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Background WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. Methods We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rateor time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. Results The overall pooled influenza-associated hospitalisation rate was 40.5 (95% confidence interval (CI) = 24.3-67.4) per 100 000 persons, with rates varying substantially by age: 224.0 (95% CI = 118.8-420.0) in children aged 0-4 years and 96.8 (95% CI = 57.0-164.3) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). Conclusions Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years. [ABSTRACT FROM AUTHOR]

Background: All countries are facing decisions about which population groups to prioritize for access to COVID-19 vaccination after the first vaccine products have been licensed, at which time supply shortages are inevitable. Our objective is to define the key target populations, their size, and priority for a COVID-19 vaccination program in the context of China. Methods: On the basis of utilitarian and egalitarian principles, we define and estimate the size of tiered target population groups for a phased introduction of COVID-19 vaccination, considering evolving goals as vaccine supplies increase, detailed information on the risk of illness and transmission, and past experience with vaccination during the 2009 influenza pandemic. Using publicly available data, we estimated the size of target population groups, and the number of days needed to vaccinate 70% of the target population. Sensitivity analyses considered higher vaccine coverages and scaled up vaccine delivery relative to the 2009 pandemic. Results: Essential workers, including staff in the healthcare, law enforcement, security, nursing homes, social welfare institutes, community services, energy, food and transportation sectors, and overseas workers/students (49.7 million) could be prioritized for vaccination to maintain essential services in the early phase of a vaccination program. Subsequently, older adults, individuals with underlying health conditions and pregnant women (563.6 million) could be targeted for vaccination to reduce the number of individuals with severe COVID-19 outcomes, including hospitalizations, critical care admissions, and deaths. In later stages, the vaccination program could be further extended to target adults without underlying health conditions and children (784.8 million), in order to reduce symptomatic infections and/or to stop virus transmission. Given 10 million doses administered per day, and a twodose vaccination schedule, it would take 1 week to vaccinate essential workers but likely up to 7 months to vaccinate 70% of the overall population. Conclusions: The proposed framework is general but could assist Chinese policy-makers in the design of a vaccination program. Additionally, this exercise could be generalized to inform other national and regional strategies for use of COVID-19 vaccines, especially in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background Laboratory-confirmed deaths grossly underestimate influenza mortality burden, so that reliable burden estimates are derived from indirect statistical studies, which are scarce in low- and middle-income settings. Objectives Here, we used statistical excess mortality models to estimate the burden of seasonal and pandemic influenza in China. Methods We modeled data from a nationally representative population-based death registration system, combined with influenza virological surveillance data, to estimate influenza-associated excess mortality for the 2004-2005 through 2009-2010 seasons, by age and region. Results The A(H1N1) pandemic was associated with 11·4-12·1 excess respiratory and circulatory ( R& C) deaths per 100 000 population in rural sites of northern and southern China during 2009-2010; these rates were 2·2-2·8 times higher than those of urban sites ( P < 0·01). Influenza B accounted for a larger proportion of deaths than pandemic A( H1 N1) in 2009-2010 in some regions. Nationally, we attribute 126 200 (95% CI, 61 000-248 400) excess R&C deaths (rate of 9·4/100 000) and 2 323 000 (1 166 000-4 533 000) years of life lost ( YLL) to the first year of A( H1 N1)pdm circulation. Conclusions The A( H1 N1) pandemic posed a mortality and YLL burden comparable to that of interpandemic influenza in China. Our high burden estimates in rural areas highlight the need to enhance epidemiological surveillance and healthcare services, in underdeveloped and remote areas. [ABSTRACT FROM AUTHOR]

The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China. [ABSTRACT FROM AUTHOR]

Objective To estimate influenza-associated mortality in urban China. Methods Influenza-associated excess mortality for the period 2003-2008 was estimated in three cities in temperate northern China and five cities in the subtropical south of the country. The estimates were derived from models based on negative binomial regressions, vital statistics and the results of weekly influenza virus surveillance. Findings Annual influenza-associated excess mortality, for all causes, was 18.0 (range: 10.9-32.7) deaths per 100 000 population in the northern cities and 11.3 (range: 7.3-17.8) deaths per 100 000 in the southern cities. Excess mortality for respiratory and circulatory disease was 12.4 (range: 7.4-22.2) and 8.8 (range: 5.5-13.6) deaths per 100 000 people in the northern and southern cities, respectively. Most (86%) deaths occurred among people aged ≥ 65 years. Influenza-associated excess mortality was higher in B-virus-dominant seasons than in seasons when A(H3N2) or A(H1N1) predominated, and more than half of all influenza-associated mortality was associated with influenza B virus. Conclusion Between 2003 and 2008, seasonal influenza, particularly that caused by the influenza B virus, was associated with substantial mortality in three cities in the temperate north of China and five cities in the subtropical south of the country. [ABSTRACT FROM AUTHOR]

Background: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals., Methods: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from 29 December 2019 to 17 April 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and log-normal distributions to time-to-event data using maximum-likelihood estimation., Results: We analyzed 82 719 laboratory-confirmed cases reported in mainland China, including 4632 deaths and 77 029 discharges. The estimated CFR was 5.65% (95% confidence interval [CI], 5.50-5.81%) nationally, with the highest estimate in Wuhan (7.71%) and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients and 0.8-10.3-fold higher than that of mild-to-severe patients. Older age (odds ratio [OR], 1.14 per year; 95% CI, 1.11-1.16) and being male (OR, 1.83; 95% CI, 1.10-3.04) were risk factors for mortality. The times from symptom onset to first healthcare consultation, to laboratory confirmation, and to hospitalization were consistently longer for deceased patients than for those who recovered., Conclusions: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Nonpharmaceutical interventions to control SARS-CoV-2 spread have been implemented with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogeneous and difficult to interpret. We describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown and post-lockdown periods to quantify changes in contact patterns. In the post-lockdown period, the mean number of contacts increased by 5 to 17% as compared to the lockdown period. However, it remains three to seven times lower than its pre-pandemic level sufficient to control SARS-CoV-2 transmission. We find that the impact of school interventions depends nonlinearly on the intensity of other activities. When most community activities are halted, school closure leads to a 77% decrease in the reproduction number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

We conducted two surveys to evaluate the health-seeking behaviors of individuals with acute respiratory infections (ARI) during the COVID-19 outbreak in Wuhan, China. Among 351 participants reporting ARI (10.3%, 351/3,411), 36.5% sought medical assistance. Children were more likely to seek medical assistance than other age-groups (66.1% vs. 28.0%-35.1%). This population-based study demonstrates that the majority of patients with ARI symptoms did not seek medical assistance during the COVID-19 outbreak in Wuhan. These findings may be used to refine the estimates of disease burden and clinical severity of COVID-19 and to plan for health resources allocation., (© 2020 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: All countries are facing decisions about which population groups to prioritize for access to COVID-19 vaccination after the first vaccine products have been licensed, at which time supply shortages are inevitable. Our objective is to define the key target populations, their size, and priority for a COVID-19 vaccination program in the context of China., Methods: On the basis of utilitarian and egalitarian principles, we define and estimate the size of tiered target population groups for a phased introduction of COVID-19 vaccination, considering evolving goals as vaccine supplies increase, detailed information on the risk of illness and transmission, and past experience with vaccination during the 2009 influenza pandemic. Using publicly available data, we estimated the size of target population groups, and the number of days needed to vaccinate 70% of the target population. Sensitivity analyses considered higher vaccine coverages and scaled up vaccine delivery relative to the 2009 pandemic., Results: Essential workers, including staff in the healthcare, law enforcement, security, nursing homes, social welfare institutes, community services, energy, food and transportation sectors, and overseas workers/students (49.7 million) could be prioritized for vaccination to maintain essential services in the early phase of a vaccination program. Subsequently, older adults, individuals with underlying health conditions and pregnant women (563.6 million) could be targeted for vaccination to reduce the number of individuals with severe COVID-19 outcomes, including hospitalizations, critical care admissions, and deaths. In later stages, the vaccination program could be further extended to target adults without underlying health conditions and children (784.8 million), in order to reduce symptomatic infections and/or to stop virus transmission. Given 10 million doses administered per day, and a two-dose vaccination schedule, it would take 1 week to vaccinate essential workers but likely up to 7 months to vaccinate 70% of the overall population., Conclusions: The proposed framework is general but could assist Chinese policy-makers in the design of a vaccination program. Additionally, this exercise could be generalized to inform other national and regional strategies for use of COVID-19 vaccines, especially in low- and middle-income countries.

The novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95% CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had a higher burden than the 2009 influenza pandemic or seasonal influenza in terms of hospitalization and mortality rates, and clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.

In China, the doubling time of the coronavirus disease epidemic by province increased during January 20-February 9, 2020. Doubling time estimates ranged from 1.4 (95% CI 1.2-2.0) days for Hunan Province to 3.1 (95% CI 2.1-4.8) days for Xinjiang Province. The estimate for Hubei Province was 2.5 (95% CI 2.4-2.6) days.

Background: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy., Methods: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R t ) at the provincial level., Findings: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33-56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0-14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0-9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8-12·4) and the mean serial interval at 5·1 days (1·3-11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74-1·54) in Shenzhen city of Guangdong province and 1·71 (1·32-2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30., Interpretation: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province., Funding: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China.

Background: Laboratory-confirmed deaths grossly underestimate influenza mortality burden, so that reliable burden estimates are derived from indirect statistical studies, which are scarce in low- and middle-income settings., Objectives: Here, we used statistical excess mortality models to estimate the burden of seasonal and pandemic influenza in China., Methods: We modeled data from a nationally representative population-based death registration system, combined with influenza virological surveillance data, to estimate influenza-associated excess mortality for the 2004-2005 through 2009-2010 seasons, by age and region., Results: The A(H1N1) pandemic was associated with 11·4-12·1 excess respiratory and circulatory (R&C) deaths per 100,000 population in rural sites of northern and southern China during 2009-2010; these rates were 2·2-2·8 times higher than those of urban sites (P<0·01). Influenza B accounted for a larger proportion of deaths than pandemic A(H1N1) in 2009-2010 in some regions. Nationally, we attribute 126,200 (95% CI, 61,000-248,400) excess R&C deaths (rate of 9·4/100,000) and 2,323,000 (1,166,000-4,533,000) years of life lost (YLL) to the first year of A(H1N1)pdm circulation., Conclusions: The A(H1N1) pandemic posed a mortality and YLL burden comparable to that of interpandemic influenza in China. Our high burden estimates in rural areas highlight the need to enhance epidemiological surveillance and healthcare services, in underdeveloped and remote areas., (© 2013 John Wiley & Sons Ltd.)

Objective: To estimate influenza-associated mortality in urban China., Methods: Influenza-associated excess mortality for the period 2003-2008 was estimated in three cities in temperate northern China and five cities in the subtropical south of the country. The estimates were derived from models based on negative binomial regressions, vital statistics and the results of weekly influenza virus surveillance., Findings: Annual influenza-associated excess mortality, for all causes, was 18.0 (range: 10.9-32.7) deaths per 100,000 population in the northern cities and 11.3 (range: 7.3-17.8) deaths per 100,000 in the southern cities. Excess mortality for respiratory and circulatory disease was 12.4 (range: 7.4-22.2) and 8.8 (range: 5.5-13.6) deaths per 100,000 people in the northern and southern cities, respectively. Most (86%) deaths occurred among people aged ≥ 65 years. Influenza-associated excess mortality was higher in B-virus-dominant seasons than in seasons when A(H3N2) or A(H1N1) predominated, and more than half of all influenza-associated mortality was associated with influenza B virus., Conclusion: Between 2003 and 2008, seasonal influenza, particularly that caused by the influenza B virus, was associated with substantial mortality in three cities in the temperate north of China and five cities in the subtropical south of the country.