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Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 10900

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Dr. Eric Yager

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Department of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA
Interests: RNA viruses; influenza; vaccine development; antiviral development; viral immunology; viral pathogenesis; molecular virology; virus–host interaction
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Dear Colleagues,

Viral respiratory infections are the most common diseases in humans, contributing to substantial morbidity, mortality, and economic losses annually worldwide. As the world continues to deal with COVID-19, upsurges in infections caused by other respiratory viruses, such as influenza, respiratory syncytial virus, parainfluenza, metapneumovirus, bocaviruses, and non-rhinovirus enteroviruses, have burdened healthcare systems in several countries. Because of their transmissibility, advances in the diagnosis and surveillance of these respiratory viruses are critically needed to guide the use of available therapeutics, the allocation of hospital as well as community resources, and the targeting of vaccination in addition to behavioral change campaigns by public health officials to mitigate their spread. Furthermore, since many of these respiratory viruses have limited therapeutic options and lack effective vaccines, there is an urgent need for further research into the biology of these viruses to help guide the development of effective strategies for the treatment and prevention of infection.

This Special Issue of Viruses seeks to attract original research and review articles focused on (1) advances and innovations in the development of highly sensitive diagnostic tests for the early detection of human respiratory virus infections; (2) timely findings on the epidemiology and transmission of human respiratory viruses; (3) the development and clinical trials of new vaccines, antivirals, and immunotherapeutics for influenza, RSV, coronaviruses, and other clinically relevant human respiratory viruses; (4) studies detailing the effectiveness and/or immunogenicity of existing vaccines; and (5) mitigation measures or strategies to reduce viral transmission/community spread, disease incidence in at-risk populations, and cross-species transmission.

Dr. Eric Yager
Guest Editor

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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.

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Keywords

influenza
adenovirus
coronoavirus
respiratory syncytial virus
rhinovirus
respiratory virus
antiviral strategies
epidemiology
diagnosis
treatment
vaccination
surveillance
vaccine development

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Related Special Issue

Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment in Viruses (15 articles)

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13 pages, 707 KB

Open AccessArticle

Pulmonary Embolism in Hospitalized COVID-19 Patients in Romania: Prevalence, Risk Factors, Outcomes

by Diana-Maria Mateescu, Adrian-Cosmin Ilie, Ioana Cotet, Cristina Guse, Camelia-Oana Muresan, Ana-Maria Pah, Marius Badalica-Petrescu, Stela Iurciuc, Maria-Laura Craciun, Adina Avram and Alexandra Enache

Viruses 2025, 17(10), 1342; https://doi.org/10.3390/v17101342 - 5 Oct 2025

Viewed by 375

Abstract

(1) Background: Pulmonary embolism (PE) is a severe complication of coronavirus disease 2019 (COVID-19), particularly in hospitalized patients. Data from Eastern Europe, including Romania, are limited, despite potential regional differences in demographics, comorbidities, and thromboprophylaxis practices. (2) Methods: This retrospective cohort study included 395 adults hospitalized with RT-PCR-confirmed COVID-19 at the “Victor Babeș” Clinical Hospital of Infectious Diseases and Pneumophthisiology, Timișoara, Romania, from September 2022 to December 2024. Demographic, clinical, laboratory, and imaging data were extracted from medical records. PE was confirmed by computed tomography pulmonary angiography (CTPA). Group comparisons used chi-square and t-tests, with multivariable logistic regression to identify independent PE predictors. (3) Results: PE was diagnosed in 47 patients (11.9%). Compared to those without PE, patients with PE had higher D-dimer (5305.00 ± 1251.00 vs. 537.00 ± 203.00 ng/mL, p < 0.001), fibrinogen (6.33 ± 0.74 vs. 3.51 ± 0.60 g/L, p < 0.001), and PT/INR (1.68 ± 0.21 vs. 1.05 ± 0.09, p < 0.001). Prior venous thromboembolism (VTE; 19.1% vs. 8.3%, p = 0.03) and prolonged immobilization (61.7% vs. 23.0%, p < 0.001) were significant risk factors. Intensive care unit (ICU) transfer occurred in 59.6% of PE cases, with a 25.5% in-hospital mortality rate. All PE patients received anticoagulation; 10.6% underwent thrombolysis. (4) Conclusions: In this Romanian cohort, one of the first large-scale studies in Eastern Europe, PE was prevalent among hospitalized COVID-19 patients, associated with elevated coagulation markers, identifiable risk factors, and high mortality. Early recognition and optimized thromboprophylaxis are critical to improve outcomes. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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16 pages, 921 KB

Open AccessArticle

Viral Burden of Respiratory Syncytial Virus and Viral Coinfections as Factors Regulating Paediatric Disease Severity

by Velia Chiara Di Maio, Rossana Scutari, Martina Mastropaolo, Luna Colagrossi, Giulia Linardos, Luana Coltella, Stefania Ranno, Eugenia Galeno, Mara Pisani, Anna Chiara Vittucci, Sebastian Cristaldi, Massimiliano Raponi, Alberto Villani, Cristina Russo and Carlo Federico Perno

Viruses 2025, 17(9), 1236; https://doi.org/10.3390/v17091236 - 11 Sep 2025

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Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs) in children. However, the clinical impact of RSV co-infection with other respiratory viruses remains unclear. This study investigates the frequency and clinical outcomes of RSV infections in a large paediatric cohort. Methods: Paediatric patients with RSV-positive respiratory samples admitted to Bambino Gesù Children’s Hospital between January 2022 and April 2024 were analysed. Results: Within 17,259 respiratory samples from 9877 paediatric patients, 952 (9.6%) were RSV-positive. Among these, 637 patients with ARI were included. RSV affected the lower respiratory tract in 549 cases (86.2%) and the upper tract in 88 (13.8%) cases. RSV mono-infection was found in 286 (44.9%) patients, while 351 (55.1%) patients had co-infections. Mono-infections showed lower cycle-threshold (CT) than co-infections in both upper and lower tract (p-value:0.002 and 0.037, respectively). Pneumonia was associated with RSV co-infection (N = 48, 15.4%), whereas bronchiolitis was mostly seen in mono-infection (N = 196, 78.1%, p-value:0.002). Regression analysis showed an association between pneumonia and co-infection (AOR: 1.97 [1.06–3.64], p-value = 0.031), higher CT (AOR [95% CI]: 1.07 [1.02–1.11], p-value = 0.006) and older age (AOR [95% CI]: 1.48 [1.31–1.68], p-value < 0.001), whereas bronchiolitis was associated with mono-infection, younger age and lower CT. Conclusions: This study highlights the role of RSV in paediatric disease and emphasises the importance of early diagnosis, personalised treatment and preventive strategies to improve outcomes and reduce the burden of disease. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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12 pages, 1526 KB

Open AccessArticle

Human-Derived H3N2 Influenza A Viruses Detected in Pigs in Northern Italy

by Laura Soliani, Ada Mescoli, Irene Zanni, Laura Baioni, Giovanni Alborali, Ana Moreno, Silvia Faccini, Carlo Rosignoli, Giorgia De Lorenzi, Laura Fiorentini, Camilla Torreggiani, Benedetta Cordioli, Alice Prosperi, Andrea Luppi and Chiara Chiapponi

Viruses 2025, 17(9), 1171; https://doi.org/10.3390/v17091171 - 27 Aug 2025

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Abstract

In recent years, the four main swine influenza A virus (IAV-S) subtypes circulating in swine in the EU have been H1avN1, H1huN2, H1N1pdm09, and H3N2. The latter emerged in 1984 from a reassortment event between a human seasonal H3N2 and H1avN1, and is currently detected at low prevalence in swine in Italy. Here, we describe nine H3N2 IAV-S isolates belonging to three novel genotypes, first detected in Italy in 2021, likely resulting from reassortment events between swine and human IAVs. The first genotype was characterized by a hemagglutinin (H3 HA) of human seasonal origin, a neuraminidase (N2 NA) derived from H1huN2 strains circulating in Italian swine, and an avian-like internal gene cassette (IGC). The second genotype differed in its IGC constellation: PB2, PB1, PA and NP segments were of pandemic origin (pdm09), while NS and M segments derived from the Eurasian avian-like lineage. The third genotype combined a human-derived H3, a Gent/84-derived N2, and a pdm09-origin IGC, except for an avian-like NS. This study aimed to characterize the genetic features of these novel H3huN2 and assess their epidemiological relevance, with implications for surveillance and control, improving preparedness and mitigating the risks posed by zoonotic influenza viruses. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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15 pages, 1446 KB

Open AccessArticle

Versatile and Scalable Nanoparticle Vaccine as a Scaffold Against Newly Emerging Influenza Viruses

by Alessandro Pardini, Dominik A. Rothen, Pascal S. Krenger, Anne-Cathrine Vogt, Romano Josi, Xuelan Liu, Kaspars Tars, Manfred Kopf, Monique Vogel and Martin F. Bachmann

Viruses 2025, 17(9), 1165; https://doi.org/10.3390/v17091165 - 26 Aug 2025

Viewed by 1584

Abstract

Influenza remains a major health threat due to its high contagiousness and global spread, affecting not only humans but also agricultural livestock and wild animals through transmission via migratory birds. Despite over 70 years of vaccination, influenza still creates epidemics and pandemics, and the ongoing use of vaccination is an essential but currently insufficient strategy. In this study, we assessed the immunogenicity and efficacy of an AP205 virus-like particle (VLP) carrying the HA head domain of the A/PR8/H1N1 strain, administered intranasally and subcutaneously in mice. For this purpose, the entire head region of A/PR8/H1N1 was genetically integrated into a sterically improved version of AP205, which exhibits capsid monomers fused into a dimer, thereby offering inexpensive and scalable production processes. The vaccine induced strong systemic anti-HA IgG and IgA antibodies via both routes, with no significant difference in the levels of IgG. Both immunisation strategies induced protection against a lethal challenge with H1PR8 mouse-adapted influenza virus. The findings demonstrate the potential of the AP205 VLP platform for HA1-based influenza vaccines and its applicability for controlling influenza in both humans and livestock. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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19 pages, 4270 KB

Open AccessArticle

Viral Inactivation by Light-Emitting Diodes: Action Spectra Reveal Genomic Damage as the Primary Mechanism

by Kazuaki Mawatari, Yasuko Kadomura-Ishikawa, Takahiro Emoto, Yushi Onoda, Kai Ishida, Sae Toda, Takashi Uebanso, Toshihiko Aizawa, Shigeharu Yamauchi, Yasuo Fujikawa, Tomotake Tanaka, Xing Li, Eduardo Suarez-Lopez, Richard J. Kuhn, Ernest R. Blatchley III III and Akira Takahashi

Viruses 2025, 17(8), 1065; https://doi.org/10.3390/v17081065 - 30 Jul 2025

Viewed by 937

Abstract

Irradiation with ultraviolet light-emitting diodes (UV-LEDs) represents a promising method for viral inactivation, but a detailed understanding of the wavelength-dependent action spectra remains limited, particularly across different viral components. In this study, we established standardized UV action spectra for infectivity reduction in pathogenic viruses using a system equipped with interchangeable LEDs at 13 different peak wavelengths (250–365 nm). The reduction in viral infectivity induced by UV-LED exposure was strongly related to viral genome damage, whereas no significant degradation of viral structural proteins was detected. Peak virucidal efficiency was observed at 267–270 nm across all tested viruses, representing a slight shift from the traditionally expected 260 nm nucleic acid absorption peak. Enveloped RNA viruses, including influenza A virus, respiratory syncytial virus, and coronavirus, exhibited greater UV sensitivity than nonenveloped viruses such as feline calicivirus and adenovirus. These observations indicate that structural characteristics, such as the presence of an envelope and genome organization, influence UV susceptibility. The wavelength-specific action spectra established in this study provide critical data for optimizing UV-LED disinfection systems to achieve efficient viral inactivation while minimizing energy consumption in healthcare, food safety, and environmental sanitation. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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8 pages, 764 KB

Open AccessCommunication

A Strand-Specific Quantitative RT-PCR Method for Detecting vRNA, cRNA, and mRNA of H7N9 Avian Influenza Virus in a Mouse Model

by Bo Wang, Guangwen Wang, Yi-han Wang, Xuwei Liu, Manman Li, Huihui Kong, Hualan Chen, Li Jiang and Chengjun Li

Viruses 2025, 17(7), 1007; https://doi.org/10.3390/v17071007 - 17 Jul 2025

Viewed by 821

Abstract

Avian influenza virus (AIV) remains a persistent threat to both the poultry industry and human health. Among the AIV subtypes posing public health threats, H7N9 AIV is responsible for five epidemic waves of human infection in China. Here, a detection system based on a mouse model was established, which can simultaneously and quantitatively analyze the dynamic changes in the viral genomic RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA) of H7N9 AIV by using reverse transcription primers with tag sequences to reverse transcribe the three species of RNAs into corresponding cDNA templates, which are then absolutely quantified using the TaqMan quantitative PCR method. This system specifically targets the PB2 and NA genes and, for the first time, enables a spatiotemporal analysis of all three viral RNA species within an animal model. Our results revealed that H7N9 AIV exhibits characteristic replication kinetics, with all three species of viral RNAs showing a rapid increase followed by a certain degree of decline. This system offers a powerful tool for us to further advance our understanding of the replication dynamics of AIV in mice. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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17 pages, 3448 KB

Open AccessArticle

Entry Inhibitors of SARS-CoV-2 Targeting the Transmembrane Domain of the Spike Protein

by Kristin V. Lyles, Shannon Stone, Priti Singh, Lila D. Patterson, Janhavi Natekar, Heather Pathak, Rohit K. Varshnaya, Amany Elsharkawy, Dongning Liu, Shubham Bansal, Oluwafoyinsola O. Faniyi, Sijia Tang, Xiaoxiao Yang, Nagaraju Mulpuri, Donald Hamelberg, Congbao Kang, Binghe Wang, Mukesh Kumar and Ming Luo

Viruses 2025, 17(7), 989; https://doi.org/10.3390/v17070989 - 16 Jul 2025

Viewed by 912

Abstract

Despite current vaccines and therapeutics targeting SARS-CoV-2, the causative agent of the COVID-19 pandemic, cases remain high causing a burden on health care systems. Spike-protein mediated membrane fusion of SARS-CoV-2 is a critical step in viral entry. Herein, we describe entry inhibitors identified by first screening a library of about 160 compounds and then analogue synthesis. Specifically, compound 261 was found to inhibit SARS-CoV-2 infection in a tissue model with IC₅₀ of 0.3 µM. Using NMR, we found that 261 interacts with key residues in the aromatic-rich region of the spike protein directly next to the transmembrane domain. Molecular dynamic simulations of the 261 binding pocket in the spike protein was also mapped to the transmembrane domain, consistent with NMR findings. The amino acids in the binding site are conserved among different coronaviruses known to infect humans; therefore, inhibitors targeting this conserved binding site could be a useful addition to current therapeutics and may have pan-coronavirus antiviral activities. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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16 pages, 1128 KB

Open AccessArticle

Surveillance of Respiratory Pathogens Among Rapid Diagnostic Test-Negative Acute Respiratory Infection Patients in Myanmar in 2023, with a Focus on Rhinovirus and Enterovirus Genotyping

by Yuyang Sun, Tsutomu Tamura, Yadanar Kyaw, Swe Setk, Moe Myat Aye, Htay Htay Tin, Su Mon Kyaw Win, Jiaming Li, Tri Bayu Purnama, Irina Chon, Keita Wagatsuma, Hisami Watanabe and Reiko Saito

Viruses 2025, 17(6), 860; https://doi.org/10.3390/v17060860 - 17 Jun 2025

Viewed by 1360

Abstract

This study explored the distribution and genetic characteristics of respiratory pathogens in outpatients with acute respiratory infections (ARIs) in Yangon, Myanmar, during the 2023 rainy season. Among 267 patients who tested negative for influenza, RSV, and SARS-CoV-2 using rapid diagnostic tests, 84.6% were positive for at least one pathogen according to a multiplex polymerase chain reaction (PCR) assay, the BioFire^® FilmArray^® Respiratory Panel 2.1. The most common viruses detected were rhinovirus/enterovirus (RV/EV) at 37.8%, respiratory syncytial virus (RSV) at 22.4%, and human metapneumovirus (hMPV) at 10.0%. These pathogens co-circulated mainly from July to September, with RV/EV consistently predominant. Symptom comparison among RV/EV-, RSV-, and hMPV-infected patients showed similar clinical features, though fever was more common in hMPV cases. Among RV/EV-positive patients, 59.3% had single infections, while 40.7% experienced co-infections, especially with RSV and adenovirus. Genotyping identified 28 types from five species, primarily RV-A and RV-C, which were genetically diverse. One EV-D68 case was also found, emphasizing its potential risk. This study underscores the genetic diversity and clinical impact of RV/EV and stresses the importance of ongoing molecular surveillance in Myanmar’s post-COVID-19 context to inform effective public health responses. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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13 pages, 5104 KB

Open AccessArticle

Structure and Antigenicity of the Porcine Astrovirus 4 Capsid Spike

by Danielle J. Haley, Sarah Lanning, Kyle E. Henricson, Andre A. Mardirossian, Iyan Cirillo, Michael C. Rahe and Rebecca M. DuBois

Viruses 2024, 16(10), 1596; https://doi.org/10.3390/v16101596 - 11 Oct 2024

Viewed by 1536

Abstract

Porcine astrovirus 4 (PoAstV4) has been recently associated with respiratory disease in pigs. In order to understand the scope of PoAstV4 infections and to support the development of a vaccine to combat PoAstV4 disease in pigs, we designed and produced a recombinant PoAstV4 capsid spike protein for use as an antigen in serological assays and for potential future use as a vaccine antigen. Structural prediction of the full-length PoAstV4 capsid protein guided the design of the recombinant PoAstV4 capsid spike domain expression plasmid. The recombinant PoAstV4 capsid spike was expressed in Escherichia coli, purified by affinity and size-exclusion chromatography, and its crystal structure was determined at 1.85 Å resolution, enabling structural comparisons to other animal and human astrovirus capsid spike structures. The recombinant PoAstV4 capsid spike protein was also used as an antigen for the successful development of a serological assay to detect PoAstV4 antibodies, demonstrating that the recombinant PoAstV4 capsid spike retains antigenic epitopes found on the native PoAstV4 capsid. These studies lay a foundation for seroprevalence studies and the development of a PoAstV4 vaccine for swine. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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10 pages, 1565 KB

Open AccessBrief Report

Virucidal Potential of 3,3′,4,4′,5,5′-Hexahydroxy-trans-Stilbene Against Respiratory Syncytial Virus

by Zoltán Bánki, Leonie Wolf, Brigitte Müllauer, Daniel Geisler-Moroder, Wegene Borena, Walter Jäger and Thomas Szekeres

Viruses 2025, 17(10), 1287; https://doi.org/10.3390/v17101287 - 23 Sep 2025

Viewed by 318

Abstract

Respiratory syncytial virus (RSV) infections have a significant impact on global health. Despite of recent advancements, the current treatment options for managing severe RSV infections remain primarily limited to supportive care, emphasizing the high priority for the development of effective antiviral therapies. Antiviral activity of 3,3′,4,4′,5,5′-hexahydroxy-trans-stilbene (HHS), a synthetic polyhydroxyphenol, has previously been demonstrated against SARS-CoV-2. In this study, we provide evidence for a direct virucidal effect of HHS against RSV infection in permissive HEp-2 cells in vitro. HHS, with an IC50 of 3.44 μM, efficiently inhibited HEp-2 cell infection with no sign of toxicity at least up to 25 μM. Interestingly, resveratrol, a polyhydroxyphenol analogue, was less efficient. Mode of action experiments revealed that HHS directly interacts with RSV particles, indicating that its virucidal activity is based on this interaction rather than affecting HEp-2 cells or post-infection processes. Together with previous data, our results suggest a broad antiviral activity of HHS against different respiratory viruses. Further studies are necessary to unveil the exact mechanism and evaluate the potential of HHS in the treatment of severe respiratory virus infections. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

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