Saturday, November 15, 2025

CDC FluView, ECDC CDT & Canada Announce Early H3N2 Subclade K Prevalence Numbers

Credit NIAID 

#18,947

Yesterday's announcement for the first known human H5N5 infection has captured a good deal of attention, but the `other' flu story we've been following this week has been the rapid spread of a new seasonal H3N2 subcade (K) virus, which emerged in the Southern Hemisphere a few months ago. 

Increasing Concerns Over A `Drifted' H3N2 Virus This Flu Season

Mid-week, in UKHSA Preprint: Early Influenza Virus Characterisation and Vaccine Effectiveness in England in Autumn 2025, A Period Dominated by Influenza A(H3N2) Subclade K, the UKHSA characterized this virus as:

The K subclade marks a notable evolution in influenza A(H3N2) viruses since the NH 2025 to 2026 candidate vaccine strains were selected (based on the J.2 subclade) and are characterised by T135K, K189R with 7 additional mutations(HA1: K2N, S144N, N158D, I160K, Q173R, ) (2 to 4).

Selection of strains for our fall vaccine must be made each February in order to give enough time to create, manufacture, and deploy hundreds of millions of doses.  The concern now is this year's flu vaccine may be less protective against this mutated H3N2 virus. 

How much less, is unknown. There are still hopes it may help reduce the severity of H3N2 infection (and there are two other strains covered by the vaccine as well)

While we've seen anecdotal reports of an early, and robust, flu season in Japan, Taiwan, and South Korea, it isn't clear whether subclade K produces more severe illness.  Its growth however, has been remarkable. 

On Wednesday the UKHSA announced that since week 35 of 2025; 156 of 179 H3N2 viruses characterized (87%) belong to this novel subclade (K).

To all of this we can add three more data points, from the CDC, the ECDC, and Canada. First, the U.S. government shutdown ended this week, and yesterday the CDC published their first FluView report since late September. 

In it - while reported flu activity remains low - they report just over 50% of all recent H3N2 viruses characterized (n=124) are now of subclade K.

The CDC also reports:

A(H3N2): 50 A(H3N2) viruses were antigenically characterized by HI or HINT, and 19 (38.0%) were well-recognized (reacting at titers that were within 4-fold of the homologous virus titer in HI or reacting at titers that were less than 8-fold of the homologous virus in HINT) by ferret antisera to cell-grown A/District of Columbia/27/2023-like reference viruses representing the A(H3N2) component for the cell- and recombinant-based influenza vaccines.

    In other words, 62% already appear to have antigenically shifted away from the J.2 vaccine, which will likely impact its effectiveness. That doesn't mean that they are all subclade K - but given the other numbers we've seen  - most probably are. 

    Yesterday, the ECDC published their weekly Communicable disease threats report, 8 - 14 November 2025, week 46, which finds that 38 of 45 H3N2 viruses characterized (86%) are of subclade K. 


    And from Canada's weekly influenza surveillance report, 17 of 24 H3N2 viruses (70%) characterized are subclade K.


    While we are still operating with limited data, H3N2 subclade K appears to have a significant growth advantage over the older J.2 subclades, and in some places (including the United States) is outpacing H1N1 this fall. 

    The $64 question, of course, is what does this all mean for the flu season ahead?

    We can't predict the future, of course, but we can look back at similar events and see what happened. While not all `drifted' H3N2 seasons have been severe, many have produced excessive morbidity and mortality, particularly in the elderly (see CDC chart below). 

    The 2014/2015, 2016/2017, and 2017/2018 H3N2 `drifted' flu seasons were typically more severe - particularly among the elderly - than other seasons.  It would not be unreasonable to expect a similar scenario this year. 

    Which is why, I've already discussed getting antivirals from my doctor (Rx by phone) should the need arise, and why I have a `Flu Buddy', who will check in on me (mostly by phone) if I should fall ill. 

    I got the flu vaccine in October, even though I already knew it was likely a mismatch on the H3N2 component, because it may still provide some degree of protection, particularly against severe infection. 

    I'm also current on my pneumococcal vaccines, and will continue to protect myself in public by wearing face masks and using copious amounts of hand sanitizer. 

    None of which guarantees I'll come through this winter unscathed. But they do greatly improve my chances. 

    Friday, November 14, 2025

    Washington State DOH: H5N5 Avian influenza confirmed in Grays Harbor County resident

     


    #18,846


    In a `the plot thickens' moment, this afternoon the Washington State Department of Health has announced their presumptive H5 case announced yesterday has tested positive - not for H5N1 - but for H5N5. 

    Regular readers know we've been following this relatively rare subtype for several years, mostly seen in Northern Europe, Iceland, and Eastern Canada.  Two months ago I wrote:

    Another thing we are watching is the slow incursion of HPAI H5N5 - which has been reported in both Canada and Northern Europe (see Svalbard: HPAI H5N5 Detected In Arctic Foxes) - into the United States.

    The USDA currently only lists 23 detections (in wild birds) across 4 states (primarily Massachusetts, along with Connecticut, Maine, and Michigan), but given the limits of surveillance and testing, this likely underrepresents its range and impact. 

    The USDA's most recent update lists 29 (out of 15,709) wild bird samples as H5N5, all reported on the Eastern Seaboard of the United States.   That it has turned up on the west coast is noteworthy, and of course, this is the first known human infection with this subtype. 

    The gist of the emailed announcement from WA DOH follows:


    For immediate release: November 14, 2025                                           (25-138)

    Contact: DOH Communications

    H5N5 Avian influenza confirmed in Grays Harbor County resident

    First detection of this strain in a human, risk to the public remains low

    OLYMPIA – A Grays Harbor resident who was hospitalized with influenza symptoms in early November has been confirmed to have influenza A H5, a type of avian influenza. Additional testing shows the virus to be H5N5, an avian influenza virus that has previously been reported in animals but never before in humans. The Centers for Disease Control and Prevention (CDC) and DOH currently considers the risk to the public from avian influenza to be low.

    The person is an older adult with underlying health conditions and remains hospitalized. The affected person has a mixed backyard flock of domestic poultry at home that had exposure to wild birds. The domestic poultry or wild birds are the most likely source of virus exposure; however, public health investigation is ongoing. The Washington State Department of Health is working with the local health department and the Washington State Department of Agriculture to complete exposure and animal health investigations.  

    Public health disease experts have not identified any increased risk to the public.  

            (Continue . . . )

    As of this posting, the WA DOH website has not been updated. 

    For more on HPAI H5N5, you may wish to revisit:

    Svalbard: HPAI H5N5 Detected In Arctic Foxes



    Icelandic Food and Veterinary Authority (MAST) : H5N5 Infection In Domestic Cat



    Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammals

    Preprint: Pre-infection COVID-19 Vaccination and Long-COVID Mental Fatigue Severity: Findings from the Johns Hopkins COVID Long Study

     

    #18,945

    A week scarcely goes by without another study showing that COVID infection - and particularly, repeated infections - can have a major impact on a person's ongoing cardiovascular and neurological health. 

    While largely ignored by the public, a list of just some of the studies published in the last 3 months includes:

    The Lancet: Vascular and Inflammatory Diseases after COVID-19 Infection and Vaccination in Children and Young People in England

    JAHA: Viral Infections and Risk of Cardiovascular Disease: Systematic Review and Meta‐Analysis

    COVID vaccines, while admittedly far from perfect, can help reduce (but not eliminate) the risks of infection, and even when breakthrough infections do occur; they can reduce the severity and/or duration of illness. 

    We've even seen studies showing vaccination may yield a marked reduction in the risk of developing Long COVID (see CIDRAP News 3 vaccine doses cut long-COVID risk by over 60%, analysis suggests). 

    This week, we've another preprint - this time from researchers at Johns Hopkins - which suggests that (pre-infection) COVID vaccination/boosters can reduce the severity of mental fatigue in recipients who were unlucky enough to go on to experience Long COVID. 

    Those who were both vaccinated & boosted saw a nearly 30% reduction in their WMFI (Wood Mental Fatigue Inventory) score. 

    This study is not without limitations and/or caveats.  It is observational in nature, relies on self-reported data for infection and symptom history, and is based on a limited cohort (skewed towards those identifying as women, white, and from higher educational backgrounds). 

    Still, its findings align with others we've seen which find significant benefits from COVID vaccination and staying current with boosters. 

    I've posted the Abstract and a small excerpt below. Follow the link to read it in its entirety. 

    Pre-infection COVID-19 vaccination and long-COVID mental fatigue severity: Findings from the Johns Hopkins COVID Long Study

    Madeline Sagona, Zhanmo Ni, Eryka Wentz, Karine Yenokyan, Thea Kammerling, Andrea DeVito, Priya Duggal, Shruti H. Mehta, Bryan Lau
    doi: https://doi.org/10.1101/2025.11.07.25339684
    This article is a preprint and has not been peer-reviewed [what does this mean?]. 

    Preview PDF

    Abstract

    Background
    Long-COVID is a post-acute sequela of SARS-CoV-2 infection characterized by persistent, multi-system symptoms. Neurologic symptoms, such as mental fatigue, are often reported. While vaccination prior to infection is known to lessen symptom burden, its impact on mental fatigue remains unclear.

    Objective Examine the association between vaccination and long-COVID-associated mental fatigue.

    Methods We analyzed data from the Johns Hopkins COVID Long Study, a cohort study of 22,811 participants with and without infection. Among 2,634 participants with complete longitudinal follow-up, we examined the association between pre-infection vaccination and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI; range 0-36, with lower scores indicating less fatigue). We considered three groups: long-COVID, recovered, and never infected, with the latter two groups as negative controls. We estimated the score differences between vaccinated and unvaccinated participants using covariate-adjusted quantile regression and mixed-effects linear models.

    Results Among participants with long-COVID, receiving a booster dose was associated with lower WMFI scores across the distribution (1.5, 2.6, and 3.8 points lower at the 25th, 50th, and 75th percentiles; p ≤ 0.02) compared to those unvaccinated. Fully vaccinated participants also had lower scores, though these differences were not statistically significant. Findings were consistent in mixed-effect linear models where boosted (4.0 points lower) and fully vaccinated (1.9 points lower) participants with long-COVID had lower WMFI scores (p < 0.05). No associations were observed among recovered or never-infected participants.

    Conclusion Pre-infection vaccination was associated with less long-COVID-associated mental fatigue, with the greatest benefit among boosted participants.

    (SNIP)

            Conclusion 

    In this nationwide virtual cohort, receiving a COVID-19 booster dose prior to SARS-CoV-2 infection was associated with lower long-COVID–associated mental fatigue. Fully vaccinated participants also hadlower WMFI scores compared to unvaccinated individuals, with smaller effects than those observed in boosted participants, consistent with a dose-response relationship. Associations were consistent across the distribution of scores and in mixed-effects models and were absent among recovered-COVID and never-infected controls, suggesting specificity to long-COVID.

    As mental fatigue remains a common and disabling symptom of long-COVID, our results underscore the potential added value of vaccination in reducing long-term functional impairment. Future work should evaluate the biological and immunological mechanisms underlying this association, assess its durability over time, and determine whether additional booster doses further modify mental fatigue severity. Long-COVID remains a serious public health concern. Understanding how vaccination affects neurological symptoms like mental fatigue can inform future prevention strategies.

            (Continue . . . )

     

    WA State DOH: Grays Harbor County Resident Tests Preliminarily Positive for Avian Influenza

     


    #18,944

    Late yesterday the Washington State Department of Health emailed out the following announcement on their first presumed H5N1 case of 2025.  It was just over a year ago (Oct 21st, 2024) that WA announced their first (4) cases, among poultry cullers.

    By the end of 2024, WA State had recorded 11 confirmed and 3 probable (mostly mild) human infections among agricultural workers, all exposed to infected poultry. 
    In early 2025 Washington State was among several states reporting cats infected with H5N1 (see Washington State (WSDA) Announces 2 Households with H5N1 Infected Cats Linked to Raw Food).

    Today's human case (which requires confirmation by the state lab) appears to be more severe, and the route of exposure has yet to be determined.  Beyond that, we know this is an older adult with comorbidities, who has been hospitalized for more than a week. 

    There is no word yet on the genotype of this virus.  In fact, we've seen very little data on any of the poultry and wild bird outbreaks this fall.  
    Last year, the B3.13 (aka `Bovine') genotype was associated with milder human infections (mostly conjunctivitis), while the D1.1 and D1.3 genotypes tended to produce more severe symptoms (including 1 death). 

    The full press release follows.   I'll have a bit more, after the break.


    Grays Harbor County resident tests preliminarily positive for avian influenza

    For immediate release: November 13, 2025 (25-136)

    Contact: DOH Communications

    If confirmed, this would be the first human case of avian influenza reported in Washington in 2025

    OLYMPIA – A Grays Harbor County resident has tested preliminarily positive for avian influenza, also known as bird flu. Confirmatory testing through the Washington State Public Health Laboratories is pending.

    Health officials are working to determine the potential sources of the infection, including contact with wild or domestic birds. The person, who is an older adult with underlying health conditions, developed a high fever, confusion, and respiratory distress and was hospitalized in early November. They are currently receiving treatment in King County after previously being treated in Thurston and Grays Harbor counties.

    Public health disease experts have not identified any risk to the public. The Washington State Department of Health is working with the local health departments and healthcare facilities to support the investigation.

    About Avian Influenza

    Avian influenza is a disease caused by influenza type A viruses, which naturally occur in wild aquatic birds around the world. These viruses can infect other bird species, and, occasionally mammals, and can be deadly to domestic birds such as chickens and turkeys. On rare occasions, avian influenza viruses can infect people and make them sick. Most cases have occurred in people who were exposed to sick or infected animals. Reported human cases of avian influenza in the United States have typically been mild, with symptoms such as conjunctivitis (red eyes), fever, and respiratory symptoms.

    The risk of avian influenza increases in the fall and winter because migratory birds can carry the virus and spread it to domestic animals including commercial poultry farms and backyard flocks.

    Transmission of avian influenza between humans is extremely rare and has never been documented in the United States. To ensure that human-to-human spread is not occurring, public health officials are contacting anyone who has been in close contact with the patient to monitor for symptoms and provide testing and treatment as needed.

    Public Health Guidance

    The Centers for Disease Control and Prevention (CDC) currently considers the risk to the public from avian influenza to be low. However, people who work with or have recreational contact with infected birds, cattle, or other potentially infected domestic or wild animals, are at higher risk and should take precautions, including wearing personal protective equipment (PPE) such as gloves, masks, eye protection, and fluid-resistant coveralls or other outerwear.

    People with backyard poultry should avoid contact with sick or dead birds and report illness to the Washington State Department of Agriculture (WSDA) by calling 1-800-606-3056 or reporting online. Veterinarians should report sick or dead domestic animals or livestock suspected of having avian influenza to WSDA. Avoid contact with sick or dead wildlife and report sick or dead wild birds or other animals to the Washington State Department of Fish & Wildlife. Never handle or allow pets near dead birds or other wildlife.

    Avoid eating raw or undercooked food products, such as unpasteurized (raw) milk or raw cheeses, and don’t feed these products to pets.

    It is especially important that people who may have exposure to sick birds get a seasonal flu vaccine. While the seasonal flu vaccine will not prevent bird flu infection, it reduces the risk of becoming sick with both human and avian influenza viruses at the same time. Seasonal flu vaccine is recommended for everyone six months and older.

    Our website is your source for a healthy dose of information. Get updates by following us on social media.

    Although the steep decline in human infections with HPAI H5N1 in the United States over the past 10 months has been somewhat reassuring, the reality is it requires a combination of both diligence and luck to detect community cases of novel influenza infection.

    It has been estimated previously that fewer than 1-in-100 novel swine flu infections are picked up by passive surveillance (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).
    Many with mild or moderate symptoms will not seek a doctor's advice, and among those who do, most will not be tested for novel influenza. And of course, asymptomatic cases are almost certain to be missed.
    In January of 2025, the CDC issued guidance (see CDC HAN: Accelerated Subtyping of Influenza A in Hospitalized Patients) calling for more robust inpatient testing - and while some progress appears to have been made - it is unclear what the level of compliance is to these guidelines across the nation.
    Obviously, these steps are only likely to capture hospitalized patients. Those attending clinics or private physicians are less likely to be tested for novel flu.  
    While one human infection does tell us much, it does confirm that the threat of human infection has not gone away. 
    Stay tuned. 

    Thursday, November 13, 2025

    UKHSA Preprint: Early Influenza Virus Characterisation and Vaccine Effectiveness in England in Autumn 2025, A Period Dominated by Influenza A(H3N2) Subclade K


    Credit ACIP/CDC  

    #18,943

    Last weekend, in Increasing Concerns Over A `Drifted' H3N2 Virus This Flu Season, we looked at early warnings of a major `drift' in this year's H3N2 virus. Since then we've seen a growing number of media headlines like:

    Flu season "Worst in over 30 years" says physician

    Warnings rise for U.S. as severe flu strain causes outbreaks in Canada, U.K.

    Mutant virus strain 'could overwhelm hospitals this winter' as health bosses sound alarm

    Much of this media consternation comes comes following reports of early season flu surges in Asia (Japan, Taiwan, Guam, China, etc.) - which followed a rough Australian  flu season (see Dr. Ian Mackay's A Flunami in July) - and a very recent preprint by Dr. Danuta Skowronski et al., which characterized recent changes in the H3N2 virus that and warned:

    This `. . . . vaccine mismatched A(H3N2) variant ' is `. . . projected to predominate during the northern hemisphere’s 2025–2026 influenza season.'

    All of which has some people wondering: Is it worth getting the flu vaccine this year?
    While my own take is ` even a little protection is better than none' (full disclosure: I get the flu vax every year), we get a more scientific take from the UK's Health Security Agency, which published a (very) early season analysis of this year's vaccine effectiveness (VE) against this year's drifted H3N2 virus. 
    Although admittedly based on limited data, early evidence suggests the current vaccine may still provide modest levels of protection against hospitalizations in adults. A few excerpts from a UKHSA News Story published this week (Flu vaccine providing important protection despite new subcladeinclude: 

    New data published today as a pre-print by the UK Health Security Agency (UKHSA) shows the 2025/26 vaccine is currently 70 to 75% effective at preventing hospital attendance in children aged 2 to 17 years and 30 to 40% effective in adults.

    The early findings confirm the vaccine provides important protection even though a drifted influenza A(H3N2) strain (also now known as subclade K) currently dominates cases in England, so the protection levels observed in children are particularly encouraging this year. Flu vaccine effectiveness varies from season to season but is typically between 30 to 60%, with higher vaccine effectiveness typically seen in younger age groups.

    High effectiveness in younger age groups may also provide indirect protection to other groups through reduced transmission.

    While this may well be a `glass half-full' take, even a 30% reduction in severe influenza would save a lot of lives, and hopefully help prevent hospitals from being completely overwhelmed with flu cases. 
    The high (70 to 75%) VE in children is encouraging, but most children in the UK receive the LAIV (nasal) vaccine; not the IIV (shot) which adults typically receive, and their vaccinations were quite recent. 

    I've reproduced some excerpts from the preprint below, but you'll want to read it in its entirety.  I'll have a bit more after the break.


    Freja CM Kirsebom1, Catherine Thompson2, Tiina Talts2, Beatrix Kele2, Heather J Whitaker3, Nurin Abdul Aziz1, Christopher Rawlinson1, Rebecca E Green1, Catherine Quinot1, Nicholas Gardner1,Elizabeth Waller1, Alex Allen1, Conall H Watson1,4, Suzanna LR McDonald1, Maria Zambon2,Richard Pebody4,5, Mary Ramsay6,7, Katja Hoschler2, Anika Singanayagam*2,4, Jamie Lopez Bernal*1,4*

    Abstract

    Influenza A(H3N2) subclade K (J.2.4.1) has dominated the start of the 2025 to 2026 influenza season in England. We found reduced reactivity of subclade K with post-infection ferret antisera raised against the Northern Hemisphere 2025 to 2026 vaccine strains, aligning with World Health Organization reports.
    Nevertheless, vaccine effectiveness against hospital attendance and admission in the early season currently remains within a typical range at 70 to 75% in children and 30 to 40% in adults. Our data indicates that vaccination remains an effective preventative tool against circulating influenza A(H3N2).
    The end of the Southern Hemisphere 2025 influenza season and the start of the Northern Hemisphere (NH) 2025 to 2026 season has seen rapid growth in activity of influenza A(H3N2)subclade K (formerly referred to as subclade J.2.4.1) which is projected to dominate among H3N2 viruses during the 2025 to 2026 season (1 to 3).
    The K subclade marks a notable evolution in influenza A(H3N2) viruses since the NH 2025 to 2026 candidate vaccine strains were selected(based on the J.2 subclade) and are characterised by T135K, K189R with 7 additional mutations(HA1: K2N, S144N, N158D, I160K, Q173R, ) (2 to 4).
    Early analysis from the World Health Organization (WHO) influenza vaccine composition meeting (VCM) in September 2025 suggest low reactivity of these viruses with post-infection ferret antisera raised against the NH vaccine strains (5). It is not yet clear how 2025 to 2026 vaccine effectiveness (VE) against clinical disease may be affected by these observations.
    Here, we report genetic and antigenic characterisation of H3N2 viruses and real-world VE against emergency department (ED)attendance and hospital admission with influenza A in England. 
    Epidemiological context
    Influenza activity in England began unusually early in the 2025 to 2026 season, with a rise in influenza like illness emergency department attendances and influenza test positivity amongteenagers and young adults followed by increases in younger children (6).
    Most all-age influenza indicators, including influenza hospitalisations and intensive care unit admissions went above baseline levels from week 43 2025, the earliest inter-pandemic start to the season in England since 2003 to 2004 (6). Almost all cases (98%) since week 40 have been influenza A and, where subtyping was available for these, 84% were A(H3N2) (Supplementary Figure 1). Early starts to the 2025 to 2026 season have also been observed elsewhere in the NH (7, 8)

    (SNIP) 

    Influenza A(H3N2) genetic characterisation

    Genetic characterisation by whole genome sequencing of viruses collected from primary and secondary care in England has shown predominance of antigenically drifted A(H3N2) viruses belonging to subclade K since week 35 2025; 156 of 179 (87%) belong to this novel subclade (Table 1 and Supplementary Figure 2). Some J.2 and J.2.4 viruses continue to be detected. The distribution of all genetically characterised influenza A detections since week 20 2025 is described in Supplementary Figure 2a.

            (SNIP)

    Overall, our results are encouraging, though it is important to note that these observations are from a period very soon after vaccination when there has been no waning in effectiveness. Recent end of season analyses highlighted waning in effectiveness in adults over the course of an influenza season (Whitaker et al., 2025, In press, DOI: 10.1111/irv.70194) and it will be important to continue to monitor duration of protection this year. 

    To date, the burden of influenza has been greatest in children and young adults in England. The lower VE results seen in adults, when compared to children, is similar to previous seasons but does not exclude a larger reduction in protection in older adults as the season progresses.

    Alternatively, the reason for the lower VE results in adults than children may be explained by higher pre-existing background immunity against the circulating strains, in which cases the vaccine would offer less additional benefit. Seroprevalence analyses will be needed to confirm this. 

    Conclusion

    Despite the emergence of a drifted influenza A(H3N2) strain driving an unusually early 2025 influenza season in England and some other countries in the NH, our early estimates provide reassurance that the 2025 to 2026 NH enhanced vaccines provide important protection in children and adults in the early period post-vaccination. The high VE in children, strengthens the case for optimising vaccine uptake in this group, where we may also see indirect protection of other age cohorts (23). 

            (Continue . . . )

    When I got my flu shot last month I already had a strong inkling that the H3N2 component was going to be `suboptimal', as the WHO had already changed the formulations for next year's Southern Hemisphere flu shot

    But the flu shot is just part of my `flu prevention' routine each year. Something I take more seriously as my age, and comorbidities, rise. 

    I continue to wear a mask in crowded indoor venues, I carry (and use) copious amounts of hand sanitizer, and I purposely avoid high risk encounters (i.e., very large crowds). 

    While none of this guarantees I'll go unscathed this year, I've had pretty good luck over the years. My last `flu' was in 2009 (after a cross-country plane trip), and I've only contracted COVID once, before the first vaccine was released. 

    Even if this year's vaccine turns out to be a total bust with H3N2, H1N1 will continue to circulate at low levels, and influenza B could loom large later in the season.  

    Flu season is, afterall, nothing if not unpredictable. 

    Wednesday, November 12, 2025

    Preprint: Spillover of H5 Influenza Viruses to Vampire Bats at the Marine-terrestrial Interface

    Credit Wikipedia


    #18,942

    One of the threats we've discussed repeatedly over the past few years has been the potential ramifications when a formerly geographically and host restricted virus - like HPAI H5Nx - begins to 1) spread globally2) spill over into new hosts, and 3) reassorts with new viruses. 

    After 2 decades of being primarily an Asian, Middle Eastern, and occasionally European problem - H5N1 (over the past 4 years) has become endemic in the Western Hemisphere, and now has its sights set on Oceania (Australia/NZ). 

    After its arrival in North America in late 2021, we saw the sudden (and continual) generation of scores of new genotypes, and the spillover into many new avian and mammalian species. For the first time, dairy cattle - and other non-poultry livestock - were at risk, along with domestic cats and other peridomestic animals

    After HPAI H5N1 found its way into South America, it quickly became endemic in marine mammals, killing tens of thousands of animals from Peru to Argentina (see Nature Comms: Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b HPAI A/H5N1 with PB2 adaptations).

    In both instances, exposure to new, immunologically naive hosts - and reassortment with locally circulating LPAI viruses - resulted in the explosive spread, and rapid evolution, of the HPAI virus. 
    With HPAI now seemingly poised to invade Australia/NZ - which boasts some of the most unique (and isolated) fauna in the world - one can't help but wonder what unexpected impacts that might have on its future course and trajectory.

    All of which brings us to a preprint which - while sounding like a premise for a cheesy made-for-cable Sci Fi movie - actually illustrates another example of the unexpected consequences of HPAI's globe-trotting, and promiscuous, ways. 

    But first, a brief side excursion into the brief history influenza A in bats. 

    • Which was unknown until 2012, when a new H17 virus (see A New Flu Comes Up To Bat) was discovered in little yellow-shouldered bats (Sturnira lilium) captured at two locations in Guatemala.
    For the next couple of years only novel `bat specific' (H17 & H18) flu subtypes were detected in bats, suggesting a wide gulf between human and bat flu. 
    But in 2015 PLoS One published Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa - which described serological evidence of prior H9 influenza infection in bats tested in Ghana - raising new questions about the range of flu viruses carried by bats. 
    In 2018 (see J. Virology: Isolation & Characterization of a Distinct Influenza A virus from Egyptian Bats) a study described the isolation and characterization of a genetically distinct Influenza A H9-like virus from Egyptian fruit bats which already had the ability to replicate in the lungs of experimentally infected mice.

    In 2023, in Preprint: The Bat-borne Influenza A Virus H9N2 Exhibits a Set of Unexpected Pre-pandemic Features, we learned that Egyptian H9N2 virus already ticked a lot of the pre-pandemic boxes;
      • it readily infects and transmits incredibly well among ferrets
      • it replicates efficiently in human (explant) lung tissue
      • is able to escape human MxA (myxovirus resistance protein A)
      • there appears to be little pre-existing community immunity to H9 viruses 
    Suddenly, the idea that bats could carry human-susceptible influenza A viruses wasn't quite so outlandish. 
    Which brings us to today's preprint, which finds serological evidence of HPAI H5 infection in coastal vampire bats (Desmodus rotundus) in Peru, a region where marine mammals have been particularly hard hit by the avian flu virus.

    At this point, there is no evidence of sustained transmission among bats, and no live virus was isolated from these samples. But this is the first evidence of HPAI H5 infection in bats, and it suggests that HPAI may have found yet another unconventional avenue by which to spread and/or evolve. 

    I've posted the Abstract, and a brief excerpt. Follow the link to read it in its entirety.  I'll have a postscript after the break. 

    Spillover of H5 influenza viruses to vampire bats at the marine-terrestrial interface
    I-Ting Tu, Christina Lynggaard, Lorin Adams, Sarah K Walsh, Hanting Chen, Savitha Raveendran, Matthew L Turnbull, Megan E Griffiths, Rita Ribeiro, Jocelyn G Perez, William Valderrama Bazan, Carlos Tello, Carlos Zariquiey, Kristhie Pillaca Rodriguez, Marco Risco, Illariy Quintero Mamani, Wendi Chavez, Roselvira Zuniga Villafuerte, Joaquin Clavijo Manuttupa, Jean Pierre Castro Namuche, Andres Moreira-Soto, Jan Felix Drexler, Gustavo Delhon, Christina Faust,Susana Cardenas-Alayza, Ed Hutchinson, Pablo R Murcia, Massimo Palmarini, VKristine Bohmann,Ruth Harvey, Daniel G Streicker
    doi: https://doi.org/10.1101/2025.11.09.686930
    This article is a preprint and has not been certified by peer review [what does this mean?].

    Preview PDF

    Abstract

    The highly pathogenic H5N1 avian influenza A virus (IAV) clade 2.3.4.4b has spread globally and spilled over into multiple mammalian species, raising concerns about its pandemic potential. In late 2022, clade 2.3.4.4b viruses devastated seabird and marine mammal populations along the Pacific coast of South America. 

    Here, we report the first evidence of H5 IAV infections in wild bats globally, focusing on common vampire bats (Desmodus rotundus) in coastal areas of Peru. Longitudinal serological screening, stable isotope analysis and metabarcoding revealed repeated exposures to H5 IAVs in vampire bats which feed on coastal wildlife species heavily impacted by the 2.3.4.4b epizootic, but no evidence of infection in populations without access to marine prey. 

    We further report bat gene flow between IAV-exposed and IAV-naive populations, and IAV infections in a vampire bat colony that fed on both marine and terrestrial livestock prey, providing insights into how future IAV epizootics might spread spatially within bats and between marine and terrestrial ecosystems if a bat reservoir were established. 

    Immunohistochemistry demonstrated that the H5 haemagglutinin protein binds to the upper respiratory tract of vampire bats, suggesting bat tissue susceptibility to H5 IAVs. Finally, vampire bat-derived kidney, liver, and lung cells supported entry, replication, and egress of avian and mammalian 2.3.4.4b viruses, confirming cellular infectivity

    These results illustrate how combining ecological inference and experimental virology can pinpoint the species origins and biological significance of viral spillover at species interfaces.
    Recurrent exposures from marine wildlife, tissue and cellular susceptibility to H5N1 IAVs, and connections to other IAV-susceptible terrestrial mammals establish the prerequisite conditions for vampire bats to spread IAVs between marine and terrestrial environments or to form a novel reservoir of highly pathogenic IAVs.

           (SNIP)

    Understanding virus spillover at species interfaces is of paramount importance to pandemic preparedness. Yet, because spillover is shaped by inter-specific interactions that create opportunities for exposure and by host physiological barriers which determine whether exposures lead to infection, assessing spillover risk has been notoriously challenging - requiring multidisciplinary efforts to unify ecological and virological processes32.
    By integrating field surveillance, molecular and chemical ecology, tissue analyses and virological assays, were construct the exposure routes of a potential novel bat host to IAV-affected species, identify onward transmission pathways through high-resolution mapping of species interactions, and experimentally rule out hard physiological barriers to infection.
    While our current data support limited H5 IAV transmission among bats, the recurrent nature of spillover events, ongoing mammalian adaptation, and prospects for reassortment with other mammalian IAVs, indicate that bats may constitute an open door for future IAV emergence which require closer investigation.

            (Continue . . . )

     

    While HPAI H5 infected vampire bats are unlikely to present a direct public health threat any time soon, they could play a role in the cross-species transmission of the virus (e.g., from marine mammals to livestock) in some regions of South America. 

    They could also potentially serve as a `mixing vessel' between HPAI and other novel flu viruses, either now or in the future. 

    Much of the spread, transmission, and evolution of HPAI H5 (and other novel viruses) occurs outside of our view. The USDA's Detections of Highly Pathogenic Avian Influenza in Mammals (see below), has seen a dramatic drop in reports from states over the past year, despite high levels of the virus reported across the nation's wild birds, cattle, and poultry. 


    Some states have yet to report a single instance, while other have reported dozens.  But even from the states that do report, we get disappointingly few details.  
    Our willingness to `look the other way' when it comes to HPAI may pay economic or political dividends in the short term, but if HPAI H5 ever gets `lucky', it could quickly become too big to ignore.  
    At which point we'll regret every day we squandered hoping it would go away.