Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the co...Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants(below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-riskinfants, lowers the burden of RSV infection in certain carefully selected patient groups.展开更多
<strong>Background:</strong><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Respiratory syncytial virus (RSV) causes significant morbidit...<strong>Background:</strong><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Respiratory syncytial virus (RSV) causes significant morbidity and mortality in patients with a history of prematurity and congenital heart disease (CHD). In 2014, the guidelines for Palivizumab became more restrictive for this population. We hypothesized the percentage of RSV+ admissions would increase overall and in this target group (TG) specifically.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">We conducted a retrospective review of patients under age 2 years admitted with bronchiolitis two seasons prior to the change (Pre) and two seasons after (Post). Our TG included patients who were eligible prior to the 2014 changes but currently no longer eligible. We used chi-square analysis to answer the two main hypotheses: 1</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent RSV+/total bronchiolitis Pre vs Post and 2</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent of TG/RSV+ Pre vs Post.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> 1283 patients (546 pre, 737 post) were admitted with the diagnosis of RSV between 2012-2016, 866 actually tested positive for RSV (367 Pre, 499 Post). There was no significant difference in the number of total patients admitted with RSV (Pre = 67.2%, Post = 67.7%) or in our TG (Pre 7.1% vs Post 8.2%). TG overall had a more complicated course: longer length of stay, median 5 days, IQR 2</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">12 vs 3 days, IQR 1</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span展开更多
Background: Palivizumab were used for the premature infant or a high-risk infant with congenital heart disease. However, recently outbreak pattern of respiratory syncytial (RS) virus infection has been varying year by...Background: Palivizumab were used for the premature infant or a high-risk infant with congenital heart disease. However, recently outbreak pattern of respiratory syncytial (RS) virus infection has been varying year by year. Moreover, it also has some regional difference. Therefore, the object of the present study was to develop early detection of the timing of that outbreak had started in each prefecture. Method: We used data in National Official Sentinel Surveillance for Infectious Diseases (NOSSID). Study period was March 16th, 2011 to December 30th, 2018. We defined stating period to initiate to take palivizumab as 8 - 12 weeks before from the peak of outbreak. We estimated whether the week is included in starting period or not from April 1st to the peak of outbreak by the past number of patients of RS virus infection on week and its squared. Additionally, we have to take delay in NOSSID into consideration. Results: In nationwide, the last two seasons, the model predicted precisely the starting period. At prefectural level, the model predicted the starting period precisely in 16.6% of all year and prefectures pairs. When we consider the delay in NOSSID into consideration, the patients can start to take in 14.9% of all year and prefectures pairs. Discussion and Conclusion: The result of the probability model was not good, and thus we have to develop more sophisticated model for prediction at prefecture level.展开更多
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 prev...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.展开更多
文摘Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants(below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-riskinfants, lowers the burden of RSV infection in certain carefully selected patient groups.
文摘<strong>Background:</strong><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Respiratory syncytial virus (RSV) causes significant morbidity and mortality in patients with a history of prematurity and congenital heart disease (CHD). In 2014, the guidelines for Palivizumab became more restrictive for this population. We hypothesized the percentage of RSV+ admissions would increase overall and in this target group (TG) specifically.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">We conducted a retrospective review of patients under age 2 years admitted with bronchiolitis two seasons prior to the change (Pre) and two seasons after (Post). Our TG included patients who were eligible prior to the 2014 changes but currently no longer eligible. We used chi-square analysis to answer the two main hypotheses: 1</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent RSV+/total bronchiolitis Pre vs Post and 2</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent of TG/RSV+ Pre vs Post.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> 1283 patients (546 pre, 737 post) were admitted with the diagnosis of RSV between 2012-2016, 866 actually tested positive for RSV (367 Pre, 499 Post). There was no significant difference in the number of total patients admitted with RSV (Pre = 67.2%, Post = 67.7%) or in our TG (Pre 7.1% vs Post 8.2%). TG overall had a more complicated course: longer length of stay, median 5 days, IQR 2</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">12 vs 3 days, IQR 1</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span
文摘Background: Palivizumab were used for the premature infant or a high-risk infant with congenital heart disease. However, recently outbreak pattern of respiratory syncytial (RS) virus infection has been varying year by year. Moreover, it also has some regional difference. Therefore, the object of the present study was to develop early detection of the timing of that outbreak had started in each prefecture. Method: We used data in National Official Sentinel Surveillance for Infectious Diseases (NOSSID). Study period was March 16th, 2011 to December 30th, 2018. We defined stating period to initiate to take palivizumab as 8 - 12 weeks before from the peak of outbreak. We estimated whether the week is included in starting period or not from April 1st to the peak of outbreak by the past number of patients of RS virus infection on week and its squared. Additionally, we have to take delay in NOSSID into consideration. Results: In nationwide, the last two seasons, the model predicted precisely the starting period. At prefectural level, the model predicted the starting period precisely in 16.6% of all year and prefectures pairs. When we consider the delay in NOSSID into consideration, the patients can start to take in 14.9% of all year and prefectures pairs. Discussion and Conclusion: The result of the probability model was not good, and thus we have to develop more sophisticated model for prediction at prefecture level.
基金supported by the National Natural Science Foundation of China(NSFC)(81991494 and 82122031)the National Key R&D Program of China(2020YFA0907100)+3 种基金the Chinese Academy of Sciences(YSBR-010)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-026)Beijing Natural Science Foundation(L222076)L.D.is supported by the Youth Innovation Promotion Association CAS,China(2018113).
文摘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.
