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Pathogens
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The Changing Landscape of Respiratory Syncytial Virus Infections
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The Changing Landscape of Respiratory Syncytial Virus Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (20 June 2023) | Viewed by 23755

Special Issue Editors

Dr. Reinout A. Bem

E-Mail Website
Guest Editor
Pediatric Intensive Care Unit, Emma Children’s Hospital, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands
Interests: pediatric critical care; bronchiolitis; respiratory syncytial virus; acute lung injury/ARDS; respiratory support
Prof. Dr. Job B.M. van Woensel

E-Mail Website
Guest Editor
Pediatric Intensive Care Unit, Emma Children’s Hospital, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands
Interests: pediatric critical care; transitional care; respiratory syncytial virus; acute lung injury/ARDS; long-term outcome

Special Issue Information

Dear Colleagues,

Respiratory syncytial virus (RSV), a negative-sense, enveloped RNA virus of the family Paramyxoviridae, subfamily Pneumovirinae, and genus Pneumovirus, is the single most important respiratory pathogen in young children. Worldwide, RSV causes major morbidity and mortality in infants below the age of two years. In high-income countries, community outbreaks of RSV are responsible for a high burden on pediatric critical care resources. However, RSV-related disease is not limited to childhood, as humoral immunity wanes over time, and re-infection in humans occurs frequently. For example, elderly and critically ill adults are susceptible to severe RSV-related lower respiratory tract infection or exacerbation of chronic lung disease. Nonetheless, the clinical entity of small airway disease, or bronchiolitis, as observed in infants remains a prototypical pediatric disease.

Currently, there are several circumstances that cause high uncertainty regarding the future burden of RSV disease. First, the current global mitigation strategies to decrease the risk of SARS-CoV-2 spread have seriously impacted RSV transmission and reduced (seasonal) outbreaks in both children and adults. With the easing of national lockdowns and personal protective measures, the patterns of RSV outbreaks will be highly unpredictable in the coming years. Second, preventive strategies using a formalin-inactivated virus (in the 1960s) or repeated passive immunization with monoclonal antibodies (e.g., palivizumab) have so far been met with limited success. However, the recent development of a recombinant extended half-life monoclonal antibody (nirsevimab), binding to the prefusion conformation of the RSV fusion protein, is highly promising with regard to reducing the severity of disease, at least in high-risk preterm infants. This may prove to be a major success in preventing disease burden in the future for various patient groups. Third, oxygen and respiratory support for hospitalized children with bronchiolitis has changed much with the widespread introduction of various non-invasive support modalities such as high flow nasal cannula. Such changes in practice may impact the burden of RSV for hospitals and critical care resources. Importantly, most of these advances in the prevention and treatment strategies for RSV thus far are mainly applicable to high-income countries. As the vast majority of the children in whom RSV is fatal live in low- and moderate-income regions, there is much to gain in making such interventions also available in these areas to address the global burden of RSV.

In conclusion, there is a changing landscape in the care for patients with RSV-related disease. Increasing our understanding of this changing landscape and how it affects healthcare systems and research on (age-related) pathophysiology of RSV around the world is fundamental. We would therefore like to invite colleagues investigating RSV within the areas of epidemiology, both public and critical healthcare, and vaccine development, respiratory management, but also (age-related) immunology and transmission, to submit their manuscripts to this Special Issue in the form of original research and reviews.

Dr. Reinout A. Bem
Prof. Dr. Job B.M. van Woensel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bronchiolitis
  • respiratory syncytial virus
  • respiratory support
  • children
  • adults
  • critical care
  • viral respiratory infections
  • vaccine
  • global health

Published Papers (8 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 178 KiB  
Editorial
The Changing Landscape of Respiratory Syncytial Virus Infections
by Reinout A. Bem and Job B. M. van Woensel
Pathogens 2023, 12(10), 1196; https://doi.org/10.3390/pathogens12101196 - 26 Sep 2023
Viewed by 638
Abstract
Respiratory syncytial virus (RSV), a negative-sense, enveloped RNA virus of the family Paramyxoviridae, subfamily Pneumovirinae, and genus Pneumovirus, is the single most important respiratory pathogen affecting infants and young children [...] Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)

Research

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16 pages, 630 KiB  
Article
Respiratory Syncytial Virus-Specific Antibodies and Atopic Diseases in Children: A 10-Year Follow-Up
by Helena Tesari Crnković, Krešo Bendelja, Vlado Drkulec, Romana Gjergja Juraški and Mirjana Turkalj
Pathogens 2023, 12(4), 546; https://doi.org/10.3390/pathogens12040546 - 01 Apr 2023
Cited by 1 | Viewed by 1427
Abstract
Background: Respiratory syncytial virus (RSV) stimulates the production of specific immunoglobulin (Ig) E and IgG4 antibodies as a hallmark of the Th2 immune response. In this paper, we evaluated the occurrence of atopic diseases in 10-year-old children who were positive for RSV-specific IgG [...] Read more.
Background: Respiratory syncytial virus (RSV) stimulates the production of specific immunoglobulin (Ig) E and IgG4 antibodies as a hallmark of the Th2 immune response. In this paper, we evaluated the occurrence of atopic diseases in 10-year-old children who were positive for RSV-specific IgG antibodies during infancy. Methods: The prospective follow-up of 72 children included a physical examination, an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the determination of RSV-specific antibodies and total and allergen-specific IgE. Results: Children with asthma had their first wheezing episode at a younger age (χ2 8.097, df = 1, p = 0.004). RSV-specific IgG4 levels at year one were positively correlated with atopic dermatitis (AD) (tau_b = 0.211, p = 0.049) and current AD (tau_b = 0.269, p = 0.012); and RSV-specific IgE levels were positively correlated with allergic rhinitis (AR) (tau_b = 0.290, p = 0.012) and current AR (tau_b = 0.260, p = 0.025). Positive RSV-specific IgE at the age of one increased the chances of asthma occurrence by 5.94 (OR = 5.94, 95% CI = 1.05–33.64; p = 0.044) and the chances of AR by more than 15 times (OR = 15.03, 95% CI = 2.08–108.72; p = 0.007). A positive family history of atopy increased the chances of asthma occurrence by 5.49 times (OR = 5.49, 95% CI = 1.01–30.07; p = 0.049), and a longer duration of exclusive breastfeeding lowered that chance (OR = 0.63, 95% CI = 0.45–0.89; p = 0.008). Prenatal smoking increased the chances of AR occurrence by 7.63 times (OR = 7.63, 95% CI = 1.59–36.53; p = 0.011). Conclusion: RSV-specific IgE and RSV-specific IgG4 antibodies could be risk markers for the development of atopic diseases in children. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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13 pages, 1938 KiB  
Article
Identifying Cross-Utilization of RSV Vaccine Inventions across the Human and Veterinary Field
by Marga Janse, Swasti D. Soekhradj, Rineke de Jong and Linda H. M. van de Burgwal
Pathogens 2023, 12(1), 46; https://doi.org/10.3390/pathogens12010046 - 27 Dec 2022
Cited by 2 | Viewed by 1778
Abstract
The respiratory syncytial virus (RSV) has two main variants with similar impact, a human and a bovine variant. The human respiratory syncytial virus (HRSV) is the most frequent cause of acute respiratory disease (pneumonia) in children, leading to hospitalization and causing premature death. [...] Read more.
The respiratory syncytial virus (RSV) has two main variants with similar impact, a human and a bovine variant. The human respiratory syncytial virus (HRSV) is the most frequent cause of acute respiratory disease (pneumonia) in children, leading to hospitalization and causing premature death. In Europe, lower respiratory tract infections caused by HRSV are responsible for 42–45 percent of hospital admissions in children under two. Likewise, the bovine respiratory syncytial virus (BRSV) is a significant cause of acute viral broncho-pneumonia in calves. To date no licensed HRSV vaccine has been developed, despite the high burden of the disease. In contrast, BRSV vaccines have been on the market since the 1970s, but there is still an articulated unmet need for improved BRSV vaccines with greater efficacy. HRSV/BRSV vaccine development was chosen as a case to assess whether collaboration and knowledge-sharing between human and veterinary fields is taking place, benefiting the development of new vaccines in both fields. The genetic relatedness, comparable pathogeneses, and similar severity of the diseases suggests much can be gained by sharing knowledge and experiences between the human and veterinary fields. We analyzed patent data, as most of pharmaceutical inventions, such as the development of vaccines, are protected by patents. Our results show only little cross-utilization of inventions and no collaborations, as in shared IP as an exchange of knowledge. This suggests that, despite the similarities in the genetics and antigenicity of HRSV and BRSV, each fields follows its own process in developing new vaccines. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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13 pages, 3612 KiB  
Article
Long-Term Pulmonary Dysfunction by Hyperoxia Exposure during Severe Viral Lower Respiratory Tract Infection in Mice
by Thijs A. Lilien, Miša Gunjak, Despoina Myti, Francisco Casado, Job B. M. van Woensel, Rory E. Morty and Reinout A. Bem
Pathogens 2022, 11(11), 1334; https://doi.org/10.3390/pathogens11111334 - 12 Nov 2022
Cited by 1 | Viewed by 1241
Abstract
Viral-induced lower respiratory tract infection (LRTI), mainly by respiratory syncytial virus (RSV), causes a major health burden among young children and has been associated with long-term respiratory dysfunction. Children with severe viral LRTI are frequently treated with oxygen therapy, hypothetically posing an additional [...] Read more.
Viral-induced lower respiratory tract infection (LRTI), mainly by respiratory syncytial virus (RSV), causes a major health burden among young children and has been associated with long-term respiratory dysfunction. Children with severe viral LRTI are frequently treated with oxygen therapy, hypothetically posing an additional risk factor for pulmonary sequelae. The main goal of this study was to determine the effect of concurrent hyperoxia exposure during the acute phase of viral LRTI on long-term pulmonary outcome. As an experimental model for severe RSV LRTI in infants, C57Bl/6J mice received an intranasal inoculation with the pneumonia virus of mice J3666 strain at post-natal day 7, and were subsequently exposed to hyperoxia (85% O2) or normoxia (21% O2) from post-natal day 10 to 17 during the acute phase of disease. Long-term outcomes, including lung function and structural development, were assessed 3 weeks post-inoculation at post-natal day 28. Compared to normoxic conditions, hyperoxia exposure in PVM-inoculated mice induced a transient growth arrest without subsequent catchup growth, as well as a long-term increase in airway resistance. This hyperoxia-induced pulmonary dysfunction was not associated with developmental changes to the airway or lung structure. These findings suggest that hyperoxia exposure during viral LRTI at young age may aggravate subsequent long-term pulmonary sequelae. Further research is needed to investigate the specific mechanisms underlying this alteration to pulmonary function. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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23 pages, 4925 KiB  
Article
Differential Expression of Mitosis and Cell Cycle Regulatory Genes during Recovery from an Acute Respiratory Virus Infection
by Ajinkya R. Limkar, Justin B. Lack, Albert C. Sek, Caroline M. Percopo, Kirk M. Druey and Helene F. Rosenberg
Pathogens 2021, 10(12), 1625; https://doi.org/10.3390/pathogens10121625 - 15 Dec 2021
Cited by 3 | Viewed by 3024
Abstract
Acute respiratory virus infections can have profound and long-term effects on lung function that persist even after the acute responses have fully resolved. In this study, we examined gene expression by RNA sequencing in the lung tissue of wild-type BALB/c mice that were [...] Read more.
Acute respiratory virus infections can have profound and long-term effects on lung function that persist even after the acute responses have fully resolved. In this study, we examined gene expression by RNA sequencing in the lung tissue of wild-type BALB/c mice that were recovering from a sublethal infection with the pneumonia virus of mice (PVM), a natural rodent pathogen of the same virus family and genus as the human respiratory syncytial virus. We compared these responses to gene expression in PVM-infected mice treated with Lactobacillus plantarum, an immunobiotic agent that limits inflammation and averts the negative clinical sequelae typically observed in response to acute infection with this pathogen. Our findings revealed prominent differential expression of inflammation-associated genes as well as numerous genes and gene families implicated in mitosis and cell-cycle regulation, including cyclins, cyclin-dependent kinases, cell division cycle genes, E2F transcription factors, kinesins, centromere proteins, and aurora kinases, among others. Of particular note was the differential expression of the cell division cycle gene Cdc20b, which was previously identified as critical for the ex vivo differentiation of multi-ciliated cells. Collectively, these findings provided us with substantial insight into post-viral repair processes and broadened our understanding of the mechanisms underlying Lactobacillus-mediated protection. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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Review

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17 pages, 904 KiB  
Review
Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)
by Dvir Gatt, Isaac Martin, Rawan AlFouzan and Theo J. Moraes
Pathogens 2023, 12(2), 154; https://doi.org/10.3390/pathogens12020154 - 17 Jan 2023
Cited by 16 | Viewed by 10387
Abstract
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. Despite its global impact on healthcare, related to its high prevalence and its association with significant morbidity, the current therapy is still mostly supportive. Moreover, [...] Read more.
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. Despite its global impact on healthcare, related to its high prevalence and its association with significant morbidity, the current therapy is still mostly supportive. Moreover, while more than 50 years have passed since the first trial of an RSV vaccine (which unfortunately caused enhanced RSV disease), no vaccine has been approved for RSV prevention. In the last two decades, our understanding of the pathogenesis and immunopathology of RSV have continued to evolve, leading to significant advancements in RSV prevention strategies. These include both the development of new potential vaccines and the successful implementation of passive immunization, which, together, will provide coverage from infancy to old age. In this review, we provide an update of the current treatment options for acute disease (RSV-specific and -non-specific) and different therapeutic approaches focusing on RSV prevention. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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6 pages, 218 KiB  
Review
Going Viral—RSV as the Neglected Adult Respiratory Virus
by Bethany Busack and Andrew F. Shorr
Pathogens 2022, 11(11), 1324; https://doi.org/10.3390/pathogens11111324 - 11 Nov 2022
Cited by 14 | Viewed by 2972
Abstract
Human respiratory syncytial virus (RSV) is increasingly recognized as a significant viral pathogen in adults with acute respiratory illness, particularly in the elderly, the immunocompromised, and those with underlying cardiopulmonary disease. Although long acknowledged as one of the most common causes of upper [...] Read more.
Human respiratory syncytial virus (RSV) is increasingly recognized as a significant viral pathogen in adults with acute respiratory illness, particularly in the elderly, the immunocompromised, and those with underlying cardiopulmonary disease. Although long acknowledged as one of the most common causes of upper respiratory tract infections (URI) in children since its discovery in 1956, the true burden of disease in adults is likely significantly under-recognized. The emerging evidence of RSV as a driver of morbidity and mortality in elderly and immunocompromised patients has sparked advances in vaccine development and renewed interest in quantifying the true burden of disease. This review attempts to summarize the findings of the most recent evidence investigating the burden of RSV related disease in adults and to highlight where future research is needed. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)

Other

8 pages, 889 KiB  
Brief Report
Lessons from SARS-CoV-2 Pandemics: How Restrictive Measures Impacted the Trend of Respiratory Infections in Neonates and Infants up to Three Months of Age
by Domenico Umberto De Rose, Stefano Caoci, Cinzia Auriti, Chiara Maddaloni, Irma Capolupo, Guglielmo Salvatori, Carla Brusco, Luana Coltella, Carlo Concato, Cristina Russo, Luna Colagrossi, Carlo Federico Perno, Annabella Braguglia, Alberto Villani, Andrea Dotta and Massimiliano Raponi
Pathogens 2022, 11(10), 1086; https://doi.org/10.3390/pathogens11101086 - 23 Sep 2022
Cited by 6 | Viewed by 1313
Abstract
(1) Background: Massive social efforts to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have affected the epidemiological features of respiratory infections. (2) Methods: The study aims to describe the trend of hospitalizations for bronchiolitis among newborns and [...] Read more.
(1) Background: Massive social efforts to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have affected the epidemiological features of respiratory infections. (2) Methods: The study aims to describe the trend of hospitalizations for bronchiolitis among newborns and infants up to three months of life in Rome (Italy), in the pre-COVID-19 era and during the pandemic. (3) Results: We observed a marked decrease in the number of neonates and infants with bronchiolitis after national lockdowns in 2020 and the first months of 2021 and a similar trend in the number of bronchiolitis caused by respiratory syncytial virus (RSV). RSV was the leading pathogen responsible for bronchiolitis before the national lockdown in March 2020 (70.0% of cases), while Rhinovirus was the leading pathogen responsible for bronchiolitis (62.5%) during the pandemic while strict restrictions were ongoing. As Italy approached the COVID-19 vaccination target, the national government lifted some COVID-19-related restrictions. A surprising rebound of bronchiolitis (particularly cases caused by RSV) was observed in October 2021. (4) Conclusions: In this study, we describe for the first time the fluctuations over time of RSV bronchiolitis among newborns and young infants in Italy in relation to the restrictive measures containing the spread of the COVID-19 pandemic. Our results are in line with other countries’ reports. Full article
(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)
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