Actualización en prevención de VRS: Nirsevimab vs vacunación en embarazadas (RSVpreF) / Update on RSV prevention: Nirsevimab vs vaccination in pregnant women (RSVpreF)

El anticuerpo monoclonal Nirsevimab fue el primero que se implantó para la prevención de infección por virus respiratorio sincitial (VRS) de todos los lactantes en sus primeros meses de vida. Recientemente se ha aprobado el uso de una vacuna en la embarazada (RSVpreF) con distinta forma de inmunización pero el mismo objetivo en el lactante. De este modo, surge la necesidad de valorar una nueva estrategia de inmunización. Desarrollo. Nirsevimab demostró en ensayos clínicos buenos datos de eficacia clínica y de seguridad. Tras su inclusión en la temporada epidémica 2023-2024, la cobertura en España ha sido muy alta y los resultados preliminares parecen mantener la tendencia de los ensayos. Queda pendiente una valoración adecuada de su eficiencia. RSVpreF tiene resultados similares pero, de momento, solo en ensayos y, aunque podría tener alguna ventaja inmunológica, se desconoce si se traduciría en eficacia real. Aún así, esta nueva vacuna respaldada por organismos sanitarios y científicos sería una alternativa segura y eficaz. Por otro lado, incluso con la implementación en el calendario vacunal de RSVpreF, Nirsevimab va a continuar siendo clave en la protección de ciertos lactantes. Conclusión. La aprobación de la vacuna en la embarazada RSVpreF añade una segunda herramienta inmunológica frente a la infección por VRS en lactantes. RSVpreF y Nirsevimab pueden desarrollar un papel complementario en la prevención de estas infecciones.(AU)

Introduction: Nirsevimab was the first monoclonal antibody to be implemented in order to prevent respiratory syncytial virus (RSV) infection in all infants in their first months of life. The use of a vaccine in pregnant women (RSVpreF) using a different way of immunization but still sharing the same objective in infants has recently been approved. Thus, there is a necessity to evaluate a new immunization strategy. Development. Nirsevimab showed good clinical efficacy and safety data in medical trials. After its inclusion in the 2023-2024 epidemic season, coverage in Spain has been very high and preliminary results seem to maintain the trend shown in the trials. An adequate assessment of its efficiency is still pending. RSVpreF has similar results but, for now, only in trials and although it could have some immunological advantages, it is unknown if it would result in actual efficacy. Even so, this new vaccine, supported by health and scientific organizations, would provide a safe and effective alternative. Nonetheless, even with the implementation in the RSVpreF vaccine schedule, Nirsevimab will continue to be a key factor in the protection of certain infants. Conclusion. The approval of the RSVpreF vaccine in pregnant women adds a second immunological tool against RSV infections in infants. RSVpreF and Nirsevimab may play a complementary role in the prevention of these infections.(AU)

Are we ready to face the next wave of RSV surge after the COVID-19 Omicron pandemic in China?

Background: China had its first wave of COVID-19 in 2020 and second wave of COVID-19 Omicron in 2022. The number of RSV cases decreased sharply in 2020 and 2022. Investigation of the resurge of RSV infections after the first wave of COVID-19 will guide us to take preventive actions before the resurge of RSV infections after the second wave of COVID-19 Omicron. Methods: We analysed epidemiological and clinical data of 59934 patients with lower respiratory tract infections (LRTI) from a prospective long-term cohort surveillance programme in Suzhou, China, collected from February 2016 to January 2022. The annual incidence of RSV infection in children aged<16 years in 2020 and 2021 was compared with the pre-pandemic years 2016 to 2019. We also compared the clinical characteristics, and RSV-related ICU admissions between pre-pandemic years and 2021. Results: Among children with LRTI, the positive rate of RSV increased by 70.7% in 2021 compared to the average level in the pre-pandemic years. The RSV resurge in 2021 was most prominently in children aged 2-4 years (a significant rise compared with the expected value 149.1%; 95%CI, 67.7% to 378%, P<.01). The percentage of RSV-related ICU admissions decreased in 2021 (3.2% vs 6.7%, P<0.01). The death rate of RSV infections in 2021 was 0.2%, while that in pre-pandemic years was only 0.02%. RSV-associated death in immunocompetent children (complicated by necrotizing encephalitis) was firstly occurred in 2021. Conclusions: Our findings raise concerns for RSV control in Southeast China after the COVID-19 pandemic especially for children aged 2-4 years. Although ICU admissions were significantly reduced in this resurgence, we could not ignore the increase of RSV-associated death.

Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness. METHODS: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401). RESULTS: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70). CONCLUSIONS: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.

Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial.

Background: Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan. Methods: This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days. Findings: Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period. Interpretation: Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study. Funding: Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.

Respiratory Syncytial Virus Disease Burden in Community-Dwelling and Long-Term Care Facility Older Adults in Europe and the United States: A Prospective Study.

Background: Data on respiratory syncytial virus (RSV) disease burden in adults remain scarce. We assessed the burden of confirmed RSV-acute respiratory infections (cRSV-ARIs) in community-dwelling (CD) adults and those in long-term care facilities (LTCFs). Methods: In this prospective cohort study covering 2 RSV seasons (October 2019-March 2020 and October 2020-June 2021), RSV-ARIs were identified through active surveillance, in medically stable CD-adults ≥50 years (Europe) or adults ≥65 years in LTCFs (Europe and the United States). RSV infection was confirmed by polymerase chain reaction from combined nasal and throat swabs. Results: Of 1981 adults enrolled, 1251 adults in CD and 664 LTCFs (season 1) and 1223 adults in CD and 494 LTCFs (season 2) were included in the analyses. During season 1, overall incidence rates ([IRs] cases/1000 person-years) and attack rates (ARs) for cRSV-ARIs were 37.25 (95% confidence interval [CI], 22.62-61.35) and 1.84% in adults in CD and 47.85 (CI, 22.58-101.4) and 2.26% in adults in LTCFs. Complications occurred for 17.4% (CD) and 13.3% (LTCFs) of cRSV-ARIs. One cRSV-ARI occurred in season 2 (IR = 2.91 [CI, 0.40-20.97]; AR = 0.20%), without complications. No cRSV-ARIs led to hospitalization or death. Viral pathogens were codetected in ≤17.4% of cRSV-ARIs. Conclusions: RSV is an important cause of disease burden in adults in CD and LTCFs. Despite the observed low severity of cRSV-ARI, our results support the need for RSV prevention strategies among adults ≥50 years old.

Virological and genetic characteristics of human respiratory syncytial viruses isolated in Russia, 2017-2018.

Isolation of human respiratory syncytial virus (HRSV) from clinical samples and storage of isolates for long period remains a considerable problem. We describe in detail the optimized conditions of HRSV isolation and cultivation in three cell cultures HeLa, HEp-2, and Vero. HRSV was detected in 35.2% (166/471) specimens by real-time PCR from symptomatic infants and children up to 15 years from October 2017 to March 2018 in Russia. HRSV-positive samples were used for virus isolation in HeLa, HEp-2, and Vero cells in different manners (in monolayer or suspension). To optimize the conditions of HRSV cultivation, these cell cultures were treated or not with receptor-destroying enzyme (RDE). Ten isolates were successfully obtained by the way of infection of the suspension of cells with subsequent RDE treatment. Among them, several isolates induced the cytopathogenic effect (CPE) by the syncytium formation in both Hela and HEp-2 cell cultures. The genetic analysis revealed that the manners of isolation by using monolayer or suspension and subsequent RDE treatment did not influence the nucleotide and amino acid structures of obtained HRSVs. The CPE characteristics of obtained viruses were the same in HeLa, HEp-2, and Vero cell cultures, and were described as large syncytium up to 150 microns or more in size with the nuclei peripheral location and an optically bright zone in the center of the formation. We showed that infection of cell suspension with the subsequent RDE treatment increased the chance of HRSVs isolation from clinical samples.

Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions.

The primary cause of morbidity and mortality from infection with respiratory syncytial virus (RSV) is the excessive innate immune response(s) (IIR) in which reactive oxygen species (ROS) play key role(s). However, the mechanisms for these processes are not fully understood. We hypothesized that expressions of IIR genes are controlled by the ROS-generated epigenetic-like mark 7,8-dihydro-8-oxo(d)guanine (8-oxo(d)Gua) and 8-oxoguanine DNA glycosylase1 (OGG1). Here, we report that ROS not only generates intrahelical 8-oxo(d)Gua, but also enzymatically disables OGG1 in RSV-infected human airway epithelial cells and mouse lungs. OGG1 bound to 8-oxo(d)Gua in gene regulatory sequences promotes expression of IIR genes, and consequently exacerbates lung inflammation, histological changes, and body weight loss of experimental animals. Pharmacological inhibition of OGG1 substrate binding decreased expression of RSV-induced chemokine and cytokines and significantly lessened clinical symptoms. Results of mechanistic studies show that OGG1 binding at 8-oxo(d)Gua promoter regions modulated loading of transcription factors via transient cooperative interactions in RSV-infected lungs and airway epithelial cells. Other base specific DNA repair proteins had no effects. Collectively, this study identifies unprecedented roles of ROS-generated DNA base lesion(s) and cognate repair protein as a determinant of RSV-induced exuberant inflammation. Pharmaceutical inhibition of OGG1 interaction with its DNA substrate may represent a novel strategy in prevention/intervention of respiratory viral infections.

Severity of bronchiolitis in infants is associated with their parents' tobacco habit.

The aim of this study was to investigate the effect of tobacco smoke exposure among severely pediatric ICU patients. A prospective epidemiological observational study was conducted among children with bronchiolitis younger than 2 years of age admitted to the Pediatric Intensive Care Unit of Children's University Hospital La Paz during the October 2017 to March 2018 outbreak. On admission, parents were asked whether they smoked. In children who required invasive mechanical ventilation, endotracheal aspirate was collected at the time of intubation. A total of 102 patients with bronchiolitis were studied. Among these, 14 (47%) of 30 infants whose parents smoked required invasive mechanical ventilation vs. 14 (19%) of 72 whose parents were nonsmokers (p = 0.007). Among patients on invasive mechanical ventilation, 10 (71%) of 14 infants with secondhand smoke exposure presented pulmonary bacterial superinfection vs. 3 (21%) of 14 in the unexposed (p = 0.012).Conclusion: Secondhand smoke exposure is an additional high risk for pulmonary bacterial superinfection and invasive mechanical ventilation in infants with severe acute bronchiolitis What is known: •Environmental tobacco smoke exposure is known to be an important risk factor for childhood lower respiratory tract infections. •Tobacco smoke makes structural changes in the respiratory tract and reduces the immune response. What in new: •Secondhand smoke exposure showed to be associated with the increased need and duration of invasive mechanical ventilation, and pediatric intensive care length of stay. •Tobacco smoke exposure is an additional risk factor for the presence of bacteria in the endotracheal aspirate.

Does airborne pollen influence COVID-19 outbreak?

The fast spread of SARS-CoV-2 presented a worldwide challenge to public health, economy, and educational system, affecting wellbeing of human society. With high transmission rates, there are increasing evidences of COVID-19 spread via bioaerosols from an infected person. The current review was conducted to examine airborne pollen impact on COVID-19 transmission and to identify the major gaps for post-pandemic research. The study used all key terms to identify revenant literature and observation were collated for the current research. Based on existing literature, there is a potential association between pollen bioaerosols and COVID-19. There are few studies focusing the impact of airborne pollen on SARS-CoV-2, which could be useful to advance future research. Allergic rhinitis and asthma patients were found to have pre-modified immune activation, which could help to provide protection against COVID-19. However, does airborne pollen acts as a potent carrier for SARS-CoV-2 transport, dispersal and its proliferation still require multidisciplinary research. Further, a clear conclusion cannot be drawn due to limited evidence and hence more research is needed to show how pollen bioaerosols could affect virus survivals. The small but growing literature review focuses on searching for every possible answer to provide additional security layers to overcome near future corona-like infectious diseases.

Analysis of Incidence and Clinical Characteristics of RSV Infection in Hospitalized Children: A Retrospective Study.

OBJECTIVE: To investigate the incidence and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection, and to provide evidence for the importance of preventive strategies and improvements in supportive care of RSV infection. METHODS: This retrospective study included children under 14 years who received throat swab test and were diagnosed with RSV infection from January 2019 to December 2020. Throat swabs and intravenous blood were the main sources of samples, which were obtained within 24 hours of hospitalization. Direct immunofluorescence assay was used to diagnose RSV infection. RESULTS: Among the 448 hospitalized children with RSV infection, males (71.9%) showed the highest proportion, the highest incidence was found in children<6 months old (45.3%), and 76.6% of them had pneumonia. Pharyngeal redness, cough, expectoration, and mental fatigue were the most common symptoms in hospitalized children of all ages. More than 60% of hospitalized children had increased lymphocyte count, aspartate aminotransferase, creatine kinase-MB form, lactate dehydrogenase, and α-HBDH levels. The rates of myocardial damage, respiratory failure, stay in the intensive care unit (ICU), use of mechanical ventilation, and absorption of oxygen were higher in children<6 months old. Except for children who were 37-60 months old, the percentage of length of hospital stay≥7 days in the other age groups was greater than 62.0%. Except for children who were 0-28 days old and>61 months old, the other age groups showed a re-hospitalization situation due to re-infection with RSV. In hospitalized children diagnosed with RSV infection from throat swabs, we also performed the RSV IgM test and found that 59.2% of them were positive, 8.0% of them were weakly positive, and 32.8% of them were negative. CONCLUSION: This study analyzes the incidence and clinical characteristics of hospitalized children with RSV infection, which provides evidence for the importance of preventive strategies and improvements in supportive care of RSV infection.

Study protocol: a multicenter, uncontrolled, open-label study of palivizumab in neonates, infants, and preschool children at high risk of severe respiratory syncytial virus infection.

BACKGROUND: The prophylactic use of anti-respiratory syncytial virus (RSV) antibody (palivizumab) for severe RSV infection is not approved in Japan in specified groups of infants with neuromuscular diseases or other rare diseases associated with reduced ventilation competence or difficulty in expectoration, which increase the risk of exacerbation of severe RSV infection. The objective of this study is to investigate the efficacy, safety, and pharmacokinetics of palivizumab in pediatric patients with those rare diseases for which palivizumab is not indicated at present. METHODS/DESIGN: This study is a multicenter, uncontrolled, open-label study planned to be carried out between July 1, 2019 and June 30, 2022 at 7 medical institutions in Japan. The study population will be recruited from among neonates, infants, or children aged 24 months or younger with a condition falling under any of the following 5 disease groups: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. The planned sample size is 18 subjects, including at least 3 subjects per disease group. Throughout the RSV season, at least 4 continuous doses of palivizumab will be administered intramuscularly at 15 mg/kg at intervals of 30 days. The efficacy and safety of palivizumab will be comprehensively evaluated based on the incidence of RSV-related hospitalization, and serum palivizumab concentration, serum anti-palivizumab antibody concentration, and the occurrence of adverse events/reactions after the start of palivizumab treatment. DISCUSSION: This study will evaluate the efficacy and safety of palivizumab in pediatric patients with rare diseases which place them at high risk of severe RSV infection, but which fall outside the current indications for palivizumab prophylaxis. The generated data will have implications for the regulatory approval of prophylactic palivizumab treatment in this patient group. TRIAL REGISTRATION: This study has been prospectively registered in Japic Clinical Trials Information, which is managed and administered by the Japan Pharmaceutical Information Center (registration number: JapicCTI-194946 , registration date: September 10, 2019).

Positive association of breastfeeding on respiratory syncytial virus infection in hospitalized infants: a multicenter retrospective study.

BACKGROUND: Breastfeeding reportedly reduces the overall frequency of infections. Respiratory syncytial virus (RSV), the most common respiratory pathogen in infants, involves recurrent wheezing and has a pathogenic mechanism related to airway structural damage. PURPOSE: This study aimed to investigate whether breastfeeding has a beneficial effect against RSV-induced respiratory infection compared to formula feeding among infants in Korea. METHODS: We retrospectively reviewed the medical records of infants under 1 year of age who were admitted with RSV infection between January 2016 and February 2018 at the department of pediatrics of 4 hospitals. We investigated the differences in clinical parameters such as cyanosis, chest retraction, combined infection, fever duration, oxygen use, oxygen therapy duration, intensive care unit (ICU) admission, and corticosteroid treatment of exclusive breast milk feeding (BMF), artificial milk formula fed (AMF), and mixed feeding (MF) groups. RESULTS: Among the 411 infants included in our study, 94, 161, and 156 were included in the BMF, MF, and AMF groups, respectively. The rates of oxygen therapy were significantly different among the BMF (4.3%), MF (8.1%), and AMF (13.5 %) groups (P=0.042). The odds ratios (ORs) for oxygen therapy was significantly higher in the AMF group than in the BMF group (adjusted OR, 3.807; 95% confidence interval, 1.22-11.90; P=0.021). The ICU admission rate of the BMF group (1.1%) was lower than that of the MF (3.5%) and AMF (4.5%) groups; however, the dissimilarity was not statistically significant (P=0.338). CONCLUSION: The severity of RSV infection requiring oxygen therapy was lower in the BMF than the AMF group. This protective role of human milk on RSV infection might decrease the need for oxygen therapy suggesting less airway damage.

Developing and Testing a Real-Time Polymerase Chain Reaction to Identify and Quantify Bovine Respiratory Syncytial Viruses.

The bovine respiratory syncytial virus (BRSV) known as Bovine orthopneumovirus according to the international classification is one of the most important etiological agents of respiratory diseases in calves. At present, rapid and reliable methods to detect and measure the concentrations of this pathogen are needed. The objectives of the survey are developing the real-time polymerase chain reaction (PCR) to identify and quantify the BRSV RNA and, based on it, determining the number of the virus genomes in the respiratory tract of sick animals during the disease outbreaks. The nucleocapsid (N) protein gene of the virus served as the target for amplification. Messenger RNA (mRNA) of bovine GAPDH was used as a reference gene. A panel of positive control samples at known concentrations was used to estimate the virus and GAPDH numbers. The concentration of viral RNA extracted from the biomaterial samples was quantified relative to the bovine GAPDH mRNA level. The analytical sensitivity of PCR demonstrating high specificity and reproducibility was 1 × 103 genome equivalents per 1 cm3. All 273 samples of biological material taken from the animals with the respiratory diseases were analyzed. The virus genome was detected in 19.4% of samples. The viral RNA was more frequently detected in the lungs, which comprised 10.61% of positive samples. It was less frequently found in the mucous membranes of trachea and bronchi and the lymph nodes of the lungs, which comprised 0.73% of positive samples each. Concentrations of the virus in samples varied. The highest concentration was recorded in the lungs (1.3 ± 0.5-4.8 ± 0.47 log10 copies of BRSV/GAPDH RNA). The developed test kit may be used to quantify the concentration of the bovine respiratory syncytial virus in disease pathogenesis and to estimate the efficiency of vaccine or antivirus preparations for animals.

Healthcare resource utilization and costs in the 12 months following hospitalization for respiratory syncytial virus or unspecified bronchiolitis among infants.

Aims: To examine healthcare resource utilization (HRU) and costs within 12 months after hospitalization for respiratory syncytial virus (RSVH) or unspecified bronchiolitis (UBH) in infants.Materials and methods: Infants born July 1, 2009-June 30, 2015 were identified in the MarketScan Medicaid and Commercial databases and were assigned to one of three cohorts: RSVH (with/without UBH), UBH, or comparator (no RSVH or UBH). Each infant was identified as pre-term (5 groups) or term (2 groups) based on weeks gestational age (wGA). Index dates were the first admission dates for RSVH or UBH infants and were randomly assigned to comparator infants based on time from birth to index in the RSVH cohort. HRU, all-cause costs, and incremental cost differences between hospitalized and comparator infants were assessed over 12 months post-index with and without the index hospitalization. Results were propensity score weighted to balance pre-index characteristics across hospitalization cohorts.Results: This study identified 15,872 RSVH infants, 6,081 UBH infants, and 986,087 comparator infants in the Medicaid population and 5,755 RSVH infants, 1,888 UBH infants, and 696,302 comparator infants in the commercial population. HRU in follow-up was greater for RSVH and UBH infants relative to comparator infants in both populations, including hospitalizations (commercial: 7.4%, 11.0%, 1.7%; Medicaid: 12.3%, 15.3%, 3.2%) and emergency department visits (commercial: 33.0%, 33.3%, 17.2%; Medicaid: 65.8%, 68.5%, 51.4%). HRU was highest among RSVH and UBH infants born at <29 wGA. Hospitalized infants had numerically higher follow-up costs than comparator infants, with incremental differences reaching $19,896 among Medicaid UBH infants and $37,417 among commercial RSVH infants.Limitations: RSV/UB may be miscoded in claims data.Conclusions: Infants hospitalized for RSV or UB largely had greater subsequent HRU and costs in the first year after index hospitalization than comparator infants. Absolute and incremental follow-up costs relative to comparator infants were highest among infants <29 wGA.

Detection of the Onset of the Epidemic Period of Respiratory Syncytial Virus Infection in Japan.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide. An annual epidemic of RSV infection generally begins around autumn, reaching a peak at the end of year in Japan, but in 2017 it started in early July and peaked in September. As the onset timing of RSV season varies, it is important to detect the beginning of an epidemic, to enable the implementation of preventive measures. However, there are currently no specified criteria or methods to determine the onset of RSV season in a timely manner. Therefore, we developed a model to detect the epidemic onset, based on data from the Infectious Diseases Weekly Report from 2012 to 2017. The 47 prefectures of Japan span 11 climate zones, which affect the timing of epidemic onset. Therefore, the onset of RSV season was assessed separately in each prefecture. Non-linear regression analysis was performed to generate a mathematical model of the annual epidemic cycle for each prefecture. A search index was used to determine the onset of RSV season, which was estimated using the number of RSV reports per week within an epidemic period (RSV-reports/w) and the number of reported cases included within an epidemic period relative to the total number of RSV reports (capture rate). A number of RSV-reports/w, which was used as a threshold (a number at onset line) to determine the condition of the onset of RSV season, was then estimated based on the search index. The mean number at the onset of RSV season for 47 prefectures was 29.7 reports/week (median 21.0, range 6.0-121.0 reports/ week). The model also showed that the onset of RSV season in 2017 was more than 1 month earlier than the previous year. In conclusion, the model detected epidemic cycles and their onset conditions in all prefectures, despite the 11 climate zones of Japan. The results are expected to contribute to infant medical care by allowing medical personnel to take preventive measures promptly at the beginning of the epidemic RSV season.

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice.

Rhein is one of active anthraquinone components in traditional Chinese herbal medicine Rheum palmatum L., possessing anti-inflammatory, antioxidant, antitumor, antiviral, and hepatoprotective activities. Human respiratory syncytial virus (RSV), a common virus, is able to result in pneumonia and bronchitis, which usually can be seen in infants. However, so far the effects of Rhein on RSV-induced pneumonia are still unknown. As the NLRP3 inflammasome is activated excessively, it is able to lead to inflammatory response and tissue injury in most viral infection process (including RSV infection) of respiratory tract. Therefore, we designed experiments to reveal whether Rhein can treat RSV-induced pneumonia by inhibiting NLRP3 inflammasome activation. In present research, we established the pneumonia model of BALB/C mice caused by RSV. First of all, the pathology of lung tissue and the weight of mice were evaluated, and the corresponding lung index was calculated. Additionally, the expression of pro-inflammatory mediators in serum and lung tissues, and related proteins (NLRP3, ASC and Caspase-1) of NLRP3 inflammasome and NF-κB pathway were detected by Enzyme-linked immunosorbent assay (ELISA), Real-time PCR (RT-PCR), Immunohistochemistry (IHC), and Western blot (WB), respectively. The determination of lung index and lung tissue pathological evaluation revealed that Rhein was able to alleviate lung infection and injury caused by RSV. The results of ELISA showed that Rhein was able to reduce the release of pro-inflammatory cytokines in the serum and lung tissues of RSV-induced BALB/c mice, including IL-1ß, IL-6, TNF-α, IL-18, and IL-33. Additionally, it was revealed that Rhein inhibited the immune inflammatory response of RSV-infected mice, which was likely to be associated with the inhibition the NLRP3 inflammasome activation via NF-κB pathway. To sum up, our results indicated that Rhein may inhibit RSV-induced pulmonary inflammatory response effectively; meanwhile, it is emphasized that Rhein therapy is likely to be a promising treatment on the RSV-infected lung inflammation and avoidance of lung tissue damage.

A new view of treatment for bronchiolitis / 中国实用儿科杂志

Bronchiolitis is a common lower respiratory tract infection in infants and young children, mostly caused by respiratory syncytial virus. At present, the treatment mainly includes oxygen therapy, control of wheezing, maintenance of internal environment stability and so on. Most cases of bronchiolitis still lack specific antimicrobial agents. To explore a new treatment method for bronchiolitis is helpful to improve the symptoms, shorten hospitalization days,and improve the prognosis of children with moderate to severe bronchiolitis, especially those younger than 6 months with high risk factors.

Respiratory syncytial virus hospitalization and incurred morbidities the season after prophylaxis.

OBJECTIVES: The primary objective of this study was to determine the incidence and incurred morbidities of Respiratory syncytial virus (RSV)-related hospitalization (RSVH), the season following completion of prophylaxis. METHODS: A retrospective study was conducted of all infants enrolled in a prophylaxis clinic in one institution during the 2009 to 2014 RSV seasons. RSV infection was identified by Diseases codes and confirmed by RSV-positivity. Data were classified into five groups based on indications for prophylaxis. The incidence of RSVH was calculated. For each subgroup, differences in characteristics between children with and without RSVH were analyzed by independent t test or chi-square test. RESULTS: During five RSV seasons, 827 infants were enrolled. RSVH incidence the season following prophylaxis was 2.1% (n=17/827). Children with chronic lung disease (CLD) had the highest RSVH incidence (7.7%; n=4/52) followed by preterms 33 to 35 weeks gestation (2.5%; n=4/162), those with complex medical disorders (2.2%; n=3/135), those with congenital heart disease (1.5%; n=1/66) and preterms less than or equal to 32 weeks gestation (1.2%; n=5/412). There was no statistically significant association between indications for prophylaxis and RSVH (Fisher exact test, P=0.060). The odds of RSVH were 4.9 times greater (odds ratio [OR]=4.9; 95% CI: 1.53, 15.55; P=0.007) in CLD compared to those without CLD. The median length of RSVH stay was 4 days; 58.8% (n=10/17) required oxygen (median 1 day); 29.4% (n=5/17) required intensive care. CONCLUSIONS: Infants with CLD are at highest risk for RSVH in the season postprophylaxis and may merit palivizumab for more than two seasons dependent on disease severity. However, larger prospective studies are necessary to confirm the findings before embarking on a strategy of providing prophylaxis for a third RSV season.

Decreased microRNA-140-5p contributes to respiratory syncytial virus disease through targeting Toll-like receptor 4.

The abnormal expression of miRNAs (miRs) has previously been reported in respiratory syncytial virus (RSV) disease. However, to the best of our knowledge, the expression of miR-140-5p in patients with an RSV infection has never been explored. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the level of miR-140-5p in the blood and nasopharyngeal airway samples. ELISAs were performed to determine the levels of tumor necrosis factor α, interleukin (IL)-1ß, IL-6 and IL-8. A dual luciferase reporter assay was also performed to investigate the possible target gene of miR-140-5p. The results demonstrated that the levels of miR-140-5p were significantly decreased in the nasal mucosal and peripheral blood samples of patients with RSV infection. It was also revealed that overexpression of miR-140-5p decreased the inflammatory responses, while inhibition of miR-140-5p enhanced the inflammatory responses. Additionally, three binding sites of miR-140-5p in the 3untranslated region (UTR) of Toll-like receptor (TLR)4 were identified and a dual luciferase reporter assay demonstrated that miR-140-5p significantly suppressed the relative luciferase activity of pmirGLO-TLR4-3UTR. Furthermore, the level of miR-140-5p was shown to be increased following interferon (IFN)α incubation. Notably, inhibition of miR-140-5p markedly attenuated IFNα-mediated downregulation of tumor necrosis factor α, and interleukin-1ß, -6 and -8 in BEAS-2B cells. In summary, decreased miR-140-5p levels are involved in RSV-infection diseases primarily through targeting TLR4.

Efficacy of palivizumab prophylaxis on the frequency of RSV-associated lower respiratory tract infections in preterm infants: determination of the ideal target population for prophylaxis.

Respiratory syncytial virus (RSV) prophylaxis in high-risk infants is an effective intervention for the prevention of severe disease. The aim of this study was to determine the ideal target preterm population that might benefit from palivizumab prophylaxis by establishing the main risk factors for acute RSV-related infections. Former premature infants born with a gestational age ≤37 weeks and ≤1 year of age at the beginning of the RSV season and admitted with respiratory infection were included. RSV status was evaluated by RSV strip test in all infants. RSV-positive and -negative infants were compared in terms of demographic features, risk factors, requirement of hospitalisation and palivizumab administration. A total of 202 preterm infants under 1 year of age were enrolled. The RSV test was positive in 34 (16.8%) infants. Maternal age was significantly lower in RSV-positive infants compared with RSV-negative infants (p = 0.03). RSV-positive infants were found to be significantly discharged during the RSV season (p = 0.03). RSV-positive infants required significantly higher rates of hospitalisation and need for mechanical ventilation. Of the RSV-positive infants, 28 (82%) had a gestational age ≥29 weeks. Seventeen (77%) RSV-positive infants that required hospitalisation were ≥29 weeks of gestation. All infants with a gestational age ≥29 weeks and without palivizumab prophylaxis developed RSV infection. Palivizumab prophylaxis should be implemented into guidelines to cover preterm infants with a gestational age >29 weeks. Palivizumab prophylaxis should also be considered in high-risk infants ≤6 months of age during the RSV season.