Referral: (OFFLU Report) Beyond poultry: Rethinking monitoring and control of HPAI H5Nx anticipating spillover risks for mammals.

 

WOAH SitRep #79

#19,091

Yesterday OFFLU - the WOAH/FAO joint network of expertise on avian influenza - published a paper from some of the most recognizable names in influenza research, that offers practical steps for combating the growing threat from HPAI H5Nx.

In a nutshell, the authors posit that we can no longer afford to think of HPAI H5Nx as simply an avian or poultry-centric disease. Its epidemiology has changed in recent years to permit sustained, year-round carriage in aquatic birds, and increased spillover to multiple mammals species. 

They argue that surveillance and reporting systems must be adapted to protect animal and human health. They warn that `. . . dedicated HPAI surveillance strategies targeting wild and domestic mammals are largely absent in most countries.' 

They also find the most critical surveillance gap is among farmed mammals, a topic we've covered often (see OFFLU Guidelines for High Pathogenicity Avian Influenza Virus Risk Mitigation in Cattle).

The authors then present a framework for creating a `spillover prevention plan' utilizing a One Health approach. One that focuses prevention and surveillance on four groups of mammals:

• Mammals housed in groups (livestock, fur farms, zoos, catteries)
• Companion animals (cats, dogs, etc.)
• Free‑ranging mammals (wild and feral)
• Humans with relevant exposures.

As I can find no explicit copyright notice anywhere in the PDF, I'm reluctant to quote extensively from the paper. However, since it is relatively short (7-pages), I can highly recommend following the link to read it its entirety.  

Beyond poultry: Rethinking monitoring and control of HPAI H5Nx anticipating spillover risks formammals.March 2026 

This document was developed by OFFLU, the Network of Expertise on Animal Influenza established by the World Organisation for Animal Health (WOAH) and the Food and Agriculture Organization of the United Nations (FAO), through its Wildlife and Avian Technical Activities. 

Authors and Affiliations Lineke Begeman* 1,2, Fabien Filaire* 1,2, Lorcan Carnegie1 , Martin Beer3 , Francesco Bonfante4 , Nicola Lewis5,6, Guillaume Fournie6,7,8 , Erik A Karlsson9 (OFFLU Vice-Chair), Marcela Uhart10 (OFFLU Chair), Ron Fouchier2 , Thijs Kuiken2 (*contributed equally). 

UC Davis: High pathogenicity Avian Influenza in Pinniped conservation

 
Credit https://doi.org/10.1098/rstb.2024.0320

#19,090

Just over 3 weeks ago, in California: Background on the Outbreak of H5N1 in Elephant Seals at Año Nuevo Natural Reserve, we looked at early reports from California Parks and UC Santa Cru on the first detection of HPAI H5N1 in North American Elephant Seals.

Initial reports suggested that at least 7 seal pups had tested positive after dozens of seals at California's Año Nuevo Reserve had developed respiratory and neurological symptoms. 

Since then, according to local news outlets (see CIDRAP report), the number of  HPAI positive seals has increased to 16, along with an otter and a sea lion.  The actual count is likely much higher, as only a limited number of mammals have been tested. 

Compared to what we've seen in South America, this remains a small outbreak, but over the past 5 years we've seen evidence of this virus becoming more `mammalian friendly'.  

Dairy cows, domestic cats, and peridomestic animals like mice, skunk, and foxes have all been affected, but marine mammals appears to be close to achieving  sustained mammal-to-mammal transmission. 

• Two years ago, in a research letter (see EID Journal: HPAI A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023), researchers wrote: ". . . it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region . . ."

• In the summer of 2024, we looked at a Preprint: Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission

• And a year ago, in Nature Comms: Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b HPAI A/H5N1 with PB2 adaptations, the authors wrote:

• Several mutations were detected months later in sea lions in the Atlantic coast, indicating that the pinniped outbreaks on the west and east coasts of South America are genetically linked. These data support sustained mammal-to-mammal transmission of HPAIV in marine mammals over thousands of kilometers of Chile’s Pacific coastline, which subsequently continued through the Atlantic coastline.

Although exact numbers are impossible to come by, a little over a year ago in Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity, we saw a partial tally.

The most noteworthy mass-mortality events include more than 200,000 wild birds in coastal areas of Peru6; 24,000 sea lions in South America7; 20,500 wild birds in Scotland8; 6,500 Cape cormorants in Namibia9; and 17,400 elephant seals, including >95% of the pups in Argentina10.

These figures, however, largely underestimate actual mortalities, owing to a pervasive lack of monitoring, testing and reporting — particularly in inaccessible areas and in disadvantaged countries4,7.

Aside from the devastating impact on these mammals and the marine ecology, the possibility exists that HPAI could make strides towards human adaptation as it spreads through other mammalian species. 

All of which brings us to a study published earlier this month in Philosophical Transactions B which details the impact of HPAI on pinnipeds, and offers some recommendations on how its impact might be managed. 

Since this article was submitted months before the current outbreak in California, I've included some excerpts from a UC Davis press release which incorporates these latest developments.

The full 17-page PDF can be downloaded at the link below. 

High pathogenicity avian influenza in pinniped conservation 

Elizabeth Ashley; Ralph Eric Thijl Vanstreels; Michelle Barbieri; Wendy Puryear; Frances Gulland; Cara Field; Christine Kreuder Johnson; Marcela Uhart  Published online: 05 Mar 2026 https://doi.org/10.1098/rstb.2024.0320

Abstract

Since 2020, H5Nx high pathogenicity avian influenza viruses (HPAIVs) have caused widespread disruptions not only to global agriculture and trade but also to the health of free-ranging wildlife. Pinnipeds have experienced greater mortality from H5Nx HPAIV than any other mammalian taxa. Emergent virus strains, persisting over long time periods and vast geographic distances, have repeatedly triggered large-scale mortality events in pinniped populations.

Of particular concern is the spread of H5Nx HPAIV to the Southern Hemisphere—including the emergence of a marine mammal-adapted clade in South America and detections in the sub-Antarctic and Antarctic—and to other remote locations such as the Hawaiian Islands. These developments elevate concern for the world’s endangered, isolated and endemic pinnipeds.

While managing HPAIV in any animal population is a formidable task, working with free-ranging marine mammals poses unique challenges. In this review and perspective piece, we attempt to synthesize complexities at this intersection. We describe lessons learned from HPAIV investigations in marine wildlife, highlight gaps in knowledge and capacity, and discuss the incorporation of outbreak risk assessment and countermeasures into pinniped conservation. Finally, we propose ways in which pinnipeds—and marine wildlife broadly—could be better integrated into existing systems for HPAIV intelligence, control and prevention. 

        (Continue . . . )

  
From the press release:

Global strategies to protect seals and sea lions from avian influenza

A birds-eye view of the impacts of H5N1 on pinniped conservation 

University of California - Davis 

News Release 19-Mar-2026

(EXCERPT)

A study from the University of California, Davis, steps back to look at the overall impact of the virus on pinnipeds worldwide and offers recommendations for moving forward to monitor, characterize risk and build resilience in the affected species. It also suggests ways to help prevent the virus from reaching currently unaffected but vulnerable pinniped species, such as the endangered Hawaiian monk seal or Galapagos sea lion.

(SNIP)

“There is a huge, unprecedented conservation risk,” said corresponding author Christine Johnson, director of the Institute for Pandemic Insights at the UC Davis Weill School of Veterinary Medicine. “Influenza is constantly changing, and that is a big problem now that it’s widely circulating in birds and marine mammals.”

(SNIP)

In late February, northern elephant seals in California marked the first cases of HPAI H5N1 in a marine mammal in the state. The speedy detection was due to routine surveillance for H5N1 that was set up over a year prior by UC Davis and Año Nuevo Natural Reserve in collaboration with UC Santa Cruz’s long-term monitoring of the northern elephant seal colony at Año Nuevo State Park.

At the end of 2025, in response to a growing number of H5N1 cases in Bay Area seabirds, the team increased surveying efforts, walking the length of the reserve to document and sample any sick or dead bird or mammal throughout the elephant seal breeding season.

These efforts in advance of the outbreak allowed teams to quickly respond to changes in the seals’ health and collect samples for testing at UC Davis. Johnson called it an “exceptionally rapid detection of an outbreak in free-ranging marine mammals,” and an example of the kinds of preemptive efforts to detect and respond to outbreaks effectively.

The paper’s key recommendations include:

• Fund and support long-term wildlife monitoring, and conduct surveillance both between and during outbreaks to detect trends early and respond swiftly before outbreaks spread.
• Build stronger communication and coordination networks among local, national and global researchers, agencies and academic partnerships to prepare for outbreaks. This includes working with public health practitioners and social scientists to engage and protect people at risk of disease exposure.
• Make wildlife health surveillance a routine part of conservation research and management activities.
• Improve technologies for non-invasive monitoring. For example, the UC Davis Institute for Pandemic Insights brings together engineers and wildlife health experts to deploy auditory and thermal imagery with satellite imagery to better understand key events or tipping points that may indicate an outbreak is likely.
• Pursue high-level policy changes and international agreements that address the root causes of avian influenza outbreaks.
• Address concurrent conservation threats. The authors emphasize that avian influenza is just one of many stressors affecting marine wildlife. Many species face challenges including habitat loss, declining food supply and climate change. Small populations are especially vulnerable.

“H5 avian influenza viruses are an emergent threat to seal and sea lion populations already facing numerous conservation pressures,” said first author Elizabeth Ashley, a graduate student researcher pursuing a dual degree in veterinary medicine and epidemiology at UC Davis. “Understanding how this virus spreads in coastal ecosystems is critical for protecting vulnerable marine wildlife.”

(Continue . . . )

Six months ago, in ISIRV: Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year, we looked at the recent inroads this HPAI virus has made into mammalian species (as of July 2025).  

Even if HPAI H5Nx somehow proves incapable of sparking a human pandemic, its impact on our fragile and interconnected biosphere could be devastating.

While I can't tell you exactly what negative impacts the loss of a Billion+ wild birds, a quarter of a million marine mammals - or unfathomable numbers of peridomestic mammals - might have on our society, one thing is certain.

We are well on our way to finding out. 

EFSA: Risk communication on Avian Flu Biosecurity

  
Credit EFSA

#19,089

Last August, in H5Nx: Reassort & Repeat, we looked at worrying signs - in both Europe and North America - that this fall's avian flu season might be unusually robust.

Again, in November (see A Robust Start To Avian Flu Season In Europe & North America), we saw additional indications that the recent trend in declining European HPAI outbreaks might be over, and that we could be on the verge of seeing a significant uptick in bird flu activity.

The above graphic from last week's EFSA quarterly report on avian flu confirms those fears, as the number of detections in wild and migratory birds dwarfs anything we've seen before, and the number of affected poultry farms is the highest we've seen in 4 years. 

Europe's avian flu season is far from over, and whatever respite they get over the summer could be short-lived. 

While it is possible that avian flu activity could decline next year, the reality is the virus is now solidly endemic in wild and migratory birds, and the threat is unlikely to go away anytime soon. 

Because of this open-ended threat, the European Commission has asked the EFSA (European Food Safety Authority) to produce a risk communications strategy.

The European Union consists of 27 member countries with 24 `official languages', which can make risk communications difficult. And, as we've seen previously with ECDC guidance, the recommendations in today's technical document are not legally binding. 

This 40-page document is part of a triad of related documents published on March 10th.

Avian flu awareness‐raising campaign communication strategy
Daniela Ulicna, Raphaël De Landsheer, Samuël Costa, Francesca Fumagalli, VERIAN GROUP BELGIUM S.A.
 
Risk communication on biosecurity in relation to poultry ‐ final report
Jenny Castillo, Francesca Porta, Victoria Levery, Noah Tozer, Vincent Fierens

A key point in this risk communications is that while general avian influenza awareness is high - knowledge of symptoms, transmission and specific biosecurity measures is uneven - particularly among small‑scale and backyard keepers who may rely on informal or unreliable channels for information.

 

This report `.  .  . proposes a phased, three-year communication strategy progressing from legitimacy-building to facilitated adoption and long-term reinforcement, supported by a coherent channel architecture and a robust evaluation framework.'

The authors of this report state:

The analysis indicates that a shift is needed from one-off awareness campaigns to structured communication approaches that support farmers across their behavioural journey. This includes improving understanding of why measures matter, building motivation through credible and context‑sensitive messages, and supporting the development of practical skills needed to sustain behaviours over time.

How much of this report is actionable, or will be accepted and pursued by member nations, remains to be seen.  A `phased, three-year plan' also assumes the panoply of HPAI viruses cooperates, and doesn't do anything crazy.

But apparently, what they've been doing up till now hasn't been working. 

I've reproduced the abstract below. Follow the link to read the full report.  I'll have a postscript after the break.

Risk communication on avian flu biosecurity: social research, audience segmentation, and communication strategy for an EU awareness-raising campaign

European Food Safety Authority (EFSA), Anthony I. M. Smith, Angela Bearth, Mario Mazzocchi, Tom Jansen, Wim Verbeke … See all authors
First published: 10 March 2026
https://doi.org/10.2903/sp.efsa.2026.EN-10003Digital Object Identifier (DOI)
 
Requestor: European Commission
Question number: EFSA-Q-2026-00130
Correspondence: Ask a Question

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2026.EN-9907; http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2026.EN-10005

PDF
 
Abstract

This report comprises EFSA's response to the European Commission's request for technical assistance in risk communication for a strengthened, evidence-based approach to awareness-raising on avian influenza (AI) biosecurity within the European Union (EU).

It integrates social research, audience segmentation and strategic communication design to inform a multi-year campaign aimed at improving the awareness and consistent uptake of biosecurity measures across diverse poultry-sector stakeholders. Its evidence base derives from two outsourcing activities: social science research and an audience segmentation carried out by ICF, and a multi-year communication strategy undertaken by Verian Group Belgium S.A.. 

These draw on a systematic literature review, 39 in-depth interviews conducted in three EU Member States, Eurostat data, and behavioural analysis using the ADKAR® framework. 

Findings indicate that while general awareness of AI is high, knowledge of transmission pathways, symptoms and the effectiveness of specific biosecurity measures is uneven, particularly among small-scale farmers and backyard keepers. Behavioural, psychological and structural barriers—rather than lack of awareness—limit consistent implementation across segments. 

Five distinct audience segments—four farmer segments and one operational workforce segment—were identified. A sixth group composed of trusted intermediaries, especially veterinarians, emerge as pivotal for communication credibility and behavioural influence. The report proposes a phased, three-year communication strategy progressing from legitimacy-building to facilitated adoption and long-term reinforcement, supported by a coherent channel architecture and a robust evaluation framework.

Overall, the report provides an integrated, evidence-driven foundation for an EU-level biosecurity communication campaign capable of enhancing awareness and resilience, strengthening behavioural uptake and contributing to reduced AI transmission risk across the poultry sector.

 

Europe is not alone in trying to bridge this `avian flu knowledge gap'; last October we looked at our own  UF/IFAS Extension: What Backyard Flock Owners Need to Know about Bird Flu (Influenza H5N1).  

Even in countries with far more experience dealing with avian flu, compliance with biosecurity has been a constant struggle (see Taiwan: H5N1 Infected Chicken Dumping Incident Investigated).

South Korea has repeatedly stated that this year's wave of HPAI is far more virulent than previous years, and they are operating under an extended state of emergency (South Korea: MAFRA Investigation Into Biosecurity Lapses on HPAI Affected Poultry Farms).

What this means for the future of HPAI is uncertain. Avian flu is constantly mutating, and sometimes that attenuates the threat, and sometimes it increases its impact.

While many governments are loath to speak frankly about the risks of avian flu - we either find better ways to convincingly communicate the risks of HPAI - or risk the virus will find a way to do it for us. 

PLoS Path.: Will Animal Reservoirs Give Us The Next SARS-CoV-2 variant?

 

#19,088

As we discussed on Monday in Nature Comms Med.: Interactions of SARS-CoV-2, Influenza and RSV Influence Epidemic Timing and Risk, a strong flu season can briefly inhibit SARS-CoV-2 transmission at the population level, but that impact is short-lived. 

Which suggests our recent lull in COVID cases is probably temporary, and another spring or summer COVID surge likely awaits. 

Surveillance and reporting on SARS-CoV-2 has deteriorated badly around the world (90% of countries no longer report COVID hospitalizations or deaths), and the WHO published their last comprehensive COVID-19 epidemiological update more than a year ago.

While much remains hidden from view, the SARS-CoV-2 virus continues to circulate, and evolve, around the globe.  And not just in humans. 

Over the years we've looked at the spillover - and onward transmission - of the SARS-CoV-2 virus in a growing number of non-human hosts; including:

PrePrint: Anthropozoonotic Spillovers Reveal Sustained Long-Term Cryptic Circulation of SARS-CoV-2 Within and Between Lithuanian Mink Farms

SARS-CoV-2 Exposure in Norway Rats in New York City

PNAS: White-Tailed Deer as a Wildlife Reservoir for Nearly Extinct SARS-CoV-2 Variants

While some of these were likely limited `dead-end' spillovers, in some species we've seen evidence of vigorous onward transmission, and continued evolution of the virus.  And from at least two of these - white-tailed deer and mink - we've seen evidence of a spillback into humans. 

Preprint: Emergence & Spread of SARS-CoV-2 Variants from Farmed Mink to Humans and Back - Denmark, June-November 2020.

Nature: Divergent SARS-CoV-2 Variant Emerges in White-tailed Deer with Deer-to-Human Transmission (Revisited)

WHO 2nd Update: SARS-CoV-2 mink-associated variant strain – Denmark

While none of these spill backs has taken hold in humans (unless you accept the theory that the Omicron variant had a mouse origin), they serve as a proof-of-concept. Unfortunately, our surveillance of non-human hosts for the SARS virus is extremely limited. 

Which brings us to a brief, and refreshingly plain-language `Pearls' article in PLoS Pathogens, which provides a 9-point review of what we know about the threat from cryptic lineages of SARS-CoV-2 spreading in non-human reservoir hosts. 

I've provided the link and a brief excerpt, but this is one you'll definitely want to read in its entirety.  I'll have a bit more after the break.

Will animal reservoirs give us the next SARS-CoV-2 variant?

Davey Smith
Published: March 3, 2026
https://doi.org/10.1371/journal.ppat.1014008

1. What does it mean that SARS-CoV-2 is now a virus with multiple natural hosts?

Like all known human coronaviruses, SARS-CoV-2 originated from animals, most likely through wildlife sold at the Huanan Seafood Market, with bats serving as the deeper evolutionary reservoir [1]. Since its emergence in humans, SARS-CoV-2 has repeatedly crossed into non-human hosts. Over five years of widespread circulation, the virus has been detected in a surprising array of animals, including white-tailed deer, mink, rats, hamsters, horses, cats, zoo animals and dogs, though sustained transmission is clearly documented only in deer and farmed mink, with other species showing limited or no onward spread. For white-tailed deer and mink, the virus has achieved sustained animal-to-animal transmission and spillback to humans [2–6].

This shift transforms SARS-CoV-2 from a purely human epidemic into a network of linked epidemics across species. Humans remain their largest host, but no longer its only long-term home. When a virus gains multiple such homes, it also gains more ecological space and evolutionary possibilities. This article does not address the original zoonotic emergence of coronaviruses broadly; instead, it focuses on the less explored problem: how sustained circulation of SARS-CoV-2 in animal reservoirs may shape future human disease.

       (SNIP)

9. Why should pathogen researchers care, even if they do not work on coronaviruses?

Animal reservoirs slow down viral extinction. They expand the virus’s evolutionary playground. They give SARS-CoV-2 places to mutate where human immunity has little influence. For virologists and pathogenesis researchers of any specialty, these reservoirs show how quickly an emerging virus can become an ecological resident [3]. Ignoring the animal side of SARS-CoV-2 means accepting surprise when spillback occurs. Paying attention gives us a chance to see the next jump coming, and maybe even prevent it.

        (Continue . . . )

Several studies (see BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events and PNAS Research: Intensity and Frequency of Extreme Novel Epidemics), suggest the number, frequency, and intensity of pandemics is only expected to increase in the years ahead.

But even if SARS-CoV-2 is unable to fully reinvent itself in a human or non-human host, there are plenty of other coronaviruses circulating in the wild with pandemic potential. 

A few (of many) recent blogs include:

• Last January (see EID Journal (Perspective): Emerging Respiratory Virus Threats from Influenza D and Canine Coronavirus HuPn-2018) we looked at 2 emerging threats, including a canine coronavirus which has spilled over into humans in Malaysia. 

• Three months ago, in The Lancet: The Threat of Another Coronavirus Pandemic, we looked at somewhat technical commentary on recently identified ACE2-using merbecoviruses - like HKU5-CoV-2 - which may represent potential future coronavirus pandemic threats.

• And exactly a year-ago today, in Viruses: Novel Rodent Coronavirus-like Virus Detected Among Beef Cattle with Respiratory Disease in Mexico, we looked at a novel coronavirus that closely resembled a rodent-coronavirus isolated in China in 2021 (see  Nature: Virus Diversity, Wildlife-Domestic Animal Circulation and Potential Zoonotic Viruses of Small Mammals, Pangolins and Zoo Animals).

And of course, MERS-CoV continues to circulate and evolve in Arabian (and likely African) camels (see Health Sci Rpts (Narrative Review): Pathogenicity and Potential Role of MERS-CoV in the Emergence of “Disease X”), while occasionally spilling over into humans.

All of which makes it highly unlikely we've seen our last coronavirus threat.

Virol Sin.: Emergence of a Novel H4N6 Avian Influenza Virus with Mammalian Adaptation Isolated from Migratory Birds in Zhejiang Province, China, 2024

 

#19,087

There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).

• LPAI viruses are common in wild birds, cause little illness, and only rarely death. They are not considered to be a serious health to public health (LPAI H7N9  & LPAI H9N2 being notable exceptions)s. The concern is (particularly with H5 & H7 strains) that some LPAI viruses have the potential to mutate into HPAI strains.

• HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result. Again, H5 and H7 viruses are of greatest concern, but other subtypes have also caused human illness and large poultry losses. 

Until about 20 years ago there was no uniform requirement to report or track LPAI infections. That changed in 2006 when the OIE made reporting of LPAI H5 & H7 viruses mandatory.

While other LPAI subtypes are not currently reportable to WOAH (see Terrestrial Animal Code Article 10.4.1.), that doesn't make them entirely benign.

This non-reportable status has hampered responses to outbreaks (see Belgium: Non-Reportable LPAI H3N1 Outbreaks Continue (n=59)) in the past, and likely contributes to the silent proliferation of these viruses.

The biggest concern right now is LPAI H9N2, which has spread globally, continues to evolve, is largely resistant to existing vaccines, and spills over with relative ease to humans (see China's list (n=17) over last 6 months).

But over the past few years we've seen a growing number of scientific papers out of China describing the shift of many other LPAI viruses towards increased mammalian adaptation. A few (of many) include:

NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens

Cell: Early-warning Signals and the Role of H9N2 in the Spillover of Avian Influenza Viruses

Vet. Research: Emergence of a Novel Reassortant H3N3 Avian Influenza Virus with Enhanced Pathogenicity and Transmissibility in Chickens in China

Transboundary & Emerg. Dis.: H3 Avian Influenza Virus Isolated from China in 2021–2022 Showed the Emerging H3N8 Posed a Threat to Human Health

Viruses: Genetic and Biological Characteristics of Duck-Origin H4N6 Avian Influenza Virus Isolated in China in 2022

Viruses: Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice

The Lancet Microbe: Novel H10N3 Avian Influenza Viruses - a Potential Threat to Public Health

While H9N2 and H3 viruses have captured the bulk of their attention, H4Nx viruses - which are ubiquitous in wild birds around the globe - have raised zoonotic concerns for years.

In 2012's in Seroprevalence Study: Avian Flu In Chinese Pigs, we looked at research that found low levels of H3, H4, and H6 subtypes of avian influenza in Chinese pigs while in 2015 we looked at reports of Avian H4N6 In Midwestern Swine.

Although human infection with H4 viruses are believed to be both mild and rare, a 2011 PLoS One study (Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers) presented serological evidence suggesting that `. . .  H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.'

This was reinforced last May in Virology Journal: Emerging Zoonotic Potential of H4N1 Avian Influenza Virus: Enhanced Human Receptor Binding and Replication via Novel Mutations, which found - at least in the laboratory - the LPAI H4N1 virus was already surprisingly well adapted to infecting, and replicating within, mammalian hosts.

All of which brings us to a letter, published in Virologica Sinica this week, which describes the detection of a novel H4N6 virus which already appears unusually well adapted to mammals. 

I've only reproduced the highlights below. Follow the link to read it in its entirety.  I'll have a postscript after the break. 

Emergence of a novel H4N6 avian influenza virus with mammalian adaptation isolated from migratory birds in Zhejiang Province, China, 2024

Yongchun Yang a 1, Han Liu a 1, Yaling Li a 1, Lin Liu a, Tiantian Chen a, Jiahao Zhang ba

Received 30 April 2025, Accepted 11 March 2026, Available online 14 March 2026.
https://doi.org/10.1016/j.virs.2026.03.005 
Under a Creative Commons license 

HIGHLIGHTS: 

• The H4N6/G030 strain, a novel H4N6 avian influenza virus (AIV), was isolated from a red-necked stint. 

•  The H4N6/G030 is a novel cross-species reassortant derived from wild bird and poultry AIV lineages. 

•  The H4N6/G030 can bind to both avian and mammalian-type sialic acid receptors, and replicate in both avian and mammalian cells and cause disease in animals.

• High seroprevalence of H4N6 was observed on surveyed poultry farms nearby.

Dear Editor,

Avian influenza viruses (AIVs) continue to evolve at the interface of wild and domestic birds, posing ongoing threats to animal and public health (Bi et al., 2020; Uyeki et al., 2022). Wild migratory birds serve as natural reservoirs and facilitate viral gene exchange through long-distance migration, whereas dense poultry farming in East Asia creates opportunities for reassortment and spillover (Li et al., 2022; Verhagen et al., 2015).

Historically, H4-subtype AIVs have been considered low-pathogenic, yet recent detections in poultry and swine suggest an expanding host range and genetic plasticity (Li et al., 2024; Song et al., 2024; Parsons et al., 2023). In this study, we identified and characterized a novel reassortant H4N6 virus isolated from a red-necked stint (Calidris ruficollis) during surveillance in Zhejiang Province, China, in May 2024 and evaluated its molecular signatures associated with mammalian adaptation.

(SNIP)

The emergence of H4N6/G030 provides further evidence for active genetic reassortment at the wild-bird-poultry interface in China. Notably, although this virus is classified as a low pathogenic avian influenza virus (LPAIV), its dual receptor-binding affinity and efficient replication in mammalian cells represent a key step toward cross-species adaptation. This adaptive potential is well-established: previous studies show that single amino-acid changes in PB2 or HA can greatly enhance viral replication and transmissibility in mammals (Lin et al., 2024; Gao et al., 2019).

Given the recent reports of H5N1 infection in cats and dairy cattle in North America (Peacock et al., 2025), enhanced surveillance of LPAIVs such as H4 has become increasingly important. The replication of H4N6 in bovine cells observed in vitro indicates that cross-species exposure cannot be ignored. Therefore, this enhanced surveillance that integrates genomic analysis, serology and biosecurity is crucial to identify emerging strains with potential public-health implications.

In conclusion, we identified a novel H4N6 avian influenza virus from migratory birds, which exhibits mammalian adaptation markers, including dual receptor-binding affinity and a reassortant genome from wild-bird and poultry lineages. This, combined with the high seroprevalence in local chickens, compounds the risk and further highlights the urgent need for ongoing molecular and epidemiological surveillance along high-risk migratory flyways.

(Continue . . . )

Lest we forget, two of the three influenza pandemics of the last century (H2N2 and H3N2) were caused by LPAI avian H2 and H3 viruses which appear to have emerged from Chinese poultry or wild birds and then reassorted with seasonal influenza.

While these non-reportable LPAI subtypes aren't officially regarded as being in the same league as H5 and H7 viruses - we continue to see studies suggesting we take these LPAI subtypes more seriously. 

Although I've no particular insight in what virus will spark the next pandemic, history has shown that LPAI viruses can be instigators or at least co-conspirators.  

And that alone ought to be enough to warrant heightened surveillance and research.

Nature Comms Med.: Interactions of SARS-CoV-2, Influenza and RSV Influence Epidemic Timing and Risk

When Epidemic Viruses Collide

#19,086

Since the introduction of the SARS-CoV-2 virus in 2020 there have been perennial concerns we could see a devastating `twin-demic' of influenza A and COVID. While some co-circulation has occurred, for the most part, each virus has peaked while the other was in retreat.

This is not a new observation; 17 years ago (during the 2009 H1N1 pandemic) some European countries that reported rampant rhinovirus outbreaks in the fall saw far less H1N1 activity than expected (see 2009 New Scientist article Common cold may hold off swine flu).

While the exact mechanism behind this blocking of competing viruses is only partially understood, many researchers believe that exposure to one virus activates not only a targeted immune response - but also the body's innate immune response - essentially temporarily raising `shields' against other possible viral invaders.

Some past blogs on this include:

When Epidemic Viruses Collide

Study: Human Rhinovirus Infection Blocks SARS-CoV-2 Replication Within the Respiratory Epithelium 

This heightened immune response is believed to persist for weeks or perhaps even months; an idea that has been dubbed the `temporary immunity hypothesis'.

Last November, in IJID: Short-Term Risks of Influenza and COVID-19 Following Influenza Infection: A Self-Controlled Case Series Study, we looked at a study from Beijing that found that influenza A infection reduces the risk of influenza reinfection by 57% for up to 8 months but increases the risk of COVID-19 infection by 48% within 6 months post-influenza.

Note: they did not study the reverse (and admittedly far more complex) COVID -> Flu scenario. 

Today we've another study from Beijing, that finds that influenza A infection briefly reduces susceptibility to COVID infection, but that protective effect lasts only about 5 weeks post infection. 

They do, however, report finding a slight increase in susceptibility to IAV following COVID infection.  RSV showed no impact on COVID. 

Unlike the IJID study cited above, this study did not attempt to calculate longer-term risks of infection.  I've reproduced the abstract, and summary below. Follow the link to read it in its entirety.

 
Open access
Published: 14 March 2026
Interactions of SARS-CoV-2, influenza and respiratory syncytial virus influence epidemic timing and risk

Yonghong Liu, Xiaoli Wang, Mengyao Li, Eimear Cleary, Zhifeng Cheng, Wenbin Zhang, Ying Shen, Hui Yao, Jiatong Han, Nick W. Ruktanonchai, Andrew J. Tatem, Shengjie Lai, Quanyi Wang & Peng Yang

Communications Medicine , Article number: (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Background

Interactions between SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) at the population level remain poorly understood. This study aimed to quantify potential interactions among these viruses and assess their influence on transmission dynamics.

Methods

We analyzed weekly surveillance data on SARS-CoV-2, influenza A and B viruses (IAV and IBV), and RSV from seven regions from October 2021 to May 2024. Distributed lag nonlinear models within a spatiotemporal Bayesian hierarchical framework were used to assess the exposure-lag-response associations among virus pairs. Additionally, we developed a two-pathogen, meta-population mechanistic transmission model to capture the co-epidemic dynamics of IAV and SARS-CoV-2, and to quantify the strength and duration of their bidirectional interactions.

Results

Among all virus pairs examined, a statistically significant association is identified only between IAV positivity and subsequent SARS-CoV-2 risk. When IAV positive rate percentile is between the 52nd and 88th percentiles, the relative risk (RR) of SARS-CoV-2 infection is significantly reduced. The lowest RR for SARS-CoV-2 (0.58, 95% CrI: 0.40-0.85) occurs at a 5-week lag when IAV positivity reaches the 70th percentile.

The fitted mechanistic model using incidence data in Beijing shows that IAV infection substantially reduces infection to SARS-CoV-2 by 94.24% (95% CrI: 88.50%–99.24%), with the protective effect lasting 38.24 days (95% CrI: 35.50–41.29 days). Conversely, SARS-CoV-2 infection is associated with a slight increase in infection to IAV.

Conclusions

Our findings indicate that IAV circulation may transiently reduce population-level infection to SARS-CoV-2, potential through ecological or immunological mechanisms.

Plain language summary

This study looks at how three common respiratory viruses - SARS-CoV-2, influenza, and RSV, which cause COVID-19, flu and common colds - affect one another when they spread in communities. We used two complementary approaches: advanced statistical model, which identify patterns in real-world data, and mechanistic transmission model, which simulates how viruses spread from person to person. Together, these methods allowed us to measure how strong these interactions are and how long their effects last. 

The data came from three years of virus activity across seven countries and regions, providing us a broad view across time and places. We found that increases in flu activity, especially influenza A, may reduce the risk of COVID-19 spread in the weeks that follow. However, these virus interactions are complex. They change over time and depend on how much of each virus is circulating.

This means that viruses do not spread in isolation, and one can potentially influence the timing and size of another epidemic. Our study shows why it is important to consider interactions between viruses when forecasting future outbreaks and planning public health interventions, especially since many respiratory viruses tend to circulate at the same time of year.

        (Continue . . . )

In 2017's PLoS Comp. Bio.: Spring & Early Summer Most Likely Time For A Pandemic, researchers used `viral interference' and/or temporary immunity to help explain why pandemics typically emerge in the spring or early summer; after the end of regular flu season.

Of course, COVID was an exception to this pattern, as it emerged in mid-winter in China and spread globally in a matter of weeks. 

All of which is a reminder that while these viruses don't act in a vacuum, there is still much we don't know about how they may impact one another, or any new ones that may appear in the future.