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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 31153

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Dr. Norbert J. Roberts, Jr.

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Guest Editor

Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
Interests: influenza virus; respiratory syncytial virus; viral pathogenesis; monocytes; macrophages; lymphocytes
Special Issues, Collections and Topics in MDPI journals

Dr. Leonard R. Krilov

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Guest Editor

NYU Long Island School of Medicine, Mineola, Long Island, NY, USA
Interests: respiratory syncytial virus; influenza virus; clinical trials; respiratory virus vaccines; RSV-related inflammation and immune responses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Respiratory syncytial virus (RSV) is a major cause of respiratory infections worldwide, with the most severe cases occurring in the very young and in elderly individuals. Infants and children having their first encounter with the virus are more likely to develop bronchiolitis and pneumonia, and even die. However, most deaths overall occur with infections of the elderly. In addition, immunocompromised individuals of any age are at greater risk of adverse outcomes.

RSV re-infection occurs throughout life, but subsequent infections are commonly less severe than the initial episode, as a result of the immune response that is established after exposure to the virus. However, the immune response is not able to prevent clinical re-infection even in the absence of RSV strain variation. This aspect makes it important to delineate as much as possible the immune response and correlates of protection, and it also suggests that RSV candidate vaccines that are being developed may not and perhaps should not be expected to prevent clinical re-infection. Such candidate vaccines should render a first infection in the young person less severe, as are subsequent infections after a natural first encounter in childhood. Such vaccines may also be expected to boost potentially waning immunity in the elderly, used at intervals to promote patient survival with the natural RSV infection.

The aim of this Special Issue of Viruses is to contribute to the current knowledge regarding innate and adaptive immunity to RSV, the mechanisms used by the virus to accomplish re-infection, the populations at risk and epidemiology of the infection, treatment approaches directed at RSV or designed to counteract the suppression of immune responses by RSV, and approaches to vaccine development that are likely to benefit the host upon subsequent natural challenge. Research articles, review articles, as well as short communications are invited. Reports of promising candidate RSV vaccines and reports of RSV co-infections (e.g., with SARS-CoV-2) are encouraged.

Submitted manuscripts should not have been published previously and should not be under consideration for publication elsewhere. All manuscripts undergo a single-blind peer-review process. Papers belonging to a Special Issue are published online in Viruses immediately after acceptance and are collected together on the Special Issue webpage. This means that there is no delay for authors who submit their work. Papers will appear shortly after acceptance, even if other papers in the Special Issue are still being processed. The Article Processing Charge for publication in this open-access journal, Viruses (IF 5.048), is CHF 2000 (Swiss Francs).

Dr. Norbert J. Roberts, Jr.
Dr. Leonard R. Krilov
Guest Editors

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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. Viruses 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 2600 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

Respiratory syncytial virus
RSV pathogenesis
Innate immunity to RSV
Adaptive immunity to RSV
RSV re-infection
RSV therapy
RSV vaccines
RSV epidemiology
RSV co-infections

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Respiratory Syncytial Virus in Viruses (5 articles)

Published Papers (11 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 166 KiB

Open AccessEditorial

Respiratory Syncytial Virus (RSV) Update

by Leonard R. Krilov and Norbert J. Roberts, Jr.

Viruses 2022, 14(10), 2110; https://doi.org/10.3390/v14102110 - 23 Sep 2022

Cited by 8 | Viewed by 3054

Abstract

Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV infections [...] Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

Research

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13 pages, 3001 KiB

Open AccessArticle

Changes in HRSV Epidemiology but Not Circulating Variants in Hospitalized Children due to the Emergence of SARS-CoV-2

by Monika Jevšnik Virant, Manca Luštrek, Rok Kogoj, Miroslav Petrovec and Tina Uršič

Viruses 2023, 15(6), 1218; https://doi.org/10.3390/v15061218 - 23 May 2023

Cited by 2 | Viewed by 1490

Abstract

This study assesses the circulation of human respiratory syncytial virus (HRSV) genotypes before, during, and toward the end of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in children and determines the influence of the pandemic on HRSV circulation patterns and evolution. Phylogenetic analysis of the hypervariable glycoprotein G gene was performed on 221/261 (84.7%) HRSV-positive samples and shows two separated clusters, one belonging to HRSV-A (129/221) and another to HRSV-B (92/221). All Slovenian HRSV-A strains contained the 72-nucleotide-long duplicated region in the attachment glycoprotein G gene and were classified as lineage GA2.3.5. All Slovenian HRSV-B strains similarly contained a 60-nucleotide-long duplicated region in the attachment glycoprotein G gene and were classified as lineage GB5.0.5a. During the 3-year period (2018–2021) covered by the study, no significant differences were observed within strains detected before the SARS-CoV-2 pandemic, during it, and after the implementation of nonpharmaceutical preventive measures. Slovenian HRSV-A strains seem to be more diverse than HRSV-B strains. Therefore, further whole-genome investigations would be required for better monitoring of the long-term impact of SARS-CoV-2 endemic circulation and the formation of new HRSV lineages and epidemiological patterns. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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20 pages, 5732 KiB

Open AccessArticle

A Multimodal Imaging-Supported Down Syndrome Mouse Model of RSV Infection

by Birger Tielemans, Lander De Herdt, Emilie Pollenus, Emiel Vanhulle, Laura Seldeslachts, Fopke Marain, Flore Belmans, Kaveh Ahookhosh, Jeroen Vanoirbeek, Kurt Vermeire, Philippe E. Van den Steen and Greetje Vande Velde

Viruses 2023, 15(4), 993; https://doi.org/10.3390/v15040993 - 18 Apr 2023

Viewed by 2392

Abstract

Individuals with Down syndrome (DS) are more prone to develop severe respiratory tract infections. Although a RSV infection has a high clinical impact and severe outcome in individuals with DS, no vaccine nor effective therapeutics are available. Any research into infection pathophysiology or prophylactic and therapeutic antiviral strategies in the specific context of DS would greatly benefit this patient population, but currently such relevant animal models are lacking. This study aimed to develop and characterize the first mouse model of RSV infection in a DS-specific context. Ts65Dn mice and wild type littermates were inoculated with a bioluminescence imaging-enabled recombinant human RSV to longitudinally track viral replication in host cells throughout infection progression. This resulted in an active infection in the upper airways and lungs with similar viral load in Ts65Dn mice and euploid mice. Flow cytometric analysis of leukocytes in lungs and spleen demonstrated immune alterations with lower CD8+ T cells and B-cells in Ts65Dn mice. Overall, our study presents a novel DS-specific mouse model of hRSV infection and shows that potential in using the Ts65Dn preclinical model to study immune-specific responses of RSV in the context of DS and supports the need for models representing the pathological development. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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18 pages, 3126 KiB

Open AccessArticle

In-Depth Analysis of the Re-Emergence of Respiratory Syncytial Virus at a Tertiary Care Hospital in Germany in the Summer of 2021 after the Alleviation of Non-Pharmaceutical Interventions Due to the SARS-CoV-2 Pandemic

by Mario Hönemann, Stephanie Thiem, Sandra Bergs, Tom Berthold, Christian Propach, Manuela Siekmeyer, Armin Frille, Tillmann Wallborn, Melanie Maier and Corinna Pietsch

Viruses 2023, 15(4), 877; https://doi.org/10.3390/v15040877 - 29 Mar 2023

Cited by 11 | Viewed by 2458

Abstract

Following the extensive non-pharmaceutical interventions (NPIs) and behavioral changes in the wake of the SARS-CoV-2 pandemic, an interseasonal rise in respiratory syncytial virus (RSV) cases was observed in Germany in 2021. The aim of this study was to characterize the local molecular epidemiology of RSV infections in comparison to the three pre-pandemic seasons. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of RSV infections. RSV detections peaked in calendar week 40 of 2021, 18 weeks earlier than the usual peak observed in the three pre-pandemic seasons. Sequence analysis revealed a close phylogenetic relatedness regardless of the season of origin. A significantly higher amount of pediatric cases (88.9% of all cases, p < 0.001) was observed for season 2021/2022. For the pediatric cases, significant differences were observed for an increased number of siblings in the household (p = 0.004), a lower rate of fever (p = 0.007), and a reduced amount of co-infections (p = 0.001). Although the mean age of the adult patients was significantly younger (47.1 vs. 64.7, p < 0.001), high rates of comorbidities, lower respiratory tract infections and intensive care unit admissions prevailed. The NPIs in the wake of the SARS-CoV-2 pandemic had a tremendous impact on the epidemiologic characteristics and seasonality of RSV and warrant further epidemiologic studies of this important pathogen. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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16 pages, 1760 KiB

Open AccessArticle

Burden of Influenza and Respiratory Syncytial Viruses in Suspected COVID-19 Patients: A Cross-Sectional and Meta-Analysis Study

by Vivaldo Gomes da Costa, Ana Júlia Chaves Gomes, Cíntia Bittar, Dayla Bott Geraldini, Pâmela Jóyce Previdelli da Conceição, Ágata Silva Cabral, Tamara Carvalho, Joice Matos Biselli, Paola Jocelan Scarin Provazzi, Guilherme Rodrigues Fernandes Campos, Paulo Ricardo da Silva Sanches, Paulo Inácio Costa, Maurício Lacerda Nogueira, João Pessoa Araujo, Jr., Fernando Rosado Spilki, Marília Freitas Calmon and Paula Rahal

Viruses 2023, 15(3), 665; https://doi.org/10.3390/v15030665 - 1 Mar 2023

Cited by 5 | Viewed by 3028

Abstract

Non-SARS-CoV-2 respiratory viral infections, such as influenza virus (FluV) and human respiratory syncytial virus (RSV), have contributed considerably to the burden of infectious diseases in the non-COVID-19 era. While the rates of co-infection in SARS-CoV-2-positive group (SCPG) patients have been determined, the burden of other respiratory viruses in the SARS-CoV-2-negative group (SCNG) remains unclear. Here, we conducted a cross-sectional study (São José do Rio Preto county, Brazil), and we collected our data using a meta-analysis to evaluate the pooled prevalence of FluV and RSV among SCNG patients. Out of the 901 patients suspected of COVID-19, our molecular results showed positivity of FluV and RSV in the SCNG was 2% (15/733) and 0.27% (2/733), respectively. Co-infection with SARS-CoV-2 and FluV, or RSV, was identified in 1.7% of the patients (3/168). Following our meta-analysis, 28 studies were selected (n = 114,318 suspected COVID-19 patients), with a pooled prevalence of 4% (95% CI: 3–6) for FluV and 2% (95% CI: 1–3) for RSV among SCNG patients were observed. Interestingly, FluV positivity in the SCNG was four times higher (OR = 4, 95% CI: 3.6–5.4, p < 0.01) than in the SCPG. Similarly, RSV positivity was significantly associated with SCNG patients (OR = 2.9, 95% CI: 2–4, p < 0.01). For subgroup analysis, cold-like symptoms, including fever, cough, sore throat, headache, myalgia, diarrhea, and nausea/vomiting, were positively associated (p < 0.05) with the SCPG. In conclusion, these results show that the pooled prevalence of FluV and RSV were significantly higher in the SCNG than in the SCPG during the early phase of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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10 pages, 1288 KiB

Open AccessArticle

Changes following the Onset of the COVID-19 Pandemic in the Burden of Hospitalization for Respiratory Syncytial Virus Acute Lower Respiratory Infection in Children under Two Years: A Retrospective Study from Croatia

by Dina Mrcela, Josko Markic, Chenkai Zhao, Daniela Veljacic Viskovic, Petra Milic, Roko Copac and You Li

Viruses 2022, 14(12), 2746; https://doi.org/10.3390/v14122746 - 9 Dec 2022

Cited by 9 | Viewed by 2337

Abstract

To understand the changes in RSV hospitalization burden in children younger than two years following the onset of the COVID-19 pandemic, we reviewed hospital records of children with acute lower respiratory infection (ALRI) between January 2018 and June 2022 in Split-Dalmatia County, Croatia. We compared RSV activity, age-specific annualized hospitalization rate, and disease severity between pre-COVID-19 and COVID-19 periods. A total of 942 ALRI hospital admissions were included. RSV activity remained low for the typical RSV epidemic during 2020–2021 winter. An out-of-season RSV resurgence was observed in late spring and summer of 2021. Before the COVID-19 pandemic, the annualized hospitalization rate for RSV-associated ALRI was 13.84/1000 (95% CI: 12.11–15.76) and highest among infants under six months. After the resurgence of RSV in the second half of 2021, the annualized hospitalization rate for RSV-associated ALRI in children younger than two years returned to the pre-pandemic levels with similar age distribution but a statistically higher proportion of severe cases. RSV immunization programs targeting protection of infants under six months of age are expected to remain impactful, although the optimal timing of administration would depend on RSV seasonality that has not yet been established in the study setting since the onset of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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20 pages, 4227 KiB

Open AccessArticle

Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy

by Pramila Lamichhane, Megolhubino Terhüja, Timothy A. Snider and Antonius G. P. Oomens

Viruses 2022, 14(11), 2474; https://doi.org/10.3390/v14112474 - 9 Nov 2022

Cited by 1 | Viewed by 1994

Abstract

The human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF^ΔCT). As preF is non-functional, RSV-preF^ΔCT was amplified in a production line expressing a functional substitute, and exhibited a single-cycle replication phenotype, which holds several unique potential advantages. RSV-preF^ΔCT prevented shedding and lung pathology after viral challenge in mice, but induced low levels of anti-attachment protein (G) antibodies (Abs). Given the significant contributions of anti-G Abs toward disease prevention, we generated modifications to RSV-preF^ΔCT in an effort to induce higher anti-G Ab levels. The Ab levels were monitored after the prime-boost vaccination of mice with modified vaccines. The most successful modification for enhancing induced anti-G Abs was seen with the placement of G in the first genome position. This vaccine also reduced the pathology after challenge with a high dose of wt RSV, and outperformed the sera from wt RSV-vaccinated mice in in vitro neutralization. Thus, raising the anti-G Ab levels induced by RSV-preF^ΔCT enhanced efficacy in vitro and in vivo, and constitutes an important next step in developing a live, single-cycle, efficacious vaccine for the human population. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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17 pages, 3170 KiB

Open AccessArticle

Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico

by Mao Akagawa, Tatsuya Shirai, Mitsuru Sada, Norika Nagasawa, Mayumi Kondo, Makoto Takeda, Koo Nagasawa, Ryusuke Kimura, Kaori Okayama, Yuriko Hayashi, Toshiyuki Sugai, Takeshi Tsugawa, Haruyuki Ishii, Hisashi Kawashima, Kazuhiko Katayama, Akihide Ryo and Hirokazu Kimura

Viruses 2022, 14(11), 2382; https://doi.org/10.3390/v14112382 - 28 Oct 2022

Cited by 2 | Viewed by 2364

Abstract

Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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13 pages, 4140 KiB

Open AccessArticle

Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus

by Rui Xiong, Rui Fu, Yong Wu, Xi Wu, Yuan Cao, Zhe Qu, Yanwei Yang, Susu Liu, Guitao Huo, Sanlong Wang, Weijin Huang, Jianjun Lyu, Xiang Zhu, Chunnan Liang, Yihong Peng, Youchun Wang and Changfa Fan

Viruses 2022, 14(8), 1740; https://doi.org/10.3390/v14081740 - 9 Aug 2022

Cited by 4 | Viewed by 2752

Abstract

Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2^−/− mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 10^9.8 copies/g and 1c10⁶ TCID₅₀ in nasal cavity, as well as 1 × 10⁸ copies/g and 1 × 10⁵ TCID₅₀ in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2^−/− mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2^−/− mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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Review

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8 pages, 248 KiB

Open AccessReview

RSV Replication, Transmission, and Disease Are Influenced by the RSV G Protein

by Harrison C. Bergeron and Ralph A. Tripp

Viruses 2022, 14(11), 2396; https://doi.org/10.3390/v14112396 - 29 Oct 2022

Cited by 16 | Viewed by 4569

Abstract

It is important to understand the features affecting virus replication, fitness, and transmissibility as they contribute to the outcome of infection and affect disease intervention approaches. Respiratory syncytial virus (RSV) is a major contributor to respiratory disease, particularly in the infant and elderly populations. Although first described over 60 years ago, there are no approved vaccines and there are limited specific antiviral treatments due in part to our incomplete understanding of the features affecting RSV replication, immunity, and disease. RSV studies have typically focused on using continuous cell lines and conventional RSV strains to establish vaccine development and various antiviral countermeasures. This review outlines how the RSV G protein influences viral features, including replication, transmission, and disease, and how understanding the role of the G protein can improve the understanding of preclinical studies. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

Other

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12 pages, 1280 KiB

Open AccessBrief Report

The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic

by Giulia Pruccoli, Emanuele Castagno, Irene Raffaldi, Marco Denina, Elisa Barisone, Luca Baroero, Fabio Timeus, Ivana Rabbone, Alice Monzani, Gian Maria Terragni, Cristina Lovera, Adalberto Brach del Prever, Paolo Manzoni, Michelangelo Barbaglia, Luca Roasio, Simona De Franco, Carmelina Calitri, Maddalena Lupica, Enrico Felici, Cinzia Marciano, Savino Santovito, Gaia Militerno, Enrica Abrigo, Antonio Curtoni, Paola Quarello, Claudia Bondone and Silvia Garazzino Show full author list Hide full author list

Viruses 2023, 15(2), 280; https://doi.org/10.3390/v15020280 - 19 Jan 2023

Cited by 28 | Viewed by 3102

Abstract

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2–3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019–2020–2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus 2.0)

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