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Objective: To investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections., Methods: In this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted., Results: Among 1,894 cases included, the RSV positivity rate was 5.91% during the 2023-2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection., Conclusions: During the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients., (© 2024. The Author(s).)

This study delineates the enhancement of a Reverse Transcription Polymerase Chain Reaction (RT-PCR) method for the amplification of the complete genome of the influenza A virus during heterosubtypic co-infection, relying on the amplification of intact gene segments. The precision of the method was assessed using all amplicons, which underwent both capillary electrophoresis and DNA sequencing. Five samples featuring co-infection of Influenza A viruses with H1N1 and H3N2 subtypes were evaluated. The improved strategy successfully amplified all eight segments of H3N2 strains in four samples, and the entire genome of H1N1 strains in three samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Studies have reported the adverse effects of cold events on influenza. However, the role of critical factors, such as characteristics of cold spells, and regional variations remain unresolved., Objective: We aimed to systematically evaluate the association between cold spells and influenza incidence in mainland China., Methods: This time series analysis used surveillance data of daily influenza from 325 sites in China in the 2014-2019 period. A total of 15 definitions of cold spells were adopted based on combinations of temperature thresholds and days of duration. A distributed lag linear model was used to estimate the short-term effects of cold spells on influenza incidence during the cool seasons (November to March), and we further explored the potential impact of cold spell characteristics (ie, intensity, duration, and timing during the season) on the estimated associations. Meta-regressions were used to evaluate the modification effect of city-level socioeconomic indicators., Results: The overall effect of cold spells on influenza incidence increased with the temperature threshold used to define cold spells, whereas the added effects were generally small and not statistically significant. The relative risk of influenza-associated with cold spells was 3.35 (95% CI 2.89-3.88), and the estimated effects were stronger during the middle period of cool seasons. The health effects of cold spells varied geographically and residents in Jiangnan region were vulnerable groups (relative risk 7.36, 95% CI 5.44-9.95). The overall effects of cold spells were positively correlated with the urban population density, population size, gross domestic product per capita, and urbanization rate, indicating a sterner response to cold spells in metropolises., Conclusions: Cold spells create a substantial health burden on seasonal influenza in China. Findings on regional and socioeconomic differences in the health effects of cold spells on seasonal influenza may be useful in formulating region-specific public health policies to address the hazardous effects of cold spells., (© Haitao Wang, Mengjie Geng, Tamara Schikowski, Ashtyn Tracey Areal, Kejia Hu, Wen Li, Micheline de Sousa Zanotti Stagliorio Coelho, Paulo Hilário Nascimento Saldiva, Wei Sun, Chengchao Zhou, Liang Lu, Qi Zhao, Wei Ma. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Background: Influenza is a contagious respiratory disease posing a huge burden of disease for children around the world. The purpose of this study was to investigate the epidemiologic changes in childhood influenza in Zhengzhou, China, before, during, and after the COVID-19 outbreak. The aim of this study was to determine the impact of the COVID-19 outbreak and related prevention and control policies on the children's influenza epidemiological trend., Methods: All influenza report card data from the Children's Hospital Affiliated with Zhengzhou University's Disease Surveillance Reporting Management System were collected and analyzed monthly from January 2018 to December 2023. The period of the study was divided into three phases for comparison: the pre-pandemic period, the pandemic period, and the post-pandemic period., Results: Between January 2018 and December 2023, a total of 82,030 children with influenza were diagnosed at our hospital, including 46,453 males and 35,577 females. A total of 11,833 of them had to be hospitalized for influenza, and 321 of them were brought to the ICU. Influenza showed low-level epidemiologic status during the COVID-19 pandemic, and there was a substantial rise in influenza and a surge in the number of cases after the COVID-19 pandemic period. The year 2023 will had the most influenza cases (40,785). The peak incidence of influenza changes in 2022, from July to October, and in 2023, from February to April and from October to December. During the post-pandemic period, the proportion of new-borns and young children among influenza patients decreased, while the proportion of school-age children increased significantly, and the proportion of influenza patients hospitalized and the proportion of ICU admissions decreased., Conclusion: Influenza showed low-level epidemiologic status during the COVID-19 pandemic. In the post-pandemic period, there is a large increase in influenza incidence, with a double peak in influenza incidence. The proportion of school-age children with influenza has also increased. As a result, we recommend that influenza vaccination for key populations, particularly school-age children, be completed by October of each year in Henan Province, and that the government and schools increase education about nonpharmacological influenza prevention approaches., (© 2024. The Author(s).)

Background: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions., Methods: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (R t ) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at R t  = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between R t and temperature, modified based on seasonal and regional characteristics., Results: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an R t of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were - 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions., Conclusion: The study findings revealed that temperature had a varying effect on influenza transmission trends (R t ) across different regions in China. By identifying region-specific temperature thresholds at R t  = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As one of the most effective measures to prevent seasonal influenza viruses, annual influenza vaccination is globally recommended. Nevertheless, evidence regarding the impact of repeated vaccination to contemporary and future influenza has been inconclusive. A total of 100 subjects singly or repeatedly immunized with influenza vaccines including 3C.2a1 or 3C.3a1 A(H3N2) during 2018-2019 and 2019-2020 influenza season were recruited. We investigated neutralization antibody by microneutralization assay using four antigenically distinct A(H3N2) viruses circulating from 2018 to 2023, and tracked the dynamics of B cell receptor (BCR) repertoire for consecutive vaccinations. We found that vaccination elicited cross-reactive antibody responses against future emerging strains. Broader neutralizing antibodies to A(H3N2) viruses and more diverse BCR repertoires were observed in the repeated vaccination. Meanwhile, a higher frequency of BCR sequences shared among the repeated-vaccinated individuals with consistently boosting antibody response was found than those with a reduced antibody response. Our findings suggest that repeated seasonal vaccination could broaden the breadth of antibody responses, which may improve vaccine protection against future emerging viruses., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Controlling the excessive inflammatory response is one of the key ways to reduce the severity and mortality of severe influenza virus infections. RAGE is involved in inflammatory responses and acute lung injuries. Here, we investigated the role of RAGE and its potential application as a target for severe influenza treatment through serological correlation analysis for influenza patients, and treatment with the RAGE inhibitor FPS-ZM1 on A549 cells or mice with influenza A (H1N1) infection. The results showed high levels of RAGE were correlated with immunopathological injury and severity of influenza, and FPS-ZM1 treatment increased the viability of A549 cells with influenza A infection and decreased morbidity and mortality of influenza A virus infection in mice. The RAGE/NF-κb inflammatory signaling pathway is a major targeting pathway for FPS-ZM1 treatment in severe influenza. These findings provide further insights into the immune injury of severe influenza and a potential targeting candidate for the disease treatment., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As one of the high pathogenic influenza viruses, H1N1 virus easily induces to serious diseases, even leading to death. To date, all detection methods for H1N1 virus had shortcomings, including high equipment cost, time consumption, and etc. Therefore, a novel detection method should be established to achieve more convenient, rapid, and low-cost detection. In this work, an isomer of HPBmN-I with aggregation-induced emission characteristic was firstly synthesized on the basis of our previous reported HPBpN-I. The results showed that HPBmN-I only selectively binds to N1 in the presence of H1, while HPBpN-I can exhibit total fluorescence response to H1 and N1 in H1/N1 mixture. The limited of detection (LOD) of HPBmN-I to N1 was estimated to be 20.82 ng/mL in normal saline (NS) according to the IUPAC-based approach. The simulation calculations based on molecular docking revealed that four HPBmN-I molecules combine well with the hydrophobic cavity of N1 and achieve the fluorescence enhancement due to size matching with each other. The combination of HPBpN-I and HPBmN-I as probes was successfully used to quantitatively detect H1 and N1 in real H1N1 virus. Compared to enzyme-linked immunosorbent assay (ELISA) method, the established method not only showed the same detection accuracy but also had the advantages of real-time, ease of preparation, and low-cost, demonstrating potential market prospects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Influenza imposes a significant disease burden on society and individuals annually, and influenza vaccination is considered a significant public health measure to prevent influenza and reduce influenza-related severe disease and death. The low influenza vaccination rate in China is partly due to certain factors affecting the willingness and behavior of individuals to receive them. Scientific research and targeted interventions on these factors can effectively improve the vaccination situation. Commonly used individual-level theoretical models for influenza vaccination behavior include the health belief model, protection motivation theory, and theory of planned behavior. This study reviews theoretical models commonly employed in researching influenza vaccination willingness and behavior. An overview of these practical applications and challenges models is presented to provide references for relevant research and intervention programs in China.

Objectives: This study aimed to assess the healthcare-seeking behaviour and related factors of people with acute respiratory symptoms in the rural areas of central and western China to estimate the disease burden of influenza more accurately., Design: Cross-sectional survey., Settings: Fifty-two communities/villages in the Wanzhou District, Chongqing, China, a rural area in southwest China, from May 2022 to July 2022., Participants: The participants were those who had been living in Wanzhou District continuously for more than 6 months and consented to participate., Outcome Measures: A semistructured questionnaire was used to determine the healthcare-seeking behaviour of participants, and the dichotomous response of 'yes' or 'no' was used to assess whether participants had acute respiratory symptoms and their healthcare-seeking behaviour., Results: Only 50.92% (360 of 707) of the patients with acute respiratory infection visited medical and health institutions for treatment, whereas 49.08% (347 of 707) avoided treatment or opted for self-medication. The primary reason for not seeing a doctor was that patients felt their condition was not serious and visiting a medical facility for treatment was unnecessary. Short distance (87.54%) and reasonable charges (49.48%) were ranked as the most important reasons for choosing treatment at primary medical and health facilities (80.27%). The primary reasons for which patients visited secondary and tertiary hospitals (7.78% and 8.61%, respectively) were that doctors in such facilities were better at diagnosis (57.14%) and at treatment (87.10%)., Conclusion: The findings provided in this study indicated that regular healthcare-seeking behaviour investigations should be conducted. The disease burden of influenza can be calculated more accurately when healthcare-seeking behaviour investigations are combined with surveillance in the hospitals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Influenza vaccination coverage is low among persons with non-communicable diseases (NCDs) in China. Chinese health workers (HWs) do not routinely recommend influenza vaccination despite evidence that recommendations increase vaccine uptake. This study aims to assess whether interventions increased primary care HWs' recommendation for influenza vaccination and measure their impact on influenza vaccine uptake in persons with NCDs., Methods: We conducted a cluster randomized controlled study in public primary healthcare clinics in Hubei from November 2018 through April 2019. In the intervention clinics, primary care HWs received training on the benefits of influenza vaccination and were asked to recommend influenza vaccine in routine primary healthcare for persons with NCDs. In the control clinics, primary care HWs did not receive training and provided standard services. We conducted questionnaire surveys before and after the intervention to collect information about recommendations made and receipt of influenza vaccines., Results: A total of 896 primary care HWs and 4552 persons with NCDs were included. After intervention, a higher percentage of HWs recommended influenza vaccines in intervention clinics compared to control clinics. Vaccinated primary care HWs were more likely to recommend vaccination. Persons with NCDs reported higher influenza vaccination coverage in intervention than control clinics, and primary care HWs' recommendation increased vaccination uptake among persons with NCDs., Conclusions: Vaccinated primary care HWs were more likely to recommend influenza vaccination than unvaccinated HWs. Promoting primary care HWs' vaccination and encouraging them to recommend influenza vaccination during routine primary healthcare could increase influenza vaccine receipt among persons with NCDs. Registration number ChiCTR2200067140., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies provided some evidence of meteorological factors influence seasonal influenza transmission patterns varying across regions and latitudes. However, research on seasonal influenza activities based on climate zones are still in lack. This study aims to utilize the ecological-based Köppen Geiger climate zones classification system to compare the spatial and temporal epidemiological characteristics of seasonal influenza in Chinese Mainland and assess the feasibility of developing an early warning system., Methods: Weekly influenza cases number from 2014 to 2019 at the county and city level were sourced from China National Notifiable Infectious Disease Report Information System. Epidemic temporal indices, time series seasonality decomposition, spatial modelling theories including Moran's I and local indicators of spatial association were applied to identify the spatial and temporal patterns of influenza transmission., Results: All climate zones had peaks in Winter-Spring season. Arid, desert, cold (BWk) showed up the first peak. Only Tropical, savannah (Aw) and Temperate, dry winter with hot summer (Cwa) zones had unique summer peak. Temperate, no dry season and hot summer (Cfa) zone had highest average incidence rate (IR) at 1.047/100,000. The Global Moran's I showed that average IR had significant clustered trend (z = 53.69, P < 0.001), with local Moran's I identified high-high cluster in Cfa and Cwa. IR differed among three age groups between climate zones (0-14 years old: F = 26.80, P < 0.001; 15-64 years old: F = 25.04, P < 0.001; Above 65 years old: F = 5.27, P < 0.001). Age group 0-14 years had highest average IR in Cwa and Cfa (IR = 6.23 and 6.21) with unique dual peaks in winter and spring season showed by seasonality decomposition., Conclusions: Seasonal influenza exhibited distinct spatial and temporal patterns in different climate zones. Seasonal influenza primarily emerged in BWk, subsequently in Cfa and Cwa. Cfa, Cwa and BSk pose high risk for seasonal influenza epidemics. The research finds will provide scientific evidence for developing seasonal influenza early warning system based on climate zones., (© 2024. The Author(s).)

Introduction: The continued emergence of human infections of H9N2 avian influenza virus (AIV) poses a serious threat to public health. The prevalent Y280/G9 lineage of H9N2 AIV in Chinese poultry can directly bind to human receptors, increasing the risk of spillover infections to humans. Since 2013, the number of human cases of H9N2 avian influenza has been increasing continuously, and in 2021, China reported the highest number of human cases, at 25., Methods: In this study, we analyzed the age, geographic, temporal, and sex distributions of humans with H9N2 avian influenza in 2021 using data from the National Influenza Center (Beijing, China). We also conducted evolutionary, gene homology, and molecular characterization analyses of the H9N2 AIVs infecting humans., Results: Our findings show that children under the age of 12 accounted for 80% of human cases in 2021, and females were more frequently affected than males. More cases occurred in winter than in summer, and most cases were concentrated in southern China. Human-infecting H9N2 viruses showed a high level of genetic homology and belonged to the prevalent G57 genotype. Several additional α2,6-SA-binding sites and sites of mammalian adaptation were also identified in the genomes of human-infecting H9N2 viruses., Discussion: Therefore, continuous monitoring of H9N2 AIV and the implementation of further measures to control the H9N2 virus in poultry are essential to reduce the interspecies transmission of the virus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Zeng, Xie, Li, Liu, Yang, Yang and Wang.)

Background: It remains unknown how ambient temperature impact pneumonia of various infectious causes., Methods: Based on the national death registry covering all counties in Chinese mainland, we conducted an individual-level case-crossover study in China from 2013 to 2019. Exposures were assigned at residential addresses for each decedent. Conditional logistic regression model combined with distributed lag non-linear models were used to estimate the exposure-response associations. The attributable fractions due to non-optimum temperature were calculated after accounting for spatial and temporal patterns for the excess risks., Findings: The exposure-response curves were inversely J-shaped with both low and high temperature increasing the risks, and the effect of low temperature was stronger. Extremely low temperature was associated with higher magnitude of influenza-related pneumonia [relative risk (RR): 2.46, 95% confidence interval (CI): 1.62-3.74], than viral pneumonia (RR: 1.89, 95% CI: 1.55-2.30) and bacterial pneumonia (RR: 1.81, 95% CI: 1.56-2.09). The magnitudes of RRs associated with extremely high temperature were similar among the three categories of pneumonia. The mortality attributable fraction for influenza-related pneumonia (29.78%) was the highest. The effects were stronger in people of low education level or residence in the north., Interpretation: This nationwide study presents findings on the varied risk and burden of pneumonia mortality of various infectious causes, and highlights the susceptibility of influenza-related pneumonia to ambient low temperature., Funding: This study is supported by the National Key Research and Development Program (2022YFC3702701), the Shanghai Municipal Science and Technology Commission (21TQ015) and Shanghai International Science and Technology Partnership Project (21230780200)., Competing Interests: Declaration of interests All authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Air pollution is a major risk factor for planetary health and has long been suspected of predisposing humans to respiratory diseases induced by pathogens like influenza viruses. However, epidemiological evidence remains elusive due to lack of longitudinal data from large cohorts., Objective: Our aim is to quantify the short-term association of influenza incidence with exposure to ambient air pollutants in Chinese cities., Methods: Based on air pollutant data and influenza surveillance data from 82 cities in China over a period of 5 years, we applied a two-stage time series analysis to assess the association of daily incidence of reported influenza cases with six common air pollutants [particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ), particulate matter with aerodynamic diameter ≤ 10 μ m ( PM 10 ), NO 2 , SO 2 , CO, and O 3 ], while adjusting for potential confounders including temperature, relative humidity, seasonality, and holiday effects. We built a distributed lag Poisson model for one or multiple pollutants in each individual city in the first stage and conducted a meta-analysis to pool city-specific estimates in the second stage., Results: A total of 3,735,934 influenza cases were reported in 82 cities from 2015 to 2019, accounting for 72.71% of the overall case number reported in the mainland of China. The time series models for each pollutant alone showed that the daily incidence of reported influenza cases was positively associated with almost all air pollutants except for ozone. The most prominent short-term associations were found for SO 2 and NO 2 with cumulative risk ratios of 1.094 [95% confidence interval (CI): 1.054, 1.136] and 1.093 (95% CI: 1.067, 1.119), respectively, for each 10   μ g / m 3 increase in the concentration at each of the lags of 1-7 d. Only NO 2 showed a significant association with the daily incidence of influenza cases in the multipollutant model that adjusts all six air pollutants together. The impact of air pollutants on influenza was generally found to be greater in children, in subtropical cities, and during cold months., Discussion: Increased exposure to ambient air pollutants, particularly NO 2 , is associated with a higher risk of influenza-associated illness. Policies on reducing air pollution levels may help alleviate the disease burden due to influenza infection. https://doi.org/10.1289/EHP12146.

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.

Background: Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017-2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies., Methods: Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns., Results: A total of 11,963,886 cases of the seven RIDs were reported during 2017-2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = -7.53%, P = 0.009; APC = -40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions., Conclusions: The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses., (© 2023. The Author(s).)

To determine the epidemiological status of influenza and understand the distribution of common respiratory viruses in adult patients with influenza-like illness (ILI) cases in Taiyuan City, Shanxi Province, China, epidemiological data between 2018 and 2019 were retrieved from the China Influenza Surveillance Information System, and two sentinel ILI surveillance hospitals were selected for sample collection. All specimens were screened for influenza virus (IFV) and the other 14 common respiratory viruses using real-time polymerase chain reaction. The results of the 2-year ILI surveillance showed that 26,205 (1.37%) of the 1,907,869 outpatients and emergency patients presented with ILI, with an average annual incidence of 297.75 per 100,000 individuals, and ILI cases were predominant in children <15 years (21,348 patients, 81.47%). Of the 2713 specimens collected from adult patients with ILI, the overall detection rate of respiratory viruses was 20.13%, with IFV being the most frequently detected (11.79%) and at a relatively lower rate than other respiratory viruses. Further subtype analysis indicated an alternating or mixed prevalence of H1N1 (2009), H3N2, Victoria, and Yamagata subtypes. This study provides a baseline epidemiological characterization of ILI and highlights the need for a nationwide detection and surveillance system for multiple respiratory pathogens.

To the best of our knowledge, no previous study has quantitatively estimated the dynamics and cumulative susceptibility to influenza infections after the widespread lifting of COVID-19 public health measures. We constructed an imitated stochastic susceptible-infected-removed model using particle-filtered Markov Chain Monte Carlo sampling to estimate the time-dependent reproduction number of influenza based on influenza surveillance data in southern China, northern China, and the United States during the 2022-2023 season. We compared these estimates to those from 2011 to 2019 seasons without strong social distancing interventions to determine cumulative susceptibility during COVID-19 restrictions. Compared to the 2011-2019 seasons without a strong intervention with social measures, the 2022-2023 influenza season length was 45.0%, 47.1%, and 57.1% shorter in southern China, northern China, and the United States, respectively, corresponding to an 140.1%, 74.8%, and 50.9% increase in scale of influenza infections, and a 60.3%, 72.9%, and 45.1% increase in population susceptibility to influenza. Large and high-intensity influenza epidemics occurred in China and the United States in 2022-2023. Population susceptibility increased in 2019-2022, especially in China. We recommend promoting influenza vaccination, taking personal prevention actions on at-risk populations, and monitoring changes in the dynamic levels of influenza and other respiratory infections to prevent potential outbreaks in the coming influenza season., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

H3N8 avian influenza viruses (AIVs) in China caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs and could be vulnerable to infection at epidemic or pandemic proportion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Numerous studies have suggested that meteorological conditions such as temperature and absolute humidity are highly indicative of influenza outbreaks. However, the explanatory power of meteorological factors on the seasonal influenza peaks varied widely between countries at different latitudes., Objectives: We aimed to explore the modification effects of meteorological factors on the seasonal influenza peaks in multi-countries., Methods: Data on influenza positive rate (IPR) were collected across 57 countries and data on meteorological factors were collected from ECMWF Reanalysis v5 (ERA5). We used linear regression and generalized additive models to investigate the spatiotemporal associations between meteorological conditions and influenza peaks in cold and warm seasons., Results: Influenza peaks were significantly correlated with months with both lower and higher temperatures. In temperate countries, the average intensity of cold season peaks was stronger than that of warm season peaks. However, the average intensity of warm season peaks was stronfger than of cold season peaks in tropical countries. Temperature and specific humidity had synergistic effects on influenza peaks at different latitudes, stronger in temperate countries (cold season: R 2 =0.90; warm season: R 2 =0.84) and weaker in tropical countries (cold season: R 2 =0.64; warm season: R 2 =0.03). Furthermore, the effects could be divided into cold-dry and warm-humid modes. The temperature transition threshold between the two modes was 16.5-19.5 °C. During the transition from cold-dry mode to warm-humid mode, the average 2 m specific humidity increased by 2.15 times, illustrating that transporting a large amount of water vapor may compensate for the negative effect of rising temperatures on the spread of the influenza virus., Conclusion: Differences in the global influenza peaks were related to the synergistic influence of temperature and specific humidity. The global influenza peaks could be divided into cold-dry and warm-humid modes, and specific thresholds of meteorological conditions were needed for the transition of the two modes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.

Background: The world is undergoing an unprecedented wave of urbanization. However, the effect of rapid urbanization during the early or middle stages of urbanization on seasonal influenza transmission remains unknown. Since about 70% of the world population live in low-income countries, exploring the impact of urbanization on influenza transmission in urbanized countries is significant for global infection prediction and prevention., Objective: The aim of this study was to explore the effect of rapid urbanization on influenza transmission in China., Methods: We performed spatiotemporal analyses of province-level influenza surveillance data collected in Mainland China from April 1, 2010, to March 31, 2017. An agent-based model based on hourly human contact-related behaviors was built to simulate the influenza transmission dynamics and to explore the potential mechanism of the impact of urbanization on influenza transmission., Results: We observed persistent differences in the influenza epidemic attack rates among the provinces of Mainland China across the 7-year study period, and the attack rate in the winter waves exhibited a U-shaped relationship with the urbanization rates, with a turning point at 50%-60% urbanization across Mainland China. Rapid Chinese urbanization has led to increases in the urban population density and percentage of the workforce but decreases in household size and the percentage of student population. The net effect of increased influenza transmission in the community and workplaces but decreased transmission in households and schools yielded the observed U-shaped relationship., Conclusions: Our results highlight the complicated effects of urbanization on the seasonal influenza epidemic in China. As the current urbanization rate in China is approximately 59%, further urbanization with no relevant interventions suggests a worrisome increasing future trend in the influenza epidemic attack rate., (©Hao Lei, Nan Zhang, Beidi Niu, Xiao Wang, Shenglan Xiao, Xiangjun Du, Tao Chen, Lei Yang, Dayan Wang, Benjamin Cowling, Yuguo Li, Yuelong Shu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.07.2023.)

Few studies have explored the associations between air pollutants and influenza across seasons, especially at large scales. This study aimed to evaluate seasons' modifying effects on associations between air pollutants and influenza from 10 cities of southern China. Through scientific evidence, it provides mitigation and adaptation strategies with practical guidelines to local health authorities and environmental protection agencies. Daily influenza incidence, meteorological, and air pollutants data from 2016 to 2019 were collected. Quasi-Poisson regression with a distributed lag nonlinear model was used to evaluate city-specific air pollutants and influenza associations. Meta-analysis was used to pool site-specific estimates. Attributable fractions (AFs) of influenza incidence due to pollutants were calculated. Stratified analyses were conducted by season, sex, and age. Overall, the cumulative relative risk (CRR) of influenza incidence for a 10-unit increase in PM 2.5 , PM 10 , SO 2 , NO 2 , and CO was 1.45 (95% CI: 1.25, 1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95% CI: 1.49, 2.03), and 1.19 (95% CI: 1.04, 1.36), respectively. Children aged 0-17 were more sensitive to air pollutants in spring and winter. PM 10 had greater effect on influenza than PM 2.5 in autumn, winter, and overall, lesser in spring. The overall AF due to PM 2.5 , PM 10 , SO 2 , NO 2, and CO was 4.46% (95% eCI: 2.43%, 6.43%), 5.03% (95% eCI: 2.33%, 7.56%), 5.36% (95% eCI: 3.12%, 7.58%), 24.88% (95% eCI: 18.02%, 31.67%), and 23.22% (95% eCI: 17.56%, 28.61%), respectively. AF due to O 3 was 10.00% (95% eCI: 4.76%, 14.95%) and 3.65% (95% eCI: 0.50%, 6.59%) in spring and summer, respectively. The seasonal variations in the associations between air pollutants and influenza in southern China would provide evidence to service providers for tailored intervention, especially for vulnerable populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Influenza A(H3N8) viruses first emerged in humans in 2022, but their public health risk has not been evaluated. Here, we systematically investigated the biological features of avian and human isolated H3N8 viruses. The human-origin H3N8 viruses exhibited dual receptor binding profiles but avian-origin H3N8 viruses bound to avian type (sialic acid α2, 3) receptors only. All H3N8 viruses were sensitive to the antiviral drug oseltamivir. Although H3N8 viruses showed lower virulence than the 2009 pandemic H1N1 (09pdmH1N1) viruses, they induced comparable infectivity in mice. More importantly, the human population is naïve to H3N8 virus infection and current seasonal vaccination is not protective. Therefore, the threat of influenza A(H3N8) viruses should not be underestimated. Any variations should be monitored closely and their effect should be studied in time for the pandemic potential preparedness purpose., (© 2023 Wiley Periodicals LLC.)

Background: Seasonal influenza activity showed a sharp decline in activity at the beginning of the emergence of COVID-19. Whether there is an epidemiological correlation between the dynamic of these 2 respiratory infectious diseases and their future trends needs to be explored., Objective: We aimed to assess the correlation between COVID-19 and influenza activity and estimate later epidemiological trends., Methods: We retrospectively described the dynamics of COVID-19 and influenza in 6 World Health Organization (WHO) regions from January 2020 to March 2023 and used the long short-term memory machine learning model to learn potential patterns in previously observed activity and predict trends for the following 16 weeks. Finally, we used Spearman correlation coefficients to assess the past and future epidemiological correlation between these 2 respiratory infectious diseases., Results: With the emergence of the original strain of SARS-CoV-2 and other variants, influenza activity stayed below 10% for more than 1 year in the 6 WHO regions. Subsequently, it gradually rose as Delta activity dropped, but still peaked below Delta. During the Omicron pandemic and the following period, the activity of each disease increased as the other decreased, alternating in dominance more than once, with each alternation lasting for 3 to 4 months. Correlation analysis showed that COVID-19 and influenza activity presented a predominantly negative correlation, with coefficients above -0.3 in WHO regions, especially during the Omicron pandemic and the following estimated period. The diseases had a transient positive correlation in the European region of the WHO and the Western Pacific region of the WHO when multiple dominant strains created a mixed pandemic., Conclusions: Influenza activity and past seasonal epidemiological patterns were shaken by the COVID-19 pandemic. The activity of these diseases was moderately or greater than moderately inversely correlated, and they suppressed and competed with each other, showing a seesaw effect. In the postpandemic era, this seesaw trend may be more prominent, suggesting the possibility of using one disease as an early warning signal for the other when making future estimates and conducting optimized annual vaccine campaigns., (©Qing Wang, Mengmeng Jia, Mingyue Jiang, Wei Liu, Jin Yang, Peixi Dai, Yanxia Sun, Jie Qian, Weizhong Yang, Luzhao Feng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 12.06.2023.)

Objective: To analyze the spatial and temporal distribution characteristics of seasonal A(H3N2) influenza [influenza A(H3N2)] in China and to provide a reference for scientific prevention and control. Methods: The influenza A(H3N2) surveillance data in 2014-2019 was derived from China Influenza Surveillance Information System. A line chart described the epidemic trend analyzed and plotted. Spatial autocorrelation analysis was conducted using ArcGIS 10.7, and spatiotemporal scanning analysis was conducted using SaTScan 10.1. Results: A total of 2 603 209 influenza-like case sample specimens were detected from March 31, 2014, to March 31, 2019, and the influenza A(H3N2) positive rate was 5.96%(155 259/2 603 209). The positive rate of influenza A(H3N2) was statistically significant in the north and southern provinces in each surveillance year (all P <0.05). The high incidence seasons of influenza A (H3N2) were in winter in northern provinces and summer or winter in southern provinces. Influenza A (H3N2) clustered in 31 provinces in 2014-2015 and 2016-2017. High-high clusters were distributed in eight provinces, including Beijing, Tianjin, Hebei, Shandong, Shanxi, Henan, Shaanxi, and Ningxia Hui Autonomous Region in 2014-2015, and high-high clusters were distributed in five provinces including Shanxi, Shandong, Henan, Anhui, and Shanghai in 2016-2017. Spatiotemporal scanning analysis from 2014 to 2019 showed that Shandong and its surrounding twelve provinces clustered from November 2016 to February 2017 ( RR =3.59, LLR =9 875.74, P <0.001). Conclusion: Influenza A (H3N2) has high incidence seasons with northern provinces in winter and southern provinces in summer or winter and obvious spatial and temporal clustering characteristics in China from 2014-2019.

Objective: To understand the influence of meteorological factors on the morbidity of influenza in northern cities of China and explore the differences in the influence of meteorological factors on the morbidity of influenza in 15 cities. Methods: The monthly reported morbidity of influenza and monthly meteorological data from 2008 to 2020 were collected in 15 provincial capital cities, including Xi 'an, Lanzhou, Xining, Yinchuan and Urumqi (5 northwestern cities), Beijing, Tianjin, Shijiazhuang, Taiyuan, Hohhot, Ji'nan, Zhengzhou (7 northern cities), Shenyang, Changchun and Harbin (3 northeastern cities). The panel data regression model was applied to conduct quantitative analyze on the influence of meteorological factors on influenza morbidity. Results: The univariate and multivariate panel regression analysis showed that after controlling the population density and other meteorological factors, for each 5 ℃ drop of monthly average temperature, the morbidity change percentage (MCP) of influenza was 11.35%, 34.04% and 25.04% in the 3 northeastern cities, 7 northern cities and 5 northwestern cities, respectively, and the best lag period months was 1, 0 and 1 month; When the monthly average relative humidity decreased by 10%, the MCP was 15.84% in 3 cities in northeastern China and 14.80% in 7 cities in northern China respectively, and the best lag period months was 2 and 1 months respectively; The MCP of 5 cities in northwestern China was 4.50% for each 10 mm reduction of monthly accumulated precipitation, and the best lag period months was 1 month; The MCPs of 3 cities in northeastern China and 5 cities in northwestern China were 4.19% and 5.97% respectively when the accumulated sunshine duration of each month decreased by 10 hours, the best lag period months was 1 month. Conclusions: In northern cities of China from 2008 to 2020, the temperature, relative humidity, precipitation and sunshine duration all had negatively impact on the morbidity of influenza, and temperature and relative humidity were the main sensitive meteorological factors. Temperature had a strong direct impact on the morbidity of influenza in 7 cities in northern China, and relative humidity had a strong lag effect on the morbidity of influenza in 3 cities in northeastern China. The duration of sunshine in 5 cities in northwestern China had a greater impact on the morbidity of influenza compared with 3 cities in northeastern China.

Major outbreaks of influenza virus occurred in China in 2017-2018. To describe the pattern of influenza circulation and timing of seasonal epidemics, we analyzed data from influenza-like illness (ILI) specimens on surveillance wards of sentinel hospitals during 2014-2018. Among 1,890,084 ILI cases, 324,211 (17.2%) tested positive for influenza. Influenza A virus (particularly A/H3N2), which circulates annually, was detected in 62% of cases, compared with influenza B virus in 38% of cases. The detection rate of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata viruses were 3.56%, 7.07%, 2.08%, and 3.45%, respectively. Influenza prevalence was generally stable over the four years analyzed, but obvious outbreaks occurred in 2015-2016 (17.28%) and 2017-2018 (22.67%), with B/Victoria and B/Yamagata contributing to these outbreaks, respectively. In the south, a characteristic peak in infections was detected in the summer (week 23-38), which was not detected in the north. Influenza B was found high frequency in school-age children (5-14 years) with 4.78% of B/Victoria and 6.76% of B/Yamagata. Therefore, the epidemiological characteristics of seasonal influenza were complex in China during 2014-2018, presenting distinctions in region, season, and susceptible population. These findings underline the importance of enhancing year-round influenza surveillance and provide a reference for the timing and variety of influenza vaccination., (© 2023. The Author(s).)

Influenza A viruses (IAVs) and influenza B viruses (IBVs) cause annual epidemics in human populations with seasonal circulation spikes. Peptide AM58-66GL9 located at residues 58-66 of M1 protein of IAVs has been recognized as an immunodominant T cell epitope with HLA-A*0201 restriction and broadly used as a positive reference in influenza immunity. This peptide also almost completely overlaps with a nuclear export signal (NES) 59-68 in IAV M1, which explains the limited escape mutations under the T cell immune pressure in this region. In this study, we investigated the potential immunogenicity and NES in the corresponding region of IBV. The long peptide covering this region can be recognized by specific T cells and induce robust expression of IFN-γ among HLA-B*1501 donors in vivo, but not in HLA-A*0201 donors. Among a series of truncated peptides derived from this region, we identified an immunodominant HLA-B*1501-restricted T cell epitope BM58-66AF9 (ALIGASICF) in the M1 protein of IBV. Furthermore, the structure of the HLA-B*1501/BM58-66AF9 complex shows that BM58-66AF9 performs a flat and featureless conformation that is similar to AM58-66GL9 presented by HLA-A*0201. In contrast with IAV, the sequence around residues 55-70 of IBV M1 does not contain an NES. Our comparative study on IBVs and IAVs provides new insights into the immune and evolution characteristics of IBVs and may shed light on vaccine development for influenza viruses., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Background: The influenza viruses pose a threat to human health and medical services, and vaccination is an important way to prevent infection. However, the effectiveness of influenza vaccines is affected by various aspects. This study aimed to explore factors related to the immune response to influenza vaccines., Methods: The study was conducted from September 2019 to September 2021, and a total of 593 volunteers were recruited from the Center for Disease Control and Prevention in 3 provinces in China. The hemagglutination inhibition assay was used to measure antibody levels. The Chi-square test, multivariable logistic regression analysis, and sum-rank test were used to analyze the factors associated with influenza vaccine immune response., Results: The Chi-square test showed that seroconversion rates and response rate were associated with age group, vaccination history, chronic conditions, the frequency of colds, and region (P < 0.05). The multivariable logistic regression analysis showed that age was an important factor that affected participants' seroconversion rates for A/H1N1, A/H3N2, B/Victoria, and response status (18-64 vs. ≤5: OR = 2.77, P < 0.001; ≥65 vs. ≤5: OR = 0.38, P = 0.01; 18-64 vs. ≤5: OR = 2.64, P = 0.03). Vaccination history was also an affecting factor for A/H1N1, B/Victoria, and response status (yes vs. no: OR = 0.4 / 0.44 / 0.25, P < 0.001). The frequency of colds and chronic conditions were also affecting factors for participants' seroconversion rates and response levels to different degrees. The sum-rank test showed that the fold changes for A/H1N1, B/Victoria, and B/Yamagata were associated with age group and vaccination history (P < 0.01). The fold changes for A/H3N2 were associated with the frequency of colds (P < 0.05), and those for B/Victoria were associated with gender and chronic conditions (P < 0.05)., Conclusions: Vaccination history, age, health condition, and frequency of colds were important factors affecting the seroconversion rate of the influenza vaccine in human. There is a need for developing optimized vaccination strategies for vulnerable groups to improve the efficacy of influenza vaccines in human., (© 2023. The Author(s).)

Influenza virus and coronavirus, two kinds of pathogens that exist widely in nature, are common emerging pathogens that cause respiratory tract infections in humans. In December 2019, a novel coronavirus SARS-CoV-2 emerged, causing a severe respiratory infection named COVID-19 in humans, and raising a global pandemic which has persisted in the world for almost three years. Influenza virus, a seasonally circulating respiratory pathogen, has caused four global pandemics in humans since 1918 by the emergence of novel variants. Studies have shown that there are certain similarities in transmission mode and pathogenesis between influenza and COVID-19, and vaccination and antiviral drugs are considered to have positive roles as well as several limitations in the prevention and control of both diseases. Comparative understandings would be helpful to the prevention and control of these diseases. Here, we review the study progress in the etiology, pathogenesis, vaccine and antiviral drug development for the two diseases.

Objective: To explore the feasibility of moving epidemic method (MEM) in the assessment of seasonal influenza (influenza) activity intensity from the perspective of urban agglomeration, assess influenza activity intensity in the Beijing-Tianjin-Hebei region from 2019 to 2021 and evaluate the reliability of surveillance data and the effectiveness of the MEM model application. Methods: The weekly reported incidence rate (IR) of influenza and the percentage of influenza-like illness (ILI%) from 2011-2021 in Beijing-Tianjin-Hebei region were collected to establish MEM models respectively. The model fitting effect and the reliability of the two data were evaluated for the purpose of establishing an optimal model to assess the influenza activity intensity in Beijing-Tianjin-Hebei region from 2019-2021. A cross-validation procedure was used to evaluate the performance of the models by calculating the Youden's index, sensitivity and specificity. Results: The MEM model fitted with weekly ILI% had a higher Youden's index compared with the model fitted with weekly IR at both Beijing-Tianjin-Hebei region level and provincial level. The MEM model based on ILI% showed that the epidemic threshold in Beijing-Tianjin-Hebei region during 2019-2020 was 4.42%, the post-epidemic threshold was 4.66%, with medium, high and very high intensity thresholds as 5.38%, 7.22% and 7.84%, respectively. The influenza season during 2019-2020 had 10 weeks (week 50 of 2019 to week 7 of 2020). The influenza season started in week 50 of 2019, and the intensity fluctuated above and below medium epidemic level for six consecutive weeks. The high intensity was observed in week 4 of 2020, the threshold of very high intensity was excessed in week 5, and the intensity gradually declined and became lower than the threshold at the end of the influenza season in week 8. The epidemic threshold was 4.29% and the post-epidemic threshold was 4.35% during 2020-2021. Influenza activity level never excessed the epidemic threshold throughout the year, and no epidemic period emerged. Conclusions: The MEM model could be applied in the assessment of influenza activity intensity in Beijing-Tianjin-Hebei region, and the use of ILI% to assess influenza activity intensity in this region was more reliable than IR data. Influenza activity intensity in Beijing-Tianjin-Hebei region was higher during 2019-2020 but significantly lower in 2020-2021.

Respiratory infectious diseases (RIDs) pose threats to people's health, some of which are serious public health problems. The aim of our study was to explore epidemic situations regarding notifiable RIDs and the epidemiological characteristics of the six most common RIDs in mainland China. We first collected the surveillance data of all 12 statutory notifiable RIDs for 31 provinces in mainland China that reported between 2010 and 2018, and then the six most prevalent RIDs were selected to analyze their temporal, seasonal, spatiotemporal and population distribution characteristics. From 2010 to 2018, there were 13,985,040 notifiable cases and 25,548 deaths from RIDs in mainland China. The incidence rate of RIDs increased from 109.85/100,000 in 2010 to 140.85/100,000 in 2018. The mortality from RIDs ranged from 0.18/100,000 to 0.24/100,000. The most common RIDs in class B were pulmonary tuberculosis (PTB), pertussis, and measles, while those in class C were seasonal influenza, mumps and rubella. From 2010 to 2018, the incidence rate of PTB and rubella decreased; however, pertussis and seasonal influenza increased, with irregular changes in measles and mumps. The mortality from PTB increased from 2015 to 2018, and the mortality from seasonal influenza changed irregularly. PTB was mainly prevalent among people over 15 years old, while the other five common RIDs mostly occurred among people younger than 15 years old. The incidence of the six common RIDs mostly occurred in winter and spring, and they were spatiotemporally clustered in different areas and periods. In conclusion, PTB, seasonal influenza and mumps remain as public health problems in China, suggesting that continuous government input, more precise interventions, and a high-tech digital/intelligent surveillance and warning system are required to rapidly identify emerging events and timely response.

Influenza causes a significant disease burden as an acute respiratory infection. Evidence suggests that meteorological factors can influence the spread of influenza; however, the association between these factors and influenza activity remains controversial. In this study, we investigated the impact of temperature on influenza across different regions of China based on the meteorological data and influenza data from 554 sentinel hospitals in 30 provinces and municipalities in China from 2010 to 2017. A distributed lag nonlinear model (DLNM) was used to analyze the exposure lag response of daily mean temperatures to the risk of influenza-like illness (ILI), influenza A (Flu A), and influenza B (Flu B). We found that in northern China, low temperatures increased the risk of ILI, Flu A, and Flu B, while in central and southern China, both low and high temperatures increased the risk of ILI and Flu A, and only low temperatures increased the risk of Flu B. This study suggests that temperature is closely associated with the influenza activity in China. Temperature should be integrated into the current public health surveillance system for highly accurate influenza warnings and the timely implementation of disease prevention and control measures., Competing Interests: The authors declare no conflict of interest.

Background: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication., Methods: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance., Results: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness., Conclusions: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to explore whether indoor or outdoor relative humidity (RH) modulates the influenza epidemic transmission in temperate and subtropical climates., Methods: In this study, the daily temperature and RH in 1558 households from March 2017 to January 2019 in five cities across both temperate and subtropical regions in China were collected. City-level outdoor temperature and RH from 2013 to 2019 were collected from the weather stations. We first estimated the effective reproduction number (R t ) of influenza and then used time-series analyses to explore the relationship between indoor/outdoor RH/absolute humidity and the R t of influenza. Furthermore, we expanded the measured 1-year indoor temperature and the RH data into 5 years and used the same method to examine the relationship between indoor/outdoor RH and the R t of influenza., Results: Indoor RH displayed a seasonal pattern, with highs during the summer months and lows during the winter months, whereas outdoor RH fluctuated with no consistent pattern in subtropical regions. The R t of influenza followed a U-shaped relationship with indoor RH in both temperate and subtropical regions, whereas a U-shaped relationship was not observed between outdoor RH and R t . In addition, indoor RH may be a better indicator for R t of influenza than indoor absolute humidity., Conclusion: The findings indicated that indoor RH may be the driver of influenza seasonality in both temperate and subtropical locations in China., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence concerning effects of air pollution on influenza-like illness (ILI) from multi-center is limited and little is known about how regional factors might modify this relationship., Methods: In this ecological study, ILI cases defined as outpatients with temperature ≥38 °C, accompanied by cough or sore throat, were collected from National Influenza Surveillance Network in China. We adopted generalized additive model with quasi-Poisson to estimate province-specific association between air pollution and ILI in 30 Chinese provinces during 2015-2019, after adjusting for time trend and meteorological factors. We then pooled province-specific association by using random-effect meta-analysis. Potential effect modifications of season and regional characteristics were explored., Findings: A total of 26, 004, 853 ILI cases and 777, 223, 877 hospital outpatients were collected. In general, effects of air pollutants were acute. An inter-quartile range increase of PM 2.5 , SO 2 , PM 10 , NO 2 and CO at lag0, and O 3 at lag0-2 was associated with 3.08% (95% CI: 1.91%, 4.27%), 3.00% (1.86%, 4.16%), 6.46% (4.71%, 8.25%), 7.21% (5.73%, 8.71%), 4.37% (3.05%, 5.70%), and -9.26% (-11.32%, -7.14%) change of ILI at national level, respectively. Associations between air pollutants and ILI varied by season and regions, with higher effect estimates in cold season, eastern and central regions and provinces with more humid condition and larger population., Interpretation: This study indicated that most air pollutants increased the risk of ILI in China. Our findings might provide implications for the development of policies to protect public health from air pollution and influenza., Funding: National Natural Science Foundation of China and Chongqing Health Commission Program., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Research assessing the changing epidemiology of infectious diseases in China after the implementation of new healthcare reform in 2009 was scarce. We aimed to get the latest trends and disparities of national notifiable infectious diseases by age, sex, province, and season in China from 2010 to 2019. The number of incident cases and deaths, incidence rate, and mortality of 44 national notifiable infectious diseases by sex, age groups, and provincial regions from 2010 to 2019 were extracted from the China Information System for Disease Control and Prevention and official reports and divided into six kinds of infectious diseases by transmission routes and three classes (A-C) in this descriptive study. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends of incidence and mortality rate. We calculated the concentration index to measure economic-related inequality. Segmented interrupted time-series analysis was used to estimate the impact of the COVID-19 pandemic on the epidemic of notifiable infectious diseases. The trend of incidence rate on six kinds of infectious diseases by transmission routes was stable, while only mortality of sexual, blood-borne, and mother-to-child-borne infectious diseases increased from 0.6466 per 100 000 population in 2010 to 1.5499 per 100 000 population in 2019 by 8.76% per year (95% confidence interval [CI]: 6.88-10.68). There was a decreasing trend of incidence rate on Class-A infectious diseases (EAPC = -16.30%; 95% CI: -27.93 to -2.79) and Class-B infectious diseases (EAPC = -1.05%; 95% CI: -1.56 to -0.54), while an increasing trend on Class-C infectious diseases (EAPC = 6.22%; 95% CI: 2.13-10.48). For mortality, there was a decreasing trend on Class-C infectious diseases (EAPC = -14.76%; 95% CI: -23.46 to -5.07), and an increasing trend on Class-B infectious diseases (EAPC = 4.56%; 95% CI: 2.44-6.72). In 2019, the infectious diseases with the highest incidence rate and mortality were respiratory diseases (340.95 per 100 000 population), and sexual, blood-borne, and mother-to-child-borne infectious diseases (1.5459 per 100 000 population), respectively. The greatest increasing trend of incidence rate was observed in seasonal influenza, from 4.83 per 100 000 population in 2010 to 253.36 per 100 000 population in 2019 by 45.16% per year (95% CI: 29.81-62.33), especially among females and children aged 0-4 years old. The top disease with the highest mortality was still AIDs, which had the highest average yearly mortality in 24 provinces from 2010 to 2019, and its incidence rate (EAPC = 14.99%; 95% CI: 8.75-21.59) and mortality (EAPC = 9.65; 95%CI: 7.71-11.63) both increased from 2010 to 2019, especially among people aged 44-59 years old and 60 or older. Male incidence rate and mortality were higher than females each year from 2010 to 2018 on 29 and 10 infectious diseases, respectively. Additionally, sex differences in the incidence and mortality of AIDS were becoming larger. The curve lay above the equality line, with the negative value of the concentration index, which indicated that economic-related health disparities exist in the distribution of incidence rate and mortality of respiratory diseases (incidence rate: the concentration index = -0.063, p < 0.0001; mortality: the concentration index = -0.131, p < 0.001), sexual, blood-borne, and mother-to-child-borne infectious diseases (incidence rate: the concentration index = -0.039, p = 0.0192; mortality: the concentration index = -0.207, p < 0.0001), and the inequality disadvantageous to the poor (pro-rich). Respiratory diseases (Dec-Jan), intestinal diseases (May-Jul), zoonotic infectious diseases (Mar-Jul), and vector-borne infectious diseases (Sep-Oct) had distinct seasonal epidemic patterns. In addition, segmented interrupted time-series analyses showed that, after adjusting for potential seasonality, autocorrelation, GDP per capita, number of primary medical institutions, and other factors, there was no significant impact of COVID-19 epidemic on the monthly incidence rate of six kinds of infectious diseases by transmission routes from 2018 to 2020 (all p > 0.05). The incidence rates of six kinds of infectious diseases were stable in the past decade, and incidence rates of Class-A and Class-B infectious diseases were decreasing because of comprehensive prevention and control measures and a strengthened health system after the implementation of the new healthcare reform in China since 2009. However, age, gender, regional, and economic disparities were still observed. Concerted efforts are needed to reduce the impact of seasonal influenza (especially among children aged 0-4 years old) and the mortality of AIDs (especially among people aged 44-59 years old and 60 or older). More attention should be paid to the disparities in the burden of infectious diseases., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Recent seasonal epidemics of influenza have been caused by human influenza A viruses of the H1N1 and H3N2 subtypes and influenza B viruses. Annual vaccination is recommended to prevent infection; however, how annual influenza vaccination influences vaccine effectiveness is largely unknown., Methods: To investigate the impact of repeated vaccination on immune and protective effect, we performed a prospective seroepidemiologic study. Participants with or without prior vaccination (2018-2019) were enrolled during the 2019-2020 influenza season. Inactivated quadrivalent influenza vaccine (IIV4) was administered through the intramuscular route, and venous blood samples were collected regularly to test hemagglutination inhibition (HAI) titers., Results: The geometric mean titers and proportion with titers ≥40 against the influenza vaccine components peaked at 30 days post-vaccination. At Day 30, the geometric mean titer and proportion with titers ≥40 in participants who had been previously vaccinated were higher for H3N2 but similar for both B lineages (Victoria and Yamagata) as compared with participants vaccinated for the first time. As for H1N1, the geometric mean titer was lower in repeated vaccinated participants, but the proportion with titers ≥40 was consistent in both groups., Conclusions: Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Currently, the clinical factors affecting immune responses to influenza vaccines have not been systematically explored. The mechanism of low responsiveness to influenza vaccination (LRIV) is complicated and not thoroughly elucidated. Thus, we integrate our in-house genome-wide association studies (GWAS) analysis result of LRIV (N = 111, Ncase [Low Responders] = 34, Ncontrol [Responders] = 77) with the GWAS summary of 10 blood-based biomarkers (sample size ranging from 62 076-108 794) deposited in BioBank Japan (BBJ) to comprehensively explore the shared genetics between LRIV and blood-based biomarkers to investigate the causal relationships between blood-based biomarkers and LRIV by Mendelian randomization (MR). The applications of four MR approaches (inverse-variance-weighted [IVW], weighted median, weighted mode, and generalized summary-data-based MR [GSMR]) suggested that the genetically instrumented LRIV was associated with decreased eosinophil count (β = -5.517 to -4.422, p = 0.004-0.039). Finally, we conclude that the low level of eosinophil count is a suggestive risk factor for LRIV., (© 2022 Wiley Periodicals LLC.)

Emerging and re-emerging viruses like influenza virus pose a continuous global public health threat. Vaccines are one of the most effective public health strategies for controlling infectious diseases. However, little is known about the immunological features of vaccination at the single-cell resolution, including for influenza vaccination. Here, we report the single-cell transcriptome atlas of longitudinally collected peripheral blood mononuclear cells (PBMCs) in individuals immunized with an inactivated influenza vaccine. Overall, vaccination with the influenza vaccine only had a small impact on the composition of peripheral immune cells, but elicited global transcriptional changes in multiple immune cell subsets. In plasma and B cell subsets, transcriptomic changes, which were mostly involved in antibody production as well as B cell activation and differentiation, were observed after influenza vaccinations. In influenza-vaccinated individuals, we found a reduction in multiple biological processes (e.g., interferon response, inflammatory response, HLA-I/II molecules, cellular apoptosis, migration, and cytotoxicity, etc.,) 7 days postvaccination in multiple immune cell subsets. However, 14 days postvaccination, these levels returned to similar levels observed in prevaccination samples. Additionally, we did not observe significant upregulation of pro-inflammatory response genes and key thrombosis-related genes in influenza-vaccinated individuals. Taken together, we report a cell atlas of the peripheral immune response to influenza vaccination and provide a resource for understanding the immunological response mechanisms of influenza vaccination., (© 2022 Wiley Periodicals LLC.)

Circulation of seasonal influenza is the product of complex interplay among multiple drivers, yet characterizing the underlying mechanism remains challenging. Leveraging the diverse seasonality of A(H3N2) virus and abundant climatic space across regions in China, we quantitatively investigated the relative importance of population susceptibility, climatic factors, and antigenic change on the dynamics of influenza A(H3N2) through an integrative modelling framework. Specifically, an absolute humidity driven multiscale transmission model was constructed for the 2013/2014, 2014/2015 and 2016/2017 influenza seasons that were dominated by influenza A(H3N2). We revealed the variable impact of absolute humidity on influenza transmission and differences in the occurring timing and magnitude of antigenic change for those three seasons. Overall, the initial population susceptibility, climatic factors, and antigenic change explained nearly 55% of variations in the dynamics of influenza A(H3N2). Specifically, the additional variation explained by the initial population susceptibility, climatic factors, and antigenic change were at 33%, 26%, and 48%, respectively. The vaccination program alone failed to fully eliminate the summer epidemics of influenza A(H3N2) and non-pharmacological interventions were needed to suppress the summer circulation. The quantitative understanding of the interplay among driving factors on the circulation of influenza A(H3N2) highlights the importance of simultaneous monitoring of fluctuations for related factors, which is crucial for precise and targeted prevention and control of seasonal influenza., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Understanding the role of meteorological factors in the transmission dynamics of respiratory infectious diseases remains challenging. Our study was to comprehensively investigate the nonlinear effects of environmental factors on influenza transmission, based on multi-region surveillance data from mainland China. An approach related to time-varying reproduction number (R t ) was proposed, which extracts the environment-related components from R t to estimate the relationship between environmental factors and influenza transmission based on a mixed-effects regression model. Nonlinear relationships for absolute humidity (the lowest transmission was observed at absolute humidity of 12 g/m 3 ) and mean temperature (the lowest transmission was observed at the mean temperature of 18 ° C) with influenza transmission were observed. Influenza transmission holds almost constant with the average precipitation below 1 mm or sunshine hour below 9 h/day, but increases for the precipitation and decreases for the sunshine hour afterward. The environmental dependence varies across subtypes: A(H3N2) maintains relatively higher transmission in high temperature and humidity conditions, compared with other influenza subtypes. Overall, the subtypes specified environmental dependence of influenza transmission could explain 23.1 %, 29.2 % and 27.1 % of the variations for A(H1N1)pdm09, A(H3N2) and B-lineage in China. The projected seasonal transmission rates based on our approach could be used as a valuable seasonal proxy to model the influenza dynamics under various meteorological spaces. Finally, our approach is also applicable to obtain novel insights into the impact of environmental factors on other respiratory infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Many studies have explored the epidemiological characteristics of influenza. However, most previous studies were conducted in a specific region without a national picture which is important to develop targeted strategies and measures on influenza control and prevention., Objectives: To explore the association between ambient temperature and incidence of influenza, to estimate the attributable risk from temperature in 30 Chinese cities with different climatic characteristics for a national picture, and to identify the vulnerable populations for national preventative policy development., Methods: Daily meteorological and influenza incidence data from the 30 Chinese cities over the period 2016-19 were collected. We estimated the city-specific association between daily mean temperature and influenza incidence using a distributed lag non-linear model and evaluated the pooled effects using multivariate meta-analysis. The attributable fractions compared with reference temperature were calculated. Stratified analyses were performed by region, sex and age., Results: Overall, an N-shape relationship between temperature and influenza incidence was found in China. The cumulative relative risk of the peak risk temperature (5.1 °C) was 2.13 (95%CI: 1.41, 3.22). And 60% (95%eCI: 54.3%, 64.3%) of influenza incidence was attributed to ambient temperature during the days with sensitive temperatures (1.6°C-14.4 °C). The ranges of sensitive temperatures and the attributable disease burden due to temperatures varied for different populations and regions. The residents in South China and the children aged ≤5 and 6-17 years had higher fractions attributable to sensitive temperatures., Conclusions: Tailored preventions targeting on most vulnerable populations and regions should be developed to reduce influenza burden from sensitive temperatures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nonpharmaceutical interventions (NPIs) have been commonly deployed to prevent and control the spread of the coronavirus disease 2019 (COVID-19), resulting in a worldwide decline in influenza prevalence. However, the influenza risk in China warrants cautious assessment. We conducted a cross-sectional, seroepidemiological study in Shandong Province, Northern China in mid-2021. Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains. A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic. The overall seroprevalence values against A/H1N1pdm09, A/H3N2, B/Victoria, and B/Yamagata were 17.8% (95% CI 16.2%-19.5%), 23.5% (95% CI 21.7%-25.4%), 7.6% (95% CI 6.6%-8.7%), and 15.0 (95% CI 13.5%-16.5%), respectively, in the study period. The overall vaccination rate was extremely low (2.6%). Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals (P < 0.001). Notably, the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic (P < 0.01). Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China., (© 2022. Higher Education Press.)

This study aimed to investigate the changes in the willingness of guardians to administer the COVID-19 vaccine to their children, allow the coadministration of other vaccines, and administer the COVID-19 vaccine booster dose. This was a follow-up study conducted 6 months after a similar previous study. The self-administered questionnaire was distributed through the "Xiao Dou Miao" app and 9424 guardians with access to this app participated in the survey that was conducted from September 15 to October 8, 2021. Of all the participating guardians, 86.68% were willing to vaccinate their children with the COVID-19 vaccine, which was approximately 16% more than those in our previous study. Guardians aged ≥40 years, healthcare workers, and those with children aged ≥3 years were more willing to vaccinate their children. Approximately 77% of the guardians were willing toward the coadministration of COVID-19 and influenza vaccines. Approximately 64% of the guardians were willing toward the coadministration of other nonimmunization program vaccines with the COVID-19 vaccine for their children. The primary reasons for reluctance toward the coadministration of vaccines were concerns about vaccine safety and effectiveness. If necessary, 92% of the guardians were willing to receive a COVID-19 vaccine booster and 82% were willing to vaccinate their children with a COVID-19 vaccine booster. We hope that this research will facilitate the formulation of successful strategies for the implementation of COVID-19 vaccinations, covaccinations, and COVID-19 booster doses, particularly for children aged <6 years.

Background: In the past few decades, globalization has rendered more frequent and intensive population movement between countries, which has changed the original disease spectrum and brought a huge health impact on the global population including China. This study aims to describe the spectrum and epidemiological characteristics of imported infections among foreign travelers travelling to China., Methods: The data on imported infections among foreign travelers were obtained from Custom Inbound Screening System (CISS) and the National Notifiable Infectious Disease Reporting System (NNIDRS). All the infections were classified into respiratory, gastrointestinal, vector-borne, blood/sex-transmitted and mucocutaneous diseases, of which case numbers and incidences were calculated and the proportions were compared among subgroups., Results: In total, 17,189 travelers diagnosed with 58 imported infectious diseases were reported from 2014 to 2018, with an overall incidence of 122.59 per million. Respiratory infection (7,351 cases, mainly influenza) and blood/sex-transmitted diseases (6,114 cases mainly Hepatitis B and HIV infection) were the most frequently diagnosed diseases, followed by vector-borne infections (3,128 cases, mainly dengue fever and malaria). The highest case number was from Asia and Europe, while the highest incidence rate was from Africa (296.00 per million). When specific diagnosis was compared, both the highest absolute case number and incidence were observed for influenza. An obvious seasonal pattern was observed for vector-borne diseases, with the annual epidemic spanning from July to November. The origin-destination matrices disclosed the movement of imported infection followed specific routes., Conclusions: Our study provided a profile of infectious diseases among foreign travelers travelling to China and pinpointed the target regions, seasons and populations for prevention and control, to attain an informed control of imported infections in China., (© 2022. The Author(s).)

Human infections with H7N9 avian influenza A virus that emerged in East China in 2013 and caused high morbidity rates were more frequently detected in men than in women over the last five epidemic waves. However, molecular markers associated with poor disease outcomes in men are still unknown. In this study, we systematically analysed sex hormone and cytokine levels in males and females with laboratory-confirmed H7N9 influenza in comparison to H7N9-negative control groups as well as laboratory-confirmed seasonal H1N1/H3N2 influenza cases (n = 369). Multivariable analyses reveal that H7N9-infected men present with considerably reduced testosterone levels associated with a poor outcome compared to non-infected controls. Regression analyses reveal that testosterone levels in H7N9-infected men are negatively associated with the levels of several pro-inflammatory cytokines, such as IL-6 and IL-15. To assess whether there is a causal relationship between low testosterone levels and avian H7N9 influenza infection, we used a mouse model. In male mice, we show that respiratory H7N9 infection leads to a high viral load and inflammatory cytokine response in the testes as well as a reduction in pre-infection plasma testosterone levels. Collectively, these findings suggest that monitoring sex hormone levels may support individualized management for patients with avian influenza infections., (© 2022. The Author(s).)