ETIDIOH - NEW

  Abstract Limited information is available on the impact of non-pharmaceutical interventions (NPIs) and immune debt on influenza during COVID-19 . This retrospective population-based research examined the effect of the COVID-19 pandemic on the prevalence of influenza-like illness (ILI) cases and influenza positive cases in Sichuan Province . Interrupted time series analysis (ITS) was conducted using data gathered from surveillance hospitals throughout 21 cities , including information on patients diagnosed with ILI and positive nucleic acid testing. Subsequent to the implementation of NPIs, there was a notable temporary reduction in both the incidence of ILI cases and confirmed influenza cases, decreasing by 94.7% and 98.0%, respectively (P<0.001). The weekly trend in influenza-positive cases was notable (+4.1%/week, P=0.001). Following the execution of the second-phase intervention, the fluctuations in the transient changes of ILI patients and influenza-positive cases varied ;...

  Abstract We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity . Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift . Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity . These findings provide timely insight for interpreting recent influenza epidemiology and informing vaccine strain selection. Competing Interest Statement The following authors declare no conflict of interests: KD, RI, LM, SR, HC, GGA, MSA, VS, ZW, SKW, JZ, BJW, DLR, JH, OML, JG, CJRI. PRM receives funding for research work for MSD. EH has received an honorarium for advisory board work for Seqirus. ET has received funding from Novavax and Astra Zeneca. Funding Statement This work was funded by the Medical Research Council (MRC) to the MRC-Universi...

  Abstract Oz virus (OZV), a member of the genus Thogotovirus in the family Orthomyxoviridae, is an emerging tick-borne virus reported in Japan . A fatal human case and seroepidemiological evidence of widespread exposure among wild animals and humans suggest its potential public health significance . However, no animal models suitable for pathogenic studies or evaluation of countermeasures are available for OZV. Here, we have established a lethal mouse model of OZV infection using cell-adapted virus and mice lacking type I interferon signaling (B6 Ifnar1 KO mice). OZV infection resulted in 100% mortality and was characterized by robust viral replication in the liver and spleen, severe hepatitis, and acute liver injury . Using this model, we also demonstrated that oral administration of T-705 , an antiviral drug widely used against RNA viruses, as well as immunization with an inactivated whole virus particle vaccine, protected B6 Ifnar1 KO mice from lethal OZV infection by mitigatin...

  Abstract Background :  Chikungunya virus (CHIKV) has historically been regarded as a low-fatality infection ; however, growing evidence from diverse study designs demonstrated a substantial mortality burden during large-scale epidemics. In 2025, Réunion Island experienced a major CHIKV outbreak , raising renewed concerns about its fatal impact.  Methods :  We conducted an ecological time-series analysis of all-cause mortality during the 2025 chikungunya epidemic. Expected deaths were estimated using two complementary approaches: (i) a baseline based on age-specific mean mortality rates from the same calendar months in the post-pandemic period and (ii) long-term Poisson regression models using a log-link function and population offset, excluding the COVID-19 pandemic period. Excess mortality was calculated as the difference between observed and expected deaths during periods when observed mortality significantly exceeded the upper bound of the 95% confidence interva...

  Abstract Influenza A viruses continually pose pandemic threats, underscoring the need for timely development of Candidate Vaccine Viruses (CVVs) that meet regulatory expectations for vaccine manufacturing. This protocol describes the procedures used at CDC to generate recombinant CVVs through reverse genetics in accordance with World Health Organization guidelines and CDC’s internal Quality System Requirements (QSR)1,2,3. The QSR incorporates relevant principles from the FDA’s Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) regulations, providing a structured framework that ensures documentation integrity, material traceability, and quality oversight during all stages of CVV development. The protocol provides detailed steps for plasmid preparation , virus rescue in Vero cells , and amplification in embryonated chicken eggs , and outlines characterization assays used to confirm the suitability and safety attributes of each CVV. This standardized, quality-drive...

  Abstract Influenza A virus (IAV) is a zoonotic pathogen with a broad host range, posing an ongoing threat to global public health . As the core subunit of the IAV polymerase , polymerase basic protein 1 (PB1) is essential for viral replication and transcription , and its mutations are key drivers of viral evolution . This review evaluates the impact of PB1 mutations on IAV evolution, with a focus on polymerase activity, host adaptation, transmissibility, and virulence. Additionally, it discusses the implications of these mutations for vaccine development. The review aims to provide insights that can inform influenza surveillance, identify novel antiviral targets, and guide vaccine design. Source:  Link:  https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1768665/full ____

  Abstract In the present study, we assessed the pathogenicity of H5N8 avian influenza viruses belongs to the clade 2.3.4.4b in chicken. Birds of three different dose groups, 10 2 , 10 4 , and 10 6 EID 50 were used in the study. No mortality was observed in 10 2 EID0 group. Percent cumulative mortality of 10 4 and 10 6 EID 50 group was 66.67 and 100 %, respectively. Varying duration of MDT of 3.2 and 2 days was observed in 10 4 and 10 6 EID 50 group, respectively. The CID 50 of virus was found to be 10 4.5 EID 50 . High no. of viral RNA copies were found both in oropharyngeal and cloacal swabs and in various organs of birds infected in 10 4 and 10 6 EID 50 group. Significant gross and histological changes and presence of viral antigen in various organs were observed in 10 4 and 10 6 EID 50 group. So, the study concludes that Indian HPAI, H5N8 isolates are highly pathogenic in nature to chicken by affecting most organs systemically. CID 50 of this H5N8 virus indicates poor adaption ...

  ABSTRACT Vaccinia virus (VACV) confers cross-protective immunity against monkeypox virus (MPXV), the causative agent of mpox, and has therefore been extensively exploited as a preventive vaccine . VACV Tiantan strain (VTT) is a second-generation smallpox vaccine used in China in the last century, and there are consistent efforts to minimize its virulence and ensure its best safety for potential clinical applications. In this study, an attenuated VACV rVTT△C12K2△A45 was constructed by deletion of gene segments related to virulence genes , host range genes, immune regulatory genes, and other functional genes from the VTT genome by genetic engineering. Attenuation characteristics of rVTT△C12K2△A45 were confirmed by smaller plaque size, lower replication capacity in various mammalian cell lines along with tests for neurotoxicity in mice , and lesion formation on rabbit skin . Immunization in BALB/c mice with rVTT△C12K2△A45 induced both anti-MPXV and anti-VACV neutralizing antibodies ...

  Abstract Comparably few lineages of influenza A virus (IAV) have evolved long-term sustained transmission in mammals . The reasons remain largely unknown , and the possibility of avian IAVs evolving sustained mammalian transmission is an ongoing concern . Here we measured the GC content and frequency of GC dinucleotides in 115,520 whole genomes of IAVs using bioinformatic analyses . We found that persistent mammalian lineages showed declining trends in GC-related content and could be reliably separated from IAVs circulating only in birds and those sporadically infecting mammals. Similarly, the earliest viruses of persistent mammalian lineages showed reduced GC-related content , suggesting that this trait might in part contribute to their eventual persistence . Recent highly pathogenic 2.3.4.4b H5 viruses that spread in mink, foxes and humans were also characterized by reduced GC-related content . While not sufficient, reduced GC-related content may be a necessary condition for su...

  Abstract The Caucasus region, including Georgia, is an important intersection for migratory waterbirds , offering potential for avian influenza virus (AIV) transmission between populations from different geographic areas. In 2022 and 2023, wild ducks were sampled during autumn migration events in Georgia to study the genetic relationships and molecular characteristics of influenza strains. Sequencing and phylogenetic analysis were used to compare the sampled strains to reference sequences from Africa, Asia, and Europe , allowing assessment of genetic relationships and virus transmission between migratory birds. Protein language modeling identified potential co-infections. Of 225 duck samples, 128 tested positive for the influenza M gene . 55 influenza-positive samples underwent whole-genome sequencing, revealing significant diversity. Analysis of the hemagglutinin (HA) segment showed notable differences among subtypes. Most samples were H6N1 and H6N6 , but co-infections with comb...

  Highlights •  Viremia in children with La Crosse Virus infection is transient; viral RNA was detected in only 3.2% of sera •  Detection of La Crosse Virus RNA in respiratory samples is slightly higher at 21.7% and may reflect the temporal distribution of the virus after infection •  NAAT has limited utility in routine diagnosis of La Crosse Virus encephalitis in children but may still be useful in cases with delayed seroconversion Abstract Background La Crosse virus (LACV), a member of family Peribunyaviridae, genus Orthobunyavirus , is the leading cause of neuroinvasive arboviral infection in children in the United States . Diagnosis relies on detecting specific antibodies (IgG or IgM), a 4-fold titer rise or seroconversion, in patients with compatible presentations. NAAT used for LACV detection has largely been limited to mosquito, animal models or postmortem brain tissue. There is a lack of data on the performance of NAATs in clinical specimens from living patie...

  Abstract Neuraminidase inhibitors (NAIs) and cap-dependent endonuclease inhibitors (CENIs) represent two classes of antiviral drugs recommended for early treatment of patients with seasonal influenza A virus (IAV) infections. However, only limited human data , particularly on combination antiviral treatment , are available to inform optimal dosing regimens against novel IAVs, including highly pathogenic avian influenza A(H5N1) virus , associated with severe disease . Clade 2.3.4.4b A( H5N1 ) viruses have caused outbreaks in avian and mammalian species worldwide , highlighting the need to assess antiviral drug efficacy against these strains. We challenged ferrets with a D1.1 genotype A(H5N1) virus and treated infected animals with the NAI oseltamivir phosphate (OST) and the CENI baloxavir acid (BXA), alone or in combination , with treatment onset commencing pre- or post-symptom onset (24- or 48-hours post-inoculation (p.i.), respectively). When administered pre- or post-illness on...

  Antiviral Res HEDSKOG C, Rodriguez L, Hu Y, Li J, et al SARS-CoV-2 Resistance Analyses From the Phase 3 BIRCH Study of Obeldesivir in High-Risk Nonhospitalized Participants With COVID-19. Antiviral Res. 2026 Jan 19:106351. doi: 10.1016/j.antiviral.2026.106351. PubMed           Abstract available BMJ HIGGS J Help me piece my story together. BMJ. 2026;392:r2624. PubMed          RUSSELL MD, Schaffer A, Bechman K, Gibson M, et al Time trends in newly recorded diagnoses of 19 long term conditions before, during, and after the covid-19 pandemic: population based cohort study in England using OpenSAFELY. BMJ. 2026;392:e086393. PubMed           Abstract available Clin Infect Dis WINOKUR P, Diya O, Fitz-Patrick D, Dever M, et al Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18?55 Years Old. Clin Infect Dis. 2026 Jan 21...

  Ann Intern Med SACKS HS In older adults, RSV prefusion F vaccine reduced hospitalization for RSV-related respiratory tract disease vs. no vaccine. Ann Intern Med. 2026 Jan 6. doi: 10.7326/ANNALS-25-05113. PubMed           Abstract available SOUMARE A, Kapfer T, Botrel T, Adda L, et al Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis. Ann Intern Med. 2025 Dec 2. doi: 10.7326/ANNALS-25-03055. PubMed           Abstract available Arch Virol LAI QR, Chen W, Yu GF, Guo YJ, et al Molecular epidemiology and clinical characteristics of human adenovirus in children in Hangzhou (2022-2023). Arch Virol. 2026;171:60. PubMed           Abstract available Biochem Biophys Res Commun WU X, Bhatt V, Liu JJ, Hong L, et al Single-cell RNA sequencing data analysis reveals differential expr...

  Abstract Clade 2.2 H5N1 influenza viruses have caused an unusually high number of human infections , providing a unique opportunity to investigate early molecular steps associated with host adaptation . Although most work has focused on hemagglutinin (HA), the contribution of neuraminidase (NA) to these early adaptive events has remained unclear. By analyzing publicly available sequences from clade 2.2-infected patients , we identified 20 NA mutations and compared their phenotypes to 20 mutations acquired during diversification in primary human airway cells under drug-free conditions. Most patient-derived NA mutations resulted in modest reductions in sialidase activity , keeping activity within a functional range that supported improved replication in α2,6 sialylglycan (α2,6 Sia)-dominant environments , whereas excessive reduction impaired fitness . Notably, the phenotypes of culture-selected and patient-derived mutations were highly concordant , suggesting that these NA changes ...

  Abstract The continuous evolution and global spread of highly pathogenic avian influenza (HPAI) H5N1 viruses , particularly clade 2.3.4.4b, pose major challenges for pandemic preparedness . This study evaluates a low-dose inactivated split-virus vaccine derived from H5N1 clade 2.3.4.4b, formulated with an Alum/CpG adjuvant , in a preclinical female mouse model . The vaccine induces strong humoral and cellular immunity , generating high titers of cross-reactive antibodies against diverse H5 hemagglutinin (HA) and across different N1 neuraminidase (NA) glycoproteins. The Alum/CpG adjuvant supports substantial antigen dose sparing and promotes a balanced Th1/Th2 profile. Functional assays show potent virus neutralization , neuraminidase inhibition , and antibody-dependent cellular cytotoxicity , alongside robust antigen-specific CD4+ and CD8+ T cell responses, efficient control of lung viral replication, and reduced lung inflammation . Vaccinated mice are fully protected from lethal...

  Abstract In November 2024, an adolescent female in British Columbia was hospitalized presenting with severe symptoms including respiratory failure due to infection with a novel H5N1 subtype influenza strain (BC24). Using cryogenic electron microscopy (cryo-EM), we show here that the N169 α2,3-linked auto-glycan that is found in the sialic acid binding site of previously studied H5 hemagglutinin (HA) proteins is absent in purified BC24 HA protein , suggesting greatly reduced affinity for α2,3-linked sialosides . Glycan microarray analysis shows that the BC24 HA protein displays reduced or no binding not just to most α2,3-linked sialosides, but also to α2,6-linked sialosides . Full-length BC24 HA expressed in A549 lung alveolar carcinoma cells drives membrane fusion, albeit at significantly lower levels than previous H5 HA proteins, and post-infection sera from the patient display strong binding to BC24 HA and HA proteins from other influenza subtypes. The high virulence of the BC2...

  Abstract The risk of highly pathogenic avian influenza infection to humans is challenging to estimate because many human avian influenza virus (AIV) infections are undetected as they may be asymptomatic , symptomatic but not tested , and as contact tracing is difficult because human-to-human spread is rare. We derive equations that consider the evolutionary mechanisms that give rise to pandemics and are parameterized to be consistent with records of past pandemics. We estimate that thousands of human AIV infections occur worldwide in an average year and estimate the infection fatality ratio as 32 deaths per 10,000 infections (95% confidence interval: [9.6, 75]). We estimate that preventing 20% of animal-to-human influenza spillovers annually would delay pandemic emergence by an average of 9.4 years . There is a high level of uncertainty in our estimates due to the few records of past pandemics, but even so this infection fatality ratio is comparable to SARS-CoV-2 during the recen...

  ABSTRACT The outbreak of highly pathogenic avian H5 influenza (HPAI) clade 2.3.4.4b in cattle has spread across the United States . Mice with pre-existing immunity to H1N1 virus or with a live-attenuated influenza vaccine showed protection against a lethal bovine-derived HPAI H5N1 viral challenge . Notably, ferrets with mixed immunity also demonstrated protection against a feline-derived H5N1 virus, independent of cross-reactive neutralization titers , but antibodies to whole virus were observed. To investigate protective factors, we conducted T cell epitope mapping using published H1N1 viral sequences and found high conservation of key T cell epitopes in the bovine HPAI H5N1 strain . Depletion of T cells in mice prior to and during primary H1N1 infection impacted cross-protective antibodies to H5N1 virus, with CD4 depletion increasing mortality and CD8 depletion mildly impacting morbidity upon H5N1 viral challenge. This underscores the need to investigate memory T cell responses...

  Abstract Diseases caused by henipaviruses, exemplified by Hendra virus and Nipah virus, pose a serious risk to public health because of their epidemic potential and high case-fatality rates and the paucity of medical countermeasures to mitigate them. In December 2024, a group of 150 scientists from 16 countries convened in Geelong, Victoria, Australia, to mark the 30th anniversary of the discovery of Hendra virus . The Hendra@30 conference built upon its predecessor conference held in 2019 in Singapore, Nipah@20, by expanding its program across broader disciplines and integrating sessions on human sociology and disease ecology into the main scientific discussions. We describe key highlights from Hendra@30 and reflect on 4 key elements that have advanced henipavirus research and medical countermeasures research and development. We propose that integrating bat ecology into henipavirus research blueprints will enable development of ecologic countermeasures that prevent spillover and...