Search

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulins G (IgG) were well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but escaped by the emerging variants., graphical Abstract

Background Current studies regarding glucocorticosteroid treatment of influenza have only estimated risk of critical illness or death which can be easily confounded by timing of treatment administration. We used severe acute respiratory infection (sARI) as an endpoint and investigated risk associated with receiving glucocorticosteroids before sARI onset. Methods sARI cases were defined as influenza-like illness (ILI) with pH1N1 infection and respiratory distress. Controls were defined as pH1N1 cases other than sARI and randomly selected from the community. We compared glucocorticosteroids and other medications used before sARI onset using a matched case control study adjusted for age group as well as underlying disease. Time-dependent risk and dose responses at different time periods over the course of sARI cases were also examined. Results Of the sARI cases, 34% received glucocorticosteroids before sARI onset compared to 3.8% of controls during equivalent days (ORM-H = 17,95%CI = 2.1–135). Receiving glucocorticosteroids before sARI onset increased risk of developing subsequent critical illness or death (ORM-H = 5.7,95%CI = 1.6–20.2), and the ORM-H increased from 5.7 to 8.5 for continued glucocorticosteroid use after sARI onset. However, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness (ORM-H = 1.1,95%CI = 0.3–4.6). Each increase in glucocorticosteroids dose of 1 mg/kg/day before sARI onset resulted in an increase of 0.62 (R2 = 0.87) in the pMEWS score at the time of sARI onset. Conclusions Early glucocorticosteroid treatment increased risk of sARI and subsequent critical illness or death; however, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness.

Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents’ sera. Encouragingly, we found that a small fraction of patients’ sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 -S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446–S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00409-4.

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers.METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels.RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients.CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response.FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.

Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests) in the previous three months. The results showed that eighty haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain range in mutations and variation in genomic abundance of SARS-CoV-2, which could be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that pangolin may not be an intermediate host. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximately 2 km), which indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately conclude that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term, which would have led to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date began from 7 December 2019, which indicated that the transmission of SARS-CoV-2 could have begun from person to person in mid to late November.

Background Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

Highlights • The research of this paper showed that some suspected SFTS cases are confused with HV infection due to similar symptoms. • No case of simultaneous infection with two or more pathogens was found. • The distribution of SFTSV has a marked regional aggregation in Hubei Province. • Combining qPCR and ELISA can increase sensitivity markedly for diagnosis of SFTSV infection., To evaluate the aetiological agents and epidemiologic features of severe fever with thrombocytopenia syndrome (SFTS) in Hubei province, China, sera from patients were collected from January to December 2011. All cases occurred from April to December, and the epidemic peaked from May to August. The ages of patients ranged from 10 to 86 years (median = 55 years), and the incidence of SFTS increased with age. The female:male ratio of cases was 1.008:1, and 54.6% (77/141) and 1.4% (2/141) of the cases were confirmed by qPCR to be SFTSV and Hantavirus (HV) infection, respectively. No case of simultaneous infection with two or more pathogens was found. The research in this paper showed that some suspected SFTS cases are confused with HV infection due to similar symptoms. The analysis showed that the distribution of SFTSV has a marked regional aggregation in Hubei province.

In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

Background Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory‐confirmed influenza in China. Methods We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. Results During the study period, 15 354 children aged

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients.

PPARγ and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). We recruited 100 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 100 normal healthy controls from Chinese Uyghur Population to assess the nature of the functional polymorphisms of PPARs and any links with IS in this unique population which has 60% European ancestry and 40% East Asian ancestry. We found that the Ala allele of the PPARγ Pro12Ala polymorphism was more common in controls than IS subjects (P = 0.008, corrected for multiple testing) in the Uyghur Population. Pro/Ala carriage may be associated with a decreased risk of IS in Uyghurs (OR 0.542, 95% CI 0.346-0.850). Additionally, the 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Uguhur IS patients and controls. Our population and ethnic-based study demonstrates that the 162Val allele frequency was extremely low in the Chinese Uyghur Population different from Some European and African populations and the PPARγ 12 Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Uyghur Population.

To understand the role of domesticated animals and rodents in the circulation and transmission of SFTSV, a total of 544 serum samples were collected from several domestic animals and rodents from SFTSV epidemic areas (Suizhou, Macheng) and non-epidemic areas (Yicheng, Qianjiang, Xiantao) in Hubei Province, China, from July 2010 to November 2016. SFTSV-specific antibodies were detected in 80 (81.63%) of 98 sheep, 39 (67.24%) of 58 cattle, 12 (63.16%) of 19 dogs, and 4 (1.08%) of 369 rodents. SFTSV RNA was detected in serum samples from sheep (3.06%) and cattle (5.17%), but was not detected in rodent tissue samples. The virus isolated from sheep shared more than 97% sequence homology with local patients. Our findings suggest that sheep and cattle act as natural hosts and might play an important role in the transmission of SFTSV.

Background The prevalence of tuberculosis (TB) in low and middle-income countries is a significant public health and social concern. TB is a common infectious disease caused by the Mycobacterium tuberculosis infection, which has a widespread infection rate. Health care-seeking delay maybe one of the most important neglected risk factors for the spread of TB. Objectives The aim of this study was to understand the situation of health care-seeking delay among rural tuberculosis patients in Hubei Province, and explore its risk factors. Methods A total of 1408 rural tuberculosis patients were surveyed using a standard structured questionnaire in three cities of Hubei Province during the past two years. Results For the 1408cases of pulmonary tuberculosis, 39.70% of them were health care-seeking delayed. Logistic regressions indicate that the Han nationality, farming careers, the over 45 min walk to the township&rsquo, s hospital, and awareness of the national TB free treatment policy, were significantly associated with higher odds of a delay in care seeking. Conclusions The prevalence of health care-seeking delay among tuberculosis patients was high in rural areas. It is essential to take comprehensive targeted interventions to reduce care-seeking delay.

PPARδ belongs to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). We recruited 200 subjects (100 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 100 normal healthy controls from Chinese Uyghur population) to assess the nature of the functional polymorphisms of PPARδ +294T/C and any links with IS in this unique population. We found that the C allele of the PPARδ +294T/C polymorphism was more common in controls than IS subjects in the Uyghur population. C allele carriage may be associated with an increased risk of IS in Uyghurs with a strong trend (OR 1.79, 95% CI: 1.11-2.89). Additionally, the PPARδ CC and TC genotypes were less frequent in Uyghur population than in Han population. Our population and ethnic-based study demonstrates that the PPARδ +294C allele maybe an independent risk of IS in Chinese Uyghurs especially in the male (OR 1.99, 95%CI:1.06-3.72) and obesity populations (OR 2.36, 95%CI: 1.19-4.67), which were consistent with Tunisian Population. Moreover, total cholesterol, fasting blood glucose, waist-to-hip ratio, hypertension, history of heart diseases, and negative events may increase the risk of IS, with a trend for HDL to be a protective factor for IS in the Uyghur population. However, larger populations are warranted to validate our findings.

Background Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear. Methods Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center. Results RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya. Conclusions Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.

Background Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype. Methods Surveillance was conducted at four hospitals in Jingzhou, China from 2010 to 2012. We enrolled hospitalized patients who had temperature ≥37·3°C and at least one of: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. A nasopharyngeal swab was collected from each case-patient within 24 hours of admission for influenza testing by real-time reverse transcription PCR. Results Of 17 172 SARI patients enrolled, 90% were aged

Endothelial nitric oxide synthase (eNOS) plays an important role in mediating endothelium-dependent vasodilatation and antithrombotic action and is thus involved in the development of ischemic stroke (IS). Controversial results regarding the association of eNOS gene variable number of tandem repeats (VNTR) polymorphism with IS have been reported by conventional PCR-polyacrylamide gel electrophoresis methods. We aimed to identify any common association of eNOS gene VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by CE with specially designed tailed primers in Chinese Han patients with IS (n = 457) and matched elderly controls without IS (n = 457). Significant differences in BMI, WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed between cases and controls. The distributions of eNOS VNTR polymorphism were not significantly associated with IS after adjustment for cardiovascular risk factors (OR = 1.18, 95% CI: 0.82–1.69). This finding was consistent with the further meta-analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b + 4a/4a genotype was significantly associated with IS risk with an OR of 1.54 (95% CI, 1.09–2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR, hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS. However, eNOS VNTR polymorphism may be not an independent major contributor for IS in Chinese Han population. The VNTR polymorphism might be associated with IS in Americans based on meta-analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV). SFTSV is associated with a high mortality rate and has been reported in China, South Korea and Japan. SFTSV undergoes rapid changes owing to evolution, gene mutations, and reassortment between different strains of SFTSV. In this review, we summarize the recent cases and general properties of SFTS, focusing on the epidemiology, genetic diversity, clinical features, and diagnostics of SFTSV in China. From 2010 to October 2016, SFTS cases were reported in 23 provinces of China, with increased numbers yearly. Infection and death cases are mainly found in central China, where the Haemaphysalis longicornis ticks are spread. The national average mortality rate of SFTS infection was 5.3%, with higher risk to elder people. The main epidemic period was from May to July, with a peak in May. Thus, SFTS reminds a significant public health problem, and development of prophylactic vaccines and effective antiviral drugs will be highly needed.

Recent genome-wide association studies (GWAS) have identified two key SNPs (rs11833579 and rs12425791) on chromosome 12p13 that were significantly associated with stroke in Caucasians. However, the validity of the association has remained controversial. We performed genetic association analyses in a very unique population which has 60% European ancestry and 40% East Asian ancestry. No significant association between these two SNPs and ischemic stroke was detected in this Chinese Uyghur population.

Background. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in China, caused by SFTS virus (SFTSV). Severe SFTS patients can quickly proceed to multiorgan dysfunction and death; however, underlying pathogenic mechanisms remain unclear. Methods. Serum samples from 15 fatal and 44 nonfatal SFTS cases were subjected to multiplex-microbead immunoassays to detect a broad spectrum of cytokines. The viral load and virus-specific IgG titers were also tested by real-time PCR and ELISA, respectively. Results. Cytokines IL-1RA, IL-6, IL-10, G-CSF, IP-10, and MCP-1 were elevated in SFTS patients and produced at robust levels in fatal cases. In contrast, cytokines PDGF-BB and RANTES decreased in SFTS patients. These cytokines reverted to normal ranges during the convalescent phase of SFTSV infection. Cytokines IL-1β, IL-8, MIP-1α, and MIP-1β showed a unique pattern of elevation in fatal cases but not in nonfatal cases. However, these cytokines increased in the convalescent phase of nonfatal SFTS cases. Our regression analysis revealed that the serum viral load correlated with these cytokines. Moreover, levels of these cytokines correlated with various clinical parameters and virus-specific IgG titers. Conclusion. The study demonstrates that SFTSV infection induces a cytokine storm with abnormally expressed cytokine profiles, which are associated with the disease severity.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently identified to be caused by a novel bunyavirus (SFTSV). The clinical diagnosis is urgently needed to differentiate the disease from other infections. Objective To develop a sensitive quantitative real-time RT-PCR assay for rapid detection of SFTSV viral RNA and evaluate potential use for clinical diagnosis of SFTS. Study design Primers and probes were designed to target the L, M, and S segments of SFTSV, and standard curves were established based on serial dilutions of in vitro transcribed viral RNA or viral RNA extracts. The serum samples collected from 70 laboratory confirmed SFTS patients, 114 non-SFTS patients, and 400 healthy donors were analyzed. Results Based on three optimized primer–probe sets to detect L, M, S genes of SFTSV, the quantitative real-time RT-PCR assay could discriminate SFTSV infection from other vector-borne viral diseases in human with potential detection limit of 10 viral RNA copies/μl or 10 TCID 50 /ml virus load. Strong linear correlations ( r 2 >0.99) between the C t values and viral RNA standards over a liner range were obtained. The assay specificity was determined by sequence alignment and experimentally tested on various related viruses. Evaluation of the study method with clinical serum samples showed 98.6% clinical diagnostic sensitivity and over 99% specificity. Conclusion The quantitative real-time RT-PCR assay established in this study can be used as a reliable method for early diagnosis of SFTSV infection.

In 2003, physicians in China were unprepared to care for people with AIDS. Project HOPE partnered with Hubei Province health authorities to train and mentor doctors and build capacity for HIV care. From 2004 to 2006, seventy-eight Chinese "master trainers" were trained, who then trained and mentored 8,759 health workers. During this period, as the free antiretroviral therapy period began, measures of physician competence in HIV care improved significantly, and annual mortality from AIDS fell from 49 percent to 8.8 percent. This international partnership created a sustainable capacity for effective HIV prevention and care that could be replicable in other settings.

To estimate the hospitalization rate of severe acute respiratory infection (SARI) cases attributable to influenza in Jingzhou city, Hubei province from 2010 to 2012.SARI surveillance was conducted at four hospitals in Jingzhou city, Hubei province from 2010 to 2012. Inpatients meeting the SARI case definition and with informed consent were enrolled to collect their demographic information, clinical features, treatment, and disease outcomes, with their respiratory tract specimens collected for PCR test of influenza virus.From April, 2010 to September, 2012, 19 679 SARI cases enrolled were residents of Jingzhou, and nasopharyngeal swab was collected from 18 412 (93.6%) cases of them to test influenza virus and 13.3% were positive for influenza. During the three consecutive 2010-2012 flu seasons, laboratory-confirmed influenza was associated with 102 per 100 000, 132 per 100 000 and 244 per 100 000, respectively. As for the hospitalization rate attributable to specific type/subtype of influenza virus, 48 per 100 000, 30 per 100 000 and 24 per 100 000 were attributable to A (H3N2), A (H1N1) pdm2009, and influenza B, respectively in 2010-2011 season; 42 per 100 000 [A (H3N2)] and 90 per 100 000 (influenza B) in 2011-2012 season; 90 per 100 000 [A (H3N2)] and one per 100 000 [influenza B] from April, 2010 to September, 2012. SARI hospitalization caused by influenza A or B occurred both mainly among children younger than five years old, with the peak in children aged 0.5 year old.Influenza could cause a substantial number of hospitalizations and different viral type/subtype result in different hospitalizations over influenza seasons in Jingzhou city, Hubei province. Children less than five years old should be prioritized for influenza vaccination in China.

Severe acute respiratory illness (SARI) surveillance began in Jingzhou City, China, in 2010. A subset of 511 children aged

Humane enterovirus 71 (HEV 71) is a common contagious agent of hand, foot and mouth disease (HFMD) which is normally mild but can caused deaths and severe neurological complications. In April 2011, an unpredicted HFMD outbreak in Xiangyang City of Hubei Province in China resulted in a high aggregation of HFMD cases including fatal cases and many severe cases. In this study, 71 clinical specimens were collected according to the different symptoms and RNA extraction and RT-PCR amplification were performed immediately. Laboratory testing and genetic analyses were used to identify the casual pathogen of this outbreak. HEV71 was confirmed as the etiological pathogen of the outbreak. Similarity and phylogenetic analyses of the VP1 gene of HEV71 from Xiangyang showed that they belong to C4a cluster of the C4 subgenotype. Intertypic recombinant events were found in the 3D region between the Xiangyang HEV71 strains and Coxsackievirus A16 (CV-A16). Intratypic recombination was found in the 3D region between two same subgenotypic Xiangyang HEV71 strains in this outbreak. It is suggested that these recombination events played important roles in the emergence of the various HEV 71 subgenotypes and different type of recombination of HEV71 might exist in one outbreak which might be the reason for the different virulent HEV71 strains in an outbreak.

To clone and sequence full-length genome of the avian influenza A/Chicken/Hubei/489/ 2004(H5N1) virus, in order to analyze genetic mutation patterns of HA gene and polygenetic relationship between A/Chicken/Hubei/489/2004 (H5N1) virus and other strains since 1996.8 genes of the avian influenza A/Chicken/Hubei/489/2004 (H5N1) virus were amplified and cloned, and then genetic mutation analysis and phylogenetic trees were made by bioinformatics software.Full-length genome of the avian influenza A/Chicken/Hubei/489/2004 (H5N1) virus were cloned into the vector of PMD18-T. Genetic evolution analysis showed that there is a specific cleavage site of "PQRERRRKKR", which was proved be related with virulence. In addition, molecular phylogenetic trees of HA gene revealed that A/Chicken/Hubei/ 489/2004 virus were closely related to H5N1 viruses of 2000-2006 isolated in Hong Kong and in Southeast Asia.The influenza A/Chicken/Hubei/489/2004 (H5N1) virus was closest genetic relatives to the influenza A/Chicken/HongKong/YU777/2002 (H5N1) virus, and it was most possible that the avian influenza outbreak was caused by the 2002 lineage of Hong Kong.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging high-fatality infectious disease, is caused by a novel bunyavirus. However, a clear natural transmission model has not yet been established. We conducted a cross-sectional study with in-depth investigation of villages to systematically understand the transmission and risk factors among humans, host animals, and vectors. Village residents were interviewed using standardized questionnaires, in which there were confirmed cases of new infections, between August 2012 and May 2013. Serum samples from all villagers and animals, as well as tick specimens, were collected for qRT-PCR and antibody testing. The seropositivity rate among villagers was 8.4% (35/419), which was lower than that among domesticated animals (54.0%, 27/50; χ2 = 81.1, P