Respiratory syncytial virus as an independent driver of a subsequent influenza epidemic in Berlin before and after the COVID-19 pandemic.

Public health benefits of maternal influenza vaccination among pregnant women and infants <6 months in the United States, 2011-2020.

Highly pathogenic avian influenza (H5N1) viruses of clade 2.3.4.4b have caused significant losses in bird populations worldwide and repeatedly infected mammals, including humans, without sustained human to human transmission. Here we show that an H5N1 virus (H5N1Tex/24) isolated from bovine milk in Texas in 2024 replicates just as efficiently in differentiated human nasal epithelial cells as a pandemic H1N1 virus strain from 2009 (H1N1HH4/09), at both 37 °C and 33 °C. The adaptive mutations PB2 M631L and PA K497R promoted replication at 33 °C but had no effect on replication at 37 °C. An H5N1 virus (H5N1BE/22) isolated from a pelican in 2022, which lacked these mutations, replicated efficiently at 37 °C but poorly at 33 °C, and this limitation was not overcome by the introduction of the PB2 M631L and PA K497R mutations. The differentiated nasal epithelial cell cultures expressed receptors for both human and avian influenza viruses. Accordingly, no HA mutations associated with altered receptor specificity were detected. H5N1Tex/24 was able to effectively suppress the production of interferon-λ, yet remained sensitive to the antiviral effects of this cytokine. These findings suggest that H5N1Tex/24 possesses intrinsic traits supporting efficient replication in differentiated human upper airway cell cultures.

Effectiveness of high-dose versus standard-dose influenza vaccines against severe respiratory and secondary cardiovascular outcomes in adults aged ≥80 years.

Heilongjiang Province shares a 2,981-km border with the Russian Federation and runs the largest land-port network in China. The sheer volume and diversity of cross-border movement at these ports complicates infectious disease surveillance and control. Although some individual ports and pathogens have been examined separately, a province-wide integrated analysis spanning all 18 border port municipalities has been absent. This study aimed to characterise the notifiable-disease burden across those municipalities and to identify the diseases warranting priority attention. Individual case records of notifiable infectious diseases reported between 1 January 2014 and 31 December 2023 were retrieved from China's National Infectious Disease Reporting Information Management System. We computed constituent ratios, crude incidence rates, and disease rankings. Joinpoint regression yielded annual percent change (APC) and average annual percent change (AAPC) estimates. Seasonality was characterised by the direct average seasonal index method. Between-group differences were evaluated with χ² or Fisher's exact tests. A two-tailed P < 0.05 was the threshold for statistical significance, and population denominators came from the Heilongjiang Provincial Statistical Yearbook. Over the decade, 64,865 statutorily notifiable cases (out of 70,244 total reported cases) were recorded, corresponding to a mean annual incidence of 220.30 per 100,000. Respiratory diseases (37.99%) and bloodborne and sexually transmitted diseases (33.68%) jointly accounted for 71.67% of the burden. The five leading diseases were pulmonary tuberculosis (23.56%), hepatitis B (15.81%), influenza (9.85%), syphilis (9.35%), and hand, foot and mouth disease (6.48%). Overall incidence was statistically stable across the period (AAPC 1.85%, 95% CI - 0.18% to 3.93%; P > 0.05), though respiratory diseases trended upward (AAPC 6.61%, P < 0.05) while enteric and zoonotic and vector-borne diseases declined significantly (P < 0.05). Monthly incidence peaked in March (seasonal index 131%) and December (128%). Males outnumbered females (male-to-female ratio 1.51:1; rising to 3.01:1 for zoonotic and vector-borne diseases). The 15-59-year age group contributed 57.54% of cases. Farmers (31.86%), homemakers and the unemployed (23.17%), and students (10.52%) were the principal occupational groups affected. The highest cumulative incidence was observed in Mishan, Suifenhe, Mohe, Muling, and Tongjiang. Respiratory infections should receive heightened prevention efforts in the winter-spring season, whereas bloodborne and sexually transmitted infections call for sustained, risk-focused measures throughout the year. Working-age adults-farmers and homemakers in particular-represent the primary target population. Mishan and Suifenhe warrant reinforced surveillance, and a strengthened China-Russia cross-border joint-prevention mechanism is needed.

Stimulation of fibroblast proliferation by growth factors from HCoV-229E-infected human nasal epithelial cells and influenza virus-infected alveolar epithelial cells: Roles of TGF-β1 and FGF-basic.

Deciphering viral infections at single-cell resolution: From immune dynamics to host-pathogen interactions.

Mechanistic insights into flavonoid-mediated regulation of human influenza virus replication.

Genomic wastewater surveillance of human and animal influenza A viruses in California during the 2024-2025 flu season

Mycobacterium tuberculosis infection is a dynamic continuum. Clinical outcomes reflect complex host-pathogen interactions. Epidemiological and animal studies have suggested influenza coinfection as a risk factor for progression from contained infection to active disease, but human studies have been lacking. Using a whole blood luminescent mycobacterial growth inhibition assay within a human influenza challenge study, we show that influenza infection reduces immunological control of mycobacterial growth. Transcriptome-wide RNA sequencing, cytokine and cellular analyses of subjects’ blood before and after influenza infection reveal that innate immune pathways, including type 1 interferon signalling, are activated by influenza but their subsequent responsiveness to mycobacteria is reduced, with multiple genes’ responses to BCG lux infection repressed by influenza coinfection. Our data suggest that influenza infection impairs immune mechanisms that contain mycobacterial growth and may be a risk factor for tuberculosis (TB) disease. Influenza vaccination might offer high risk, high prevalence populations protection against TB disease.

BackgroundAfter the relaxation of COVID‑19 containment measures, we investigated the pathogen spectrum and epidemiological characteristics of acute respiratory infections (ARIs) in Quzhou City from 2023 to 2024.ObjectiveThis study aimed to investigate the pathogen spectrum and epidemiological characteristics of acute respiratory infections (ARIs) in Quzhou City from 2023 to 2024, providing a scientific basis for local prevention and control strategies.MethodsA total of 2,800 respiratory specimens were collected from November 2023 to July 2024, comprising 1,960 influenza-like illness (ILI) cases from outpatient/emergency departments and 840 severe acute respiratory infection (SARI) cases from inpatient departments. All samples were tested for 13 common respiratory pathogens using multiplex fluorescence quantitative PCR. Etiological and epidemiological analyses were performed based on detection results and case information.ResultsThe overall ARI positivity rate was 59.28% (1,660/2,800), with a male-to-female ratio of 1.07:1 (1,447/1,353). The three most prevalent pathogens were influenza virus (Flu, 23.21%, 650/2,800), Streptococcus pneumoniae (SP, 13.14%, 368/2,800), and adenovirus (ADV, 8.39%, 235/2,800). Single pathogen infections accounted for 73.55% (1,221/1,660) of positive cases, while co-infections with two or more pathogens accounted for 26.45% (439/1,660), yielding an overall co-infection rate of 15.68% (439/2,800). No significant gender difference was observed in detection rates. However, significant differences were found across case types, temporal periods, age groups, and geographic regions (P < 0.01). Children aged ≤5 years exhibited the highest positivity rate (78.00%, 378/525), while adults aged ≥65 years showed the lowest (34.53%, 144/417). Among surveillance regions, Kaihua County had the highest positivity rate (72.47%), and Changshan County the lowest (40.55%).ConclusionsMultiple respiratory pathogens and co-infections are prevalent in Quzhou City, with distinct age-specific and seasonal patterns. These findings underscore the need for continuous multi-pathogen surveillance and integrated prevention strategies for influenza and other respiratory infectious diseases in the post-pandemic era.

Seasonal human influenza A viruses (H1N1 and H3N2) are frequently transmitted to swine populations. Continued transmission of these viruses among swine results in genetic and phenotypic changes, creating new lineages of swine influenza viruses that differ from their parent strains. This contributes to increased viral genetic diversity and the emergence of zoonotic risks. The aim of this study was to assess the prevalence of influenza viruses, including presumably human-origin A(H3N2) strains, on swine farms in Kazakhstan from 2022 to 2025. Real-time RT-PCR was used to test nasal swab antigens, and hemagglutinin inhibition test, and ELISA were used to determine serum antibody levels. Influenza A/H1N1 and A/H3N2 viruses, as well as the A(H7) hemagglutinin genes, were detected in swine. Serological analysis confirmed the presence of antibodies to the A/H1N1pdm09 and A/H3N2 viruses. The influenza A(H3N2) isolates were found to be genetically similar to human viruses of the J.2 or 3C.2a1b.2a.2a.3a.1 clade, possibly indicating transmission from humans to animals. The ongoing exchange of influenza viruses between humans and swine poses a threat of future pandemics. These studies highlight the need for continuous monitoring of swine influenza in Kazakhstan to understand virus evolution and protect public health.

Respiratory Viral Infections and Disease Severity in Hospitalized Children: A Pre-Immunoprophylaxis Baseline Study Highlighting the Role of Human Metapneumovirus.

Human influenza viruses demonstrate immense antigenic variability as a strategy to evade host immunity. The process of evolving to evade host antibody responses, known as antigenic drift, allows influenza viruses to evade epitope-specific antibodies, leading to seasonal influenza outbreaks. Neutralizing antibodies, the major drivers of antigenic drift, target a wide range of epitopes in hemagglutinin and neuraminidase, including functionally conserved regions. In this review, we describe antibody targets of influenza viruses, how influenza viruses have evolved to evade these antibody specificities, and how epistasis helps maintain viral fitness. Then we discuss emerging approaches to study and predict antigenic drift that may improve strain selection for seasonal influenza vaccines.

Pneumococcal disease remains a major cause of morbidity and mortality among adults, particularly in older individuals and those with underlying comorbidities. In the Russian Federation, the incidence of community-acquired pneumonia (CAP) rose sharply in 2024 to 866.6 cases per 100,000 population – twice the long-term average – accompanied by a twofold increase in pneumococcal etiology. This trend is further driven by increasing antimicrobial resistance in Streptococcus pneumoniae, with penicillin non-susceptibility reaching 29.3%. Since 2025, the 20-valent pneumococcal conjugate vaccine (PCV20, Prevnar 20) has been introduced in Russia. It expands coverage by including all PCV13 serotypes along with seven additional serotypes that are highly relevant in adult populations. Clinical and real-world evidence indicates that PCV20 elicits immune responses comparable to PCV13 for shared serotypes and similar to the 23-valent polysaccharide vaccine (PPSV23) for most of the additional serotypes. The vaccine demonstrates a favourable safety profile with a low rate of serious adverse events. In a large real-world study (A. Miles et al., 2026), PCV20 was associated with a 25.6% reduction in invasive pneumococcal disease and a 15.2% reduction in CAP of any cause, corresponding to the prevention of 758 cases per 100,000 person-years. The greatest benefit was observed in individuals aged 85 years and older and in immunocompromised patients. In patients with chronic obstructive pulmonary disease, the incidence of pneumococcal infection is 18 times higher than in the general population. Streptococcus pneumoniae is the most common cause of bacterial community-acquired pneumonia in hospitalized patients of this group. Vaccination in this group has been shown to reduce CAP incidence by 67–71% and improve disease control. PCV20 provides robust immunogenicity in adults with risk factors comparable to that seen in the general population and may be considered a preferred option for patients with chronic respiratory conditions. Importantly, it can be administered concomitantly with influenza and coronavirus disease 2019 (COVID-19) vaccines without compromising immunogenicity or safety.

Avian influenza continues to evolve as a zoonotic threat with important implications for clinical practice and global health preparedness. Sustained circulation in wild birds, repeated spillover into poultry, and an increasing number of infections across diverse mammalian hosts have reshaped exposure pathways and broadened the risk landscape for human infection. For clinicians, this evolving ecology translates into atypical presentations and increased diagnostic uncertainty. Recent global activity has been characterised by widespread animal outbreaks and the emergence of new transmission interfaces, including occupational exposures and livestock-associated events. Human infections remain largely zoonotic and geographically heterogeneous, with patterns influenced by surveillance intensity, exposure context, and healthcare access. We synthesise current evidence on the virology, transmission, global epidemiology, clinical manifestations, diagnosis, treatment, and prevention of avian influenza in humans. We highlight evolving mammalian adaptation and changing risk interfaces that complicate risk assessment. Improved clinician awareness, early diagnosis, and integrated One Health surveillance remain central to strengthening preparedness for future influenza threats.

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD) are multifactorial neurodegenerative disorders driven by complex interactions among genetic susceptibility, aging, and environmental exposures. Growing epidemiological and mechanistic evidence implicates neurotropic viral exposomes, defined as cumulative lifetime viral infections, as significant contributors to AD risk. Viral encephalitis and common viral infections, including herpes simplex virus type 1 (HSV-1), human immunodeficiency virus (HIV), cytomegalovirus (CMV), SARS-CoV-2, and influenza, have been associated with an increased incidence of AD/ADRD; however, the molecular mechanisms underlying these associations remain incompletely understood. A systematic literature review was conducted using PubMed, Web of Science, Scopus, and Google Scholar (1990-2025) to identify epidemiological, experimental, and mechanistic studies linking viral infections to AD-related pathology. Systems biology approaches were applied using Cytoscape, STRING, KEGG, WikiPathways, and Ingenuity Pathway Analysis to construct protein-protein interaction networks and identify convergent biological processes shared between AD and viral host-response pathways. Functional enrichment analyses focused on neuroinflammation, amyloid-β (Aβ) metabolism, tau pathology, autophagy, and blood-brain barrier (BBB) integrity. Across diverse viral infections, strong convergence was observed in innate immune activation pathways, including microglial priming and NLRP3 inflammasome signaling, accompanied by chronic production of proinflammatory cytokines (IL-1β, TNF-α, IFN-γ). Multiple viruses modulated amyloidogenic APP processing, impaired Aβ clearance, promoted tau hyperphosphorylation, disrupted autophagy-lysosomal systems, and compromised BBB integrity. Systems-level analyses revealed overlapping signaling hubs, including NF-κB, MAPK, PI3K-Akt, and cGAS-STING that amplify neurodegenerative cascades, with effects most pronounced in genetically susceptible populations such as APOE4 carriers. Collectively, current evidence supports a mechanistic link between viral exposomes and AD/ADRD mediated through convergent neuroinflammatory, and proteostatic pathways. Although viral infections alone are unlikely to be sufficient to cause AD, recurrent or persistent viral exposures may act as potent disease modifiers that accelerate neurodegenerative processes. Integrating viral biomarkers, genetic risk stratification, and systems biology approaches offers promising opportunities for early diagnosis, prevention, and development of mechanism-guided therapeutic strategies.

Influenza A viruses continue to pose a major threat to global public health. In addition to H1N1 and H3N2 subtypes causing seasonal epidemics that result in an estimated 3–5 million severe cases and 290,000–650,000 deaths annually, other subtypes, including avian H5, H7, and H9, have shown cross-species transmission potential, leading to thousands of human infections in multiple countries. The development of broad-spectrum antiviral drugs capable of inhibiting different influenza virus subtypes is key for alleviating the severity of diseases caused by influenza viruses and reducing mortality rates. Here, we constructed five nanobody-based proteolysis-targeting chimeras (Nb-PROTACs) by fusing NP-specific nanobodies to the α-domain of the Von Hippel‒Lindau (VHL) E3 ubiquitin ligase. We found that two of these chimeras (VHL-Nb135 and VHL-Nb170) efficiently induced NP degradation across all 16 recognized influenza A subtypes (H1–H16). VHL-Nb135 and VHL-Nb170 efficiently inhibited the replication of human (H1N1, H3N2) and avian (H5N1, H7N9, H9N2) influenza viruses in vitro. In animal studies, when VHL-Nb170 was administered intratracheally to mice via adeno-associated virus serotype LungM3 (AAV-LungM3), virus replication was significantly inhibited in the respiratory tract, and 90% and 80% of the mice survived infection with lethal H1N1 and H5N1 viruses, respectively. Our study indicates that Nb-PROTACs offer a robust platform for the development of broad-spectrum therapies against influenza viruses and hold potential for clinical translation as innovative antiviral candidate drugs.

Lung tissue-resident CD8+ T cells facilitate viral clearance and protective immunity to influenza viruses in animal models. Their role during acute human infection is not clear. Here we use bronchoalveolar lavage samples collected from human subjects naturally infected with influenza B virus to show that influenza-specific CD8+ T cells are expanded in the lower airways during acute infection and target only a few epitopes from phylogenetically conserved internal influenza virus proteins. The lower airway influenza-specific CD8+ T-cell immunodominance hierarchy is different from the hierarchy observed in matched blood samples. Transcriptional and protein-level analyses using HLA class I tetramers reveal a tissue-resident profile and less expression of cytotoxic effector molecules in lower airway influenza-specific CD8+ T cells. Collectively, our data show that high-frequency influenza-specific CD8+ T cells with a tissue-resident phenotype are found in the lower airways during viral clearance. These cells recognize a handful of conserved viral epitopes and exhibit a functional phenotype different from cells found in blood. These cells may play a role in controlling human influenza infection.

Influenza sentinel surveillance in Libya was formally established in 2022 by the Libyan National Center for Disease Control (NCDC). Between 2022 and 2024, a total of 1864 nasopharyngeal specimens were collected from patients presenting with influenza-like illness and tested using the GeneXpert for influenza A virus, influenza B virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV). Influenza A virus was detected in 21.1% (393/1864) of samples and influenza B virus was detected in 5.4% of samples (100/1864). SARS-CoV-2 and RSV were identified in 11.6% (216/1864) and 4.1% (77/1864) of specimens, respectively. A subset of 22 influenza A-positive samples was selected based on sample availability and sufficient remaining volume after the initial test for confirmatory testing and further molecular characterization. Real-time RT-PCR subtyping identified 11 A(H1N1)pdm09 and four A(H3N2) viruses. Whole-genome sequencing was successfully performed for 11 isolates, followed by phylogenetic analysis. Genetic characterization revealed that all A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.2a (5a.2a), while A(H3N2) viruses clustered within clade 3C.2a1b.2a.2a.3a.1 (2a.3a.1) were based on hemagglutinin gene mutations. No neuraminidase mutations associated with antiviral resistance were detected. This study represents the first molecular and phylogenetic characterization of circulating human influenza viruses in Libya, with sequence data submitted to the Global Initiative on Sharing All Influenza Data (GISAID) to establish baseline genetic data for influenza viruses in Libya.