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10 pages, 258 KiB  
Article
COVID-19 Clinical Predictors in Patients Treated via a Telemedicine Platform in 2022
by Liliane de Fátima Antonio Oliveira, Lúcia Regina do Nascimento Brahim Paes, Luiz Claudio Ferreira, Gabriel Garcez de Araújo Souza, Guilherme Souza Weigert, Layla Lorena Bezerra de Almeida, Rafael Kenji Fonseca Hamada, Lyz Tavares de Sousa, Andreza Pain Marcelino and Cláudia Maria Valete
Trop. Med. Infect. Dis. 2025, 10(8), 213; https://doi.org/10.3390/tropicalmed10080213 - 29 Jul 2025
Viewed by 202
Abstract
Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, whose 2020 outbreak was characterized as a pandemic by the World Health Organization. Restriction measures changed healthcare delivery, with telehealth providing a viable alternative throughout the pandemic. This study analyzed a [...] Read more.
Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, whose 2020 outbreak was characterized as a pandemic by the World Health Organization. Restriction measures changed healthcare delivery, with telehealth providing a viable alternative throughout the pandemic. This study analyzed a telemedicine platform database with the goal of developing a diagnostic prediction model for COVID-19 patients. This is a longitudinal study of patients seen on the Conexa Saúde telemedicine platform in 2022. A multiple binary logistic regression model of controls (negative confirmation for COVID-19 or confirmation of other influenza-like illness) versus COVID-19 was developed to obtain an odds ratio (OR) and a 95% confidence interval (CI). In the final binary logistic regression model, six factors were considered significant: presence of rhinorrhea, ocular symptoms, abdominal pain, rhinosinusopathy, and wheezing/asthma and bronchospasm were more frequent in controls, thus indicating a greater chance of flu-like illnesses than COVID-19. The presence of tiredness and fatigue was three times more prevalent in COVID-19 cases (OR = 3.631; CI = 1.138–11.581; p-value = 0.029). Our findings suggest potential predictors associated with influenza-like illness and COVID-19 that may distinguish between these infections. Full article
15 pages, 790 KiB  
Review
A Review of Avian Influenza Virus Exposure Patterns and Risks Among Occupational Populations
by Huimin Li, Ruiqi Ren, Wenqing Bai, Zhaohe Li, Jiayi Zhang, Yao Liu, Rui Sun, Fei Wang, Dan Li, Chao Li, Guoqing Shi and Lei Zhou
Vet. Sci. 2025, 12(8), 704; https://doi.org/10.3390/vetsci12080704 - 28 Jul 2025
Viewed by 528
Abstract
Avian influenza viruses (AIVs) pose significant risks to occupational populations engaged in poultry farming, livestock handling, and live poultry market operations due to frequent exposure to infected animals and contaminated environments. This review synthesizes evidence on AIV exposure patterns and risk factors through [...] Read more.
Avian influenza viruses (AIVs) pose significant risks to occupational populations engaged in poultry farming, livestock handling, and live poultry market operations due to frequent exposure to infected animals and contaminated environments. This review synthesizes evidence on AIV exposure patterns and risk factors through a comprehensive analysis of viral characteristics, host dynamics, environmental influences, and human behaviors. The main routes of transmission include direct animal contact, respiratory contact during slaughter/milking, and environmental contamination (aerosols, raw milk, shared equipment). Risks increase as the virus adapts between species, survives longer in cold/wet conditions, and spreads through wild bird migration (long-distance transmission) and live bird trade (local transmission). Recommended control measures include integrated animal–human–environment surveillance, stringent biosecurity measures, vaccination, and education. These findings underscore the urgent need for global ‘One Health’ collaboration to assess risk and implement preventive measures against potentially pandemic strains of influenza A viruses, especially in light of undetected mild/asymptomatic cases and incomplete knowledge of viral evolution. Full article
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8 pages, 701 KiB  
Communication
Non-Influenza and Non-SARS-CoV-2 Viruses Among Patients with Severe Acute Respiratory Infections in Tanzania: A Post-COVID-19 Pandemic Snapshot
by Maria Ezekiely Kelly, Frank Msafiri, Francisco Averhoff, Jane Danda, Alan Landay, Azma Simba, Ambele Elia Mwafulango, Solomoni Mosha, Alex Magesa, Vida Mmbaga and Sandra S. Chaves
Viruses 2025, 17(8), 1042; https://doi.org/10.3390/v17081042 - 25 Jul 2025
Viewed by 479
Abstract
Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in [...] Read more.
Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in Tanzania to understand the distribution of respiratory viruses shortly after nonpharmaceutical interventions (NPIs) were lifted. A total of 475 samples that tested negative for SARS-CoV-2 and influenza from March through May 2022 were included in this study. The samples were tested for 16 virus targets using Anyplex II RV16 multiplex assays. The findings indicate that most hospitalizations (74%) were among children under 15 years, with human bocavirus (HBoV) being the most prevalent (26.8%), followed by rhinovirus (RV, 12.3%), parainfluenza viruses (PIVs1–4, 10.2%), respiratory syncytial virus (RSV, 8.7%), adenovirus (AdV, 4.3%), and metapneumovirus (MPV, 2.9%). Notably, 54% of respiratory hospitalizations had no viruses detected. The findings highlight the broad circulation of respiratory viruses shortly after NPIs were lifted in Tanzania. Surveillance for respiratory pathogens beyond influenza and SARS-CoV-2 can inform public health officials of emerging threats in the country and should be considered an important pandemic preparedness measure at a global level. Full article
(This article belongs to the Section Coronaviruses)
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13 pages, 1231 KiB  
Article
Respiratory Virus Prevalence Across Pre-, During-, and Post-SARS-CoV-2 Pandemic Periods
by Michele Manno, Grazia Pavia, Simona Gigliotti, Marta Pantanella, Giorgio Settimo Barreca, Cinzia Peronace, Luigia Gallo, Francesca Trimboli, Elena Colosimo, Angelo Giuseppe Lamberti, Nadia Marascio, Giovanni Matera and Angela Quirino
Viruses 2025, 17(8), 1040; https://doi.org/10.3390/v17081040 - 25 Jul 2025
Viewed by 359
Abstract
The COVID-19 pandemic significantly impacted the circulation, seasonality, and disease burden of viral respiratory infections. This study aimed to evaluate the impact of SARS-CoV-2 on the frequency of viral respiratory infections at a teaching hospital in Southern Italy by comparing data from before, [...] Read more.
The COVID-19 pandemic significantly impacted the circulation, seasonality, and disease burden of viral respiratory infections. This study aimed to evaluate the impact of SARS-CoV-2 on the frequency of viral respiratory infections at a teaching hospital in Southern Italy by comparing data from before, during, and after the COVID-19 pandemic and by investigating how the emergence of SARS-CoV-2 affected the circulation and seasonality of other respiratory viruses. This retrospective and prospective study was performed on de-identified nasopharyngeal specimens classified as pre-COVID-19 (before 15 March 2020), during-COVID-19 (from 16 March 2020 to 5 May 2023), and post-COVID-19 (from 6 May 2023 to 31 December 2024). Overall, 790 out of 3930 (20%) patient samples tested positive for at least one respiratory virus. The mean age of patients was 60 ± 19 years, with significant positivity rates observed in the 65–98 age group (p ≤ 0.05) across all periods. In the pre-COVID-19 period, the most prevalent virus was influenza A (47.5%, 47/99), followed by the human rhinovirus (19.2%, 19/99). During the COVID-19 pandemic, SARS-CoV-2 was the most prevalent (64.9%, 290/447), before decreasing to 38% (92/244) after the pandemic, while influenza A’s positivity prevalence increased to 14.3% (35/244). Rhinovirus/enterovirus remained relatively stable throughout all periods. The pandemic notably altered viral co-infection dynamics, with its effects lasting into the post-COVID-19 period. Specifically, a marked decrease in influenza A circulation was observed, while respiratory syncytial virus (RSV) epidemiology remained stable and significant co-circulation of rhinovirus/enterovirus with SARS-CoV-2 persisted. Therefore, since COVID-19 and influenza affect the same high-risk groups, those individuals must be vaccinated against both viruses. Full article
(This article belongs to the Section Coronaviruses)
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10 pages, 203 KiB  
Article
Molecular Detection of Various Non-Seasonal, Zoonotic Influenza Viruses Using BioFire FilmArray and GenXpert Diagnostic Platforms
by Charlene Ranadheera, Taeyo Chestley, Orlando Perez, Breanna Meek, Laura Hart, Morgan Johnson, Yohannes Berhane and Nathalie Bastien
Viruses 2025, 17(7), 970; https://doi.org/10.3390/v17070970 - 10 Jul 2025
Viewed by 516
Abstract
Since 2020, the Gs/Gd H5N1 influenza virus (clade 2.3.4.4b) has established itself within wild bird populations across Asia, Europe, and the Americas, causing outbreaks in wild mammals, commercial poultry, and dairy farms. The impacts on the bird populations and the agricultural industry has [...] Read more.
Since 2020, the Gs/Gd H5N1 influenza virus (clade 2.3.4.4b) has established itself within wild bird populations across Asia, Europe, and the Americas, causing outbreaks in wild mammals, commercial poultry, and dairy farms. The impacts on the bird populations and the agricultural industry has been significant, requiring a One Health approach to enhanced surveillance in both humans and animals. To support pandemic preparedness efforts, we evaluated the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel for their ability to detect the presence of non-seasonal, zoonotic influenza A viruses, including circulating H5N1 viruses from clade 2.3.4.4b. Both assays effectively detected the presence of influenza virus in clinically-contrived nasal swab and saliva specimens at low concentrations. The results generated using the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel, in conjunction with clinical and epidemiological findings provide valuable diagnostic findings that can strengthen pandemic preparedness and surveillance initiatives. Full article
(This article belongs to the Section Animal Viruses)
11 pages, 811 KiB  
Article
Comparative Analysis of Severe Clinical Outcomes in Hospitalized Patients with RSV, Influenza, and COVID-19 Across Early and Late COVID-19 Pandemic Phases (2021–2024)
by Yuying Xing and Amit Bahl
J. Clin. Med. 2025, 14(14), 4894; https://doi.org/10.3390/jcm14144894 - 10 Jul 2025
Viewed by 471
Abstract
Background: COVID-19, influenza, and respiratory syncytial virus (RSV) are major respiratory infections with overlapping clinical presentations. Comparative data on the severity of these infections in hospitalized adults are limited, particularly across phases of the COVID-19 pandemic. Objectives: The objectives of this study are [...] Read more.
Background: COVID-19, influenza, and respiratory syncytial virus (RSV) are major respiratory infections with overlapping clinical presentations. Comparative data on the severity of these infections in hospitalized adults are limited, particularly across phases of the COVID-19 pandemic. Objectives: The objectives of this study are to compare the risk of severe outcomes among hospitalized patients with COVID-19, influenza, or RSV and to evaluate the role of vaccination and demographic subgroups using recent, real-world data. Design: This is a retrospective cohort study. Setting: Eight hospitals within the Corewell Health system in Michigan, USA, were studied. Participants: The participants included adults aged ≥ 18 years hospitalized between 1 January 2021 and 20 July 2024 with a principal diagnosis of COVID-19, influenza, or RSV. Main Outcomes and Measures: The primary outcome was a composite of ICU admission, mechanical ventilation, or in-hospital death. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs), with subgroup analyses in terms of vaccination status, age group, and time period. Results: Among 27,885 hospitalized patients (90.5% COVID-19, 7.2% influenza, 2.3% RSV), COVID-19 was associated with a higher risk of severe outcomes compared to influenza (aHR 1.30, 95% CI: 1.11–1.54). RSV showed no significant difference from influenza. Across all infection groups, older age (≥65 years), high comorbidity burden, and immunocompromised status were associated with an increased risk of severe outcomes. Recent COVID-19 vaccination was protective, particularly among older adults. Differences in severity were more pronounced in the pre-March 2022 period. Conclusions: Using one of the most recent large-scale datasets, this study is among the first to directly compare the severity of COVID-19, influenza, and RSV in hospitalized adults. COVID-19 continues to pose a higher risk of severe illness compared to the other viral infections. The findings underscore the importance of up-to-date vaccination and focused clinical strategies for older and high-risk individuals. This study offers timely evidence to guide future respiratory virus response strategies across hospital settings. Full article
(This article belongs to the Section Infectious Diseases)
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28 pages, 854 KiB  
Review
H5N1 Avian Influenza: A Narrative Review of Scientific Advances and Global Policy Challenges
by Alison Simancas-Racines, Claudia Reytor-González, Melannie Toral and Daniel Simancas-Racines
Viruses 2025, 17(7), 927; https://doi.org/10.3390/v17070927 - 29 Jun 2025
Viewed by 857
Abstract
The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance [...] Read more.
The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination, public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global spread among wildlife and domestic animals underscore the urgent need for robust preparedness. International organizations have called for comprehensive pandemic response plans, enhanced multisectoral collaboration, and investment in targeted research. Priorities include expanding surveillance to asymptomatic animal hosts, evaluating viral shedding and transmission routes, and developing strain-specific and universal vaccines. Strengthening global cooperation and public health infrastructure will be critical to mitigate the growing threat of H5N1 and reduce the risk of a future influenza pandemic. Full article
(This article belongs to the Special Issue Controlling Zoonotic Viral Diseases from One Health Perspective 2025)
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27 pages, 1689 KiB  
Review
Occupational Risk from Avian Influenza Viruses at Different Ecological Interfaces Between 1997 and 2019
by Maria Alessandra De Marco, Alessandra Binazzi, Paola Melis, Claudia Cotti, Michela Bonafede, Mauro Delogu, Paola Tomao and Nicoletta Vonesch
Microorganisms 2025, 13(6), 1391; https://doi.org/10.3390/microorganisms13061391 - 14 Jun 2025
Viewed by 648
Abstract
Unprotected exposures to infected poultry or wild birds, and/or to the related avian influenza virus (AIV)-contaminated environments, could account for AIV infection in workers. This study was aimed at highlighting the ecological interfaces related to domestic poultry and wild birds posing an occupational [...] Read more.
Unprotected exposures to infected poultry or wild birds, and/or to the related avian influenza virus (AIV)-contaminated environments, could account for AIV infection in workers. This study was aimed at highlighting the ecological interfaces related to domestic poultry and wild birds posing an occupational risk regarding AIV. A search of all the articles investigating the possible presence of AIV in workers attested through virological and serological techniques and published up to August 2019 was performed on PubMed and Scopus electronic databases. Ninety-four articles consisting of 11 virological, 67 serological, and 16 mixed (both virological and serological) studies were obtained. Both virological and serological evidences of AIV infection were mainly related to H5, H7, and H9 subtypes. In addition, one piece of virological evidence for H10 subtype was reported, whereas seropositivity to all hemagglutinin subtypes from H4 to H11 was detected by serological studies. The number of AIV subtype exposures inferred from serological results showed that workers from large-scale industrial poultry farms and markets were the most represented, whereas workers from small-scale and backyard poultry farms showed seropositivity to a greater number of AIV subtypes. Workers exposed to wild bird habitats tested seropositive to H5, H9, and H11. In the occupational settings, direct contact with infected poultry or wild birds could account for AIV infection in workers. This AIV spillover can result in severe health complications for the workers, also posing a potential pandemic risk to the general population. From a public health perspective, the surveillance and early detection of AIV in workplaces should be a priority faced by a one-health approach. Full article
(This article belongs to the Special Issue Ecology of Influenza A Viruses: 2nd Edition)
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18 pages, 797 KiB  
Article
Risk of Incidence and Lethality by Etiology of Severe Acute Respiratory Syndrome in Hospitalized Children Under 1 Year of Age in Brazil in 2024: A Cross-Sectional Study
by Tamires de Nazaré Soares, Natasha Cristina Oliveira Andrade, Suziane do Socorro dos Santos, Marcela Raíssa Asevedo Dergan, Karina Faine Freitas Takeda, Jully Greyce Freitas de Paula Ramalho, Luany Rafaele da Conceição Cruz, Perla Katheleen Valente Corrêa, Marli de Oliveira Almeida, Joyce dos Santos Freitas, Wilker Alves Silva, Marcos Jessé Abrahão Silva, Daniele Melo Sardinha and Luana Nepomuceno Gondim Costa Lima
Trop. Med. Infect. Dis. 2025, 10(6), 168; https://doi.org/10.3390/tropicalmed10060168 - 14 Jun 2025
Viewed by 671
Abstract
Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), [...] Read more.
Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), influenza, rhinovirus, and SARS-CoV-2, each with distinct potential to cause severe illness and death. Understanding the specific incidence and lethality by etiological agents in the recent Brazilian context (2024), after the COVID-19 pandemic, is essential to guide surveillance and public health strategies. This study aimed to analyze the risk of incidence and lethality by specific etiology of SARS in children under one year of age hospitalized in Brazil during the year 2024. A descriptive cross-sectional study was performed using secondary data from the 2024 Influenza Epidemiological Surveillance Information System (SIVEP-Gripe), obtained via OpenDataSUS. Reported cases of SARS hospitalized in children <1 year of age in Brazil were included. Distribution by final classification and epidemiological week (EW) was analyzed; the incidence rate by Federative Unit (FU) (cases/100,000 < 1 year) with risk classification (Low/Moderate/High) was assessed; and, for cases with positive viral RT-PCR, the etiological frequency and virus-specific lethality rate (deaths/total cases of etiology ×100), also with risk classification, were extracted. A multivariate logistic regression model was performed for the risk factors of death. A total of 66,170 cases of SARS were reported in children under 1 year old (national incidence: 2663/100,000), with a seasonal peak between April and May. The majority of cases were classified as “SARS due to another respiratory virus” (49.06%) or “unspecified” (37.46%). Among 36,009 cases with positive RT-PCR, RSV (50.06%) and rhinovirus (26.97%) were the most frequent. The overall lethality in RT-PCR-positive cases was 1.28%. Viruses such as parainfluenza 4 (8.57%), influenza B (2.86%), parainfluenza 3 (2.49%), and SARS-CoV-2 (2.47%) had higher lethality. The multivariate model identified parainfluenza 4 (OR = 6.806), chronic kidney disease (OR = 3.820), immunodeficiency (OR = 3.680), Down Syndrome (OR = 3.590), heart disease (OR = 3.129), neurological disease (OR = 2.250), low O2 saturation (OR = 1.758), SARS-CoV-2 (OR = 1.569) and respiratory distress (OR = 1.390) as risk factors for death. Cough (OR = 0.477) and RSV (OR = 0.736) were associated with a lower chance of death. The model had good calibration (Hosmer–Lemeshow p = 0.693) and overall significance (p < 0.001). SARS represented a substantial burden of hospitalizations, with marked seasonal and geographic patterns. RSV and rhinovirus were the main agents responsible for the volume of confirmed cases but had a relatively low to moderate risk of lethality. In contrast, less frequent viruses such as parainfluenza 4, influenza B, parainfluenza 3, and SARS-CoV-2 were associated with a significantly higher risk of death. These findings highlight the importance of dissociating frequency from lethality and reinforce the need to strengthen etiological surveillance, improve diagnosis, and direct preventive strategies (such as immunizations) considering the specific risk of each pathogen for this vulnerable population. Full article
(This article belongs to the Special Issue Respiratory Infectious Disease Epidemiology and Control)
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5 pages, 176 KiB  
Commentary
Highly Pathogenic Avian Influenza A(H5N1) Virus: How Far Are We from a New Pandemic?
by Giovanni Di Guardo
Vet. Sci. 2025, 12(6), 566; https://doi.org/10.3390/vetsci12060566 - 9 Jun 2025
Cited by 2 | Viewed by 1128
Abstract
The focus of this commentary is represented by the pandemic risk associated with the highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b. More in detail, the herein dealt pandemic alarm appears to be primarily justified by the huge and progressively growing number [...] Read more.
The focus of this commentary is represented by the pandemic risk associated with the highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b. More in detail, the herein dealt pandemic alarm appears to be primarily justified by the huge and progressively growing number of virus-susceptible domestic and wild birds and mammals, including threatened marine mammal species like South American sea lions and elephant seals as well as harbour porpoises, bottlenose dolphins and polar bears. Of major concern is the susceptibility of dairy cattle to HPAI A(H5N1) virus, particularly the documented and unprecedented colonization of host’s mammary gland tissue, resulting in viral shedding through the milk alongside a large series of cases of infection in dairy farm workers in several USA locations. Despite well-documented zoonotic capability, no evidences of a sustained and efficient HPAI A(H5N1) viral transmission between people have been hitherto reported. If this were to happen sooner or later, a new pandemic might consequently arise. Therefore, keeping all this in mind and based upon the lessons taught by the COVID-19 pandemic, a “One Health, One Earth, One Ocean”-centered approach would be absolutely needed in order to deal in the most appropriate way with the HPAI A(H5N1) virus-associated zoonotic and pandemic risk. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
21 pages, 2197 KiB  
Article
Production and Immune Response Against Pandemic Influenza Candidate Vaccines as Preparedness Against the Circulating H5N1 Influenza Viruses
by Paulo Lee Ho, Yordanka Medina-Armenteros, Lívia Mendonça Munhoz Dati, Daniela Cajado-Carvalho, Christian Savio Silva, Pollyanna Fernandes Campos, Patrícia Antonia Estima Abreu, Júlia Tavares de Castro, Paulo Newton Tonolli, Mahyumi Fujimori, Rhubia Silveira Martins Rosa, Soledad Palameta, Michael Edward Miller, Vitor Anselmo Sakihara, Fernanda de Lima Valadares, Fabiana Lauretti Ferreira, Bianca Pereira Carvalho Holanda, Douglas Gonçalves de Macedo, Priscila Comone, Natully de Souza Suffert Fogaça, Alexandre Bimbo, Felipe Catanzaro De Moraes, Stephane Tereza Queiroz de Andrade, Helena Lage Ferreira, Edison Luiz Durigon, Clarice Weis Arns, Esper George Kallás, Milena Apetito Akamatsu and Ricardo das Neves Oliveiraadd Show full author list remove Hide full author list
Vaccines 2025, 13(6), 620; https://doi.org/10.3390/vaccines13060620 - 8 Jun 2025
Viewed by 1775
Abstract
Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization [...] Read more.
Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Results: Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. Conclusions: Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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14 pages, 3124 KiB  
Article
Lycorine Inhibits Influenza Virus Replication by Affecting Nascent Nucleoporin Nup93 Synthesis
by Haiyan Yan, Huiqiang Wang, Kun Wang, Shuo Wu, Jiandong Jiang and Yuhuan Li
Int. J. Mol. Sci. 2025, 26(11), 5358; https://doi.org/10.3390/ijms26115358 - 3 Jun 2025
Viewed by 604
Abstract
The influenza A virus (IAV) is a major cause of recurrent seasonal epidemics and global pandemics, posing a significant threat to public health. Although lycorine has demonstrated broad-spectrum antiviral activity, its specific mechanisms of action against IAV remain incompletely understood. In this study, [...] Read more.
The influenza A virus (IAV) is a major cause of recurrent seasonal epidemics and global pandemics, posing a significant threat to public health. Although lycorine has demonstrated broad-spectrum antiviral activity, its specific mechanisms of action against IAV remain incompletely understood. In this study, we characterized the potent inhibitory effects of lycorine on seasonal and drug-resistant IAV subtypes (H1N1/H3N2) as well as the influenza B virus, showing its ability to suppress viral mRNA, viral titers, and M2 protein expression across multiple cell lines. Time-of-addition and time-course assays revealed that lycorine exerts multiphasic interference, and the critical late stage of the IAV life cycle aroused our interest to study this further. Mechanistically, we discovered that lycorine specifically interferes with the de novo synthesis of nucleoporin Nup93, thereby disrupting the nuclear export of viral nucleoprotein (NP). These findings not only establish lycorine as a promising broad-spectrum anti-influenza candidate but also provide new insights for developing host-targeted antiviral strategies. Full article
(This article belongs to the Section Molecular Microbiology)
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18 pages, 2033 KiB  
Article
Imiquimod, a Promising Broad-Spectrum Antiviral, Prevents SARS-CoV-2 and Canine Coronavirus Multiplication Through the MAPK/ERK Signaling Pathway
by Josefina Vicente, Freddy Armando Peñaranda Figueredo, Stefania Mantovani, Daniela Laura Papademetrio, Sergio Ivan Nemirovsky, Andrea Alejandra Barquero, Carina Shayo and Carlos Alberto Bueno
Viruses 2025, 17(6), 801; https://doi.org/10.3390/v17060801 - 31 May 2025
Viewed by 873
Abstract
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. [...] Read more.
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. Unfortunately, mutations have already emerged that confer resistance to these antivirals. In addition, there is an urgent need for broad-spectrum antivirals to address the unpredictable emergence of new viruses with pandemic potential. One promising strategy involves modulating the innate immune response and cellular signaling. Imiquimod, a Toll-like receptor 7 (TLR7) agonist, has shown efficacy in murine models of influenza and respiratory syncytial virus (RSV). Additionally, it demonstrates antiviral activity against herpes simplex virus type 1 (HSV-1) and RSV independent of the TLR7/nuclear factor kappa B (NF-κB) pathway, with protein kinase A (PKA) as a crucial downstream effector. In this study, we demonstrate that imiquimod exhibits concentration-dependent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and canine coronavirus (CCoV) in epithelial cells, underscoring its broad-spectrum action against coronaviruses. Moreover, its anti-coronavirus effect appears to be independent of the TLR/NF-κB and PKA/exchange protein directly activated by cyclic adenosine monophosphate (EPAC) pathways and may instead be linked to the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The ability of imiquimod to inhibit coronavirus replication via the MEK/ERK pathway, coupled with its immunomodulatory properties, highlights its potential as a broad-spectrum antiviral. Full article
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16 pages, 4152 KiB  
Article
Analysis of Epidemiological and Evolutionary Characteristics of Seasonal Influenza Viruses in Shenzhen City from 2018 to 2024
by Weiyu Peng, Hui Liu, Xin Wang, Chao Li, Shunwu Huang, Shiyu Qi, Zhongnan Hu, Xiaoying Xu, Haihai Jiang, Jinyu Duan, Hui Chen, Manyu Huang, Ying Sun, Weihua Wu, Min Jiang, Xuan Zou and Shisong Fang
Viruses 2025, 17(6), 798; https://doi.org/10.3390/v17060798 - 30 May 2025
Viewed by 647
Abstract
The SARS-CoV-2 pandemic and the implementation of associated non-pharmaceutical interventions (NPIs) profoundly altered the epidemiology of seasonal influenza viruses. To investigate these changes, we analyzed influenza-like illness samples in Shenzhen, China, across six influenza seasons spanning 2018 to 2024. Influenza activity declined markedly [...] Read more.
The SARS-CoV-2 pandemic and the implementation of associated non-pharmaceutical interventions (NPIs) profoundly altered the epidemiology of seasonal influenza viruses. To investigate these changes, we analyzed influenza-like illness samples in Shenzhen, China, across six influenza seasons spanning 2018 to 2024. Influenza activity declined markedly during the SARS-CoV-2 pandemic compared with the pre-pandemic period but returned to or even exceeded pre-pandemic levels in the post-pandemic era. Phylogenetic analysis of hemagglutinin (HA) and neuraminidase (NA) genes from 58 H1N1pdm09, 78 H3N2, and 97 B/Victoria isolates revealed substantial genetic divergence from the WHO-recommended vaccine strains. Notably, key mutations in the HA genes of H1N1pdm09, H3N2, and B/Victoria viruses were concentrated in the receptor-binding site (RBS) and adjacent antigenic sites. Hemagglutination inhibition (HI) assays demonstrated that most circulating viruses remained antigenically matched to their corresponding vaccine strains. However, significant antigenic drift was observed in H3N2 clade 3C.2a1b.1b viruses during the 2018–2019 season and in B/Victoria clade V1A.3a.2 viruses during the 2023–2024 season. These findings highlight the impact of NPIs and pandemic-related disruptions on influenza virus circulation and evolution, providing critical insights for future surveillance and public health preparedness. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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Article
Syndromic Testing in the Pandemic Era and Beyond: Rapid Detection for Respiratory Infections in Istanbul
by Mustafa Onel, Hayriye Kırkoyun Uysal, Arat Hulikyan, Yasemin Ayse Ucar, Gizem Yapar, Aytaj Allahverdiyeva, Serra Zeynep Akkoyunlu, Eray Yurtseven, Mehmet Demirci, Sevim Mese and Ali Agacfidan
Viruses 2025, 17(6), 776; https://doi.org/10.3390/v17060776 - 29 May 2025
Viewed by 513
Abstract
The aim of the study was to determine the prevalence rates of respiratory pathogens using syndromic tests and also to show which respiratory viruses were detected in suspected cases, especially during and after the pandemic period. A total of 1984 different respiratory tract [...] Read more.
The aim of the study was to determine the prevalence rates of respiratory pathogens using syndromic tests and also to show which respiratory viruses were detected in suspected cases, especially during and after the pandemic period. A total of 1984 different respiratory tract samples from various departments were included and studied with the QIAstat-Dx device in 2021–2023. The samples were studied with the QIAstat-Dx1 Respiratory SARS-CoV-2 Panel. The kit used was a fully automated, multiplex syndromic test that detected SARS-CoV-2 and 21 other respiratory tract pathogens. As a result of the study, the prevalence of Rhinovirus/Enterovirus (RV/EV) (18.59%), RV/EV-SARS-CoV-2 (42.74%), SARS-CoV-2 (5.04%), and Influenza A Virus (IAV) (5.59%) agents was found to be higher than other agents during the period investigated. Among the 1984 patients examined, 959 (48.33%) had a single viral agent, 156 (7.86%) had double coinfection, 11 (0.55%) had triple coinfection and 1 patient had quadruple coinfection. Nearly half of the patients had a straightforward infection, which helps clinicians in directing specific treatment methods. The study results demonstrate that during the pandemic period, the detection of respiratory pathogens such as SARS-CoV-2 and RV/EV was not only critical for accurate diagnosis but also served as an important indicator of the broader epidemiological trends in respiratory infections. The seasonal distribution showed that while RV/EV was frequently present, its coinfection with SARS-CoV-2 was notably observed only in the first trimester. In light of our findings showing high rates of SARS-CoV-2 and RV/EV detection, along with diverse patterns of coinfection in clinical samples, such comprehensive testing not only assists in rapid diagnosis but also informs public health strategies by reflecting the evolving landscape of respiratory infections in the pandemic and post-pandemic era. Full article
(This article belongs to the Section General Virology)
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