Genomic characterization of influenza A (H7N9) viruses isolated in Shenzhen, Southern China, during the second epidemic wave.

There were three epidemic waves of human infection with avian influenza A (H7N9) virus in 2013-2014. While many analyses of the genomic origin, evolution, and molecular characteristics of the influenza A (H7N9) virus have been performed using sequences from the first epidemic wave, genomic characterization of the virus from the second epidemic wave has been comparatively less reported. In this study, an in-depth analysis was performed with respect to the genomic characteristics of 11 H7N9 virus strains isolated from confirmed cases and four H7N9 virus strains isolated from environmental samples in Shenzhen during the second epidemic wave. Phylogenetic analysis demonstrated that six internal segments of the influenza A (H7N9) virus isolated from confirmed cases and environmental samples in Shenzhen were clustered into two different clades and that the origin of the influenza A (H7N9) virus isolated from confirmed cases in Shenzhen was different from that of viruses isolated during the first wave. In addition, H9N2 viruses, which were prevalent in southern China, played an important role in the reassortment of the influenza A (H7N9) virus isolated in Shenzhen. HA-R47K and -T122A, PB2-V139I, PB1-I397M, and NS1-T216P were the signature amino acids of the influenza A (H7N9) virus isolated from confirmed cases in Shenzhen. We found that the HA, NA, M, and PA genes of the A(H7N9) viruses underwent positive selection in the human population. Therefore, enhanced surveillance should be carried out to determine the origin and mode of transmission of the novel influenza A (H7N9) virus and to facilitate the formulation of effective policies for prevention and containment of a human infection epidemics.

Seroprevalence to avian influenza A(H7N9) virus among poultry workers and the general population in southern China: a longitudinal study.

BACKGROUND: Confirmed cases of avian influenza A(H7N9) virus infection in humans continue to occur in mainland China. Few confirmed cases have occurred in poultry workers despite potentially higher rates of exposure. METHODS: A serological survey was conducted in May and December 2013 in poultry market workers, and in March and September 2013 in the general population. Blood samples were collected and tested for antibodies to H7N9 and H5N1 viruses by hemagglutination inhibition (HI) assays. Multivariable analysis was employed to identify risk factors related to H7N9 infection indicated by serology among poultry workers. RESULTS: In the poultry workers, 36 of 501 (7.2%) in May and 56 of 375 (14.9%) in December had HI antibody titers ≥1:160 to H7N9. Of 96 individuals who participated in both surveys, 52 (54.2%) workers had a ≥4-fold rise in H7N9 antibody titers from May to December. In a multivariable analysis, female sex (odds ratio [OR], 2.713; 95% confidence interval [CI], 1.098-6.705) and ≥10 years of occupational exposure (OR, 3.592; 95% CI, 1.246-10.354) were identified as risk factors for infection. Seroprevalence against H5N1 at ≥1:160 was low in May (4/501 [0.8%]) and December (3/375 [0.8%]). In the general population, 0 of 417 individuals in March and 0 of 408 individuals in September had antibody titers ≥1:160 to H7N9 or to H5N1. CONCLUSIONS: Although none of the participants in our study had virologically confirmed H7N9 infection, the high proportion of poultry workers with serologic evidence of H7N9 infection between May and December 2013 suggests a substantial risk of mild H7N9 infections in this group, supporting stricter control measures in live poultry markets.

[The analyses of HIV-1 quasispecies in HIV-infected subjects by the application of single genome amplification assay].

OBJECTIVE: To establish the single genome amplification (SGA) method and analyze the quasispecies in HIV-infected patients. METHODS: All 6 sample RNA acquired in 2010 in Shenzhen and genetic sequenced as overlap peaks were extracted and diluted to a single copy, nest-PCR after one step RT-PCR was employed to amplify HIV-1 genome, and then PCR products was purified and sequenced. Mega 4.02 software was used to analyze the genetic distance among HIV-1 quasispecies, and phylogenetic tree was constructed. RESULTS: Our data showed that viral sequences derived from different patients were grouped into different clusters. Subcluster was also observed in several clusters, indicating these existed competition and preferential replication of certain viral strains. The genetic distance within one cluster of 6 samples were between 0.008 and 0.06, it was likely to associate with the duration since infection and viral load. CONCLUSION: SGA is a useful approach to gain information on quasispecies, the genetic distance within one cluster may help to determine the infection time and immune escaping. The analysis of related affecting factors need more samples.

Expert consensus on One Health for establishing an enhanced and integrated surveillance system for key infectious diseases.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

Temporal dynamics of SARS-CoV-2 genome mutations that occurred in vivo on an aircraft.

We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3-31 days later. All 47 nasopharyngeal swabs were deep-sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n = 31), Beta (n = 1), and C.1.2 (n = 1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95% CI]: 2.77-10.22) than did the first samples (T1; median: 2; 95% CI: 1.63-3.74; Wilcoxon test, P = 0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

Inactivated SARS-CoV-2 Vaccine Booster Against Omicron Infection Among Quarantined Close Contacts.

Importance: Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective: To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants: This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure: A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures: The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results: Among 119 438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66 201 men [55.4%]), 86 251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33 187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance: In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.

Possible recombination between two variants of concern in a COVID-19 patient.

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

Analysis of the comprehensive non-pharmaceutical interventions and measures in containing the COVID-19 epidemic in Shenzhen: a retrospective study.

OBJECTIVE: To analyse the epidemiological characteristics of family clusters of COVID-19 and the three stages of the comprehensive non-pharmaceutical interventions and measures implemented in Shenzhen. METHODS: The epidemic curve of COVID-19 was drawn and the impact of the comprehensive non-pharmaceutical interventions and measures was analysed by the different periods of the epidemic. RESULTS: A total of 427 cases (417 confirmed cases and 10 asymptomatic infectious cases) were reported in Shenzhen, of which 259 (60.7%) were clustered cases. 97 cluster events were drawn and most cluster events (97.3%) occurred in families. There were three stages of the COVID-19 epidemic in Shenzhen. The epidemic increased rapidly, but the peak lasted for a short time, while the decline in incidence was rapid and large. CONCLUSIONS: Family clusters were the main feature of the COVID-19 outbreak in Shenzhen in 2020, and the Shenzhen government rolled out a quick response to the epidemic. Non-pharmaceutical interventions and measures were proven to have effectively contained community transmission, limit the transmission to aggregation and reduce the scale of transmission within a household.

Modelling the transmission and control strategies of varicella among school children in Shenzhen, China.

OBJECTIVES: Varicella (chickenpox) is a highly transmissible childhood disease. Between 2010 and 2015, it displayed two epidemic waves annually among school populations in Shenzhen, China. However, their transmission dynamics remain unclear and there is no school-based vaccination programme in Shenzhen to-date. In this study, we developed a mathematical model to compare a school-based vaccination intervention scenario with a baseline (i.e. no intervention) scenario. METHODS: Data on varicella reported cases were downloaded from the Infectious Disease Reporting Information Management System. We obtained the population size, age structure of children aged 15 or under, the class and school distribution from Shenzhen Education Bureau. We developed an Agent-Based Susceptible-Exposed-Infectious-Recovered (ABM-SEIR) Model that considered within-class, class-to-class and out-of-school transmission modes. The intervention scenario was that school-wide vaccination intervention occurred when an outbreak threshold was reached within a school. We varied this threshold level from five to ten cases. We compared the reduction of disease outbreak size and estimated the key epidemiological parameters under the intervention strategy. RESULTS: Our ABM-SEIR model provided a good model fit to the two annual varicella epidemic waves from 2013 to 2015. The transmission dynamics displayed strong seasonality. Our results suggested that a school-based vaccination strategy could effectively prevent large outbreaks at different thresholds. CONCLUSIONS: There was a considerable increase in reported varicella cases from 2013 to 2015 in Shenzhen. Our modelling study provided important theoretical support for disease control decision making during school outbreaks and the development of a school-based vaccination programme.