#Genetic and #biological characterization of a #duck-origin clade 2.3.4.4b #H5N6 avian #influenza virus reveals partial #mammalian #adaptation

 

Highlights

• Duck-origin H5N6 virus A/Duck/Jiangsu/628/2022 shares high homology with the human strain A/Yangzhou/125/2022.

• The 628 strain shows mammalian adaptation markers: HA mutations enhance human receptors affinity and NA mutations reduce sensitivity to neuraminidase inhibitors.

• Limited airborne transmission but detectable droplet-mediated spread suggests increased mammalian transmission risk.

Abstract

Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S037811352600146X?via%3Dihub

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Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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Prompt and Intensive #Antiviral #Chemoprophylaxis in Nursing Home #Influenza #Outbreaks

 

Key Points

-- Question:  Is initiation of antiviral chemoprophylaxis with oseltamivir for 70% or more of eligible nursing home (NH) residents within 2 days of outbreak detection associated with lower 14-day and 30-day mortality and hospitalization compared with a nonintensive approach?

-- Findings:  In this cohort study of 404 influenza outbreaks across 318 NHs with 35 086 resident-trial observations using a sequential target trial emulation and the randomize-censor-weight approach, hospitalization but not death was lower at 14 days post outbreak in NHs that implemented intensive antiviral chemoprophylaxis; 30-day estimates were directionally similar but less precise.

-- Meaning:  Results of this study suggest that clinicians should promptly initiate antiviral chemoprophylaxis in at least 70% of NH residents within 2 days of an influenza outbreak to markedly reduce influenza-related hospitalizations.

Abstract

Importance  

Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear.

Objective  

To examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

Design, Setting, and Participants  

Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018–May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.

Exposures  

Intensive antiviral chemoprophylaxis with oseltamivir (≥70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Main Outcomes and Measures  

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Results  

Among 404 outbreaks in 318 NHs, 35 086 resident-trial observations (29 683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17 155 observations; 17 931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of –0.06% (95% CI, −0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of –0.96% (95% CI, −1.78% to −0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.

Conclusions and Relevance  

Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

Source: 

Link: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2846967

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Use of #baloxavir as adjunctive #antiviral #therapy to neuraminidase inhibitors in severely immunocompromised individuals infected with #influenza

 

ABSTRACT

Immunocompromised patients are at risk of developing severe influenza, with protracted viral shedding and development of resistance-associated mutations under antiviral treatment. We report a case series of severely immunocompromised hematology patients, including allogeneic hematopoietic cell transplantation (HCT) recipients, treated with both baloxavir and oseltamivir and describe clinical and virological outcomes and the safety profile of prolonged combination therapy. Allogeneic HCT recipients with influenza infection treated with baloxavir were retrieved via institutional databases. All hospitalized allogeneic HCT patients treated with a combination therapy of baloxavir and oseltamivir over five influenza seasons between October 2019 and May 2025 were included. Six influenza-infected hematology patients (5/6 allogeneic HCT recipients) were treated with combination therapy of oseltamivir and baloxavir. All patients presented with lower respiratory tract infections. Oseltamivir treatment duration ranged from 5 to 31 days, and the number of administered baloxavir doses ranged between one and five. Baloxavir administration was well tolerated, and no adverse events could be attributed to the administered antiviral treatment. All-cause mortality at 3 months post-infection was 66% (4/6), mainly driven by underlying disease. In two patients with protracted shedding, combination therapy did not prevent the development of resistance mutation(s). Combination treatment with prolonged courses of oseltamivir and repeated doses of baloxavir was well tolerated. No definitive conclusions on the efficacy of this approach could be drawn from this study. More data are required on the best treatment of hematology patients infected with influenza.

Source: 

Link: https://journals.asm.org/doi/10.1128/aac.01659-25

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#Oseltamivir aziridines are potent #influenza #neuraminidase #inhibitors and imaging agents

 

Significance

Influenza remains a major global health threat. We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine. This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes, selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development.

Abstract

Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals, including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir, are limited by noncovalent binding and emerging resistance. We hypothesized that Oseltamivir aziridines would unite transition-state mimicry for tight binding, with aziridine-enabled covalent capture of the catalytic tyrosine, thereby supporting both therapy and activity-based quantification. Here, we present oseltamivir-based aziridines, inspired by cyclophellitol chemistry, that act as covalent inhibitors and activity-based probes via an N-acylaziridine warhead. Free-energy calculations, and NMR observations, indicate a 4H5 half-chair preference consistent with the NA transition state, and selected analogues inhibit multiple NA subtypes with low nanomolar binding constants. Diverse evidence establishes covalency: time-dependent inactivation, inhibitor washout, intact-mass shifts, MS/MS identification of a tyrosine adduct, and QM/MM reaction profiles, while cryoEM of N1 aligns with the proposed binding mode, revealing an elimination product. The inhibitors demonstrate formidable activity against diverse viral neuraminidases, including H5N1, and further enable imaging and quantification of active NA. With their dual therapeutic and diagnostic potential, these first-in-class inhibitors indeed benefit from transition state mimicry and covalency, and thus offer a powerful platform for antiviral development and neuraminidase imaging, addressing urgent global health needs in influenza treatment and prevention.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2504045123

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14th Meeting of #WHO #Expert Working Group of the Global #Influenza #Surveillance and Response System (GISRS) for Surveillance of #Antiviral Susceptibility (March 20 '26)

Weekly epidemiological record 

20 MARCH 2026, 101th YEAR, No 12, 2026, 101, 53–56

http://www.who.int/wer 

Executive Summary 

The WHO Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (AVWG) supports the WHO GISRS by providing practical guidance for monitoring antiviral susceptibility of seasonal and emerging influenza viruses through global surveillance efforts. 

The 14th WHO-AVWG meeting was held in virtual format on 10-12 June 2025. 

Update on susceptibility of seasonal influenza viruses to approved antiviral agents 

From approximately May 2024 to May 2025, five WHO Collaborating Centres (CCs) and two National Influenza Centres (NICs) reported co-circulation of influenza A(H1N1) pdm09, A(H3N2), and B/Victoria viruses. 

A(H1N1)pdm09 dominated in Eastern Asia{1}. Elevated frequency of influenza neuraminidase (NA) inhibitor (NAI) reduced inhibition/ highly reduced inhibition (RI/HRI) was identified among A(H1N1)pdm09 viruses, largely conferred by the NA-H275Y substitution. 

Reporting frequency was 3.8% in China, lower (≤1%) in other reporting regions, but still measurable and were in some cases a result of prior antiviral use or specific local outbreaks (e.g., a hospital in Iceland with a NA-H275Y+S247N cluster, a primary school classroom outbreak in Japan{2}. The NA-S247N substitution (≤3.3%) was also noted by three centres, but these viruses exhibited normal inhibition (NI) by NAIs when available isolates were tested. 

Incidence of RI/HRI or NA-associated markers were less frequently reported for A(H3N2) and B/Victoria viruses than A(H1N1)pdm09 viruses. 

Markers and incidence of reduced susceptibility to baloxavir was detected at low frequencies of 0.07 to 2.2%, where the latter value represented a small sample set of only 2 of 89 viruses in Japan. 

Reduced susceptibility or amino acid markers indicative of reduced susceptibility were observed only in influenza A viruses and not influenza B. 

Update on susceptibility of zoonotic and animal influenza viruses  to approved antiviral agents 

From approximately May 2024 to May 2025, global surveillance data from WHO CCs, NICs, and associated partners including WHO Essential Regulatory Laboratories and the OFFLU (WOAH/FAO Network of Expertise on Animal Influenza) network reported that most zoonotic and avian influenza viruses, particularly circulating A(H5N1/x) HA clade 2.3.4.4b and 2.3.2.1a/e viruses, were broadly susceptible to NAIs and baloxavir. 

A(H5N1) 2.3.4.4b virus oseltamivir inhibitory concentrations remain elevated vs. seasonal N1 viruses. 

Small and isolated incidence of NAI associated RI/HRI or markers included: NA-D199G mediated oseltamivir/zanamivir RI detected in A(H5N1) 2.3.4.4b poultry in the Russian Federation (February 2024, reported June 2025), NA-N295S in poultry in India A(H5N1) 2.3.2.1a isolates, and 8 poultry farms in British Columbia, Canada exhibiting A(H5N1) 2.3.4.4b with NA-H275Y. 

Only two viruses with reduced baloxavir susceptibility were identified, 1 human virus with PA-I38M (California, USA) and 1 environmental virus isolate with PA-V100I (China, Hong Kong Special Administrative Region). 

Beyond A(H5N1/x), nearly 30 avian influenza subtypes including A(H9N2), A(H7N2), A(H7N7), and A(H7N9), and A(H10N7) were analysed across surveillance sites in the Bangladesh, Egypt, the Netherlands and the United States of America (USA). 

They generally lacked NA or PA genotypic markers of reduced drug susceptibility and when available for phenotypic testing, were susceptible to both NAIs and baloxavir. 

A(H7N2) and A(H7N7) viruses from the Netherlands displayed oseltamivir RI compared to human seasonal references, but this may be due to foldchange comparison to a mismatched NA subtype. 

Swine-origin variant viruses (A(H1N1)v, A(H1N2)v, A(H3N2)v) tested across the USA and Europe were largely free of genotypic or phenotypic indicators of reduced susceptibility/inhibition to NAIs or baloxavir. 

Some viruses (the  Netherlands) showed slightly higher NAI median inhibitory concentrations to historical or human seasonal baselines, but all remained below NAI RI thresholds. 

Update of protocols and guidance for GISRS laboratories 

Both genotypic and phenotypic assays may be used as tools to monitor susceptibility of influenza viruses to NAIs and baloxavir. 

The WHO-AVWG routinely reviews and updates influenza NA and PA amino acid substitutions associated with reduced susceptibility to NAIs and baloxavir; updated tables for the previous reporting period were included on the WHO website{3–5}. 

The US CDC continues to update and ship reference virus panels that can be used for NAI and baloxavir susceptibility testing, available via the International Reagent Resource{6} 

Further guidance on baloxavir and other PA inhibitor testing included the Influenza Replication Inhibition Neuraminidase-based Assay (IRINA), published by the Centers for Disease Control and Prevention, USA{7} and included on the WHO website{8}. 

The WHO AVWG continues to develop algorithms for NICs to aid in influenza response planning (zoonotic, pandemic, and antiviral resistance-specific events), guidance to aid in decisions making for testing strategies (genotypic vs. phenotypic), and guidance for consideration of baloxavir and PA inhibitor specific amino acid substitutions associated with reduced drug susceptibility{9}. 

Additionally, the WHO-AVWG has worked with GISAID to continue to refine and implement modifications to existing tools to facilitate identification of NA and PA substitutions upon sequence submission. 

Outbreak and pandemic preparedness with clinicians’ perspectives 

Two physicians, Profs. Prof. David Hui and Bin Cao, were invited to present recently updated WHO guidance on clinical practice guidelines for influenza{10}. 

Significant updates and discussion surrounded inclusion of baloxavir, which was conditionally recommended for non-severe disease high-risk patients and post-virus exposure prophylaxis (PEP) including influenza viruses associated with high mortality. 

Conditional recommendation against any NAI or baloxavir intervention remains for non-severe disease low-risk patients or seasonal virus PEP. 

Data was presented on multiple PA inhibitors rapidly moving through late-stage clinical trials in China which may have implications on expanded usage of this newer class of influenza drugs. 

Review of External Quality Assessment Programme (EQAP) panels 

EQAP was initiated in 2007 to monitor the quality of GISRS, NICs, other national influenza reference laboratories’ capacity for influenza diagnosis and detection. 

An optional antiviral phenotypic NAI panel was introduced in 2013, and genotypic baloxavir susceptibility was introduced in 2020. 

Results for the 2024 Global EQAP panel were reported during the 14th WHO-AVWG meeting. 

Of the 194 participating laboratories, 26.3% participated in NAI susceptibility testing. 

Results and subsequent discussion from this year’s panel were used by members of WHO-AVWG to assess the training needs of NICs. 

Way forward 

The 2020–2023 Annual Global Update on the Susceptibility of Influenza Viruses (Global AVS) manuscript was published{11} and drafting of a 2023–2025 publication is underway. The next WHO-AVWG meeting will be held in June 2026.

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{1} World Health Organization. Influenza Transmission Zones. 2026. https://cdn.who.int/media/docs/ default-source/influenza/influenzaupdates/2025_09_24_influenza-transmission-zones. pdf?sfvrsn=22361408_3&download=true. 

{2} Takashita E, Shimizu K, Usuku S, Senda R, Okubo I, Morita H, et al. An outbreak of influenza A(H1N1) pdm09 antigenic variants exhibiting cross-resistance to oseltamivir and peramivir in an elementary school in Japan, September 2024. Euro Surveill. 2024;29(50).

{3} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by neuraminidase inhibitors (NAIs). 2025. https://cdn.who.int/media/docs/default-source/ influenza/laboratory---network/quality-assurance/human-nai-marker-table_ for-publication_final_20240918.pdf. 

{4} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by NA inhibitors (NAIs) among avian influenza viruses of Group 1 (N1, N4, N5, N8 subtypes) and Group 2 (N2, N3, N6, N7, N9 subtypes) NAs. 2025. https://cdn.who.int/media/ docs/default-source/influenza/avwg/avian-nai-marker-whotable__10-10-2025.pdf?sfvrsn=bc0d1e9a_10 

{5} World Health Organization. Summary of polymerase acidic protein (PA) amino acid substitutions assessed for their effects on PA inhibitor (PAI) baloxavir susceptibility. 2025. https://cdn.who.int/media/docs/default-source/influenza/ laboratory---network/quality-assurance/antiviral-susceptibility-influenza/ pa-marker-who-table_28-11-2025_updated.pdf?sfvrsn=5307d6fe_4. 

{6} International Reagent Resource. 2026. https://www. internationalreagentresource.org/. 

{7} Patel MC, Flanigan D, Feng C, Chesnokov A, Nguyen HT, Elal AA, et al. An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance. Antiviral Res. 2022;208:105457. 

{8} World Health Organization. Baloxavir Susceptibility Assessment using Influenza Replication Inhibition Neuraminidase-based Assay (IRINA). https:// cdn.who.int/media/docs/default-source/influenza/avwg/cdc-phenotypic-lp492rev01d---baloxavir-susceptibility-assessment-using-irina.pdf? 

{9} Patel MC, Nguyen HT, Mishin VP, Pascua PNQ, Champion C, Lopez-Esteva M, et al. Antiviral susceptibility monitoring: testing algorithm, methods, and f indings for influenza season, 2023-2024. Antiviral Res. 2025;244:106299. 

{10} World Health Organization. Clinical practice guidelines for influenza 2024. https://www.who.int/publications/i/item/9789240097759.

{11} Hussain S, Meijer A, Govorkova EA, Dapat C, Gubareva LV, Barr I, et al. Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res. 2025:106217.

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Source: 

Link: https://iris.who.int/server/api/core/bitstreams/1ea408da-cd90-438b-b80c-b00aaf4e7315/content

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#Report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on #Influenza during 2024

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. During 2024, influenza A(H1N1)pdm09 and A(H3N2) viruses predominated, accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria. Of note, one influenza A(H5N1) virus was also received in 2024. The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024. Of 4,007 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, twelve A(H1N1)pdm09 viruses and one B/Victoria virus showed highly reduced inhibition against oseltamivir or zanamivir. Of 3,294 total samples sequenced for baloxavir susceptibility, 18 of the 1,825 A(H3N2) samples were identified with genetic evidence of reduced susceptibility to baloxavir marboxil in the PA gene.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3449

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#Baloxavir outperforms #oseltamivir, #favipiravir, and #amantadine in treating lethal #influenza #H5N1 HA clade 2.3.4.4b #infection in #mice

 

Abstract

Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. Amantadine provided no benefits. Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning.

Source: 

Link: https://www.nature.com/articles/s41467-026-69721-5

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#Prognostic factors in #H7N9 avian #influenza: a systematic review based on case reports

 

Abstract

Objective

The H7N9 avian influenza virus, identified in China in 2013, has posed a significant threat to public health due to its high mortality rate. This systematic review aims to evaluate the clinical characteristics and mortality risk factors of H7N9 patients.

Methods

English and Chinese databases (PubMed, Web of Science, Embase, CNKI, VIP, Wanfang) were searched for studies on laboratory-confirmed H7N9 cases with available data on symptom onset, diagnosis time, clinical features, oseltamivir administration, and outcomes. Univariate and multivariate analyses were performed on the pooled case data to assess the relationship between clinical factors and mortality risk.

Results

A total of 166 studies including 237 H7N9 cases were analyzed, with an overall mortality rate of 41.77%. Univariate analysis showed higher mortality in patients with advanced age ≥ 66 years (62.50%), those with underlying diseases (60.20%), those who received oseltamivir ≥ 8 days after symptom onset (54.17%), and those diagnosed ≥ 11 days after onset (62.75%), whereas patients treated with oseltamivir within 2 days of onset had the lowest mortality (17.39%). Multivariate analysis identified advanced age ≥ 66 years (OR = 3.10, 95% CI: 1.07–8.99, P = 0.037) and delayed oseltamivir administration after symptom onset (OR = 4.63, 95% CI: 1.12–19.18, P = 0.034) as independent predictors of mortality, while sex, underlying diseases, and onset-to-diagnosis time were not statistically significant.

Conclusion

Older age and delayed initiation of oseltamivir are key independent predictors of mortality in H7N9 infection. Prompt diagnosis is crucial to facilitate early antiviral treatment, which may improve survival. Future prospective studies are needed to validate these findings and optimize clinical management.

Clinical trial registration

Not applicable.

Source: 

Link: https://link.springer.com/article/10.1186/s12879-026-12908-4

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Genomic #Evolution of #Influenza A Virus During the 2024-2025 Season, the Johns Hopkins Health System: Antigenic Drift Reduces Serum Neutralization

 

Abstract

Introduction

Seasonal influenza causes significant global morbidity, mortality, and economic burden. Ongoing viral evolution can lead to vaccine mismatch and the emergence of antiviral resistance, highlighting the importance of genomic surveillance. The 2024–2025 influenza season was characterized by high incidence and increased hospitalizations.

Methods

We analyzed influenza A virus (IAV) genomes and clinical characteristics from the 2024–2025 season. Whole-genome sequencing was performed on 648 influenza A–positive clinical specimens collected between October 2024 and April 2025.

Results

Hemagglutinin (HA) sequences were recovered from 74.23% (481/648) of samples and used for subtyping and phylogenetic analysis. A(H1N1)pdm09 and A(H3N2) viruses co-circulated, representing 55.5% and 44.5% of cases, respectively. Among A(H1N1)pdm09 viruses, the HA1 substitution T120A, located near the Sa antigenic site, increased more than twofold compared with the prior season. Circulating A(H3N2) viruses belonged to multiple HA subclades and exhibited distinct amino acid substitutions at key antigenic sites. Neutralization assays using sera from individuals vaccinated with the 2024–2025 seasonal influenza vaccine demonstrated reduced neutralization of three dominant A(H1N1)pdm09 isolates and two A(H3N2) isolates compared with vaccine strains, consistent with antigenic drift. In addition, the neuraminidase substitution S247N, previously associated with reduced oseltamivir susceptibility, was detected in 13.9% of A(H1N1)pdm09 samples.

Discussion

These findings demonstrate ongoing antigenic drift and the presence of antiviral resistance–associated mutations during the 2024–2025 influenza season, underscoring the need for continued genomic surveillance to guide vaccine and antiviral strategies.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag069/8461561#google_vignette

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#Oseltamivir and #baloxavir monotherapy and combination #therapy efficacy against clade 2.3.4.4b #H5N1 #influenza virus infection in #ferrets

 

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 onset, BXA, but not OST, monotherapy provided significant reduction of clinical signs and significantly decreased infectious viral levels (in both respiratory and extrapulmonary specimens) compared with mock-treated animals. Combination OST/BXA treatment, when administered pre- or post-symptom onset, resulted in significant improvements in both metrics versus OST monotherapy. These data support continued investigation of antiviral treatment modalities that include both NAI and CENI for patients with mild and severe A(H5N1) disease.

Source: 

Link: https://www.nature.com/articles/s42003-026-09607-w

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#Clinical Features and #Management of a Critical #Human Case of #H10N3 Avian #Influenza: A Case Report and Literature Review

 

Highlights

• Nonspecific early signs hinder prompt diagnosis of H10N3 infection.

• H10N3 human infection remains rare but with high clinical severity.

• All patients had bird exposure and developed fever, cough, and dyspnoea.

• Diagnosis was confirmed by sequencing; imaging revealed viral pneumonia.

Abstract

Background

Since the first human case of H10N3 Avian Influenza in Jiangsu, China (April 2021), three cases have been reported globally. However, clinical and treatment data remain limited. Therefore, we describe the fourth patient’s epidemiology, clinical manifestations, diagnostics, treatment.

Case presentation

A 23-year-old woman, previously well, presented on 12 Dec 2024 with fever, dry cough and breathlessness after pig and chicken contact. CT showed bilateral pneumonia. Despite high-flow oxygen and broad-spectrum antibiotics she deteriorated, requiring intubation, lung-protective ventilation and VV-ECMO. Bronchoalveolar lavage isolated H10N3 influenza virus. Treatment with oseltamivir and baloxavir plus prone-position ventilation led to clinical improvement.

Conclusion

Due to its nonspecific early symptoms, H10N3 is difficult to diagnose promptly, increasing the risk. Early recognition, antiviral therapy, and aggressive support are essential in managing severe infections.

Source: 

Link: https://www.ijidonline.com/article/S1201-9712(26)00002-0/fulltext

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A case of #H10N3 avian #influenza in a young woman

 

Context and significance

The avian influenza A virus subtype H10N3 is a possible candidate for causing a fatal flu and may present a serious public health threat. Research increasingly shows that the avian influenza virus H10N3 can be transmitted from birds to humans, causing severe viral pneumonia and potentially leading to acute respiratory distress syndrome and respiratory failure. Researchers at the Fourth People’s Hospital of Nanning (China) provide evidence supporting the cross-species transmission of the avian influenza virus H10N3 to humans, which can give rise to severe pneumonia. The authors report that a female patient with avian influenza virus H10N3 infection, who was suffering from severe pneumonia, respiratory failure, pneumothorax, and numbness and dysesthesia in her feet, recovered after receiving appropriate therapy and was discharged from the hospital.

Highlights

• A young woman contracted the avian influenza virus H10N3

• Secondary infections, pneumothorax, and foot numbness developed consecutively

• Baloxavir marboxil and oseltamivir were administered

Summary

Background

Avian influenza viruses, frequently identified in wild waterfowl and poultry, have occasionally been transmitted to humans, causing severe respiratory diseases. This report covers the fourth case of a human contracting the H10N3 subtype of avian influenza virus.

Methods

A case of novel avian influenza virus subtype H10N3 was detected in a female patient hospitalized in Nanning, China, in December 2024. Blood, feces, urine, and bronchoalveolar lavage fluid were collected from the patient for medical analysis during the hospitalization.

Findings

A case of novel avian influenza virus subtype H10N3 was detected in a female patient hospitalized in Nanning, China, in December 2024. She also had a history of exposure to live poultry. This case represents the fourth documented instance of H10N3 infection in humans. She was treated with a combination of baloxavir marboxil and oseltamivir. She exhibited extensive lung lesions. Additionally, she presented complicating factors, including secondary infection, pneumothorax, and numbness in her feet. She recovered and was discharged on March 27, 2025, amid comprehensive supportive care, which included therapy with baloxavir marboxil, oseltamivir, fluconazole, tigecycline, amikacin, extracorporeal membrane oxygenation, and rehabilitation therapy.

Conclusions

The virus was effectively cleared by the combination therapies. The internal genes of the H10N3 virus in this patient were highly homologous to the corresponding genes from the A/Yunnan/2024 virus (GenBank accession numbers, hemagglutinin [HA] [GenBank: PP555669] and PB-2 [GenBank: PP555666]).

Funding

This work was funded by the Fourth People’s Hospital of Nanning - Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) Clinical Treatment Center of Guangxi (Nanning).

Source: Med., https://www.cell.com/med/abstract/S2666-6340(25)00272-7

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Differential modulation of #Interferon and Cell Death Responses defines #Human vs Avian #Influenza A Virus Strain-Specific Virulence and guides Combination #Therapy.

Abstract

Influenza A virus (IAV) poses a significant global health risk, with highly pathogenic strains like H5N1 (CFR ~52%) causing severe disease compared to less lethal but more transmissible strains like H1N1 (CFR 0.01-0.03%). Although IAV primarily infects lung epithelial cells, causing cell death and tissue damage, the molecular basis of strain-specific pathogenesis remains poorly understood. Here we show that in cell culture, H5N1 induced more rapid and extensive cell death than H1N1. Since Interferon (IFN) signaling is key to innate immunity, we examined its role in virus-induced cell death using STAT1-knockout A549 cells and JAK/STAT pathway inhibitors like Baricitinib. Both approaches reduced cell death across various IAV strains, including H1N1, H5N1, H7N9, and H3N2. However, inhibition increased viral titers, raising concerns about its clinical use in isolation. To overcome this, we tested a combination of Oseltamivir (antiviral) and Baricitinib (anti-inflammatory). Post-infection treatment in a murine model reduced lung inflammation and improved survival. Given that both drugs are FDA-approved, this approach has strong translational potential for clinical IAV treatment.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Wellcome Trust/DBT India Alliance, IA/I/18/1/503613

Indian Council of Medical Research, IIRPIG-2023-0000978

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.31.667854v1

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The combinatorial activities of #oseltamivir and #molnupiravir against #influenza virus infections in vitro and in vivo

Highlights

• Mol shows greater antiviral effects against IAV and IBV in cell cultures.

• Mol and Ose together showed a synergistic effect against IAV.

• In mice, Mol alone or with Ose reduced lung injury and viral load.

Abstract

Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections. However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir, a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections. In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses, when compared to oseltamivir treatment. Combination of NHC with oseltamivir exhibited a synergistic antiviral effect against the influenza A/Puerto Rico/8/34 H1N1 strain, but not the influenza B/Washington/02/2019 strain. In a mouse model infected with the PR/8 virus strain, treatment with molnupiravir alone or in combination with oseltamivir effectively attenuated lung injury and reduced viral load in the tissue. Taken together, molnupiravir can be explored in combination with oseltamivir to treat influenza, especially for patients infected with the oseltamivir-resistant strains, whereas further research is warranted.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225002557?via%3Dihub

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#Antiviral #therapy for #HPAI and reported #oseltamivir #resistance in #Canada

{Excerpt}

Highly pathogenic avian influenza (HPAI) A(H5Nx) clade 2.3.4.4b viruses have been circulating in North America since late 2021. Since their initial incursion, they have been associated with unprecedented mortality in wild birds, domestic poultry, and marine mammals throughout the Americas, and are now seen across all global regions except Oceania. Furthermore, transmission among dairy cattle and poultry in the United States has led to growing numbers of human cases, and there was a severe human case in Canada with no known infected animal exposure (1,2).

(...)

Source: Journal of the Association of Medical Microbiology and Infectious Disease Canada, https://utppublishing.com/doi/10.3138/jammi-2025-0307

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A 15-year study of #neuraminidase #mutations and the increasing of S247N mutation in #Spain

Highlights

• In a landscape of a very narrow arsenal of influenza antivirals, resistance mutations are a significant threat.

• Resistance mutations were present in 0.5-5% in A and B influenza viruses during the last 15 years.

• However, S247N resistance mutation in the NA gene sharply increased during 2023-2024 season.

• While this mutation does not confer strong resistance by itself, their fixation could increase the risk of resistance in the future if other resistance mutations appears or get fixed together with it.

Abstract

The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations, especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain. To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences, and analyzed the resistance mutations using FluSurver software. Our results showed that the occurrence of NA resistance mutations remained constant in the four viruses during the 15 seasons evaluated, being around 0.5-5%. Most of the resistance was found in the A(H1N1)pdm09 subtype (around 70%), especially from the 2023-2024 season onwards, when a significant increase in the occurrence of S247N mutation was observed. The occurrence of this type of mutation before 2022 was rare, but in the 2023-2024 season a total of 44 influenza viruses harboring S247N mutations were detected, while in the other years, only two cases were observed. Some studies have described a significant increase in this mutation over the past two seasons and although it appears to confer only slightly reduced inhibition to oseltamivir, its increase is noteworthy and should be a reason for increased their vigilance.

Source: Virus Research, https://www.sciencedirect.com/science/article/pii/S0168170225000760?via%3Dihub

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#Global #update on susceptibilities of #influenza viruses to #neuraminidase #inhibitors and the cap-dependent endonuclease inhibitor #baloxavir, 2020–2023

Highlights

• Antiviral susceptibility to NA inhibitors and PA inhibitor baloxavir was determined for seasonal and zoonotic influenza viruses circulating globally during 2020–2023.

• Low global frequencies (0.1-0.2%) of seasonal influenza viruses with reduced or highly reduced inhibition by NAI inhibitors were observed as in previous years.

• Low global frequencies of seasonal influenza viruses (∼ 0.1%) with reduced susceptibility to baloxavir were observed, with the rate in Japan elevated (3.3%) in 2022–2023, as has been seen previously.

• For zoonotic viruses, 2.7% contained genetic markers associated with reduced or highly reduced inhibition to NA inhibitors and none contained markers associated with reduced susceptibility for baloxavir.

• For the treatment of influenza, NA inhibitors and baloxavir remain suitable.

ABSTRACT

Antiviral susceptibility of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Response System. This study describes a global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs, oseltamivir, zanamivir, peramivir, laninamivir) and the cap-dependent endonuclease inhibitor (CENI, baloxavir) for three periods (May to May for 2020–2021, 2021–2022 and 2022–2023). In particular, global influenza activity declined significantly in 2020-2021 and 2021-2022 when compared to the pre-pandemic period of COVID-19. Combined phenotypic and NA sequence-based analysis revealed that the global frequency of seasonal influenza viruses with reduced or highly reduced inhibition (RI/HRI) by NAIs remained low, 0.09% (2/2224), 0.12% (27/23465) and 0.23% (124/53917) for 2020–2021, 2021–2022 and 2022–2023, respectively. As in previous years, NA-H275Y in A(H1N1)pdm09 viruses was the most frequent substitution causing HRI by oseltamivir and peramivir. Sequence-based analysis of polymerase acidic (PA) protein supplemented with phenotypic testing revealed low global frequencies of seasonal influenza viruses with reduced susceptibility (RS) to baloxavir, 0.07% (1/1376), 0.05% (9/18380) and 0.12% (48/39945) for 2020–2021, 2021–2022 and 2022–2023, respectively; commonly associated substitutions were PA-I38T/M/L. In Japan, the rate was 3.3% (16/488) during 2022–2023, with 11 A(H3N2) viruses having PA-I38T/M substitutions. For zoonotic viruses, 2.7% (3/111) contained substitutions, one each NA-H275Y, NA-S247N and NA-N295S, associated with RI/HRI NAI phenotypes, and none contained PA substitutions associated with RS to baloxavir. In conclusion, the great majority of seasonal and zoonotic influenza viruses remained susceptible to NAIs and CENI baloxavir.

Source: Antiviral Research, https://www.sciencedirect.com/science/article/abs/pii/S0166354225001433?via%3Dihub

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#Oseltamivir #Treatment vs Supportive Care for Seasonal #Influenza Requiring #Hospitalization

Key Points

-- Question:  In adults with influenza requiring admission to hospital, is oseltamivir treatment within the first 2 days of admission, when compared with supportive care without oseltamivir, associated with a decreased risk of death in hospital?

-- Findings: In this cohort study of 11 073 patients hospitalized with influenza, oseltamivir treatment was associated with an adjusted risk reduction of 1.8% for in-hospital mortality when compared with supportive care.

-- Meaning: The findings of this study support current guidelines that recommend oseltamivir treatment for patients admitted to hospital with influenza; clinical trials should be conducted to generate better quality evidence.

Abstract

Importance  

Current guidelines recommend oseltamivir treatment for all patients hospitalized with influenza, but this guidance is based on suboptimal evidence.

Objective  

To evaluate outcomes associated with oseltamivir treatment when compared with supportive care for severe seasonal influenza requiring hospitalization.

Design, Setting, and Participants  

This retrospective cohort study using target trial emulation included adult patients admitted to hospital with influenza from 30 hospitals in Ontario, Canada, from January 2015 to June 2023. Data were analyzed from November 2024 to March 2025.

Exposure  

Oseltamivir treatment on hospital day 0 or 1 vs supportive care without oseltamivir.

Main Outcome and Measures  

The primary outcome was in-hospital mortality. Secondary outcomes included time to being discharged alive and readmission within 30 days. Overlap weighting of propensity scores was used to balance covariates, and a competing risk model was used to compare time to being discharged alive.

Results  

Of 11 073 patients (mean [SD] age, 72.6 [16.8] years; 5793 female [52.3%]), there were 7632 patients (68.9%) and 3441 patients (31.1%) in the oseltamivir and supportive care groups, respectively. In hospital, 268 patients (3.5%) and 168 patients (4.9%) in the oseltamivir and supportive care groups died, respectively, with an adjusted risk difference of −1.8% (95% CI, −2.8% to −0.9%; P < .001). The oseltamivir treatment group was more likely to be discharged alive (adjusted subdistribution hazard ratio, 1.20; 95% CI, 1.15 to 1.25; P < .001). After discharge, 645 patients (8.5%) and 336 patients (9.8%) were readmitted in the oseltamivir and supportive care groups, respectively, with an adjusted risk difference of −1.5% (95% CI, −2.8% to −0.2%; P = .02).

Conclusions and Relevance  

In this cohort study of patients hospitalized with influenza, oseltamivir treatment was associated with a lower in-hospital mortality risk, earlier discharge, and lower readmission rate, supporting evidence for the current guideline recommendation of oseltamivir treatment for severe influenza. Clinical trials are needed to definitively answer this question.

Source: JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2835158

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#Surveillance of avian #influenza through #bird #guano in remote regions of the global south to uncover transmission dynamics

Abstract

Avian influenza viruses (AIVs) pose a growing global health threat, particularly in low- and middle-income countries (LMICs), where limited surveillance capacity and under-resourced healthcare systems hinder timely detection and response. Migratory birds play a significant role in the transboundary spread of AIVs, yet data from key regions along migratory flyways remain sparse. To address these surveillance gaps, we conducted a study between December 2021 and February 2023 using fresh bird guano collected across 10 countries in the Global South. Here, we show that remote, uninhabited regions in previously unsampled areas harbor a high diversity of AIV strains, with H5N1 emerging as the most prevalent. Some of these H5N1 samples also carry mutations that may make them less responsive to the antiviral drug oseltamivir. Our findings documented the presence of AIVs in several underrepresented regions and highlighted critical transmission hotspots where viral evolution may be accelerating. These results underscore the urgent need for geographically targeted surveillance to detect emerging variants, inform public health interventions, and reduce the risk of zoonotic spillover.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59322-z

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