Respiratory syncytial virus and airway microbiota -- A complex interplay and its reflection on morbidity

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

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Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽

10.3390/pathogens11010047 ◽

2021 ◽

Vol 11 (1) ◽

pp. 47

Author(s):

Catalina A. Andrade ◽

Alexis M. Kalergis ◽

Karen Bohmwald

Keyword(s):

Respiratory Syncytial Virus ◽

Viral Infections ◽

Respiratory Infections ◽

The Elderly ◽

Cell Types ◽

Potential Effect ◽

Viral Agent ◽

Pulmonary Manifestations ◽

Syncytial Virus ◽

Tract Infections

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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Respiratory Syncytial Virus Disease Severity in Young Children

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1612 ◽

2020 ◽

Author(s):

Zaid Haddadin ◽

Stockton Beveridge ◽

Kailee Fernandez ◽

Danielle A Rankin ◽

Varvara Probst ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Young Children ◽

Disease Severity ◽

Severity Score ◽

Respiratory Infections ◽

Virus Disease ◽

Younger Age ◽

Inpatient Settings ◽

Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children. Methods Children aged <5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children’s Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children. Results From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B. Conclusions RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children.

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Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

European Respiratory Journal ◽

10.1183/09031936.00085614 ◽

2014 ◽

Vol 45 (3) ◽

pp. 718-725 ◽

Cited By ~ 14

Author(s):

Corné H. van den Kieboom ◽

Inge M.L. Ahout ◽

Aldert Zomer ◽

Kim H. Brand ◽

Ronald de Groot ◽

...

Keyword(s):

Gene Expression ◽

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Pathogen Detection ◽

Severe Disease ◽

Host Gene ◽

Host Gene Expression ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.

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First Detection of Human Coronavirus HKU1 in Greece, in an Immunocompromised Patient With Severe Lower Respiratory Tract Infection

Acta medica Lituanica ◽

10.15388/amed.2021.28.1.21 ◽

2021 ◽

Vol 28 (1) ◽

pp. 21

Author(s):

Vasiliki Epameinondas Georgakopoulou ◽

Georgios Petsinis ◽

Konstantinos Mantzouranis ◽

Christos Damaskos ◽

Despoina Melemeni ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Respiratory Infections ◽

Severe Disease ◽

Respiratory Illness ◽

Human Coronavirus ◽

First Case ◽

Syncytial Virus ◽

Tract Infections

Human coronavirus HKU1 (HCoV-HKU1) is a RNA virus which gets in the human cells by binding to the receptor of N-acetyl-9-O-acetylneuraminic acid. Human Coronaviruses (HCoVs), including HCoV-HKU1, are globally found. HCoV-HKU1 is responsible for upper and lower respiratory tract infections, usually with mild symptoms. In severe cases, HCoV-HKU1 can cause life-threatening respiratory illness especially in vulnerable hosts such as elderly, children and immunocompromised patients. In Greece, Respiratory Syncytial Virus (RSV) and influenza are the most common viruses causing respiratory tract infections. Traditionally, HCoVs are responsible for less than 3% of respiratory infections in Greek population. HCoVs 229E and OC43 have been shown to circulate in Greece. We report the first case of lung infection in an immunocompromised woman due to HCoV-HKU1, that has never been before detected in Greece. HCoV-HKU1 is related to severe disease even in healthy individuals and must be considered in the differential diagnosis of severe respiratory infections.

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Association of Viral Load With Disease Severity in Outpatient Children With Respiratory Syncytial Virus Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa076 ◽

2020 ◽

Vol 222 (2) ◽

pp. 298-304 ◽

Cited By ~ 3

Author(s):

Erika Uusitupa ◽

Matti Waris ◽

Terho Heikkinen

Keyword(s):

Viral Load ◽

Respiratory Syncytial Virus ◽

Disease Severity ◽

Respiratory Infections ◽

Respiratory Illness ◽

Lower Viral Load ◽

Primary Analysis ◽

Rsv Infection ◽

Syncytial Virus ◽

Outpatient Children

Abstract Background There are scarce data on whether viral load affects the severity of respiratory syncytial virus (RSV) disease in outpatient children. Methods We analyzed the association between viral load and disease severity among children who participated in a prospective cohort study of respiratory infections. The children were examined and nasal swabs for the detection of RSV were obtained during each respiratory illness. Quantification of RSV load was based on the cycle threshold (Ct) value. For the primary analysis, the children were divided into 2 groups: higher (Ct < 27) and lower viral load (Ct ≥ 27). Results Among 201 episodes of RSV infection, children with higher viral load had significantly longer median durations of rhinitis (8 vs 6 days; P = .0008), cough (8 vs 6 days; P = .034), fever (2 vs 1 days; P = .018), and any symptom (10 vs 8 days; P = .024) than those with lower viral load. There were statistically significant negative correlations between the Ct values and durations of all measured symptoms. Conclusions Our findings support the concept that viral load drives the severity of RSV disease in children. Reducing the viral load by RSV antivirals might provide substantial benefits to outpatient children.

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Survey of WU and KI polyomaviruses, coronaviruses, respiratory syncytial virus and parechovirus in children under 5 years of age in Tehran, Iran

Iranian Journal of Microbiology ◽

10.18502/ijm.v12i2.2622 ◽

2020 ◽

Author(s):

Fahimeh Sadat Aghamirmohammadali ◽

Kaveh Sadeghi ◽

Nazanin Zahra Shafiei-Jandaghi ◽

Zahra Khoban ◽

Talat Mokhtari-Azad ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Infections ◽

Virus Detection ◽

Respiratory Viruses ◽

Hospitalized Children ◽

Acute Respiratory Infections ◽

Older Children ◽

Viral Pathogen ◽

Syncytial Virus ◽

Tract Infections

Background and Objectives: Severe acute respiratory infections (SARI) remain an important cause for childhood morbid- ity worldwide. We designed a research with the objective of finding the frequency of respiratory viruses, particularly WU and KI polyomaviruses (WUPyV & KIPyV), human coronaviruses (HCoVs), human respiratory syncytial virus (HRSV) and human parechovirus (HPeV) in hospitalized children who were influenza negative. Materials and Methods: Throat swabs were collected from children younger than 5 years who have been hospitalized for SARI and screened for WUPyV, KIPyV, HCoVs, HRSV and HPeV using Real time PCR. Results: A viral pathogen was identified in 23 (11.16%) of 206 hospitalized children with SARI. The rate of virus detection was considerably greater in infants <12 months (78.2%) than in older children (21.8%). The most frequently detected vi- ruses were HCoVs with 7.76% of positive cases followed by KIPyV (2%) and WUPyV (1.5%). No HPeV and HRSV were detected in this study. Conclusion: This research shown respiratory viruses as causes of childhood acute respiratory infections, while as most of mentioned viruses usually causes mild respiratory diseases, their frequency might be higher in outpatient children. Mean- while as HRSV is really sensitive to inactivation due to environmental situations and its genome maybe degraded, then for future studies, we need to use fresh samples for HRSV detection. These findings addressed a need for more studies on viral respiratory tract infections to help public health.

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Immune profiles provide insights into respiratory syncytial virus disease severity in young children

Science Translational Medicine ◽

10.1126/scitranslmed.aaw0268 ◽

2020 ◽

Vol 12 (540) ◽

pp. eaaw0268 ◽

Cited By ~ 7

Author(s):

Santtu Heinonen ◽

Victoria M. Velazquez ◽

Fang Ye ◽

Sara Mertz ◽

Santiago Acero-Bedoya ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Disease Severity ◽

Virus Disease ◽

Severe Disease ◽

Mild Disease ◽

Hla Dr ◽

Increased Risk ◽

Determining Factors ◽

Rsv Infection ◽

Syncytial Virus

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a “safe and protective” immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

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Immunological, Viral, Environmental, and Individual Factors Modulating Lung Immune Response to Respiratory Syncytial Virus

BioMed Research International ◽

10.1155/2015/875723 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Silvia Vandini ◽

Paolo Bottau ◽

Giacomo Faldella ◽

Marcello Lanari

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Animal Models ◽

Respiratory Tract Infections ◽

Clinical Course ◽

Respiratory Infections ◽

Syncytial Virus ◽

High Risk Infants ◽

Tract Infections ◽

Lung Response

Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. Several studies have been performed to investigate the immune response that determines the clinical course of the infection. In the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunological factors. These mechanisms have often been studied in animal models and in the present review we also summarize the main findings obtained from animal models as well as the limits of each of these models. Understanding the lung response involved in the pathogenesis of these respiratory infections could be useful in improving the preventive strategies against respiratory syncytial virus.

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Evaluation of Human Respiratory Syncytial Virus and Human Parainfluenza Virus Type 3 among Hospitalized Children in Northwest of Iran

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2021/2270307 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Zahra Ramezannia ◽

Javid Sadeghi ◽

Shahram Abdoli Oskouie ◽

Mohammad Ahangarzadeh Rezaee ◽

Hossein Bannazadeh Baghi ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Respiratory Infections ◽

Winter Season ◽

Human Respiratory Syncytial Virus ◽

Respiratory Pathogens ◽

Limited Information ◽

Syncytial Virus ◽

Tract Infections

Background. Acute respiratory tract infections (ARTIs) are the leading cause of illnesses in children. Human respiratory syncytial virus (HRSV) and human parainfluenza viruses (HPIVs) are among the most common etiologic agents associated with viral respiratory tract infections in children worldwide. Nevertheless, limited information is available on the spread of infections of these two viruses in northwest Iran. Objective. The purpose of the current study is to evaluate the frequency of RSV and HPIV-3 and clinical features among Iranian children with confirmed respiratory infections between April 2019 and March 2020. Methods. 100 nasopharyngeal swabs were collected from hospitalized patients (under 5 years old) with ARTI from Tabriz Children’s Hospital. Detection of respiratory viruses was performed using the nested RT-PCR method. Results. Respiratory syncytial virus and HPIV-3 were recognized in 18% (18/100) and 2% (2/100) of children, respectively. Ten (55.6%) of the RSV-positive samples were male, while 8 (44.4%) were female. HPIV‐3 was found only among 2 male patients (100%). Most patients (61.1%) with RSV infection were less than 12 months old. Additionally, samples that were positive for HPIV-3 were less than 12 months old. RSV infections had occurred mainly during the winter season. Conclusions. This study confirms that RSV can be one of the important respiratory pathogens in children in northwestern Iran. However, according to this study, HPIV-3 has a lower prevalence among children in this area than RSV. Therefore, implementing a routine diagnosis for respiratory pathogens can improve the management of respiratory infections in children.

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Prevalence of human respiratory syncytial virus, parainfluenza and adenoviruses in East Africa Community partner states of Kenya, Tanzania, and Uganda: A systematic review and meta-analysis (2007–2020)

PLoS ONE ◽

10.1371/journal.pone.0249992 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249992

Author(s):

Therese Umuhoza ◽

Wallace D. Bulimo ◽

Julius Oyugi ◽

Jean Pierre Musabyimana ◽

Alison A. Kinengyere ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

East Africa ◽

Subgroup Analysis ◽

Severe Disease ◽

Grey Literature ◽

Respiratory Viruses ◽

Community Partner ◽

Pooled Prevalence ◽

Syncytial Virus ◽

Tract Infections

Background Viruses are responsible for a large proportion of acute respiratory tract infections (ARTIs). Human influenza, parainfluenza, respiratory-syncytial-virus, and adenoviruses are among the leading cause of ARTIs. Epidemiological evidence of those respiratory viruses is limited in the East Africa Community (EAC) region. This review sought to identify the prevalence of respiratory syncytial virus, parainfluenza, and adenoviruses among cases of ARTI in the EAC from 2007 to 2020. Methods A literature search was conducted in Medline, Global Index Medicus, and the grey literature from public health institutions and programs in the EAC. Two independent reviewers performed data extraction. We used a random effects model to pool the prevalence estimate across studies. We assessed heterogeneity with the I2 statistic, and Cochran’s Q test, and further we did subgroup analysis. This review was registered with PROSPERO under registration number CRD42018110186. Results A total of 12 studies met the eligibility criteria for the studies documented from 2007 to 2020. The overall pooled prevalence of adenoviruses was 13% (95% confidence interval [CI]: 6–21, N = 28829), respiratory syncytial virus 11% (95% CI: 7–15, N = 22627), and parainfluenza was 9% (95% CI: 7–11, N = 28363). Pooled prevalence of reported ARTIs, all ages, and locality varied in the included studies. Studies among participants with severe acute respiratory disease had a higher pooled prevalence of all the three viruses. Considerable heterogeneity was noted overall and in subgroup analysis. Conclusion Our findings indicate that human adenoviruses, respiratory syncytial virus and parainfluenza virus are prevalent in Kenya, Tanzania, and Uganda. These three respiratory viruses contribute substantially to ARTIs in the EAC, particularly among those with severe disease and those aged five and above.

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