#Oseltamivir #Resistance in #Human #Influenza #H5N1 and #H7N9 Infections: A Mini Review

 

Abstract

Avian influenza viruses (AIVs) have been reported to cause infections in humans following avian-to-human transmission, resulting in a range of clinical outcomes. A(H5N1) and A(H7N9) infections, which constitute the majority of human AIV cases, are responsible for severe infections leading to high mortality. The neuraminidase inhibitor oseltamivir is expected to play a major role for the control of AIV infections in humans. However, the emergence of resistance may compromise the impact of antiviral therapy. The objective of this article is to review human cases of A(H5N1) and A(H7N9) infections for which mutations of oseltamivir resistance were detected. Neuraminidase mutations rapidly occurred in a subtype-specific manner, with H274Y and N294S substitutions predominating in A(H5N1) cases and the R292K substitution in A(H7N9) cases. Serious clinical outcomes and mortality were seen in most A(H5N1) and A(H7N9) cases despite oseltamivir therapy, thus highlighting the need for improving antiviral strategies against these AIVs.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag393/8722865

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Evolving #dynamics of #H5Nx avian #influenza in #China revealed by long-term wild bird #surveillance

 

Abstract

H5Nx highly pathogenic avian influenza viruses pose persistent threats to poultry, wildlife, and public health. Over the past two decades, their geographic and host ranges have expanded across migratory networks whose epidemiological connectivity has become increasingly apparent through recent surveillance and genomic analyses. To elucidate these dynamics, we conduct long-term nationwide wild-bird surveillance in China, integrating active and passive monitoring. Our analyses reveal the maintenance, reassortment, and transmission of H5Nx viruses in wild birds, highlighting the value of sustained surveillance in capturing viral evolution. We identify distinct ecological patterns among major clades, with 2.3.4.4b showing the widest distribution and acting as the main lineage mediating intercontinental spread. Since 2020, most 2.3.4.4b viruses detected in wild birds in China have clustered with lineages originating outside China, consistent with repeated reintroduction rather than sustained local circulation. This shift underscores the growing role of migratory connectivity in shaping global viral exchange and the need for coordinated international active surveillance.

Source: 

Link: https://www.nature.com/articles/s41467-026-76039-9

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Identifying the viral and #epidemiological factors behind the apparent global #extinction of #influenza B/Yamagata

 

Abstract

Until 2020, two lineages of the influenza B virus had co-circulated globally. Measures to control the COVID-19 pandemic led to a near-absence of influenza infections. While B/Victoria reemerged in late 2021, there have been no reports of B/Yamagata since the pandemic. To investigate which epidemiological and immunological factors were primarily responsible for the extinction of B/Yamagata, we developed a global model for the two influenza B lineages. To mimic the transmission impacts of the pandemic, we implemented a transient reduction in contacts and identified parameter values that recapitulated viral coexistence dynamic before the pandemic and the qualitative post-pandemic outcomes of B/Victoria (reemergence in late 2021) and B/Yamagata (extinction). Our results suggest that, rather than immunological or evolutionary mechanisms, the extinction of B/Yamagata was mainly driven by its lower basic reproduction number making the virus particularly vulnerable during the early phase of the pandemic. Stochastic simulations of our best-fitting model suggest that B/Victoria was also close to extinction during this period. We investigate the model to assess the feasibility of B/Victoria eradication through vaccination and the potential for a sustained re-emergence of B/Yamagata in the 2026-27 flu season, thus highlighting important considerations for biosafety.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.07.22.26358639v1

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Characterization and evolutionary history of novel #SARS-CoV-2-related viruses in #bats from #Cambodia

 

Abstract

Circulating bat coronaviruses present a significant pandemic threat, yet our understanding of their genetic diversity and evolutionary dynamics remains limited. Over 3 years, we sampled 1,462 bats in Cambodia’s Steung Treng province, identifying extensive and diverse coronaviruses co-circulation. Using metatranscriptomic and amplicon sequencing, we generated 33 complete sarbecovirus genomes sequences, revealing novel lineages that cluster into four distinct groups, each associated with different Rhinolophus bat species. Our analysis highlights rapid migration and recombination of sarbecovirus lineages over short distances and timescales. Of note, the receptor-binding domains of two novel viral groups exhibit high similarity to SARS-CoV-2, and pseudovirus assays confirmed the ability of this spike protein to mediate entry into cells expressing human ACE2, suggesting a potential zoonotic risk. The observed genetic diversity underscores the urgent need for continuous surveillance to identify high-risk animal-to-human interfaces and inform pandemic preparedness.

Source: 

Link: https://www.nature.com/articles/s41467-026-75954-1

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#SARS-CoV-2 BA.3.2.2 is more evasive of #neutralisation by #plasma from young #children

 

{Excerpt}

(...)

These findings suggest that susceptibility to emerging SARS-CoV-2 variants could diverge across age groups with different exposure histories. Adults in the USA and other countries have accumulated broader immunity through repeated infection and vaccination across antigenically distinct lineages, starting with the ancestral strain, whereas younger children and infants possess narrower exposure histories that are largely shaped by recent variants. The continued surveillance of SARS-CoV-2 variants should consider age-stratified differences in immunity, to anticipate or explain disproportionate burden of infections in some populations. Furthermore, studies of potential age-specific vaccine formulations targeting different variants are warranted, to investigate whether age-specific target selection could lead to broader protection across subpopulations with known differences in their exposure histories and susceptibility to co-circulating variants.

(...)

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00349-X/fulltext?rss=yes

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#Geographic Concentration of #Genomic #Surveillance for Highly Pathogenic Avian #Influenza #H5, South #Asia, 2015-2025

 

Abstract

Early detection of mammalian adaptation in highly pathogenic avian influenza A(H5) depends on genomic surveillance, yet its distribution across high-burden regions is poorly characterized. We quantified open-access (GenBank/INSDC) H5 genomic coverage relative to reported outbreak burden across nine South Asian countries during 2015-2025, linking isolates to FAO EMPRES-i/WOAH events. Of 919 H5 isolates, 814 (89%) came from one country (Bangladesh); the other eight contributed 105. India, with the largest burden (322 events), yielded only 42 isolates (13 per 100); Nepal, 2 of 78; Afghanistan, none of 5. Concentration was extreme (Gini 0.83) and unchanged by adding restricted GISAID records (1,297 combined isolates; Bangladesh 89%) or by normalizing to poultry or human population. Because reported outbreaks track reporting effort, these coverage ratios are directional, not rates. This single-country dependency, deepest where burden is highest, is a regional early-warning vulnerability.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.07.20.26358505v1

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Within- and between-host #dynamics of highly pathogenic avian #influenza in domestic #birds from #Pennsylvania #farms and live bird #markets

 

Abstract

Since late 2021, highly pathogenic avian influenza viruses (HPAI) of the H5 subtype clade 2.3.4.4b have spread across the Americas, devastating wildlife, agricultural animals, and resulting in dozens of human spillovers. National surveillance strategies generally provide only a single representative sequence per poultry outbreak, precluding fine-scale geographic transmission inference or studies of within-outbreak evolution. We produced high-quality deep sequence data from 46 infected Galliformes and Anseriformes sampled from commercial farm and live bird market (LBM) outbreaks in Pennsylvania from 2023-2025. We found that H5N1 viruses were introduced into Pennsylvania at least 68 independent times. We recover independent origins of live bird market outbreaks within the same county 3 weeks apart, and transmission between Pennsylvania LBM and New York commercial birds, suggesting high transmission risk within the Northeast live bird market distribution system. Analyses of within-farm variant populations show frequent variant sharing between samples from the same outbreak, suggesting that variants are propagated among epidemiologically linked infections. We identified 9 known adaptive mutations in these samples, including one instance of PB2 D701N in a LBM chicken sample, suggesting that while rare, concerning mammalian adaptive mutations can be present within these domestic outbreaks. Our data suggest that domestic bird outbreaks support high circulating diversity and wide transmission bottlenecks, increasing the risk of minority variants arising and propagating between infections. These data can help inform targeted biosecurity measures and better quantify the risk of viral adaptation during agricultural outbreaks.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIAID, NIH 75N93021C00015

Pew Charitable Trusts

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.17.739193v1

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A lethal #human #H5N5 #influenza virus isolate exhibits low #pandemic #risk traits

 

Abstract

In fall of 2025, a fatal infection of highly pathogenic avian influenza (HPAI) virus H5N5 occurred. To define the risk of this emerging virus to humans, we performed a comprehensive analysis based on our established triage. Serological analysis revealed that humans across all birth years had no detectable neutralizing antibodies to this H5N5 isolate. Further characterization revealed a lack of phenotypic signatures associated with epidemiologically successful influenza viruses in humans, including reduced replication in human airway cells and an avian-like pH of inactivation. Additionally, assessment of H5N5 in ferrets revealed a lack of direct contact transmission and moderate disease severity. H5N5 infection in ferrets with prior immunity against the 2009 H1N1 pandemic strain resulted in fewer clinical signs and reduced viral shedding. Together our data suggest that the current H5N5 HPAI lineage poses a low pandemic risk.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.20.739507v1

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Elicitation of #stem-directed #antibodies in rhesus #macaques by a conventional #hemagglutinin immunogen

 

Abstract

Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIH NIAID, Division of Microbiology and Infectious Diseases, P01-AI089618

NIH NIAID Division of AIDS, Center for HIV/AIDS Vaccine Immunology, U19-AI067854

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.16.738984v1

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Loss of #hemagglutination ability by #H3N2 #influenza A virus, subclade K.

 

Abstract

Seasonal human H3N2 influenza viruses, subclade K (J.2.4.1), have been the predominant influenza A viruses in the Northern hemisphere influenza season of 2025/2026. Since 2024, the vaccine virus A/Darwin/6/21 has emerged in different antigenic variants. Antigenic changes are frequently caused by amino acid substitutions near the hemagglutinin (HA) receptor-binding pocket, which can also affect receptor binding properties, such as hemagglutination. Hemagglutination is crucial for assessing antigenicity using the hemagglutination inhibition (HAI) assay, and a loss of binding to turkey erythrocytes could significantly hamper this process. In this study, we explored how substitutions in or around the HA receptor-binding site affect binding to glycans at the molecular level. We employed ELISA, glycan array, flow cytometry, hemagglutination assays, and tissue staining. Substitutions at positions 140, 192, and 223 establish clade J viruses that emerged in 2024. Computational analysis of HA in complex with an elongated glycan reveals that mutation F192 forms a CH-Pi interaction to stabilize the binding. Based on this background, substitutions in antigenic sites A and B within subclade K viruses exhibit a binding preference for elongated glycans, which are not displayed on turkey erythrocytes. Conversely, our previously established glyco-remodeled erythrocytes are efficiently bound by these subclade K H3N2 viruses and could support influenza surveillance and vaccine development.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

CSC fellowship, (202209120001)

National Institute of Allergy and Infectious Diseases, R01 AI165692

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.20.739523v1

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Highly Pathogenic Avian #Influenza #H5N5 in a Polar #Bear and Atlantic #Walrus, #Svalbard, 2026, with Widespread Seroconversion in Polar Bears

 

Abstract

Highly pathogenic avian influenza virus (HPAIV) subtype H5N5 was detected in a one-year-old polar bear (Ursus maritimus) and an adjacent adult Atlantic walrus (Odobenus rosmarus rosmarus), both found deceased in Raudfjorden, Svalbard. This represents the first confirmed case of HPAI in a European polar bear and the second in an Atlantic walrus. Viral genomes were nearly identical and harbored PB2-E627V, a marker associated with mammalian adaptation. Several polar bears, including the deceased individual, had previously been observed feeding on the walrus carcass. Antibodies against H5 were detected in 75% of polar bears in 2023 (n=36) and 97% in 2024-2025 (n=65), suggesting extensive circulation of HPAIV in the population following the first detections in birds in Svalbard in 2022, whereas no antibodies were detected in samples from 2014-2022 (n=243).

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Project OH4Surveillance, funded by the European Union, Grant Agreement No 101132473

Morris Animal Foundation, Grant ID# D25ZO-430; KJB

Norwegian Veterinary Institute, 12311 SvalVilt

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.20.739480v1

____

Detection of #H5N1 HPAIV Clade 2.3.4.4b Avian #Influenza Virus in Backyard #Chickens in #CostaRica

 

Abstract

Influenza A virus is a segmented, negative-sense RNA virus. Since the early 2020s, H5 clade 2.3.4.4b viruses have spread widely across Europe, Africa, and Asia, affecting wild birds and poultry. Costa Rica reported its first H5 clade 2.3.4.4b avian influenza virus (AIV) case on 19 January 2023. This study describes an outbreak in backyard chickens and ducks. Initial serum samples collected on 24 January showed three chickens negative for AIV, while one duck tested positive by ELISA and agar gel immunodiffusion (AGID). During a second visit on 27 January, three of four chicken sera collected tested positive by ELISA and AGID. Tissue samples were positive for influenza A by qRT-PCR. Next-generation sequencing recovered five of the eight viral genomic segments, and the hemagglutinin cleavage site sequence (REKRRKR↓G) confirmed a highly pathogenic avian influenza virus (HPAIV) H5 strain. The samples were submitted to the National Veterinary Services Laboratories for confirmation. Serological testing showed reactivity to North American low pathogenic H5 antigens, and qRT-PCR amplified influenza A and N1 genes. Virus isolation and next-generation sequencing (NGS) of all eight viral genome segments were successfully performed at the WHO Collaborating Centre at St. Jude Children’s Research Hospital (SJCRH).

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/799

____

Multiorgan #Outcomes Following #BNT162b2 #mRNA #Vaccination vs #SARS-CoV-2 #Infection: A 30-Million-Person Real-World Cohort Analysis

 

Abstract

SARS-CoV-2 infection and BNT162b2 mRNA vaccination carry distinct cardiovascular risk profiles, yet direct comparative evidence across all immunological exposure groups and both sexes remains limited. Using the TriNetX Research Network (December 2020–December 2024), we stratified 30.3 million individuals into four mutually exclusive cohorts: uninfected/unvaccinated controls (G1), infected/unvaccinated (G2), vaccinated-only (G3), and hybrid immunity (G4). Fifty prespecified cardiovascular, cerebrovascular, and mortality outcomes were evaluated across four temporal windows (0–3, 3–6, 6–9, and >9 months) with analyses stratified by biological sex. SARS-CoV-2 infection was associated with 3- to 5-fold increases in cardiovascular events during the acute phase, including myocarditis (males: RR 4.44; females: RR 5.59) and all-cause mortality (males: RR 4.53), with risks persisting beyond nine months. BNT162b2 vaccination conferred 65-76% reductions in major adverse cardiovascular events (0–3 months). Post-infection vaccination (hybrid immunity) provided an additional 36–38% MACE reduction; males exhibited late pericarditis elevation beyond nine months. Completing the two-dose primary series maximally reduced mortality (by 77%) and myocarditis (by 62%) versus single dosing. In this US cohort, SARS-CoV-2 infection confers substantially greater and more sustained cardiovascular risk than BNT162b2 vaccination across all comparisons and both sexes, consistent with a favorable cardiovascular risk-benefit profile for vaccination.

Source: 

Link: https://www.nature.com/articles/s41541-026-01528-3

____

Excess #mortality attributable to the 2025 #Iberian Peninsula #blackout

 

Abstract

On 28 April 2025, a widespread power outage affected mainland Portugal and Spain for around ten hours, causing major disruptions and eight reported deaths. Health impacts of blackouts range from direct effects, such as medical equipment failure, to indirect effects such as disrupted healthcare. Here we show that the 2025 Iberian blackout is associated with increased mortality in Spain, but not in Portugal. We find little evidence of excess mortality on the day of the event itself. In Spain, however, mortality rises over the next two days (+167 deaths; 95% credible interval: +28 to +300; +2.4% relative increase), particularly among women aged 85+. We also observe regional differences, but their drivers remain uncertain and may include variation in outage severity, underlying vulnerabilities, or local health-system and infrastructure conditions. These findings highlight the underestimated health burden of blackouts and the need for improved preparedness in a changing climate.

Source: 

Link: https://www.nature.com/articles/s41467-026-75581-w

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#Genomic Characterization of #SARS-CoV-2 #NB.1.8.1 and #PQ.2 from the #Infants and Young #Children with #Gastrointestinal Symptoms

 

Abstract

Purpose: 

This study investigated the viral genomic characteristics of infants and young children who presented to our hospital with gastrointestinal symptoms during a local COVID-19 epidemic and were confirmed to have SARS-CoV-2 infection.

Patients and methods: 

Between May and August 2025, pharyngeal swab samples were collected from four infants and young children who presented to the outpatient department of Meizhou People’s Hospital in Meizhou, with gastrointestinal symptoms. Nucleic acid testing and whole-genome sequencing were performed. The viral mutation profile was analyzed, and the potential impact of mutations on protein function was predicted.

Results: 

Pangolin typing identified the NB.1.8.1 variant in three patients and the PQ.2 variant in one patient. Genome sequences from three of the four viral variants displayed varying degrees of mutation. The nonsynonymous mutations for both variants were concentrated in the spike protein. A comparison with the parental XDV.1.5.1 lineage revealed 14 specific mutations, with 7 nonsynonymous sites conserved across all gene sequences. Five of these mutation sites, NSP12: D284Y, ORF3a: L46F, ORF3a: F207C, N: Q9H, and N: Q384H, were predicted to be functionally deleterious and structurally destabilizing.

Conclusion: 

SARS-CoV-2 variants from specimens obtained from four infants and young children exhibited varying degrees of mutation, providing evidence for the ongoing evolution of emerging variants in pediatric patients. However, monitoring genomic changes of circulating variants requires further clinical specimens, which contributes to understanding the dynamic changes at mutation sites, thereby supporting epidemic prevention and control.

Source: 

Link: https://www.dovepress.com/genomic-characterization-of-sars-cov-2-nb181-and-pq2-from-the-infants--peer-reviewed-fulltext-article-IDR

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#Bovine-derived #H5N1 #influenza virus efficiently infects lactating #swine via the #mammary gland

 

Abstract

Since 2024, highly pathogenic influenza A(H5N1) viruses have spread extensively among U.S. dairy cattle, where they replicate efficiently in the mammary gland and are shed at high titers in milk. To directly assess susceptibility of commercial swine populations to bovine-derived H5N1 virus, lactating sows with prior influenza virus vaccination histories representative of U.S. commercial swine production systems were inoculated via the intramammary route and co-housed with their 1-week-old piglets to evaluate disease outcomes, viral replication, and potential for vertical transmission. Intramammary inoculation of lactating sows resulted in sustained viral RNA shedding in milk, while piglets exhibited sporadic oral viral RNA positivity that mirrored viral kinetics in milk. Lesions in mammary tissue and viral antigen staining, as well as development of neutralizing antibody responses and changes in milk color and consistency, further confirmed infection in the sows. Despite these molecular findings, none of the animals developed overt clinical disease, and respiratory involvement was not noted during the study period. Collectively, we demonstrate that intramammary exposure results in productive influenza A(H5N1) virus infection in lactating sows despite their vaccination histories, indicating the potential threat of viral spillover into commercial swine populations. The clinically inapparent nature of infection presents a risk of subclinical spread and underscores the importance of expanding viral surveillance to swine.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Swine Health Information Center, 25-020

United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA), 2025-39601-44639

National Institutes of Health, P30 CA016058

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.18.739312v1

____

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Characterization of #bovine-derived #H5N1 viruses expressing fluorescent and luminescent reporter #proteins

ABSTRACT

Highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses present a broad host range, with recent spillover and sustained transmission in dairy cattle reported in the USA. Replication-competent reporter viruses are critical tools that enable real-time monitoring of virus replication, facilitating high-throughput screens. In this study, we engineered three recombinant H5N1 clade 2.3.4.4b reporter viruses expressing nanoluciferase (NLuc) and two fluorescent reporter proteins, miniGFP2 and UnaG within the open reading frame of the nonstructural gene of the bovine A/Cattle/Texas/063224-24-1/2024 (TX2/24) virus. All reporter viruses replicated efficiently in vitro, presenting replication kinetics comparable to the parental rTX2/24 virus, but exhibited smaller plaque sizes, suggesting reduced cell-to-cell spread. In vivo infection studies in mice showed comparable pathogenicity among all four viruses, although rTX2/24-miniGFP2 and rTX2/24-UnaG exhibited decreased virus shedding relative to rTX2/24 and rTX2/24-NLuc. Virus titrations and in situ localization of virus replication sites demonstrated robust replication in respiratory tissues, with slightly attenuated systemic dissemination of all three reporter viruses. Fluorescent virus neutralization assays using miniGFP2 and UnaG reporter viruses accurately quantified neutralizing antibody titres in sera from naturally infected dairy cattle, consistent with wild-type virus assays. Additionally, the utility of the NLuc reporter virus for antiviral screening was validated against oseltamivir in vitro. Collectively, these results establish the H5N1 TX2/24-based reporter viruses as versatile and biologically relevant tools for investigating H5N1 pathogenesis and for use in serological and antiviral drug screens.

Source: 

Link: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002298

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Immune correlates of #risk for #SARS-CoV-2 #infection in #children: a prospective, community-based cohort study

 

Abstract

Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022–2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log10-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve.

Source: 

Link: https://www.nature.com/articles/s41467-026-74684-8

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