Experts’Consensus on the Management of Respiratory Disease Syndemic

The global burden of respiratory diseases is a significant and increasing threat to individuals worldwide.In 2017,there were 544.9 million cases of chronic respiratory diseases,a 39.8%increase since 1990(1).These diseases were the third leading cause of global mortality in 2017,accounting for 7.0%of all deaths,an 18.0%increase compared to 1990.

Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

Human adenovirus B7(HAdV-B7)causes severe acute lower respiratory tract infections in children.However,neither the child-specific antivirals or vaccines are available,nor the pathogenesis is clear.Autophagy,as part of innate immunity,plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity.This study provided evidence that HAdV-B7 infection induced complete autophagic flux,and the pharmacological induction of autophagy decreased HAdV-B7 replication.In this process,the host protein Bcl2-associated athanogene 3(BAG3)mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain.These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.

Clinical epidemiology and disease burden of adenoviral encephalitis in hospitalized children in China:A nationwide cross-sectional study

Importance:Adenovirus encephalitis is a significant infectious disease of the central nervous system that commonly affects children under the age of 5 and has a profound impact on the health of infants and young children throughout China.National multicenter epidemiological studies have significant public health implications.Objective:This study aims to report the epidemiology of adenovirus encephalitis in hospitalized children in China,providing valuable guidance for clinicians.Methods:The data utilized in this study were extracted from the comprehensive Futang Update Medical Records database,which comprises discharge medical records collected by 27 tertiary children’s hospitals between January 2016 and December 2018 in China.Specifically,the face sheet of discharge medical records encompassed critical sociodemographic variables and basic medical care details.Results:In this database,a total of 544 children were hospitalized due to adenoviral encephalitis.The male-to-female ratio was 1.62:1,with more boys being affected across different age groups and places of residence.Of the children hospitalized,the highest number of hospitalizations occurred in the 1–3-year age group and the number of hospitalizations decreased each year from 2016 to 2018.The disease exhibits seasonal characteristics with a pronounced peak in the summer months of June and July.While most children(58%)did not have any significant complications,one-third of them developed respiratory complications,including pneumonia and acute bronchitis.The median length of stay for adenoviral encephalitis was 7 days,and the median cost of hospitalization was 2145.56 US dollars.Interpretation:This study highlights the prevalence of adenovirus encephalitis in hospitalized children in China.Children aged 1–3 years were found to be the main demographic hospitalized due to this condition,with boys being significantly more affected than girls.The seasonal variations of adenovirus encephalitis were also found to be significant.Fortunately,the fatality rate associated with this condition was low,and the prognosis was generally favorable.

A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein

Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.

Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement

Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City,China,by January 30,2020,a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China.Among the confirmed cases,1527 were severe cases,171 had recovered and been discharged at home,and 213 died.And among these cases,a total of 28 children aged from 1 month to 17 years have been reported in China.For standardizing prevention and management of 2019-nCoV infections in children,we called up an experts' committee to formulate this experts' consensus statement.This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections.The present consensus statement summarizes current strategies on diagnosis,treatment,and prevention of 2019-nCoV infection in children.

Molecular Epidemiology of Echovirus 18 Circulating in China's Mainland from 2015 to 2016

Echovirus 18(E18), a serotype of Enterovirus B(EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in China's Mainland, but became the predominant pathogen associated with viral encephalitis(VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in China's Mainland, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease(HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from China's Mainland after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 50-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiplerecombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.

Epidemiological characteristics and disease burden of infectious mononucleosis in hospitalized children in China:A nationwide retrospective study

Epstein-Barr virus(EBV)is very common,with the infection rate in adults over 90%worldwide.Infectious mononucleosis(IM)is caused by primary infection with EBV.Most IM patients are generally considered to have a favorable prognosis,but a few patients will also develop complications.Children with severe symptoms will require hospitalization.However,the disease burden of children hospitalized with IM in China has been rarely described.In this study,we included the Face sheets of discharge medical records from 27 member children's hospitals of Futang Research Center of Pediatric Development from Jan 1st,2016 to Dec 31st,2020,and medical information such as gender,age,region,time of admission,length of stay and expenditure were extracted.There were 24,120 IM cases,which accounted for 0.42%(24,120/5,693,262)of all hospitalized cases during this period.The ratio of male to female was 1.48:1.Hospitalization for IM in the 4-6 years age group was the highest among inpatients of all age groups.Case numbers increased year by year between 2016 and 2020,and the monthly hospitalization was generally high from Jul to Sep but reduced from Jan to Feb per year.Bronchitis/pneumonia and hepatic dysfunction were two common complications in hospitalized IM patients.The median length of stay was 8 days,and the median cost of hospitalization was 970.59 US dollars.This study will help understand the epidemiological characteristics and disease burden of hospitalized children with IM in China.

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland

Community-acquired pneumonia(CAP) is one of the leading causes of morbidity and mortality in children worldwide.In this study,we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland.During November2014 to June 2016,the prospective study was conducted in 13 hospitals.The hospitalized children under 18 years old who met the criteria for CAP were enrolled.The throat swabs or nasopharyngeal aspirates(NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay.Viral pathogens were present in 56.6%(1539/2721) of the enrolled cases,with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases.The most frequently detected virus was respiratory syncytial virus(RSV)(15.2%,414/2721).The highest detection rate of virus was in <6-month-age group(70.7%,292/413).RSV,human metapneumovirus(HMPV),human parainfluenza viruses(HPIVs) and influenza B virus(Flu B) showed the similar prevalence patterns both in north and south China,but HPIVs,Flu A,human bocavirus(HBoV),human adenovirus(HAdV) and human coronaviruses(HCoVs) showed the distinct circulating patterns in north and south China.Human enterovirus/human rhinovirus(HEV/HRV)(27.6%,27/98),HBoV(18.4%,18/98),RSV(16.3%,16/98) and HMPV(14.3%,14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection.In conclusion,viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP.RSV was the most important virus in hospitalized children with CAP in Chinese mainland.

Clinical characteristics and effectiveness of antiviral agents in hospitalized children with infectious mononucleosis in China:A multicenter retrospective study

Importance:The clinical characteristics of infectious mononucleosis(IM)in Chinese children have not been evaluated in multicenter studies,and the effectiveness of antiviral treatment are controversial.Objective:To investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients.Methods:Hospitalized patients with IM were enrolled between 2018 and 2020 in five children’s hospitals in China.The clinical characteristics were compared among four age groups:<3 years,3-<6 years,6-<10 years,and≥10 years.The clinical characteristics of IM and effectiveness of antiviral therapy were compared among patients receiving acyclovir(ACV),ganciclovir(GCV),and no antiviral therapy(i.e.,non-antiviral group).Results:In total,499 patients were analyzed;most patients were 3-<6 years of age.The most common symptoms and signs included fever(100%),lymphadenopathy(98.6%),pharyngitis(86.4%),eyelid edema(76.8%),and snoring(72.9%).There were significant differences in rash,hepatomegaly,and liver dysfunction among the four age groups.Patients aged<3 years had a lower incidence of liver dysfunction and a higher incidence of rash.Among the 499 patients,50.1%were treated with GCV,26.3%were treated with ACV,and 23.6%received no antiviral therapy.Compared with the non-antiviral group,patients in the ACV and GCV groups had longer durations of fever(P<0.001).There were no significant differences in the incidences of complications among the three treatment groups.Interpretation:The incidence of IM in Chinese children peaked at 3-<6 years of age.Clinical features of IM varied according to age.Patients receiving antiviral therapy exhibited more serious clinical manifestations than did patients without antiviral therapy.The effectiveness of antiviral therapy for IM requires further analysis.

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.

Recombinant GII.4[P31] Was Predominant Norovirus Circulating in Beijing Area, China, 2018–2020

Dear Editor,Acute gastroenteritis(AGE)is a leading infectious cause of morbidity worldwide,particularly among children in developing countries(Mortality and Causes of Death2016).With the introduction of rotavirus vaccines,noroviruses have been identified as a leading cause of AGE outbreaks and sporadic disease worldwide(Hall et al.

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.

Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China

To investigate the molecular epidemiology and genetic variation of human adenovirus type 7(HAdV-7)in children with acute respiratory infections(ARI)in China.HAdV-7-positive respiratory samples collected from children with ARI in Beijing,Shijiazhuang,Wenzhou and Guangzhou from 2014–2018 were selected for gene amplification and sequence analysis.Fifty-seven HAdV-7 clinical strains with hexon,penton base and fiber gene sequences were obtained.Meanwhile17 strains were selected randomly from different cities for whole genome sequencing.Phylogenetic and variation analyses were performed based on the obtained sequences,HAdV-7 prototype strain Gomen(AY594255),vaccine strains(AY495969 and AY594256)and representative sequences of strains.The phylogenetic trees constructed based on whole genome sequences,major capsid protein genes(hexon,penton base and fiber)and the early genes(E1,E2,E3 and E4)were not completely consistent.The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980 s to the present.Compared with the HAdV-7 prototype strain Gomen(AY594255),some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed.Recombination analysis showed that partial regions of 55 k Da protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3,respectively.Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention,control and vaccine development of HAdV-7.

Pay attention to SARS-CoV-2 infection in children

The novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS・CoV-2)has been prevalent for nearly two months.The first case of COVID-19 was reported in Wuhan,Hubei Province,China in mid-December,2019.On January 9,2020,Chinese scientists isolated and obtained the genome sequence of the new virus;they shared the genome information on releva nt international websites one day later.

Seroprevalence of SARS-CoV-2 infections among children visiting a hospital

Importance:In this study,we retrospectively investigated the seroprevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibodies within serum samples from children in Beijing,China.These findings provide preliminary guidance regarding population susceptibility to SARS-CoV-2,which will aid in establishing policy toward coronavirus disease 2019(COVID-19)prevention and control.Objective:To understand the seropositivity of anti-SARS-CoV-2 IgM/IgG antibodies among children in Beijing,China,evaluate the susceptibility of children in Beijing to SARS-CoV-2,and provide prima facie evidence to guide SARS-CoV-2 prevention and control.Methods:IgM/IgG antibody kits(colloidal gold)were used to conduct preliminary screening of SARS-CoV-2 IgM/IgG antibodies in serum samples of children who presented to Beijing Children’s Hospital,Capital Medical University,having fever or requiring hospitalization,from March 2020 to August 2020.Statistical analysis of anti-SARS-CoV-2 antibody seropositivity was performed according to the children’s general demographic characteristics,timing of admission to hospital,presence of pneumonia,and viral nucleic acid test results.Results:The study included 19797 children with both IgM and IgG antibody results.Twenty-four children had anti-SARS-CoV-2 IgM-positive results(positive rate of 1.2‰),twelve children had anti-SARS-CoV-2 IgG-positive results(positive rate of 0.6‰).Viral nucleic acid test results were negative for the above-mentioned children with positive antibody findings;during the study,two children exhibited positive viral nucleic acid test results,but their anti-SARS-CoV-2 IgM/IgG antibody results were negative.Anti-SARS-CoV-2 IgM antibody seropositivity was higher in the<1-year-old group than in the≥6-year-old group.The rates of anti-SARS-CoV-2 IgM seropositivity was highest in August from March to August;IgG results did not significantly differ over time.The rates of anti-SARS-CoV-2 IgM or IgG seropositivity among children with and without suspected pneumonia did not significantly differ between groups.Interpretation:During the study period,the rates of anti-SARS-CoV-2 IgM/IgG antibody seropositivity were low among children who presented to Beijing Children’s Hospital,Capital Medical University.The findings suggest that children in Beijing are generally susceptible to SARS-CoV-2 infection;COVID-19 prevention and control measures should be strengthened to prevent disease in children.

Serotypes of human enteroviruses causing pediatric viral encephalitis and meningitis in Hebei province, China, from 2013 to 2015

Importance:Viral encephalitis and meningitis are severe infectious diseases responsible for substantial morbidity and mortality in children.Enteroviruses are typically the most common causative agents of viral encephalitis and meningitis.Objective:This study aimed to investigate the etiology of viral encephalitis and meningitis among children in Hebei province,China.Methods:Cerebrospinal fluid samples from children with viral encephalitis (n=309) and meningitis (n=133) were collected between Nov 2013 and Dec 2015 and viral pathogens were identified by real-time and multiplex PCR.Amplification and sequencing of partial VP1 genes was used to type enteroviruses.Results:The causative pathogen was successfully detected in 176 (57％) patients with viral encephalitis and 82 (61.7％) patients with viral meningitis.The most common causative agents of both viral encephalitis and meningitis were enteroviruses (55.7％ and 64.6％ of cases,respectively).The most common enterovirus serotypes identified were echovirus 18,echovirus 6 and echovirus 30.Echovirus 18 accounted for 74.4％ of all typed enteroviruses and caused a viral encephalitis and meningitis outbreak in Hebei province in 2015.By contrast,the major enterovirus serotypes circulating in 2014 were echovims 6 and echovirus 30.Interpretation:Enteroviruses were the main causative agents of viral encephalitis and meningitis in children in Hebei province from Nov 2013 to Dec 2015.Echovirus 18 became the leading cause of viral encephalitis and meningitis for the first time in Hebei province in 2015.

Global Pediatric Pulmonology Alliance(GPPA)proposal for COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.

Non-hepatotropic viral hepatitis and its causative pathogens:The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology

ELEVATEDINCIDENCEOFSEVERE ACUTEHEPATITISOFUNKNOWN ETIOLOGYINCHILDRENIN2022 As of June 22,2022,920 probable cases of severe acute hepatitis of unknown etiology had been reported in 33 countries.l The numbers of reported cases were the highest in the United States and the United Kingdom.

A Simple and Rapid Method for Quantitative Detection of Hepatitis B Virus Drug-resistant Mutations

Hepatitis B virus(HBV)is a small-enveloped virus enclosing a partially double-stranded DNA genome,belongs to the hepadnaviruses family.1 To date,10 genotypes(A–J)of HBV with distinct geographical distribution have been described,based on a divergence of at least 8%over the entire genomic sequence or>4%in the S gene sequence,with B and C being most prevalent and confined to Asia and Oceania.2 HBV is a highly contagious pathogen that can lead to acute infection or chronic hepatitis B(CHB),cirrhosis and hepatocellular carcinoma(commonly known as HCC)in humans through immune anergy or upon immunosuppression.

Concerning the discovery of mechanism for enterovirus B infection published in Cell

To Professor Xie: We just noticed that your team, collaborated with other two teams published a paper entitled 'Human neonatal Fc receptor is the cellular uncoating receptor for enterovirus B' in Cell.1 This research is very important for understanding the mechanisms of pathogenesis of enterovirus and new drug development. Since most of the readers of our journal are pediatric clinicians, we have some questions related to the potential clinical application.