infection-fatality risk were used to estimate disease burdens, characterized as number of hospital admissions, ICU admissions, and deaths. Results: We estimated that in absence of behavioral change, the XBB outbreak in spring 2023 would have resulted in 0.86 billion infections (∼61% of the total population). Our counterfactual analysis shows that the synergetic effect of vaccination (70% vaccination coverage), antiviral treatment (20% receiving antiviral treatment), and moderate nonpharmaceutical interventions (20% isolation and L1 PHSMs) could reduce the number of deaths to levels close to seasonal influenza (1.17 vs. 0.65 per 10,000 individuals and 5.85 vs. 3.85 per 10,000 individuals aged 60+, respectively). The maximum peak prevalence of hospital and ICU admissions are estimated to be lower than the corresponding capacities (8.6 vs. 10.4 per 10,000 individuals and 1.2 vs. 2.1 per 10,000 individuals, respectively). Conclusion: Our findings suggest that the capacity of the Chinese healthcare system was adequate to face the Omicron XBB wave in spring 2023 but, at the same time, supports the importance of administering highly effective vaccine with long-lasting immune response, and the use of antiviral treatments.

A Versatile Topology-Optimized Compliant Actuator for Soft Robotic Gripper and Walking Robot.

The remarkable interaction capabilities of soft robots within various environments have captured substantial attention from researchers. In recent years, bionics has provided a rich inspiration for the design of soft robots. Nevertheless, predicting the locomotion of soft actuators and determining material layouts solely based on intuition or experience remain a formidable challenge. Previous actuators predominantly targeted separate applications, leading to elevated costs and diminished interchangeability. The objective of this article is to extract the common requirements of diverse application domains and develop a versatile compliant actuator. A mathematical model of the compliant mechanism is proposed under the framework of topology optimization, resulting in an optimal distribution of both structure and material. Through comparison with empirical and semioptimal designs, the results show that the proposed versatile actuator has the advantages of both stiffness and flexibility. We propose an associative design strategy for soft grippers and walking robots. The soft gripper can perfectly complete adaptive grasping of objects with varying sizes, shapes, and masses. The successful in-water gripping experiment underscores the robust cross-medium operational capabilities of the soft gripper. Notably, our experimental results show that the walking robot can move quickly for 5 cycles in 8.25 s and can guarantee the control accuracy of continuous motion. Moreover, the robot swiftly switches walking directions within a mere 0.45 s. The optimization and design strategy presented in this article can furnish novel insights for shaping the next generation of soft robots.

Recovery of residual carbon from coal gasification fine slag by a combined gravity separation-flotation process.

Recovering inner residual carbon is important for fully utilizing coal gasification fine slag (CGFS) resources. In this study, we adopted a combined gravity-separation and flotation process to efficiently recover residual carbon by considering the characteristics of the CGFS and optimizing the operating factors of the process. CGFS is principally a mixture of residual carbon and ash, with low-density particles containing more of the former. Accordingly, residual carbon is preliminarily enriched by gravity separation, in which gas velocity (vg) and water velocity (vw) significantly impact separation efficiency, followed by feed volume (m). The residual carbon in the initial concentrate was preliminarily enriched (i.e., loss on ignition (LOI): 55.90%; combustible recovery (Ro): 72.36%) under appropriate operating conditions (i.e., vw = 0.04 m/s, vg = 3 m/s, m = 150 g). Moreover, the quality of the flotation concentrate was most influenced by collector dosage (mc), followed by aeration rate (η), frother dosage (mf), stirring speed (w), and grinding time (t) during flotation of the primary concentrate. The flotation concentrate exhibited LOI and Ro values of 90.95% and 50.34%, respectively, under the optimal flotation conditions (i.e., mc = 20 kg/t, mf = 15 kg/t, w = 2600 rad/min, η = 200 L/h, t = 360 s); it has a high residual carbon content and is an ideal raw material for preparing fuels or carbon materials.

Association between long-term exposure to low level air pollutants and incident end-stage kidney disease in the UK Biobank: A prospective cohort.

BACKGROUND: Previous studies suggest that air pollution can increase the risk of incident chronic kidney disease (CKD). However, the association between end-stage kidney disease (ESKD) and co-exposure to relatively low-level air pollutants remains unclear. METHODS: A prospective cohort was designed based on UK Biobank. From 1 January 2010 to 12 November 2021, 453,347 participants were followed up over a median of 11.87 years. Principal component analysis was used to identify major patterns of five air pollutants, including PM2.5, PM2.5-10, PM10, NO2, and NOx. Sub-distribution hazards models were used to estimate the associations between air pollution, individually or jointly, and incident ESKD, CKD, and all-cause death, respectively. RESULTS: Principal component analysis identified two principal components, namely RC1 (PM2.5, NO2, and NOx) and RC2 (PM2.5-10 and PM10). An elevated risk of incident ESKD was associated with an interquartile range (IQR) increase in PM2.5 (hazard ratio: 1.11, 95% confidence interval: 1.02-1.22), NO2 (1.16, 1.04-1.30), NOx (1.08, 1.00-1.17), and RC1 (1.12, 1.02-1.23). An elevated risk of incident CKD was associated with an IQR increase in PM2.5 (1.05, 1.03-1.07), NO2 (1.04, 1.02-1.06), NOx (1.03, 1.02-1.05), and RC1 (1.04, 1.02-1.06). An increased risk of all-cause mortality was associated with an IQR increase in PM2.5 (1.02, 1.00-1.04). Restricted cubic spline analyses indicated a monotonic elevating association of PM2.5, NO2, NOx, and RC1 with ESKD incidence. CONCLUSIONS: Long-term exposure to PM2.5, NO2, NOx, and their complex was associated with elevated ESKD incidence, even at relatively lower levels of air pollution.

Risk Factors Associated with the Spatiotemporal Spread of the SARS-CoV-2 Omicron BA.2 Variant - Shanghai Municipality, China, 2022.

What is already known about this topic?: Previous studies have explored the spatial transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have assessed the associated risk factors. However, none of these studies have quantitatively described the spatiotemporal transmission patterns and risk factors for Omicron BA.2 at the micro (within-city) scale. What is added by this report?: This study highlights the heterogeneous spread of the 2022 Omicron BA.2 epidemic in Shanghai, and identifies associations between different metrics of spatial spread at the subdistrict level and demographic and socioeconomic characteristics of the population, human mobility patterns, and adopted interventions. What are the implications for public health practice?: Disentangling different risk factors might contribute to a deeper understanding of the transmission dynamics and ecology of coronavirus disease 2019 and an effective design of monitoring and management strategies.

Beating the break-even point with a discrete-variable-encoded logical qubit.

Quantum error correction (QEC) aims to protect logical qubits from noises by using the redundancy of a large Hilbert space, which allows errors to be detected and corrected in real time1. In most QEC codes2-8, a logical qubit is encoded in some discrete variables, for example photon numbers, so that the encoded quantum information can be unambiguously extracted after processing. Over the past decade, repetitive QEC has been demonstrated with various discrete-variable-encoded scenarios9-17. However, extending the lifetimes of thus-encoded logical qubits beyond the best available physical qubit still remains elusive, which represents a break-even point for judging the practical usefulness of QEC. Here we demonstrate a QEC procedure in a circuit quantum electrodynamics architecture18, where the logical qubit is binomially encoded in photon-number states of a microwave cavity8, dispersively coupled to an auxiliary superconducting qubit. By applying a pulse featuring a tailored frequency comb to the auxiliary qubit, we can repetitively extract the error syndrome with high fidelity and perform error correction with feedback control accordingly, thereby exceeding the break-even point by about 16% lifetime enhancement. Our work illustrates the potential of hardware-efficient discrete-variable encodings for fault-tolerant quantum computation19.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

STUDY OBJECTIVES: Increased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed. METHODS: Individual records of narcolepsy patients were collected from 15 of 42 hospitals across China known to diagnose cases. Incidence was estimated assuming the representativeness of these hospitals. Age-specific incidence, epidemiological and clinical characteristics of patients were evaluated before, during, and after the 2009 H1N1 pandemic. Sensitivity analyses were conducted by including NT1 cases only and excluding the effect of the 2009 H1N1 vaccination. RESULTS: Average annual incidence was 0.79 per 100 000 person-years (PY) from 1990 to 2017 and 1.08 per 100 000 PY from 2003 to 2017. Incidence increased 4.17 (95% CI 4.12, 4.22) and 1.42 (95% CI 1.41, 1.44) fold during and after the 2009 H1N1 pandemic when compared to baseline. These results were robust in sensitivity analyses. Patients with the onset of narcolepsy during the pandemic period were younger (notably in 5-9-year-old strata), and the age shift toward younger children reversed to baseline following the pandemic. CONCLUSIONS: Increased incidence of narcolepsy was observed during the 2009 H1N1 pandemic period. This is likely to be associated with the circulation of the wild type A(H1N1)pdm09 virus. This observation should be considered for future influenza pandemic preparedness plans.

Regional characteristics of influenza seasonality patterns in mainland China, 2005-2017: a statistical modeling study.

OBJECTIVES: To quantify the seasonal and antigenic characteristics of influenza to help understand influenza activity and inform vaccine recommendations. METHODS: We employed a generalized linear model with harmonic terms to quantify the seasonal pattern of influenza in China from 2005-2017, including amplitude (circulatory intensity), semiannual periodicity (given two peaks a year), annual peak time, and epidemic duration. The antigenic differences were distinguished as antigenic similarity between 2009 and 2020. We categorized regions above 33° N, between 27° N and 33° N, and below 27° N as the north, central, and south regions, respectively. RESULTS: We estimated that the amplitude in the north region (median: 0.019, 95% CI: 0.018-0.021) was significantly higher than that in the central region (median: 0.011, 95% CI: 0.01-0.012, P <0.001) and south region (median: 0.008, 95% CI: 0.007-0.008, P <0.001) for influenza A virus subtype H3N2 (A/H3N2). The A/H3N2 in the central region had a semiannual periodicity (median: 0.548, 95% CI: 0.517-0.577), while no semiannual pattern was found in other regions or subtypes/lineages. The antigenic similarity was low (below 50% in the 2009-2010, 2014-2015, 2016-2018, and 2019-2020 seasons) for A/H3N2. CONCLUSION: Our study depicted the seasonal pattern differences and antigenic differences of influenza in China, which provides information for vaccination strategies.

Diagnostic performance of different specimens in detecting enterovirus A71 in children with hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is a major public health problem among children in the Asia-Pacific region. The optimal specimen for HFMD virological diagnosis remains unclear. Enterovirus A71 (EV-A71) neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity, specificity, positive and negative predictive value of throat swabs, rectal swabs, stool, blood samples and cerebrospinal fluid (CSF) by RT-PCR or ELISA assay. In this study, clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens. Our results showed that stool had the highest sensitivity (88%, 95% CI: 74%-96%) and agreement with the reference standard (91%). The order of diagnostic yield for EV-A71 infection was stool sample â€‹≥ â€‹rectal swab â€‹> â€‹throat swab â€‹> â€‹blood sample â€‹> â€‹CSF sample, and using a combination of clinical samples improved sensitivity for enterovirus detection. The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR (serum/plasma: 62% vs. 2%, CSF: 47% vs. 0%) (P â€‹< â€‹0.002). In conclusion, our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD. If stool is unavailable, rectal swabs can be collected to achieve a similar diagnostic yield. Otherwise, throat swabs may be useful in detecting positive samples. Although IgM in blood or CSF is diagnostically accurate, it lacks sensitivity, missing 40%-50% of cases. The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.

Estimating mortality associated with seasonal influenza among adults aged 65 years and above in China from 2011 to 2016: A systematic review and model analysis.

BACKGROUND: Estimation of influenza disease burden is crucial for optimizing intervention strategies against seasonal influenza. This study aimed to estimate influenza-associated excess respiratory and circulatory (R&C) and all-cause (AC) mortality among older adults aged 65 years and above in mainland China from 2011 to 2016. METHODS: Through a systematic review, we collected influenza-associated excess R&C and AC mortality data of older adults aged 65 years and above for specific cities/provinces in mainland China. Generalized linear models were fitted to estimate the corresponding excess mortality for older adults by province and nationwide, accounting for the potential variables of influenza virus activity, demography, economics, meteorology, and health service. All statistical analyses were conducted using R software. RESULTS: A total of 9154 studies were identified in English and Chinese databases, and 11 (0.1%) were included in the quantitative synthesis after excluding duplicates and screening the title, abstract, and full text. Using a generalized linear model, the estimates of annual national average influenza-associated excess R&C and AC mortality among older adults aged 65 years and above were 111.8 (95% CI: 92.8-141.1) and 151.6 (95% CI: 127.6-179.3) per 100,000 persons, respectively. Large variations in influenza-associated excess R&C and AC mortality among older adults were observed among 30 provinces. CONCLUSIONS: Influenza was associated with substantial excess R&C and AC mortality among older adults aged 65 years and above in China from 2011 to 2016. This analysis provides valuable evidence for the introduction of the influenza vaccine into the National Immunization Program for the elderly in China.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022.

An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February 26 to June 30, 2022. We use official reported data retrieved from Shanghai municipal Health Commissions to estimate the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and RT-PCR sensitivity, we provide estimates of clinical severity, including the infection fatality ratio, symptomatic case fatality ratio, and risk of developing severe/critical disease upon infection. The overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age, noted in individuals aged 80 years or older. The overall fatality ratio and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.09-0.10%) and 0.27% (95% CI: 0.24-0.29%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022.

Background: An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February to June 2022. The government organized multiple rounds of molecular test screenings for the entire population, providing a unique opportunity to capture the majority of subclinical infections and better characterize disease burden and the full spectrum of Omicron BA.2 clinical severity. Methods: Using daily reports from the websites of the Shanghai Municipal Health Commission, we estimated the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and Reverse Transcription-Polymerase Chain Reaction (RT□PCR) sensitivity, we provide estimates of clinical severity, including the infection fatality risk, symptomatic case fatality risk, and risk of developing severe/critical disease upon infection. Findings: From February 26 to June 30, 2022, the overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age with the highest rates of 125.29 (95% CI: 117.05-133.44) per 100,000 and 57.17 (95% CI: 51.63-62.71) per 100,000 individuals, respectively, noted in individuals aged 80 years or older. The overall fatality risk and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.08-0.10%) and 0.23% (95% CI: 0.20-0.25%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Interpretation: Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death. Funding: Key Program of the National Natural Science Foundation of China (82130093). Research in context: Evidence before this study: We searched PubMed and Europe PMC for manuscripts published or posted on preprint servers after January 1, 2022 using the following query: ("SARS-CoV-2 Omicron") AND ("burden" OR "severity"). No studies that characterized the whole profile of disease burden and clinical severity during the Shanghai Omicron outbreak were found. One study estimated confirmed case fatality risk between different COVID-19 waves in Hong Kong; other outcomes, such as fatality risk and risk of developing severe/critical illness upon infection, were not estimated. One study based on 21 hospitals across the United States focused on Omicron-specific in-hospital mortality based on a limited sample of inpatients (565). In southern California, United States, a study recruited more than 200 thousand Omicron-infected individuals and estimated the 30-day risk of hospital admission, intensive care unit admission, mechanical ventilation, and death. None of these studies estimated infection and mortality rates or other indictors associated with disease burden. Overall, the disease burden and clinical severity of the Omicron BA.2 variant have not been fully characterized, especially in populations predominantly immunized with inactivated vaccines.Added value of this study: The large-scale and multiround molecular test screenings conducted on the entire population during the Omicron BA.2 outbreak in Shanghai, leading to a high infection ascertainment ratio, provide a unique opportunity to capture the majority of subclinical infections. As such, our study provides a comprehensive assessment of both the disease burden and clinical severity of the SARS-CoV-2 Omicron BA.2 sublineage, which are especially lacking for populations predominantly immunized with inactivated vaccines.Implications of all the available evidence: We estimated the disease burden and clinical severity of the Omicron BA.2 outbreak in Shanghai in February-June 2022. These estimates are key to properly interpreting field evidence and assessing the actual spread of Omicron in other settings. Our results also provide support for the importance of strategies to prevent overwhelming the health care system and increasing vaccine coverage to reduce mortality.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number ( R t ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, R t remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing R t below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093). Research in context: Evidence before this study: On May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak.Added value of this study: We collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China.Implications of all the available evidence: This descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

Modeling transmission of SARS-CoV-2 Omicron in China.

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

Assessing the transition of COVID-19 burden towards the young population while vaccines are rolled out in China.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3-11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

Investigating vaccine-induced immunity and its effect in mitigating SARS-CoV-2 epidemics in China.

BACKGROUND: To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. METHODS: We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided. RESULTS: We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50-62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021. CONCLUSIONS: Efforts should be taken to increase population's confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.

Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis.

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection-mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6-4.7-fold), 1.8-fold (1.4-2.4-fold), and 3.2-fold (2.4-4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2-1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5-9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7-4.4-fold) for messenger RNA platform, and 2.5-fold (1.7-2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.

Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials.

BACKGROUND: Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. METHODS: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 µg dose or 6 µg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 µg, 3 µg, or 6 µg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 µg groups, since 3 µg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. FINDINGS: 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 µg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. INTERPRETATION: A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. FUNDING: National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.