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 The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs.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.

Pathogenetic detection, retrospective and pathogenicity analysis of a fatal case of Vibrio vulnificus in Shenzhen, China.

We report a 36-year-old male patient died of V. vulnificus-induced septicaemia and multiple organ failure syndrome after oyster consumption at a restaurant. We isolated and identified V. vulnificus vv16015 from the patient's blood sample and antibiotic susceptibility tests indicated sensitivity to all 21 antibiotics. Oyster samples were subsequently collected from the restaurant's supplier and three strains of V. vulnificus were isolated. Whole genome sequencing and analysis revealed vv16015 to be distantly related to these strains and confirmed that V. vulnificus contamination was present in the seafood of the restaurant and supplier. Using a Galleria mellonella larvae infection model, the virulence of vv16015 was determined to be higher than that of comparison strains isolated from a surviving patient (vv15018) and an oyster (vv220015). The human and environment distribution of V. vulnificus in Shenzhen is sporadic and heterogeneous, and vv16015 is highly virulent compared to other strains.

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.

Distribution of drug-resistant genes in alveolar lavage fluid from patients with psittacosis and traceability analysis of causative organisms.

Background: Chlamydia psittaci is a small bacterium often found in birds, including poultry, and domesticated mammals, which causes psittacosis (or parrot fever) in humans. Different strains of C. psittaci respond variably to antibiotics, suggesting a possible risk of antibiotic resistance. In general, different genotypes of C. psittaci have relatively stable hosts and different pathogenicity. Methods: Macrogenomic sequencing was performed using nucleic acids extracted from psittacosis patients' alveolar lavage fluid samples and analyzed for genetic variability and antibiotic resistance genes. Nucleic acid amplification sequences specific to the core coding region of the C. psittaci ompA gene were used, and a phylogenetic tree was constructed with C. psittaci genotypic sequences from other sources, including Chinese published sources. The C. psittaci found in each patient were genotyped by comparing ompA gene sequences. In addition, to better illustrate the relationship between genotype and host of C. psittaci, 60 bird fecal samples were collected from bird-selling stores for screening and C. psittaci typing. Results: Macrogenomic sequence alignment revealed the presence of resistance genes in varying abundance in samples from all three patients, including C. psittaci resistance gene sequences from two patients that matched those previously published on NCBI. Based on ompA genotyping, two patients were infected with C. psittaci genotype A and one patient was infected with genotype B. All five C. psittaci-positive samples obtained from bird-selling stores were genotype A. Both genotypes are reported to be infectious to humans. The host origin of the samples and the previously reported main sources of each genotype suggested that all but one of the C. psittaci genotype A in this study were derived from parrots, while genotype B was probably derived from chickens. Conclusion: The presence of bacterial resistance genes in psittacosis patients may affect the efficacy of clinical antibiotic therapy. Focusing on the developmental progression of bacterial resistance genes and differences in the therapeutic efficacy may facilitate effective treatment of clinical bacterial infections. Pathogenicity genotypes (e.g., genotype A and genotype B) are not limited to one animal host, suggesting that monitoring the development and changes of C. psittaci may help prevent transmission to humans.

Pathogenetic characterization of a Micrococcus luteus strain isolated from an infant.

Purpose: To explore the clinical characteristics of Micrococcus luteus bloodstream infection in an infant and characterize the phenotype and genotype of the isolated strains, as well as seek suitable infection models for assessing virulence. Methods: Clinical data was collected from an infant patient diagnosed with M. luteus bloodstream infection. Metagenomic sequencing was performed on the isolated blood sample. The strain was isolated and underwent mass spectrometry, biochemical tests, antibiotic susceptibility assays, and whole-genome sequencing. The Galleria mellonella infection model was used to assess M. luteus virulence. Results: Patient responded poorly to cephalosporins, but recovered after Linezolid treatment. Metagenomic sequencing identified M. luteus as the predominant species in the sample, confirming infection. They were identified as M. luteus with a high confidence level of 98.99% using mass spectrometry. The strain showed positive results for Catalase, Oxidase, and Urea tests, and negative results for Mannose, Xylose, Lactose, Mannitol, Arginine, and Galactose tests, consistent with the biochemical profile of M. luteus reference standards. M. luteus susceptibility to 15 antibiotics was demonstrated and no resistance genes were detected. Predicted virulence genes, including clpB, were associated with metabolic pathways and the type VI secretion system. The infection model demonstrated dose-dependent survival rates. Conclusion: The infant likely developed a bloodstream infection with M. luteus due to compromised immunity. Although the isolated strain is sensitive to cephalosporin antibiotics and has low pathogenicity in infection models, clinical treatment with cephalosporins was ineffective. Linezolid proved to be effective, providing valuable guidance for future clinical management of such rare infections.

A Peptide-Based Ligand-Directed Chemistry Enables Protein Functionalization.

The ligand-directed (LD) chemistry provides powerful tools for site-specific modification of proteins. We utilized a peptide with an appended methionine (Met) as a ligand; then, the Met thioether was modified into sulfonium which enabled a proximity induced group transfer onto protein cysteine in the vicinity upon peptide-target binding. The sulfonium warhead could be easily constructed with unprotected peptides, and the transferable group scope was conducted on model protein PDZ and its ligand peptides. In addition, a living cell labeling was successfully achieved.

SARS-CoV-2 Aerosol Transmission Through Vertical Sanitary Drains in High-Rise Buildings - Shenzhen, Guangdong Province, China, March 2022.

What is already known about this topic?: Aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via sanitary pipelines in high-rise buildings is possible, however, there is a lack of experimental evidence. What is added by this report?: The field simulation experiment confirmed the existence of a vertical aerosol transmission pathway from toilet flush-soil stack-floor drains without water seal. This report provided experimental evidence for vertical aerosol transmission of clustered outbreaks on 18 floors of a 33-story residential building. What are the implications for public health practice?: The water seal on floor drains is a necessary barrier to prevent the risk of vertical aerosol transmission of infectious disease pathogens in buildings. It is necessary not only to have a U-shaped trap in the drainage pipe, but also to be filled with water regularly.

Chinese expert consensus on immunoprophylaxis of common respiratory pathogens in children (2021 edition).

Respiratory tract infections are infectious diseases involving the respiratory tract (such as the sinuses, throat, airways or lungs), which are the common respiratory disorders in children. With the development of society and the improvement of economic conditions, great progress has been made in China in the prevention of common respiratory pathogens in children. As a result, the incidence and mortality of respiratory tract infections in children have dropped sharply in the past decades. However, there is still a certain gap compared with the international leading levels, which can be partly attribute to insufficient public awareness of vaccination, uneven vaccination services of vaccinators, and so on. On the basis of comprehensive analysis of the clinical evidence of immunoprophylaxis of common respiratory pathogens among children in China and abroad, combined with the clinical situation and the experience of experts, the consensus focuses on the characteristics of transmission, clinical manifestations and immunoprophylaxis of common respiratory pathogens in children, so as to provide reference for clinical practice. This consensus document applies to all Centers for Disease Control and Prevention (CDC) staff levels engaged in the prevention and control of related pathogens, vaccinators at vaccination sites, and medical staff in pediatric, respiratory, and infectious diseases departments at all levels in medical institutions.

Development and multi-center clinical trials of an up-converting phosphor technology-based point-of-care (UPT-POCT) assay for rapid COVID-19 diagnosis and prediction of protective effects.

BACKGROUND: Quantitative point-of-care testing assay for detecting antibodies is critical to COVID-19 control. In this study, we established an up-conversion phosphor technology-based point-of-care testing (UPT-POCT), a lateral flow assay, for rapid COVID-19 diagnosis, as well as prediction of seral neutralizing antibody (NAb) activity and protective effects. METHODS: UPT-POCT was developed targeting total antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Using ELISA as a contrast method, we evaluated the quantitation accuracy with NAb and serum samples. Cutoff for serum samples was determined through 70 healthy and 140 COVID-19 patients. We evaluated the cross-reactions with antibodies against other viruses. Then, we performed multi-center clinical trials of UPT-POCT, including 782 patients with 387 clinically confirmed COVID-19 cases. Furthermore, RBD-specific antibody levels were detected using UPT-POCT and microneutralization assay for samples from both patients and vaccinees. Specifically, the antibodies of recovered patients with recurrent positive (RP) reverse transcriptase-polymerase chain reaction test results were discussed. RESULTS: The ratios of signal intensities between the test and control bands on the lateral flow strip, namely, T/C ratios, was defined as the results of UPT-POCT. T/C ratios had excellent correlations with concentrations of NAb, as well as OD values of ELISA for serum samples. The sensitivity and specificity of UPT-POCT were 89.15% and 99.75% for 782 cases in seven hospitals in China, respectively. We evaluated RBD-specific antibodies for 528 seral samples from 213 recovered and 99 RP COVID-19 patients, along with 35 seral samples from inactivated SARS-CoV-2 vaccinees, and we discovered that the total RBD-specific antibody level indicated by T/C ratios of UPT-POCT was significantly related to the NAb titers in both COVID-19 patients (r = 0.9404, n = 527; ρ = 0.6836, n = 528) and the vaccinees (r = 0.9063, ρ = 0.7642, n = 35), and it was highly relevant to the protection rate against RP (r = 0.9886, n = 312). CONCLUSION: This study reveals that the UPT-POCT for quantitative detection of total RBD-specific antibody could be employed as a surrogate method for rapid COVID-19 diagnosis and prediction of protective effects.

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.

Seropositive Reaction Rates of 9 B-Cell Epitopes of the SARS-CoV-2 Spike Protein and the Relationship between the Epitopes and Neutralizing Antibody.

OBJECTIVE: The aim of the study was to analyze the relationship between serum antibody and neutralizing antibody titers in convalescent coronavirus disease 2019 (COVID-19) patients with different disease severities, and the seropositive reaction rates of 9 reported B-cell epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Serum IgG and total antibody titers of 165 convalescent COVID-19 patients were determined by chemiluminescence, the serum neutralization antibody titers were determined by microneutralization assay, and the S/CO values of 9 peptides were detected by indirect enzyme-linked immunosorbent assay. Correlations between the aforementioned indexes were statistically analyzed, and differences in patients with different diseases severities were evaluated. RESULTS: IgG, total antibody, and neutralizing antibody titers increased with disease severity. The positive rate of the receptor-binding region (RBD) was 100%, and the average positive rate for all the 9 peptides was above 50% in 165 patients. IDf showed the highest rate of positivity (86.06%), with a rate of 95% for the (IDf + IDa) pattern. Moreover, S/CO values of RBD and mix (IDh) were significantly correlated with IgG, total antibody titers, and neutralizing antibody titers (p < 0.001), whereas the S/CO values for other 8 peptides showed no obvious correlation. CONCLUSION: In this study, a large sample was used to confirm that the peptide IDf had a high positive reaction rate for all patients (86.06%) and also had the highest detection rate in asymptomatic patients (86.67%). Only long peptide and mixed peptide showed correlation with neutralizing antibody titers, suggesting that the ability of SARS-CoV-2 antibody to neutralize virus infectivity may require the interaction of multiple sites.

A global assessment of the impact of school closure in reducing COVID-19 spread.

Prolonged school closure has been adopted worldwide to control COVID-19. Indeed, UN Educational, Scientific and Cultural Organization figures show that two-thirds of an academic year was lost on average worldwide due to COVID-19 school closures. Such pre-emptive implementation was predicated on the premise that school children are a core group for COVID-19 transmission. Using surveillance data from the Chinese cities of Shenzhen and Anqing together, we inferred that compared with the elderly aged 60 and over, children aged 18 and under and adults aged 19-59 were 75% and 32% less susceptible to infection, respectively. Using transmission models parametrized with synthetic contact matrices for 177 jurisdictions around the world, we showed that the lower susceptibility of school children substantially limited the effectiveness of school closure in reducing COVID-19 transmissibility. Our results, together with recent findings that clinical severity of COVID-19 in children is lower, suggest that school closure may not be ideal as a sustained, primary intervention for controlling COVID-19. This article is part of the theme issue 'Data science approach to infectious disease surveillance'.

Soaring Asymptomatic Infected Individuals Bring About Barriers and Difficulties for Interruption of COVID-19 Prevalence in China.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, which has caused unprecedented damage to human health and life. The present study aimed to carry out and discover asymptomatic infected individuals in Shenzhen, China. The data will provide the control measures to stop COVID-19 prevalence. Methods: The study was a retrospective review of medical records from 462 confirmed patients with COVID-19 and 45 asymptomatic infected individuals in Shenzhen from January 19 to April 30, 2020; this is a retrospective, observational multicenter study. Results: A total of 462 confirmed cases were diagnosed in Shenzhen from January 19 to April 30, 2020. The cohort included 423 domestic cases (91.56%, 95% confidence interval [CI]: 88.67-93.76) and 39 (8.44%, 95% CI: 6.24-11.33) imported cases from other countries. Moreover, a total of 45 asymptomatic infections were found, encompassing 31 (68.89%, 95% CI: 54.34-80.47) local infections and 14 (31.11%, 95% CI: 19.53-45.66) individuals imported from other countries. The proportion of asymptomatic infected persons in Shenzhen is continuously increasing (Z = 13.19, p < 0.0001). The total number of local asymptomatic infections was more than that in other provinces (χ2 = 118.83, p < 0.0001). The proportion of asymptomatic infected individuals among cases imported from other countries was higher than the domestic cases (χ2 = 22.51, p < 0.0001, odds ratio = 4.90, 95% CI: 2.40-9.98). Conclusions: The proportion of asymptomatic infection is increasing. Hence, development and application of the diagnosis method with high sensitivity and specificity play a critical role in reducing COVID-19 global epidemics.

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.

A newly identified linear epitope on non-RBD region of SARS-CoV-2 spike protein improves the serological detection rate of COVID-19 patients.

BACKGROUND: Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. RESULTS: Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients' convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). CONCLUSION: Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.