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.

Cambodia MOH Announces 2nd H5N1 Case of 2026

 

#19,085

With thanks for the head's up from @E_A_Karlsson, we have the following announcement from Cambodia's Ministry of Health on their 2nd confirmed HPAI H5N1 human infection of 2026; this time involving a 45 y.o. woman from Banteay Meanchey Province who was hospitalized on March 14th.

The MOH announcement, along with the translation, follows:

A case of bird flu in a 45-year-old woman

The Ministry of Health of the Kingdom of Cambodia would like to inform the public that there is 1 case of bird flu in a 45-year-old woman who was confirmed to be positive for the H5N1 avian influenza virus on March 14, 2026 by the National Institute of Public Health. The patient lives in Ropai village, Chinu Meanchey commune, Preah Net Preah district, Banteay Meanchey province, and there have been reports of sick and dead chickens and ducks in the village. On the same day, the patient was placed in isolation at the hospital and treated with Tamiflu and received close medical care. Upon questioning, it was revealed that the patient raised chickens and ducks, some of which were sick and dead. Three days before testing positive, she had come into contact with the dead chickens.

The emergency response team of the national and sub-national ministries of health has been collaborating with the teams of the provincial agriculture departments and local authorities at all levels to actively investigate the outbreak of bird flu and respond according to technical methods and protocols, find the source of transmission in both animals and humans, and search for suspected cases and contacts to prevent further transmission in the community, as well as distribute Tamiflu to close contacts and conduct health education campaigns among residents in the affected villages.

The Ministry of Health would like to remind all citizens to always pay attention to and be vigilant about bird flu because H5N1 bird flu continues to threaten the health of our citizens. We would also like to inform you that if you have a fever, cough, runny nose, or difficulty breathing and have a history of contact with sick or dead chickens or ducks within 14 days before the onset of symptoms, do not go to gatherings or crowded places and seek consultation and examination and treatment at the nearest health center or hospital immediately. Avoid delaying this, which puts you at high risk of eventual death.

        (Continue . . . .)

Just over 3 years ago an older clade of H5N1 (2.3.2.1.x) reemerged in Cambodia's population after a 9 year absence, spilling over into 6 humans in 2023, 10 people in 2024, and 18 people in 2025.   

The majority of these cases have been in children and adolescents, and sadly, > 40% have died. Contact with sick or dead poultry has often been cited as the source of infection. 

Unlike H5N1 cases reported in the United States - which are due to a milder clade 2.3.4.4b - recent Cambodian cases have been caused by a new reassortment of an older clade of the H5N1 virus (recently renamed 2.3.2.1e) - which appears to be spreading rapidly through both wild birds and local poultry.

While we tend to focus primarily on clade 2.3.4.4b H5N1 viruses which have become endemic in North and South America, Europe,and much of Asia - other incarnations of HPAI H5 are circulating around the globe - and new ones continue to emerge; with each on their own evolutionary trajectory.

In addition to this very active Cambodia lineage of H5N1, some of the other HPAI H5 contenders we are following include:

South Korea: H5N9 Rising

Viruses: Novel Reassortant H5N2 Highly Pathogenic Avian Influenza Viruses from Backyard Poultry in Mexico

Preprint: Emergence of a Novel Reassorted HPAI A(H5N2) Virus Associated with Severe Pneumonia in a Young Adult

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

Preprint: HPAI A (H5N1) Clade 2.3.2.1a Virus Infection in 2 Domestic Cats, India, 2025

EID Journal: Influenza A(H5N1) Virus Clade 2.3.2.1a in Traveler Returning to Australia from India, 2024

Exactly where H5Nx goes from here is anyone's guess. Some strains may lose virulence, while others may grow stronger. New variants may emerge, while others will likely fade away. The virus we see tomorrow may look quite different from the virus we see today.

The only thing we can say with any certainty is these viruses continue to evolve, and that their current trajectory is still on the ascendent.

Which is a trend we ignore at our own considerable risk.

USDA Report 9 More Live Bird Markets Infected With HPAI H5

Credit USDA

#19,084

A little over 3 weeks ago, in When You're in the Market For Bird Flu, we looked the USDA's reports of  9 HPAI H5 outbreaks in live bird markets around the country (5 in NYC, 4 in PA) since late December 2025.

Since then, the pace has increased, with 9 more outbreaks (8 in NYC, 1 in Fl) reported over the past 16 days (see USDA chart above).  

Less than halfway through the month, and already March 2026 is tied for the 2nd highest number (n=8) of outbreaks (see below), only exceeded by the March 2025 total of 15 outbreaks.   

Based on USDA Data - Graph created with Gemini

As the following graphic illustrates, New York leads the nation with lion's share of of live market outbreaks (44 of 73, or just over 60%), followed by Florida (18%), and Pennsylvania and New Jersey each at 9.6%.

Based on USDA Data - Graph created with Gemini

These outbreaks tend to get far less publicity today than they did even a year ago, but on March 12th the New York State Department of Agriculture and Markets issued the following Health Alert.

Health Alerts

Highly Pathogenic Avian Influenza

Detections in New York

March 12, 2026 - To date, 78 flocks in New York State have tested positive for HPAI since February 2022. The Department is working closely with the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) on a joint incident response and is also collaborating with partners at the Department of Health and Department of Environmental Conservation.

According to the U.S. Centers for Disease Control and Prevention, the public health risk associated with these avian influenza detections remains low. As a reminder, the proper handling and cooking of poultry and eggs to an internal temperature of 165 ˚F kills bacteria and viruses. Birds from the affected flocks have not entered the food system.

Biosecurity

The detections of HPAI in New York prompt reminders for commercial and hobby poultry farmers to increase their biosecurity measures to help prevent the spread of the disease. The Department encourages all poultry producers, from small backyard to large commercial operations, should review their biosecurity plans and take precautions to protect their birds. Poultry biosecurity materials and checklists can be found on the USDA’s “Defend the Flock” website. Best practices include:

• Discourage unnecessary visitors and use biosecurity signs to warn people not to enter buildings without permission.
• Ask all visitors if they have had any contact with any birds in the past five days.
• Forbid entry to employees and visitors who own any kind of fowl.
• Require all visitors to cover and disinfect all footwear.
• Lock all entrances to chicken houses after hours.
• Avoid non-essential vehicular traffic on-farm.
• After hauling birds to processors, clean and disinfect poultry transport coops and vehicles before they return to the farm.
• Report anything unusual, especially sick or dead birds, to AGM.

In addition to practicing good biosecurity, poultry owners should keep their birds away from wild ducks and geese and their droppings. Outdoor access for poultry should be limited at this time.

To report sick birds, unexplained high number of deaths, or sudden drop in egg production, please contact the Department’s Division of Animal Industry at (518) 457-3502 or the USDA at (866) 536-7593.

While government agencies are quick to reassure the public that the risk of contracting avian influenza remains low in the United States, exposure to live birds is a known risk factor (see CDC graphic below).

It was just over a year ago that the United States reported its first human H5N1 fatality in a Louisiana Man who kept live poultry in his backyard.  

LDH reports first U.S. H5N1-related human death

Current general public health risk remains low

Baton Rouge, Louisiana, Jn 06, 2025 - The Louisiana Department of Health reports the patient who had been hospitalized with the first human case of highly pathogenic avian influenza (HPAI), or H5N1, in Louisiana and the U.S. has died. The patient was over the age of 65 and was reported to have underlying medical conditions. The patient contracted H5N1 after exposure to a combination of a non-commercial backyard flock and wild birds.

Over the past couple of years somewhere in excess of 30 people have been infected from exposure to poultry or wild birds in North America (2 fatal). Most were agricultural workers, but some had undetermined exposures.

As we've discussed previously (see Mixed Messaging On HPAI Food Safety), there is some degree of risk in the slaughtering of live birds and preparation of raw poultry; especially from birds raised at home or purchased from live markets.

PAHO (the Pan-American Health Organization) mentions this on their Avian Influenza landing page:  Plucking, handling infected poultry carcasses, and preparing poultry for consumption, especially in domestic settings, may also be risk factors.

And in 2024 the WHO published  Interim Guidance to Reduce the Risk of Infection in People Exposed to Avian Influenza Viruses, which lists a number of `risk factors', including:

• keep live poultry in their backyards or homes, or who purchase live birds at markets;

• slaughter, de-feather and/or butcher poultry or other animals at home;

• handle and prepare raw poultry for further cooking and consumption;

These risks go far beyond just human exposure, of course,  as live markets also bring together different types of birds which may also silently carry LPAI viruses like H3N2 and H6N2, which could reassort with HPAI H5. 

As we discussed last year in J. Virology: Zoonotic Disease Risk at Traditional Food Markets (Minireview), live animal markets present special risks.

While strict regulation and better biosecurity can substantially reduce the risks, LBMs remain a source of concern. 

CDC MMWR: Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness — United States, September 2025–February 2026

 
2025-2026 Flu Season - Credit CDC

#19,083

While the 2025-2026 flu season still continues (albeit on a downward trajectory), yesterday the CDC released their first estimate of this year's flu vaccine VE (Vaccine Effectiveness).  A final, revised, report should be issued in a few months.

In early November it became apparent that a new `drifted' H3N2 virus (subclade K) had recently emerged on the world stage, one which was antigenically distinct from this year's H3N2 vaccine strain. 

Early estimates (see UKHSA Preprint: Early Influenza Virus Characterisation and Vaccine Effectiveness in England in Autumn 2025, A Period Dominated by Influenza A(H3N2) Subclade K) suggested that the fall vaccine wasn't a total bust, but that it's VE would suffer. 

This is a scenario we've seen play out before - particularly with the H3N2 subtype (see 2017's The Enigmatic, Problematic H3N2 Influenza Virus) - which is more mutable, and more genetically diverse, than H1N1. 

The CDC Seasonal Flu Vaccine Effectiveness Studies webpage shows some of the variability of the flu vaccine VE over the years. While the dominant flu strain each year isn't shown, the lowest VE years were dominated by H3N2.

While most years we get a breakdown in VE between influenza A subtype (H1N1 and H3N2), this year H3N2 overwhelmed the flu season, and there was apparently insufficient data on H1N1 to break out those numbers. 

I've reproduced the summary and abstract of the MMWR interim report below. Follow the link to read it in its entirety.  

I'll have a bit more when you return.

Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness — United States, September 2025–February 2026

Weekly / March 12, 2026 / 75(9);116–123

Patrick Maloney, PhD1,2; Emily L. Reeves, MPH1; Kristina Wielgosz, MPH1; Ashley M. Price, MPH1; Karthik Natarajan, PhD3,4; Malini B. DeSilva, MD5; Kristin Dascomb, MD, PhD6; Nicola P. Klein, MD, PhD7; Sara Y. Tartof, PhD8,9; Stephanie A. Irving, MHS10; Shaun J. Grannis, MD11,12; Toan C. Ong, PhD13; Zachary A. Weber, PhD14; Jennifer E. Schuster, MD15; Danielle M. Zerr, MD16; Marian G. Michaels, MD17; Julie A. Boom, MD18; Natasha B. Halasa, MD19; Mary A. Staat, MD20; Geoffrey A. Weinberg, MD21; Stacey L. House, MD, PhD22; Elie A. Saade, MD23; Krissy Moehling Geffel, PhD24; Manjusha Gaglani, MBBS25; Karen J. Wernli, PhD9,26; Vel Murugan, PhD27; Emily T. Martin, PhD28; Natalie A. B. Bontrager, MPH29; Marie K. Kirby, PhD1; Amanda B. Payne, PhD30; Fatimah S. Dawood, MD30; Ayzsa Tannis, MPH30; Heidi L. Moline, MD30; Sifang Kathy Zhao, PhD1; Katherine Adams, DrPH1; Jennifer DeCuir, MD, PhD1; Samantha M. Olson, MPH1; Jessie R. Chung, MPH1; Nathaniel Lewis, PhD1; Brendan Flannery, PhD1; Carrie Reed, DSc1; Shikha Garg, MD1; Sascha Ellington, PhD1; CDC Influenza Vaccine Effectiveness Collaborators (VIEW AUTHOR AFFILIATIONS)View suggested citation

Summary

What is already known about this topic?

CDC routinely monitors influenza vaccine effectiveness (VE). Annual influenza vaccination is available for all eligible persons aged ≥6 months.

What is added by this report?

Interim 2025–26 seasonal influenza VE estimates were derived from three U.S. VE networks. Among children and adolescents, VE was 38%–41% against influenza-associated outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%–34% against influenza-associated outpatient visits and 30% against influenza-associated hospitalization.

What are the implications for public health practice?

Receipt of a 2025–26 influenza vaccine reduced the risk for influenza-associated outpatient visits and hospitalizations. These findings support CDC’s influenza vaccination recommendations.

Article PDF 

Abstract

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025–26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness–associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025–26 influenza season, using a test-negative case-control design.

• Among children and adolescents aged <18 years, VE was 38%–41% against influenza outpatient visits and 41% against influenza-associated hospitalization.
• Among adults aged ≥18 years, VE was 22%–34% against influenza outpatient visits and 30% against influenza-associated hospitalization.
• Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings.
• Among children and adolescents, VE against influenza A(H3N2)–associated outpatient visits was 35% and against influenza A(H3N2)–associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%–71% among children and adolescents and was 63% among adults.

Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025–26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

        (Continue . . . )

Yesterday the FDA followed the WHO's lead and announced their recommendations for next fall's flu vaccine (see CIDRAP report FDA vaccine advisers recommend adding subclade K to fall shots), which swaps out all 3 flu strains. 

Despite offering only moderate protection, and being vulnerable to late-arriving `drifted' flu strains, I've gotten the flu shot every year for the past 20+ years, and have only once contracted the flu (summer 2009). 

Admittedly, I take other precautions, including wearing a mask in crowded indoor venues and using hand sanitizer.  But when combined with the flu vaccine, it has proven to be a very effective combination. 

Everyone has to make their own risk-reward calculation, of course. 

But given everything we've learned about influenzas' extrapulmonary impacts on the body (see Risk of Cardiovascular Events After Influenza), it seems a reasonable enough trade off to me.