Human adenovirus(HAdV)infection in children with acute respiratory tract infections in Guangzhou,China,2010–2021:a molecular epidemiology study

Background Human adenovirus(HAdV)infection can cause a variety of diseases.It is a major pathogen of pediatric acute respiratory tract infections(ARIs)and can be life-threatening in younger children.We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou,China.Methods We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and 2021.HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis.Results Before the COVID-19 outbreak in Guangzhou,the annual frequency of adenovirus infection detected during this period ranged from 3.92%to 13.58%,with an epidemic peak every four to fve years.HAdV demonstrated a clear seasonal distribution,with the lowest positivity in March and peaking during summer(July or August)every year.A signifcant increase in HAdV cases was recorded for 2018 and 2019,which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7.The latter was associated with a more severe disease compared to HAdV-3.The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38%but increased to 20%in severe cases.After COVID-19 emerged,HAdV cases dropped to 2.68%,suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community.Conclusion Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

Effectiveness and Safety of Jinye Baidu Granules(金叶败毒颗粒)for Acute Upper Respiratory Tract Infection:A Systematic Review and Meta-analysis

To evaluate the effectiveness and safety of Jinye Baidu Granules(金叶败毒颗粒)for acute upper respiratory tract infection(AURTI).Database such as CNKI,Wan-fang,VIP,Sino Med,Web of science,Clinical Trials gov,Medline、EMBASE,CENTRAL,Cochrane Library were retrieved to collect randomized controlled trials(RCTs)on Jinye Baidu Granules(金叶败毒颗粒)in treating AURTI from the estabslishment of the database to March 2019.A total of 2 reviewers independently screened the literature according to the inclusion and exclusion criteria,and extracted material and the quality evaluation of the included studies.Quality evaluation adopted Cochrane Handbook 5.1 evaluation standards and tools.Rev Man5.3 was used to perform Meta-analysis for the adopted study.Finally a total of 4 RCTs involving 636 patients were included.Meta-analysis results showed that:compared with conventional Western medicine alone,Jinye Baidu Granules(金叶败毒颗粒)combined with Western medicine in the treatment of acute upper respiratory tract infection can improve the total effective rate of clinical efficacy[RR=0.13,95%CI(0.06,0.29),P<0.00001],shorten the time of antipyretic time for acute upper respiratory tract infection[MD=–1.22,95%CI(–1.43,–1.00),P<0.00001],shorten the time of pharyngeal pain[MD=–1.97,95%CI(–2.97,–0.96),P<0.0001]and shorten the cough disappear time[MD=–1.97,95%CI(–2.97,–0.96),P<0.0001].There were 2 papers reporting adverse reactions during the study period,and one of them specifically reported diarrhea,nausea,vomiting and stomachache in the experimental group.In the control group:diarrhea,nausea and adverse reactions disappeared after drug withdrawal;the incidence of adverse reactions was 3.92%in the control group and 5.88%in the observation group.There was no significant difference between the 2 groups(P>0.05).Based on existing data and methods,the systematic evaluation showed that,compared with Western medicine alone,Jinye Baidu Granules(金叶败毒颗粒)combined with Western medicine alone could improve the total effective rate of clinical efficacy,reduce the time of fever,sore throat,and the disappearance of cough with less adverse reactions.However,due to the low quality of the included study,large samples,multicenter,randomized,double-blind trials and trials are still needed to randomized controlled trials with reference to the CONSORT standard and the STRICTA statement.

Meta-analysis of the comparison between reduning injection and ribavirin injection for acute upper respiratory tract infection in children

Objective:To systematically evaluate the effectiveness and safety of reduning injection in acute upper respiratory tract infection of children.Methods:Use computer to search PubMed,the Cochrane Library,EMBASE,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,Weipu database(VIP)and China Biomedical studies Service System(CBM)for randomized controlled trials(RCT)of acute upper respiratory tract infection in children,and the retrieval time is from their establishment to May,2022.After two researchers independently screened the studies,extracted data and evaluated the risk bias of studies,RevMan5.3 software was used to perform meta-analysis.Results:10 studies in total were included,involving 1466 patients.Results of the meta-analysis:total effective rate[RR=1.12,95%CI(1.07,1.16),P<0.00001],cure time[MD=-1.51,95%CI(-1.71,-1.32),P<0.00001],antipyretic time[MD=-1.32,95%CI(-1.72,-0.92),P<0.00001],disappearing time of nasal obstruction and nose running[MD=-1.04,95%CI(-1.45,-0.62),P<0.00001],disappearing time of cough[MD=-1.35,95%CI(-1.58,-1.13),P<0.00001],disappearing time of throat congestion[MD=-1.36,95%CI(-1.68,-1.03),P<0.00001],disappearing time of sore throat[MD=-1.55,95%CI(-1.74,-1.35),P<0.00001],the incidence of adverse reactions[RR=0.34,95%CI(0.20,0.57),P<0.0001].The differences between two groups in total effective rate,cure time,antipyretic time,disappearing time of nasal obstruction and nose running,disappearing time of cough,disappearing time of throat congestion,disappearing time of sore throat and the incidence of adverse reactions are all statistically significant(P<0.05).The sensitivity analysis demonstrates that three outcomes(total effective rate,cure time and disappearing time of sore throat)have unstable results,while others having stable results.Conclusion:Reduning injection is more effective than ribavirin injection in clinical,and it is better than ribavirin injection at relieving fever,nasal obstruction and nose running,cough and throat congestion.In addition,it’s safer in clinical than ribavirin injection.

Association Between Diurnal Temperature Range and Respiratory Tract Infections

Objective This study aimed to assess the association between emergency-room visits for respiratory tract infection （RTI） with diurnal temperature range （DTR）, a weather parameter closely associated with urbanization and global climate change. Methods We conducted a semiparametric time-series analysis to estimate the percentage increase in emergency-room visits for RTI associated with changes in DTR after adjustment for daily weather conditions （temperature and relative humidity） and outdoor air pollution. Results DTR was significantly associated with daily emergency-room visits for RTI. An increase of 1 ~C in the current-day （LO） and in the 2-day moving average （L01） DTR corresponded to a 0.94% [95% confidence interval （CI）, 0.34%-1.55%] and 2.08% （95% CI, 1.24%-2.93%） increase in emergency-room visits for RTI, respectively. Conclusion DTR was associated with increased risk of RTI. More studies are needed to understand the impact of DTR on respiratory health.

Lung Function in Wheezing Infants after Acute Lower Respiratory Tract Infection and Its Association with Respiratory Outcome

Background： Wheezing is common in early childhood and remains an important health concern. The aim of this study was to assess the lung function of wheezing infants and to investigate the relationship between lung function and respiratory outcome. Methods： Infants 〈2 years of age with acute lower respiratory tract infection （ALRTI） who had undergone lung function tests were included in the study. They were assigned to wheeze or no wheeze group based on physical examination. Infants without any respiratory diseases were enrolled as controls. Lung function was measured during the acute phase and 3 months after ALRTI. One-year follow-up for infants with ALRTI was achieved. Results： A total of 252 infants with ALRTI who had acceptable data regarding tidal breathing were included in the final analysis. Compared with the control and the no wheeze groups, infants in the wheeze group had significantly decreased time to peak tidal expiratory flow as a percentage of total expiratory time （TPTEF/TE） （20.1 1 6.4% vs. 34.4 ± 6.2% and 26.4 ±8.3%, respectively, P 〈 0.0001） and significantly increased peak tidal expiratory flow （PTEF） （90.7 ± 26.3 ml/s vs. 79.3 ± 18.4 ml/s and 86.1 ± 28.0 ml/s, respectively, P 〈 0.01）, sReff and Reff. The infants in the wheeze group still had lower TPTEF/TE and volume to peak tidal expiratory flow as a percentage of total expiratory volume （VPTEF/VE） than the no wheeze infants 3 months after the ALRT1. Moreover, there was a significant inverse relationship between TPTEF/TE, VPTEF/VE, and the recurrence of wheezing and pneumonia. Conclusions： Impaired lung function was present in wheezing infants with ALRTI and the deficits persisted. In addition, the lower level of TPTEF/TE and VPTEF/VE was a risk factor for poor respiratory outcome.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study

Human metapneumovirus(HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples(5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two(67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus(EV) or rhinovirus(RhV)(38.0%),followed by respiratory syncytial virus(RSV)(32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36strains were subgrouped into subtypes A2c(75%), eight strains were included in subtype B1(16.7%), and four strains were included in subtype B2(8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25(92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Current status of human adenovirus infection in China

Background Outbreaks of severe,acute hepatitis among children have recently attracted global attention.The pathogen causing the outbreak remains unknown,but there is growing evidence that it may be associated with human adenovirus(HAdV).Data sources A review of adenovirus-related clinical studies,epidemiological studies,etiological studies,and case reports was conducted by reviewers independently.Results HAdV can cause a wide variety of clinical symptoms.In the Mainland of China,HAdV infection accounts for 5.8%–13%of patients with acute respiratory infections,and these infections are mainly caused by species B,C,and E of HAdV.For acute conjunctivitis,39.8%–74.9%of sporadic cases were infected by B and D species of HAdV.Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country.In pediatric patients with acute gastroenteritis,HAdV-41 was the predominant HAdV type,followed by HAdV species B and C.Several types of HAdV,including HAdV-5,HAdV-7,HAdV-1,and HAdV-2,have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients.However,few HAdV-related hepatitis cases have been reported in China to date.Conclusions There are no systematic surveillance and clinical studies on HAdV hepatitis in China.Therefore,it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical,epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.