A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Characterising the changes in RSV epidemiology in Beijing, China during 2015-2023: results from a prospective, multi-centre, hospital-based surveillance and serology study.

Background: Respiratory syncytial virus (RSV) has posed substantial morbidity and mortality burden to young children and older adults globally. The coronavirus disease 2019 (COVID-19) pandemic was reported to have altered RSV epidemiology and could have important implications for RSV prevention and control strategies. We aimed to compare RSV epidemiology in different phases of the COVID-19 pandemic with the pre-pandemic period by leveraging epidemiological, molecular, and serological data collected from a prospective respiratory pathogen surveillance and serology study. Methods: This study was based on the data during July 1, 2015 to November 30, 2023 from the Respiratory Pathogen Surveillance System (RPSS), a sentinel-hospital based surveillance system of acute respiratory infections consisting of 35 hospitals that represent residents of all ages from all 16 districts in Beijing, China. RSV infection status was tested by RT-PCR and gene sequencing and phylogenetic analysis was conducted among the identified RSV strains. We further supplemented RPSS data with three serology surveys conducted during 2017-2023 that tested RSV IgG levels from serum specimens. RSV detection rate was calculated by calendar month and compared across RSV seasons (defined as the July 1 through June 30 of the following year). RSV IgG positivity proportion was calculated by quarter of the year and was correlated with quarterly aggregated RSV detection rate for understanding the relationship between infection and immunity at the population level. Findings: Overall, a total of 52,931 respiratory specimens were collected and tested over the study period. RSV detection rates ranged from 1.24% (94/7594) in the 2017-2018 season to 2.80% (219/7824) in the 2018-2019 season, and from 1.06% (55/5165) in the 2022-2023 season to 2.98% (147/4938) in the 2021-2022 season during the pre-pandemic and pandemic period, respectively. ON1 and BA9 remained the predominant genotypes during the pandemic period; no novel RSV strains were identified. RSV circulation followed a winter-months seasonal pattern in most seasons. One exception was the 2020-2021 season when an extensive year-round circulation was observed, possibly associated with partial relaxation of non-pharmaceutical interventions (NPIs). The other exception was the 2022-2023 season when very low RSV activity was observed during the usual winter months (possibly due to the concurrent local COVID-19 epidemic), and followed by an out-of-season resurgence in the spring, with RSV detection persisting to the end of the study period (November 2023). During the two seasons above, we noted an age-group related asynchrony in the RSV detection rate; the RSV detection rate in young children remained similar (or even increased with borderline significance; 43/594, 7.24%, and 42/556, 7.55% vs 292/5293, 5.52%; P = 0.10 and P = 0.06, respectively) compared with the pre-pandemic seasons whereas the detection rate in older adults decreased significantly (8/1779, 0.45%, and 3/2021, 0.15% vs 160/10,348, 1.55%; P < 0.001 in two comparisons). Results from serology surveys showed significantly declined RSV IgG positivity in the 2022-2023 season compared to the pre-pandemic seasons (9.32%, 29/311 vs 20.16%, 100/496; P < 0.001); older adults had significantly higher RSV IgG positivity than young children in both pre-pandemic and pandemic periods (P values < 0.001). Interpretation: Our study documented the trajectory of RSV detection along with the changes in the stringency of NPIs, measured IgG positivity, and local COVID-19 epidemics. The findings suggest the interplay between contact patterns, immunity dynamics, and SARS-CoV-2 infection in shaping the RSV epidemics of population of different ages. These findings provide novel insights into the potential drivers of RSV circulating patterns and have important implications for RSV prevention and control strategies. Funding: The High-qualified Public Health Professionals Development Project, Capital's Funds for Health Improvement and Research, and the Public Health Personnel Training Support Program.

Genetic characterization of pediatric SARI-associated human adenoviruses in eight Chinese provinces during 2017-2021.

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.

Genome sequencing reveals molecular epidemiological characteristics and new recombinations of adenovirus in Beijing, China, 2014-2019.

To investigate the molecular epidemiological characteristics and genetic variations of human adenovirus (HAdV) in acute respiratory tract infections in Beijing. Whole-genome sequencing and phylogenetic analyses were performed for 83 strains of HAdV with different types in Beijing from 2014 to 2019. The clinical characteristics of HAdV infection were analyzed statistically. HAdV-B was divided into four genotypes, including B3 (n = 11), B7 (n = 13), B14 (n = 4), and B55 (n = 2). HAdV-C was divided into three genotypes, including C1 (n = 14), C2 (n = 13), and C5 (n = 10). In HAdV-C, nine recombinant adenovirus strains were identified in type 1, and seven recombinant strains were found in type 2. In type 1, we found three newly emerged intraspecific recombinant strains (A47, A48, and A52) collected in 2017, 2018, and 2019, respectively. In addition, the previously reported recombinant strains of HAdV-C1 showed more severe disease than other strains of HAdV-C, causing severe community-acquired pneumonia in both the elderly and children. Continuous population-wide molecular epidemiological surveillance of HAdV is essential for the prevention and control of respiratory infectious diseases.

Anisotropic Deformation Behavior and Indentation Size Effect of Monocrystalline BaF2 Using Nanoindentation.

In this study, our objective is to investigate the anisotropic deformation behavior and the indentation size effect (ISE) of monocrystalline barium fluoride (BaF2) using nanoindentation experiments with a diamond Berkovich indenter. BaF2 is known for its anisotropy, which results in significant variations in its mechanical properties. This anisotropy poses challenges in achieving high processing quality in ultra-precision machining. Through our experiments, we observed numerous pop-in events in the load-displacement curves, indicating the occurrence of plastic deformation in BaF2 crystals, specifically in the (100), (110), and (111) orientations; these pop-in events were observed as the indentation depth increased to 56.9 nm, 58.2 nm, and 57.8 nm, respectively. The hardness-displacement and elastic modulus-displacement curves were obtained from the tests exhibiting the ISE. The nanoindentation hardness of BaF2 is found to be highly dependent on its crystallographic orientation. Similarly, for BaF2 in the (100) orientation, the range is from 2.43 ± 0.74 and 1.24 ± 0.12 GPa. For BaF2 in the (110) orientation, the values range from 2.15 ± 0.66 to 1.18 ± 0.15 GPa. For BaF2 in the (111) orientation, the values range from 2.12 ± 0.53 GPa to 1.19 ± 0.12 GPa. These results highlight the significant influence of crystallographic orientation on the mechanical properties of BaF2. To better understand the ISE, we employed several models including Meyer's law, the Nix-Gao model, the proportional specimen resistance (PSR) model, and the modified PSR (mPSR) model, and compared them with our experimental results. Among these models, the mPSR model demonstrated the best level of correlation (R2>0.9999) with the experimental measurements, providing a reliable description of the ISE observed in BaF2. Our reports provide valuable insights into the anisotropic mechanical characteristics of BaF2 materials and serve as a theoretical guide for the ultra-precision machining of BaF2.

SARS-CoV-2-specific antibody and T-cell immunity in convalescents after infection wave in Beijing in late 2022.

OBJECTIVES: To evaluate SARS-CoV-2-specific antibody and T-cell responses in convalescents 5 months after infection wave in Beijing from December 2022 to January 2023 to prevent reinfection and severe disease. METHODS: Convalescents and uninfected individuals vaccinated with different doses were enrolled to assess the IFNγ T-cell responses against SARS-CoV-2 prototype strain, BF.7, BQ.1, and XBB. Neutralizing antibodies against prototype strain, BF.7, BA.5, and XBB and immunoglobulin G antibody were further analyzed. RESULTS: In convalescents, the IFNγ T-cell response was significantly higher than that of uninfected individuals (all P < 0.001), and the T-cell response against XBB had no significant difference from that of SARS-CoV-2 prototype strain and BF.7 and BQ.1 (all P > 0.05). The seropositive rates of IgG antibodies were 100% (303/303) with a median concentration of 90.52 (95% CI, 82.52-99.37). The neutralizing antibodies titers of convalescents against BF.7 and BA.5 were higher than that against the prototype strain (both P < 0.001), while XBB.1.5 was lower (P < 0.001). T-cell response, IgG and neutralizing antibodies had no significant difference in convalescents vaccinated with different doses (all P > 0.05). CONCLUSIONS: The immunities may have some protective effect against possible future outbreaks and severe diseases of COVID-19.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Comparison of infections with respiratory syncytial virus between children and adults: a multicenter surveillance from 2015 to 2019 in Beijing, China.

The objective of this study is to investigate the epidemiological and clinical characteristics of the acute respiratory tract infections (ARTI) caused by respiratory syncytial virus (RSV) among the population of all age categories in Beijing, China. Outpatients and inpatients with ARTI were enrolled from 35 sentinel hospitals in Beijing between March 2015 and February 2019. They were interviewed and their medical records were collected using a standardized form. Their respiratory specimens were collected and tested for the nucleic acid of RSV. The RSV-positive specimens were further genotyped into RSV-A and RSV-B groups. A total of 29,923 cases were included in this study. RSV was detected in 623 (2%, 623/29923) patients, with 391 (62.8%) genotypd as RSV-A, 126 (20.2%) as RSV-B, and 106 (17.0%) untyped. The RSV epidemic season usually occurred between October and March covering approximately 90% of annual RSV infections. The RSV-infected children aged < 5 years accounted for 52.2% of the total RSV infections with cough and fever as the most common manifestations. The RSV-infected elderly adults aged ≥ 60 years have the second largest proportion (25.2%) with dyspnea and lymphocytopenia as the most common manifestations and showed an elevated rate of hospitalization, an increased rate of ICU admission, an extended length of hospital stay, and an elevated mortality compared to the RSV-infected children. The RSV infections aged ≥ 60 years old, as the second largest population of the total annual RSV infections, usually developed worse outcomes than children and should be taken seriously.

Mycoplasma pneumoniae triggers pneumonia epidemic in autumn and winter in Beijing: a multicentre, population-based epidemiological study between 2015 and 2020.

ABSTRACTThe objective of this paper is to explore the characteristics of Mycoplasma pneumoniae (MP) epidemics in Beijing, China. Patients with acute respiratory tract infection (ARTI) were enrolled from 35 sentinel hospitals in Beijing, 2015-2020. Their medical records were reviewed and respiratory specimens were collected for assay for nucleic acids of 24 respiratory pathogens, including MP. The genotypes of MP were analysed using a real-time PCR method. The domain V of 23s rRNA gene was sequenced to identify macrolide-resistant mutations. A total of 41,677 specimens of ARTI patients were included, with an MP positive rate of 6.16%. MP prevalence mainly occurred between August and January, and peaked in October. The increase in the MP detection rate was coincident with the elevation of the reported number of patients with pneumonia in the 35 sentinel hospitals. One or more respiratory pathogens were co-detected in 27.1% of the MP-positive patients. Type 1 MP remained predominant, and the macrolide-resistant rate of MP had exceeded over 90%. A2063G mutation accounted for 99.0% of macrolide-resistant MP infections. MP epidemic in Beijing mainly occurred between August and January with a remarkable high macrolide-resistant rate. MP is one of the important contributors to the pneumonia epidemic in autumn and winter in Beijing.

Genetic diversity and epidemiological features of respiratory syncytial virus, Beijing, 2015-2019: A multicenter and all-age groups study.

OBJECTIVE: To investigate the genetic variability and the epidemiological features of respiratory syncytial virus (RSV) in Beijing during five consecutive seasons from 2015 to 2019. METHODS: We collected 36,927 samples (ages ranged from 1 day to 101 years old) from cases with acute respiratory tract infections (ARTI) using the Respiratory Pathogens Surveillance System (RPSS) in Beijing, 2015-2019. G gene sequencing and phylogenetic analysis were performed to identify RSV genotypes, clusters, and amino acid (aa) changes. RESULTS: In total, 764 (2.1%, 764/36927) cases were RSV positive, 52.1% cases were children under 5 years old, and 25.8% were elderly ≥ 60 years old. We obtained 369 sequences of the G gene. ON1 and BA9 were the dominant genotypes in Beijing. Sub-lineage 4 of ON1, which contains four aa substitutions (T113I, N178G, H258Q, and H266L), emerged in 2017 and became the predominant variant in 2018-2019. Sub-lineage 4 of BA9, which contains two aa changes (A131T, T137I), emerged in 2017 and became the predominant variant in 2019. We also observed 10 rarely reported nucleotide deletions in the 3' end of the G gene from five sequences of the ON1 genotype. CONCLUSION: With the exception of children < 5 years old, RSV infection mainly occurred in the elderly ≥ 60 years old. Newly emerged sub-lineages have replaced existing sub-lineage over time and become predominant in Beijing. Continued surveillance of the genetic diversity of RSV is necessary.

Seroepidemiology of enterovirus D68 in a healthy population in Beijing, China, between 2012 and 2017: A retrospective study.

To investigate the seroepidemiological features of enterovirus D68 (EV-D68) in the healthy population from 2012 to 2017 in Beijing, China. A retrospective cross-sectional investigation was conducted using serum specimens collected from healthy individuals in Beijing from 2012 to 2017. These samples were tested for neutralization antibodies (NtAbs) against EV-D68. The sera from six EV-D68 infected patients in the acute or convalescent phase were used to determine the protection level of NtAbs against EV-D68. The geometric means of the titers (GMT) of EV-D68 NtAbs in 2012 and 2017 were 92.82 and 242.91, respectively; the seroprevalences of EV-D68 were 89.43% and 98.43%, respectively. The GMT reached its peak in the 11 to 15 age group in 2012, while in 16 to 20 age group in 2017. We also observed that EV-D68 NtAbs titers of six sera from the acute phase were all less than equal to 1:64 and that of three sera from the convalescent phase were all more than 1:64. Anti-EV-D68 NtAbs in the population remained low from 2012 to 2016 but increased significantly in 2017. Although most of the EV-D68 infections remain undetected in Beijing, the risk of a large outbreak of EV-D68 exists and should be taken seriously.

Seroprevalence of poliovirus antibodies before and after polio vaccine switch in 2012 and 2017 in Beijing.

In 2000, China was declared polio-free. However, in 2018, wild poliovirus (WPV) was still endemic in two of its neighboring countries, making WPV importation and outbreak alarming possibilities. This study documents the seroprevalence of poliovirus antibodies before and after the polio vaccine switch in 2012 and 2017 in Beijing. Cross-sectional population-based serologic surveys were conducted in 2012 and 2017 in Beijing. The study subjects were selected from 10 different age groups (<1, 1-4, 5-9, 10-14, 15-19, 20-24, 25-29, 30-34, 35-39, and ≥40 y) using a multi-stage-stratified sampling method. Neutralizing antibody titers against poliovirus serotypes 1 (P1), 2 (P2), and 3 (P3) were assayed by World Health Organization standards. The seropositive rates (SR) and geometric mean titer (GMT) of the neutralizing antibodies were 91.71% and 1:130.26, respectively, for P1, 94.09% and 1:113.39, respectively, for P2, and 88.78% and 1:79.65, respectively, for P3 before the switch in 2012, and 87.78% and 1:108.93, respectively, for P1, and 81.67% and 1:70.56, respectively, for P3 after the switch in 2017, with a statistically significant difference for P1 and P3 between 2012 and 2017. The neutralizing antibodies for all poliovirus serotypes differed among different age and vaccination groups in both 2012 and 2017. After switching polio vaccines twice in 2014 and 2016, the P1 and P3 polio antibody levels were lower in 2017 than in 2012. The P2 antibody levels were determined from the first dose of IPV. The seroprevalence of poliovirus antibodies after adjustment of the immunization schedule of the polio vaccine on January 1, 2020, must be further monitored.

Human Enterovirus C105, China, 2017.

We report a case of enterovirus C105 infection in an 11-year-old girl with lower respiratory tract symptoms that was identified through the Respiratory Virus Surveillance System, which covers 30 sentinel hospitals in all 16 districts of Beijing, China. The presence of this virus strain in China confirmed its geographically wide distribution.

Upsurge of Enterovirus D68 and Circulation of the New Subclade D3 and Subclade B3 in Beijing, China, 2016.

We conducted a surveillance among acute respiratory tract infection (ARTI) cases to define the epidemiology, clinical characteristics and genetic variations of enterovirus D68 (EV-D68) in Beijing, China from 2015 to 2017. Nasopharyngeal swabs and sputum were collected from 30 sentinel hospitals in Beijing and subjected to EV and EV-D68 detection by real-time PCR. The VP1 gene region and complete genome sequences of EV-D68 positive cases were analyzed. Of 21816 ARTI cases, 619 (2.84%) were EV positive and 42 cases were EV-D68 positive. The detection rates of EV-D68 were 0 (0/6644) in 2015, 0.53% (40/7522) in 2016 and 0.03% (2/7650) in 2017, respectively. Two peaks of EV-D68 infections occurred in late summer and early-winter. Ten cases (23.81%) with upper respiratory tract infection and 32 cases (76.19%) presented with pneumonia, including 3 cases with severe pneumonia. The phylogenetic analysis suggested 15 subclade D3 strains and 27 subclade B3 strains of EV-D68 were circulated in China from 2016 to 2017. A total of 52 amino acid polymorphisms were identified between subclades D1 and D3. These data suggest an upsurge of EV-D68 occurred in Beijing in 2016, the new subclade D3 emerged in 2016 and co-circulated with subclade B3 between 2016 and 2017.

Distribution of the atypical pathogens of community-acquired pneumonia to disease severity.

BACKGROUND: To investigate the epidemiological characteristics of 11 atypical pathogens of community-acquired pneumonia (CAP) among Chinese, and to determine whether or not there is an association between these pathogens and the severity of illness. METHODS: We conducted a surveillance study for CAP in 30 hospitals of Beijing. Epidemiological data and clinical specimens were systematically collected from enrolled CAP patients. The detection for 11 atypical pathogens [9 respiratory viruses, Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP)] was performed. Risk factors of severe CAP and death in Hospital were evaluated. RESULTS: A total of 6,008 CAP patients [including 1,071 severe CAP (SCAP)] were enrolled. The overall detection rate of the 11 atypical pathogens was 42.4% among 1,925 child CAP (39.9% among 274 child SCAP), and 25.8% among 4,083 adult CAP (22.8% among 797 adult SCAP). The most frequent atypical pathogen among child SCAP was parainfluenza virus (10.2%) followed by respiratory syncytial virus (RSV) (8.4%). However, the most frequent atypical pathogen among adult SCAP was influenza virus (8.9%) followed by parainfluenza virus (3.8%). Multivariate analyses showed that the important predictors for SCAP were an age ≤9 years, an age ≥65 years and co-existing diseases. These factors, except an age ≤9 years, were also predictors of death in Hospital. None of these 11 atypical pathogens was included as the risk factors of SCAP or death in Hospital. CONCLUSIONS: Although these 11 atypical pathogens were the common causes of CAP (including SCAP) among Chinese, they were not observed to increase risks for SCAP or death in Hospital.

The suppression of innate immune response by human rhinovirus C.

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-ß mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-ß activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.