Preprint: Inoculation with HPAI H5N1 Genotype D1.1 in Naïve Dairy Cows and Dairy Cows Previously Exposed to Genotype B3.13

 

#19,007

HPAI H5N1, which has infected more than 1,000 U.S. dairy herds, continues to surprise. Until earlier this year, cattle spillovers were exclusively due to genotype B3.13, but we've now seen genotype D1.1 in dairy cows in at least 3 states.  

Earlier studies had suggested that dairy cows build a robust immunity to H5N1 after initial infection, but that study was conducted at a time when only B3.13 was thought to infect cattle.

Since the USDA doesn't report on reinfected herds (or on individual cows), we don't have a lot of data on how often reinfections might occur.  We also don't know how a past infection with genotype B3.13 might impact a cow exposed to genotype D1.1. 

In an attempt to answer some of those questions we have a preprint from researchers at the USDA and Iowa State University that looks at both naïve and previously exposed (B3.13) dairy cows that are inoculated with the newer D1.1 genotype. 

What they found was previously infected dairy cows were still susceptible to the D1.1 virus, albeit producing milder symptoms and shedding less virus. Something that could also make it more difficult to detect new spillovers. 

First the link and abstract to the preprint, after which I'll have a brief postscript. 

Inoculation with highly pathogenic avian influenza H5N1 genotype D1.1 in naïve dairy cows and dairy cows previously exposed to genotype B3.13

Kaitlyn Sarlo Davila1,,Meghan Wymore Brand1,,Ellie Putz1,,Paola Boggiatto1, Hannah Seger1, Amy Baker2, Tavis Anderson3, Carl Hutter1, Alexandra Buckley1,  Allison Vander Plaats, Rachel Friedrich4, Patrick Gordon4,  Bailey Arruda1, Carine Souza1, Brittney Davidson1, Mitchell Palmer1

This is a preprint; it has not been peer reviewed by a journal.
https://doi.org/10.21203/rs.3.rs-8339573/v1
This work is licensed under a CC BY 4.0 License

Abstract

USDA confirmed by whole genome sequence the first detection of HPAI H5N1 clade 2.3.4.4b genotype D1.1 in dairy cattle. While genotype D1.1 has been the dominant strain circulating in migratory birds in North America, the Nevada cases represent the first detection of a genotype other than B3.13 in cattle and the second known spillover event from wild birds into lactating dairy cattle. D1.1 clinical presentation in dairy herds in both Nevada and Arizona was mild compared to HPAI B3.13. However, this is based on a small number of affected herds and may not be the case for the broader population.

Here we sought to experimentally reproduce infection of dairy cattle with HPAI H5N1 genotype D1.1. and also sought determine if cattle with serum antibodies following natural infection with HPAI B3.13 were protected against reinfection with HPAI D1.1. Four adult Holstein lactating cows were moved into ABSL-3-Ag containment, two cows free of influenza A virus and two cows free of influenza A virus, but with serum antibodies from a natural H5N1 infection (genotype B3.13 ).

All cows were inoculated via the intramammary route with 1 ml of 1 x 105.4 TCID50/ml A/dairy cattle/Nevada/24-002644-003/2025 into two contralateral quarters. The drop in milk production and rumination observed in this study were similar to those reported in experimental intramammary challenge of lactating cows with HPAI B3.13, as well as natural infections, indicating that clinical presentation of HPAI D1.1 was similar in severity to experimental challenge with HPAI B3.13. 

Unlike the HPAI B3.13 intramammary challenges, HPAI D1.1 migrated and infected a non-inoculated quarter. The two B3.13 convalescent cows were susceptible to reinfection with D1.1, demonstrating clinical signs including a drop in milk production and rumination, pyrexia, and mastitis.

However, milk production and rumen motility recovered more quickly in the two convalescent cows than in the two naïve cows and pyrexia was not as severe. Viral RNA was also not detected in the milk of the convalescent cows after 10 DPI while it was detected in the milk of the naïve cows for the durations of the study.

Furthermore, while viral RNA was detected in the milk of both convalescent cows, no viable virus was isolated. While convalescent cows with serum but not milk antibodies to B3.13 are susceptible to reinfection with D1.1 and clinical disease antibodies can transudate into the milk and bind virus, likely preventing further spread throughout the herd.

The single-nucleotide variant analyses of whole genome sequences virus recovered from the milk of previously naïve cows also uncovered some potentially important patterns. Genes HA and MP were found to have strong evidence for natural selection and analysis indicates a fitness advantage is conferred through some key mutations that could lead to antigenic drift and immune escape.

        (Continue . . . )

The takeaway from all of this is that while reinfection with the same genotype might be limited, previously infected herds cannot be assumed to be immune to newer/different H5N1 genotypes.

Another reminder, as if we needed it, that early assumptions about emerging pathogens often require frequent reexamination. 

When Seasonal Flu Exceeds Expectations

Flu Virus binding to Receptor Cells – Credit CDC

#19,006

It is summer down under, and typically the nadir of the Australian flu season, but this year - as Virologist and blogger Dr. Ian McKay reports - seasonal flu is still going strong more than 3 months after their calendar-based flu season should have ended. 

A few days ago Ian wrote: 

Instead of the annual epidemic returning to baseline levels, cases stopped declining in October and have started to rise again in November, December, and perhaps also in January (still a few days left). Just to note, there is always some flu around, just usually at very low levels outside the epidemic peak period.

I would invite you to read Ian's entire analysis, because the same subclade K of seasonal H3N2 which emerged there last July, is now running roughshod over the United States, Canada, Europe, Asia, and the rest of the Northern Hemisphere. 

Due to the holidays, surveillance and reporting over the past few weeks have  likely under-represented its current impact here in the United States. We'll get another belated FluView on Monday, but it often takes until mid-January before reporting returns to normal. 

Meanwhile, early reports (see WHO EURO Statement: More than half of WHO European Region experiencing intense, early influenza season driven by new strain) and the latest FluView data (which is at least 2 weeks old at this point), attest to its impact. 

Whether we'll experience the same protracted flu season as has Australia remains to be seen - but it is certainly possible - making it still very much worth getting this year's flu vaccine if you haven't already. 

Despite concerns that this year's vaccine may not be as effective against this drifted subclade; it is still expected to provide valuable protection against severe disease (see UKHSA Preprint: Early Influenza Virus Characterisation and Vaccine Effectiveness in England in Autumn 2025, A Period Dominated by Influenza A(H3N2) Subclade K)

How much protection?  Well, we probably won't have good data until later this month, and the full story won't be known until next summer.  But anything that reduces your chances of being hospitalized with severe influenza has value. 

Which is why I also wear a mask in public, use copious amounts of hand sanitizer, and try to avoid crowded indoor spaces.  A strategy which has helped keep me respiratory illness free for nearly 5 years.  

Last year was pegged as being the worst flu season in nearly a decade (see MMWR: Influenza-Associated Hospitalizations During a High Severity Season (United States, 2024–25)), but this year could end up being even more challenging.

 

Already New York state is reporting a faster start to this year's flu season (see dashboard below) and last week their DOH reported (New York State Department of Health Confirms Most Flu Cases Ever Recorded in One Week).

While many people trivialize the flu, numerous studies suggest strong links between influenza infection and cardiovascular events like heart attacks and strokes (see also Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke).

In early 2023, in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, we also looked at a study published in Cell Neuron which found a statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.

And every once in a while seasonal flu will serve us up a curveball, sometimes even in the middle of the season.  A few examples:

• In 2008, H1N1 abruptly developed nearly 100% resistance to oseltamivir;
• In 2014, we saw a late summer mutation appear in the H3N2 virus (see HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) which greatly reduced the effectiveness of that year's flu vaccine.
• in 2016, we saw warnings over mutated (D225G) H1N1 viruses in Russia and in Europe (see ECDC Risk Assessment : Reports Of Severe A(H1N1)pdm09 In Europe);
• And while it has had only limited impact so far, we are now watching another slow rise in antiviral resistance in H1N1

But the biggest seasonal flu aberration may well have been the Liverpool Flu of 1951, which - for about six weeks - caused a virulent flu virus to spread across the UK and into Canada was as deadly as the 1918 pandemic.

This graphic comes from the March 16th, 1951 Proceedings of The Royal Society of Medicine – page 19 – and shows in detail the tremendous spike in influenza deaths in early 1951 over the (admittedly, unusually mild) 1948 flu season.  

In 2006 the CDC's EID Journal published a stellar account of this event, and it is very much worth reading. 

Viboud C, Tam T, Fleming D, Miller MA, Simonsen L. 1951 influenza epidemic, England and Wales, Canada, and the United States. Emerg Infect Dis [serial on the Internet]. 2006 Apr [date cited].

A sobering reminder that even seasonal flu deserves our respect. 

WHO Statement: COVID-19 Still Causes Severe Disease & Renewed Vaccination Recommendations

#19,005

Six years ago last night - a little before midnight - the dedicated newshounds at FluTrackers began posting reports of a `SARS-like' illness reported in the capital city of Hubei province; Wuhan.

Around 2am Sharon Sanders messaged me on Skype, and by 4am I had posted the first of 3 blogs (see China: 27 Cases of `Atypical Viral Pneumonia' Reported In Wuhan, Hubei) I'd write on New Year's Eve day on that event (see also here & here).

Although it would take nearly a week before the WHO and CDC would publicly address the situation, and nearly three weeks (Jan 18th) before China would admit to `limited human-to-human transmission' of the virus, the world had already abruptly, and irrevocable, changed. 

We just didn't know it yet. 

We'll never truly know how many people have died from COVID - because the world stopped counting early on - but the UN posted the following estimate for just the first 24 months.

New estimates from the World Health Organization (WHO) show that the full death toll associated directly or indirectly with the COVID-19 pandemic (described as “excess mortality”) between 1 January 2020 and 31 December 2021 was approximately 14.9 million (range 13.3 million to 16.6 million).

While deaths have slowed, they have not stopped.  And tens of millions of others  have suffered chronic or long-lasting sequelae from infection, ranging from strokes and heart attacks, to `brain fog' and extreme fatigue from `Long COVID'.

Repeated infections have been linked to increased damage, and the risk of developing a chronic post-COVID illness (see Preprint: Incidence of Long COVID Following Reinfection with COVID-19).

Yet for various economic, societal, and political reasons, we have trivialized the virus.  

Once 90% of the world decided to stop counting (and reporting) deaths and hospitalizations (see 2023's No News Is . . . Now Commonplace), vaccine uptake and the use of masks plummeted. 

Today WHO EURO released a statement on the 6th anniversary of the Wuhan revelations, and the need to continue to treat COVID as a legitimate public health threat.  

First the press release, after which I'll return with a postscript.

COVID-19 still causes severe disease, but up-to-date vaccines are effective, new research shows
31 December 2025
News release Reading time: 3 min (817 words)

Six years ago, on 31 December 2019, the first reports of cases of pneumonia appeared on the website of the Wuhan Municipal Health Commission in China. Those early cases were the beginning of the COVID-19 pandemic. Almost 3 and a half years later, in May 2023, after an estimated global death toll of over 6.9 million people, WHO declared the end of the Public Health Emergency of International Concern due to COVID-19.

However, while the pandemic is behind us, COVID-19 is not. Recent research led by WHO/Europe together with partners in 7 Member States shows that SARS-CoV-2, the virus that causes COVID-19, continues to cause hospitalizations and deaths throughout the WHO European Region. It also confirms that getting an up-to-date COVID-19 vaccine continues to be the most effective way of preventing severe disease from COVID-19.

In the years since the COVID-19 pandemic ended, WHO/Europe has collaborated with partners in ministries of health in countries and areas in the eastern part of the Region to conduct enhanced surveillance for respiratory infections through a regional network of hospitals. This network, named the European Severe Acute Respiratory Infection Vaccine Effectiveness (EuroSAVE) Network, was created in 2021 and currently includes countries and areas in the Balkans, South Caucasus and Central Asia.

Severe disease

The EuroSAVE network study included 6 countries and areas. Out of nearly 4000 patients who were hospitalized for acute respiratory infections between May 2023 and April 2024 – the year after the pandemic was declared over – nearly 10% had COVID-19. The study found that more than two thirds of hospitalized patients were older than 60 and over two thirds had at least one chronic disease – people who the WHO recommends get an annual up-to-date COVID-19 vaccine. However, only 3% of hospitalized patients had received a COVID-19 vaccine within the past 12 months.

The study also found that COVID-19 continued to cause very severe disease: 13% of COVID-19 patients were admitted to an intensive care unit (ICU) and 11% of COVID-19 patients died.

Another EuroSAVE study compared patients hospitalized for respiratory infections with COVID-19 to those hospitalized with influenza during a 3-year period (2022–2024). Results showed that throughout the study period, patients hospitalized with COVID-19 were more likely to have severe outcomes – including requiring oxygen, being admitted to the ICU and death – compared to influenza patients.

“Our studies, using data from the EuroSAVE network, highlight that, while COVID-19 is not leading to the widespread disease we saw during the pandemic, it has still been causing a considerable number of hospitalizations and deaths. Moreover, the impact of the virus seems to still be as severe, and sometimes more severe, than influenza,” noted Dr Mark Katz, a medical epidemiologist with the Pandemic Threats, Communicable Diseases and Anti-Microbial Resistance Unit of WHO/Europe.

Up-to-date vaccines

Two additional studies from the EuroSAVE network reaffirmed the effectiveness of an up-to-date COVID-19 vaccine. One study, which analysed 3 years of data from Kosovo*, found that an up-to-date COVID-19 vaccine received in the past 6 months was 72% effective at preventing hospitalization related to COVID-19 and 67% effective in preventing more severe outcomes related to COVID-19, including admission to the ICU and death.

Another study, which included data from the 6 countries and areas that are part of EuroSAVE, found that receiving a COVID-19 vaccine in the previous 6 months prevented 60% of hospitalizations.

In all 4 studies, EuroSAVE surveillance data showed that very few hospitalized patients who were in high-risk groups had actually received an up-to-date COVID-19 vaccine in the previous year. Furthermore, in some of the countries included in the analysis, COVID-19 vaccines were no longer available.

“Our analysis of EuroSAVE surveillance data showed the importance of getting an up-to-date COVID-19 vaccine to prevent severe disease from COVID-19,” said Dr Silvia Bino, Head of the Department of Epidemiology and Control of Infectious Disease at the Institute of Public Health in Albania and a co-author of the multi-country EuroSAVE vaccine effectiveness study.

“We found that most hospitalized patients were older or had chronic diseases. These people are in risk groups that are recommended to get annual COVID-19 shots, but most hadn’t received an up-to-date vaccine.”

Revaccination

In light of the fact that COVID-19 continues to cause morbidity and mortality across the globe, WHO continues to emphasize the importance of revaccination for groups at higher risk of severe disease and death. These include older adults, people with comorbidities, immunocompromized individuals and pregnant persons. Revaccination of health workers is also recommended.

WHO/Europe and ministries of health will continue conducting enhanced surveillance through the EuroSAVE network in order to better understand the burden of COVID-19 and other respiratory viruses, evaluate the effectiveness of up-to-date COVID-19 vaccines and answer other urgent public health questions about infections due to respiratory pathogens, old and new.

*All references to Kosovo in this document should be understood to be in the context of the United Nations Security Council resolution 1244 (1999).

As we discussed a year ago in The Wrong Pandemic Lessons Learned - not only have we developed societal amnesia over the impact of COVID - we seem to be less well prepared today to deal with another global health crisis than we were a decade ago.

Our collective trauma following six years of COVID, the travails of navigating day-to-day life, and inconsistent messaging (and actions) from governments and health authorities, have left society numb, vulnerable, and increasingly apathetic.  

Hopefully it will be years before we endure another severe pandemic, but at some point our luck will run out (see BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events).

While no two pandemics are alike, they all do seem to share one common feature.

You never know you're in one until it's too late to prepare.

PLoS GPH: Quantifying H5N1 Outbreak Potential and Control Effectiveness in High-risk Agricultural Populations

 

R₀ (pronounced R-nought) or
Basic Reproduction Number

#19,004

In the spring of 2023, in UK Novel Flu Surveillance: Quantifying TTD, we looked at a technical briefing from the UKHSA which attempted to quantify (via statistical modelling) the UK's ability to detect community transmission of a novel flu virus, such as HPAI H5N1.

At that time, the UKHSA estimated it would likely take between 3 and 10 weeks before community spread would become apparent to authorities, after anywhere between a few dozen to a few thousand community infections.

This is their `best case' R₀ 1.2 scenario

Soberingly, this was for the UK; where public health and testing capabilities are far stronger than in a lot of countries currently dealing with HPAI. Even so, detecting community spread early in an outbreak would require a good deal of luck. 

With HPAI H5 now primarily a disease of poultry (and in some countries, other livestock), the ideal place to detect, and halt, human transmission would be on the farm.   

Today we've a new study from researchers from the UKHSA and the University of Bristol which attempts to model the ability for basic public health tools to control the early spread of HPAI (up to an R₀ of 1.1) among agricultural workers.  

The authors first surveyed bird‑exposed farm workers about how many people they met in a day, and then generated computer models of outbreaks starting from a single human infection at various R₀ rates (0 up to 1.1 in steps of 0.1).  

Note: The 2023 UKHSA Community Transmission study assumed an R₀ starting at 1.2, up to 2.0.  

What they found was - using somewhat idealized public health tools (contact tracing of symptomatic cases’ contacts & self‑isolation of symptomatic traced contacts) - that when the transmission R₀ was < 1, the number of cases would remain low; often under 10 cases. 

But, as the  R₀  approaches 1.0, or if the number of asymptomatic cases go up, cluster sizes increase. 

Due to its length and technical nature, I've only presented a brief overview. Below you'll find the abstract and a few excerpts, but you'll want to follow the link to read the report in its entirety. 

I'll have a bit more after the break.  

Quantifying H5N1 outbreak potential and control effectiveness in high-risk agricultural populations

Izel Avkan ,Suzanne Gokool,Louise E. Smith,Genevieve Clapp,Rachel Cox,Amy C. Thomas,Ellen Brooks-Pollock
PLOS x Published: December 29, 2025
https://doi.org/10.1371/journal.pgph.0005463

Abstract

Avian influenza is a global public health threat. Since 2021, the ongoing H5N1 panzootic has brought a major shift in H5Nx epidemiology, including unprecedented spread, wide host range and lack of seasonality. Infections in marine mammals, wildlife and livestock have heightened concern for human-to-human transmission and pandemic potential. Contact tracing and self-isolation are used as public health measures in the UK to manage contacts of confirmed human cases of avian influenza.

In this study, we aimed to estimate potential outbreak sizes and evaluate the effectiveness of contact tracing and self-isolation in managing community outbreaks of H5N1 following spillover from birds to people. We characterised contact patterns from an underrepresented agricultural population at high risk of avian influenza exposure through contact with birds (Avian Contact Study).

 Informed by these realistic social contact data, we modelled outbreak sizes using a stochastic branching process model. Most simulations resulted in small-scale outbreaks, ranging from 0 to 10 cases.

When the basic reproduction number was 1.1, contact tracing and self-isolation reduced the average outbreak size from 41 cases (95% Confidence Interval (CI): 37–46 cases) to 7 cases (95% CI: 6–8 cases), preventing, on average, 8 out of every 10 infections. 

However, controls became less effective in reducing the outbreak size when a higher proportion of cases were asymptomatic. Overall, our findings suggest that contact tracing and self-isolation can be effective at preventing zoonotic infections. 

Increasing awareness, encouraging self-isolation, and detecting asymptomatic cases through routine surveillance are important components of zoonotic infection containment strategies.

(SNIP)

Principal findings

Our model provides insights into the potential outbreak size of avian influenza among humans under different levels of transmission and a full range of proportions of asymptomatic infections to account for uncertainties around these values. Most simulations resulted in small-scale outbreaks, with outbreaks exceeding 100 cases when the basic reproduction number was above 0.8, consistent with previous estimates [34].

Contact tracing and self-isolation reduced outbreak size, but their potential effectiveness in preventing cases decreased as the proportion of asymptomatic infections increased, since they rely on symptomatic cases.

Additionally, larger values of R0 would increase outbreak size and the number of contacts, which may slow down contact tracing efforts and reduce the effectiveness of current interventions. Previous modelling studies similarly concluded that contact tracing and self-isolation alone were highly unlikely to prevent large outbreaks, particularly when asymptomatic infections were present [28,35]. Our findings support and extend these conclusions to a different pathogen.

        (Continue . . . )

The late George E. P. Box (18 October 1919 – 28 March 2013) - Professor Emeritus of Statistics at the University of Wisconsin - is often credited with coining the familiar adage:

“All models are wrong, but some models are useful.”

It is impossible to account for all of the variables in a real-life situation, and so certain parameters must be set, such as capping the R₀ at 1.1.  

Some assumptions in this model that may depart from reality are that (1) all symptomatic farm workers would be immediately tested, (2) that contact tracing would be timely and 100% effective, and (3) that all contacts would fully self-isolate. 

Even if this remarkable hat-trick could be achieved in the UK, the reality is that surveillance, testing, contact tracing, and reporting from many other countries is - to put it kindly - suboptimal. 

None of this is to suggest we shouldn't try, of course.  

If the missing ingredient to human-adaptation of HPAI H5 is a long-chain of human infections (plausible, but not certain), then anything we can do to prevent or limit that type of uncontrolled serial passage experiment is very much worth the effort. 

But whether we have the political and societal will do to so, is far less certain. 

Preprint: Emergence of D1.1 Reassortant H5N1 Avian Influenza Viruses in North America

 

#19,003

As we discussed at some length last August in H5Nx: Reassort & Repeat, in the Northern hemisphere millions of migratory birds spend their summers in their high latitude breeding areas in Alaska, Canada, Siberia, and even the Arctic.

During their stay, they hatch a new generation of (flu naive) fledglings while mingling with other species, potentially sharing avian viruses picked up the previous spring (see 2016's Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

These factors can lead to the creation and spread of new reassortants (genetic hybrids). While most are genetic failures - and unable to compete with existing strains - every once in a while a `new and improved' virus appears.

In the fall of 2024, while most `flu watchers' were concentrating on the B3.13 `bovine' genotype infecting hundreds of U.S. dairy herds (and mildly infecting dairy workers), a new, genotype (D1.1) emerged in wild birds, and swiftly crossed the country from west to east.

Unlike the `bovine' version, however, it produced a few severe (and 2 fatal) illness among a handful of human infections (see map above).  

D1.1 was also joined last fall by two `lesser' reported emerging genotypes (D1.2 and D1.3), the former found in infected pigs in Oregon, and the latter infecting an ostrich farm in Canada and producing a human case in Ohio.

Not to be outdone by B3.13,  D1.1 also spilled over into cattle (twice) in early 2025, with a 3rd spillover reported in Wisconsin early this month. 

Since its arrival to North America in 2021, more than 100 new genotypes have been identified, with scores more circulating in Europe, Asia, and South America. As flu viruses are notoriously promiscuous, new genetic combinations are certain to emerge. 

Most will be less `biologically fit' than their competitors, and will fall by the wayside, but occasionally a new, better adapted, variant will emerge. Although B3.13 and D1.1 currently have the bulk of our attention, they are simply stepping stones to the `next' viral iteration. 

All of which brings us to a new preprint, released last week, which describes what we know about this emerging genotype, including the swapping out of its NA gene (Eurasian neuraminidase with a North American LPAI N1), and the remarkable continent-wide dispersal of this strain. 

While D1.1 may not be ready for prime time, it continues to hone its abilities - mostly outside of our view - and that should give us pause. 

Due to its length, I've just posted the Abstract and a few excerpts. Follow the link to read the paper in its entirety. 

Emergence of D1.1 reassortant H5N1 avian influenza viruses in North America
Alvin Crespo-Bellido, Nídia S. Trovão, Alexander Maksiaev, Guy Baele, Simon Dellicour, Martha I. Nelson
doi: https://doi.org/10.64898/2025.12.19.695329
This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF

Summary

Since 2021, highly pathogenic avian influenza viruses (HPAIV) belonging to H5N1 clade 2.3.4.4b have caused high mortality in North American wild birds and poultry. In 2025, a new D1.1 genotype caused two human deaths and host-switched to dairy cattle. However, the evolutionary origins and dynamics of D1.1 have not been fully characterized.

Here, our phylogenetic analysis of 17,516 H5N1 genome sequences uncovers how D1.1 introduced a major shift in the antigenic diversity and ecology of the H5N1 epizootic in North America.

D1.1 is the first major H5N1 genotype to (a) emerge in the Pacific flyway and spread west-to-east faster than any prior genotype; (b) antigenically shift via reassortment with the North American N1 segment, displacing the previously fixed Eurasian N1; and (c) transmit to a broader range of host species than any H5N1 genotype to date, introducing mammalian adaptations 

(SNIP)

Thus far, Eurasia has been a major source of H5N1 viruses for North America, and there is little evidence of D1.1, B3.2, or other dominant North American genotypes migrating back to Europe or Asia. However, H5N1 is routinely changing patterns. Understanding the risk that major evolutionary changes in H5N1 in the Americas presents to the rest of the world is a central question going forward. 

(Continue . . . )

There's an old joke about a tourist asking a NYC cabbie, `What’s the best way to get to Carnegie Hall?” and the cabby replies, “Practice, practice, practice”.

In many ways, that applies to viruses. They usually get better (i.e. adapt) following repeated spillovers.  

And right now - in countless wild birds, poultry, cattle, pets, mammalian wildlife, and occasionally humans - it's getting a lot of practice. 

A Brief History of Influenza A in Canines & Canadian Report On A Recent Fatal H5N1 Dog Infection

 
Just one of many scenarios - Dogs as `mixing vessels' for Influenza 

#19,002

Until a little over 2 decades ago dogs and cats were thought to be poorly susceptible to influenza A viruses; but that all changed in 2004 when scores of captive cats (tiger, lions, etc.) in South East Asian zoos - fed on a diet of raw poultry - began dying from HPAI H5N1 (see 2006 WHO DON).

At roughly the same time dogs at a Florida racetrack unexpectedly began to fall ill from a variant of the equine H3N8 virus (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).

Three years later another flu virus (avian H3N2) jumped to dogs in South Korea (see Transmission of Avian Influenza Virus (H3N2) to Dogs). The HA and NA genes of the A/canine/Korea/01/2007 (H3N2) isolate were closely related to those identified in chickens and doves in South Korea in 2003.

After nearly a decade of spreading in  Asia, in 2015 canine H3N2 finally landed in North America (see CDC Statement On H3N2 Canine Influenza In Chicago Region) and quickly spread across the United States.

As a result, during the middle of the last decade the notion that dogs might serve as intermediate hosts - or even mixing vessels - for novel influenza began to gain traction.  A few, of many, reviews include:

Viruses Review: Potential Intermediates in the Cross-Species Transmission of Influenza A Virus to Humans

J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

Study: Dogs As Potential `Mixing Vessels’ For Influenza

Admittedly, cats appear to be far more susceptible than dogs (see 2023's A Brief History Of Avian Influenza In Cats) - with hundreds more infections reported since - but as dogs tend to show fewer symptoms than cats, they may be less likely to be tested.

While rare, severe and even fatal canine infections with HPAI H5 have been reported, as we saw detailed in 2024's Microorganisms: Case Report On Symptomatic H5N1 Infection In A Dog - Poland, 2023, where the authors wrote:

The case described in our report confirms that on rare occasions the A/H5N1 virus can also induce a natural severe respiratory disease in dogs. While in some of them the infection remains asymptomatic, capable of shedding the virus [35], others exhibit mild symptoms such as transient fever [34], or even fatal disease [20].

In 2023, Canada reported a fatal H5N1 infection in a domestic dog in Ontario (see press release below), which renewed concerns, particularly for those with hunting dogs. 

Domestic dog tests positive for avian influenza in Canada

From: Canadian Food Inspection Agency

Statement

April 4, 2023 – Ottawa, Ontario

Today, the Canadian Food Inspection Agency and the Public Health Agency of Canada issued the following joint statement:

The Canadian Food Inspection Agency's (CFIA) National Centre for Foreign Animal Disease, confirmed on April 1, 2023, that a domestic dog in Oshawa, Ontario has tested positive for highly pathogenic avian influenza (HPAI).

The domestic dog was found to have been infected with avian influenza after chewing on a wild goose, and died after developing clinical signs. The necropsy was completed on April 3, 2023, and showed respiratory system involvement. Further testing is underway. It is the only case of its kind in Canada.

       (Continue . . . )

A year later, in EID Journal: Antibodies to Influenza A(H5N1) Virus in Hunting Dogs Retrieving Wild Fowl, Washington, USA, researchers reported finding a low - but significant - number of healthy hunting dogs with antibodies to H5N1 (tested over a 2 month period in 2023).

Spillovers into companion animals are particularly worrisome because of their potential for spreading the virus to other animals, or to humans (see JAVMA: Companion Animals and H5N1 Highly Pathogenic Avian Influenza: Cause for Concern?).

All of which brings us to the following memo from the Office of the Chief Provincial Veterinarian dated December 16, 2025, hosted on the Canadian Veterinary Medical Association (CVMA) website. 



While dog owners may be relieved by the relatively rare severe presentation of HPAI H5N1 in canines, as the following report indicates, that may present problems of its own. 

In 2023's Eurosurveillance: Asymptomatic infection with clade 2.3.4.4b HPAI A(H5N1) in carnivore pets, Italy, April 2023, the authors wrote:

Here we report a case of influenza A(H5N1) infection in a domestic cat and five dogs living on a rural backyard poultry farm where an HPAI H5N1 outbreak was notified; the infection in poultry was caused by an HPAI H5N1 virus strain belonging to the BB genotype that was characterised by the presence of a PB2 mutation related to mammalian adaptation.

In contrast, the affected pets in this report were completely asymptomatic, raising concerns over the possibility of subclinical infections with zoonotic viruses in animals in close contact with humans.

       (Continue . . . )

While the risks for the general public of contracting avian flu are currently very low, those who have pets that are allowed to roam outdoors may be at slightly greater risk, along with anyone who deals with animal rescue or rehoming operations (see California: San Mateo County Warns Residents After Stray Cat Found With H5N1).

The thing about risk, though, is it can change abruptly. And given the limits of surveillance and reporting, a specific risk may become elevated for days or even weeks before we ever learn about it.

While I dislike the phrase `the new normal', as long as HPAI H5 continues to circulate at high levels in our environment, we have to accept that this has become our `new reality'.