[Analysis of common viral infection in surveillance cases of febrile respiratory syndrome in 9 provinces of China from 2009 to 2021].

Objective: To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China. Methods: The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M (Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China (P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion: HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

[Application of oral fluid in SARS-CoV-2 nucleic acid and antibody detection].

This study aimed to explore the application value of new biological specimen oral fluid in SARS-CoV-2 nucleic acid and antibody detection. Oral fluid and paired respiratory and blood specimens from 7 confirmed cases of two COVID-19 cluster epidemic were collected in Beijing from October to November 2021. SARS-CoV-2 virus and IgG antibody were detected by real time PCR kits and serum antibody detection reagents, and SARS-CoV-2 IgG antibody in oral fluids was detected by a new established method of magnetic particle chemiluminescence. The results showed that the nucleic acid amplification test of SARS-CoV-2 on nasopharyngeal swabs, throat swabs and oral fluid specimens from 3 confirmed cases of COVID-19 was positive, among which the Ct value for ORF1a/b and N gene of oral fluid samples in 2 cases was close to that of throat swab, and the Ct value of oral fluid sample for 1 case was higher than that of throat swab. The complete genome sequence of one oral fluid specimen was obtained, which belonged to the VOC/Delta variant strain. The SARS-CoV-2 IgG antibodies of the paired oral fluid and serum were all positive, and the S/CO values of oral fluid were all lower than those of serum. The series of oral fluid results showed that SARS-CoV-2 IgG antibody level increased from 11 to 32 days after the onset of the disease.

[Consideration on the emerging acute severe hepatitis cases with unknown etiology in children of some countries].

Since January 2022, acute severe hepatitis cases with unknown etiology in children have occurred in many countries in Europe and the United States, and 43.8% of the cases were positive for human adenovirus (HAdV), and some cases were identified as HAdV-41. However, more evidences including etiology, genomics, liver pathology, and immunohistochemistry are needed to determine the main cause of this outbreak. At present, due to the lack of systematic surveillance and research on hepatitis caused by HAdV infection, it is impossible to determine whether there are similar hepatitis cases occurred in China. It is urgent to carry out HAdV virolgocial surveillance based on clinical symptom, and potential risk of acute severe hepatitis should be studied as soon as possible according to the available relevant clinical, epidemiological and virological data, as well as risk factor information, which will provide scientific and technical support for the prevention and control of HAdV-related diseases.

[Advances on molecular typing methods and evolution of human parainfluenza virus].

Human parainfluenza viruses (HPIVs) is one of the main causes of acute respiratory tract infections in children. HPIVs have been grouped into four serotypes (HPIV1~HPIV4) according to serological and genetic variation. Different serotypes of HPIVs have diverse clinical disease spectrum, epidemic characteristics and disease burden. Based on the nucleotide variation in structural protein genes, HPIVs can be further divided into distinct genotypes and subtypes with diverse temporal and spatial distribution features. The standard molecular typing methods are helpful to clarify the gene evolution and transmission patterns of HPIVs in the process of population transmission. However, the development of molecular epidemiology of HPIVs has been hindered by the lack of a standardized molecular typing method worldwide. Therefore, this study reviewed the viral characteristics, genome structure, existing genotyping methods and evolution of HPIVs, and screened the reference strains for molecular typing, so as to improve the understanding of gene characteristics and molecular typing of HPIVs, and provide an important scientific basis for the monitoring and research of molecular epidemiology of HPIVs in China.

[Contribution of measles virus IgG antibody avidity assay to the identification of measles cases].

Objective: To evaluate the value of measles IgG antibody avidity assay in identifying the measles cases. Methods: Data from the Measles Surveillance Information System was used to collect laboratory confirmed or discarded cases in 2013-2015, and then tracing back the blood specimens from all measles network laboratories in Tianjin. Measles antibody avidity assay was used to detect and to redefine cases from the discarded ones. Results: A total of 326 measles cases including 267 laboratory-confirmed and 59 discarded cases were enrolled into this study, with 92.33% (301/326) of them aged ≥20 years. Result from the measles IgG antibody avidity assay showed that the ratio of high-avidity was 91.23%(52/57) of the discarded cases, which was significantly higher than 66.95% (158/236) of the laboratory confirmed cases (χ2=13.33, P<0.001). According to the case criterion, 15.25% (9/59) of the discarded cases were redefined as measles cases. Eight out of the nine cases were high-avidity with measles containing vaccine (MCV) vaccination history that named as SVF cases. One in nine cases with low-avidity was with typical clinical symptomatic measles but with no vaccination history of MCV. Conclusion: Measles IgG antibody avidity assay could provide reference serological evidence to reduce the error from those discarded cases caused by false negative results on IgM antibody, when diagnosing the measles cases.

[Viral pathogenic spectrum analysis of severe acute respiratory infection cases in Luohe City, Henan province from 2017 to 2019].

Objective: The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019. Methods: Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed. Results: The age of 783 SARI cases shown as M (P25, P75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion: Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

[Distribution and infectious characteristics of re-positive cases infected with SARS-CoV-2].

Domestic and foreign literatures related to the persistence of SARS-CoV-2 and the re-positive cases infected with SARS-CoV-2 were reviewed, and the characteristics and infectivity of the re-positive cases were analyzed to provide scientific evidence for the improvement of case management and the development of measures to stop the spread of SARS-CoV-2. Existing studies have shown that re-positive rate of SARS-CoV-2 ranged from 2.4% to 19.8%, the median of interval between re-positive detection and discharge was 4-15 days. Following the second course of the disease, the anti-SARS-CoV-2 IgM, IgG and IgA positive rates of the cases were 11.11%-86.08%, 52.00%-100.00% and 61.54%-100.00% respectively, the total antibody and neutralizing antibody positive rates were 98.72% and 88.46%. The viral load of the re-positive cases was lower than that in the initial infection. At least 3 380 re-positive cases have been reported globally. SARS-CoV-2 strains were isolated from the samples of 3 re-positive cases (1 immunodeficiency case and 2 cases with abnormal pulmonary imaging). There were close contacts that were infected by an asymptomatic case taking immunosuppressive agents. In conclusion, the infectivity of re-positive cases infected with SARS-CoV-2 is generally very low. Rare re-positive cases infected with SARS-CoV-2 might cause further transmission. The management approach for the re-positive cases can be based on the assessment of the individual transmission risk according to the pathogen detection results.

[Genotype and genetic characteristics of human respiratory syncytial virus circulating in Quanzhou, 2018-2019].

Objective: To study the prevalence and genetic characteristics of human respiratory syncytial virus (HRSV) in Quanzhou city, from 2018 to 2019. Methods: A total of 141 throat swabs were collected from children patients of lower respiratory tract infection in Quanzhou children Hospital, Fujian Province from November 2018 to May 2019. RT-PCR was used to amplify the 3 'end of G gene HRSV. Sequencer 5.0 and MEGA5.05 softwares were used for sequence editing, phylogenetic tree construction and genotyping analysis. Results: Twenty-five samples were positive for HRSV. Seventeen samples succeeded to obtain the target gene, including 13 of HRSVA and 4 of HRSVB. Two genotypes were identified: ON1 genotype (13 samples, HRSVA) and BA9 genotype (4 samples, HRSVB). Five strains of ON1 genotype sequences were clustered with the ON1 sequences prevalent in Beijing, Changchun and Zhejiang from 2012 to 2015 (cluster1); one strain (FJ19-02) was clustered with the sequences of ON1 genotype circulating in many regions of China from 2012 to 2015 (cluster2); Seven strains were clustered independently (cluster FJ). FJ18-02, FJ19-14 and FJ19-15 of HRSVB were clustered with the BA9 genotype sequences prevalent in Changchun, Jilin Province in 2015, while FJ19-13 was closely related to the BA9 genotype sequences prevalent in Guangzhou and Zhejiang Province in 2013. Both the ON1 and BA9 genotypes showed variations of nucleotide and amino acid in 72 and 60 insertion segments. Amino acid mutation (H266L) only occurred among the sequence of cluster-FJ, and the mutations of H261Q and Q265L only appeared in strain FJ19-13. Conclusion: BA9 and ON1 genotypes were prevalent in Quanzhou city, from 2018 to 2019. Cluster-FJ was a newly discovered independent transmission chain, which may continue to circulate in local Quanzhou area.

[Progress in research of specific antibody dynamic characteristics in patients with COVID-19].

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.

[Genetic characteristics of five human adenovirus type 53 strains isolated from Taiyuan city in 2016, China].

Objective: The genetic characteristics of the human adenovirus type 53 (HAdV-53) strains isolated from Taiyuan city of Shanxi Province were studied to obtain the baseline data of their molecular characteristics. Methods: Conjunctival swabs (n=79) were collected from epidemic keratoconjunctivitis (EKC) patients in Shanxi eye Hospital in 2016, and five HAdV-53 strains were obtained after virus isolation and identification based on the three major capsid genes sequences including Penton base, Hexon and Fiber gene. And the corresponding sequences of global epidemic HAdV-53 strains and the strains with the same genetic origin as HAdV-53 were also downloaded from GenBank database, and then the three gene database were established, respectively. With the database, phylogenetic tree was constructed, and the genetic and molecular evolutionary characteristics were analyzed with bioinformatics software. Results: Five HAdV-53 strains in Shanxi Province in 2016 showed high consistency with the HAdV-53 strains prevalent in other countries in 1996-2014 (>99.8%). All HAdV-53 strains were in the same evolutionary branch with their recombinant source genotypes (HAdV-37 and HAdV-8) in Penton base and Fiber gene, respectively, and maintained a high degree of consistency in gene sequences. In Hexon gene, HAdV-53 strains were more closed to its recombinant source genotype HAdV-22, the nucleotide and amino acid sequences between two types were highly homologous, while HAdV-53 and HAdV-22 belonged to different evolutionary branches, and the evolution rate of HAdV-53 based on Hexon gene was 3.51×10(-5) substitution/site/year. Conclusion: HAdV-53 has become an important new ocular infectious pathogen of Taiyuan. HAdV-53 strain are relatively conservative and stable based on Penton base, Hexon, and Fiber gene.

[The application of measles specific IgM and IgG antibody detection in classification measles vaccine failure, Tianjin].

Objective: To study the application of measles specific IgM and IgG antibody detection in classification of primary vaccination failure (PVF) and secondary vaccination failure (SVF). Methods: Measles surveillance information system was used to collect measles confirmed cases in Tianjin, 2013-2015, and their blood specimens were collected, totally 284 cases were enrolled. Measles IgM and IgG were detected with enzyme-linked immunosorbent assay (ELISA), and the relative avidity index (RAI) was used to express the result of measles avidity. Measles IgM, IgG and IgM/IgG was analyzed with receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC) as evaluation indicators. In addition, compared with a measles outbreak (26 cases) of a middle school in Tianjin in 2016, for making further verification on the diagnostic value of vaccination failure with IgM, IgG and IgM/IgG. Results: The age of cases ranged was 0-58 years old, the interval median (P(25), P(75)) of serum collection after rash onset was 2 (1, 4) days. The positive rate of measles IgM and IgG in acute phase specimens were 76.06% (216 cases) and 88.38% (251 cases). According to the ROC curve analysis, the area under the ROC curve (AUC) of IgM, IgG and IgM/IgG were 0.753, 0.891 and 0.952, indicating that IgM/IgG was the best index to distinguish PVF and SVF. The best cut off value for IgM/IgG was 0.06, the sensibility and specificity were 88.75% and 86.63%. When IgM/IgG >1, 96.30% cases were low-avidity (RAI <40%), only 1 case was equivocal response (RAI: 40%-60%). 97.14% cases were high-avidity (RAI >60%) when IgM/IgG <0.01, only 3 cases were equivocal response (RAI 40%-60%). The threshold of IgM/IgG was used to verify the measles outbreak of a middle school in Tianjin, 2016. In the acute phase specimens, 100% (26 cases) of IgM/IgG were <0.06, 84.62% (22 cases) of IgM/IgG were <0.01. Conclusion: The detection of measles IgM and IgG with ELISA, and IgM/IgG is a valuable diagnostic tool to distinguish PVF and SVF.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients.

Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS-type pneumonia and the SARS-specific IgG response. Sixteen patients with SARS, 19 patients with community-acquired pneumonia (CAP) (Streptococcus pneumonia) and 16 healthy control subjects were enrolled in the study. Plasma SP-D and anti-SARS-CoV N protein IgG were measured using ELISA. SP-D was significantly elevated in SARS-type pneumonia [median (95% CI), 453 (379-963) ng/ml versus controls 218 (160-362) ng/ml, P < 0.05] like in patients with CAP. SP-D significantly correlated with anti-SARS-CoV N protein IgG (r(2) = 0.5995, P = 0.02). The possible re-emergence of SARS or SARS-like infections suggests a need for minimal traumatic techniques for following the alveolar compartment, e.g. during testing of antivirals. We suggest that monitoring systemic SP-D may be useful in monitoring the alveolar integrity in SARS-type pneumonia. The significant correlation between plasma SP-D and anti-SARS-CoV-specific antibodies support the role for SP-D in interlinking innate and adaptive immune pathways.