EFSA: An LPAI H9N2 Mystery

#19,240

A little over a week ago the EFSA published their quarterly avian flu review - which in addition to documenting the last 3 months of Europe's extraordinary 2025-2026 avian flu season - announced the surprise finding of an older, Middle-Eastern/African clade of LPAI H9N2 circulating in Hungary's poultry. 

Despite being clearly zoonotic - LPAI H9N2 is considered a `non-reportable' disease in poultry or wild birds by WOAH (see Terrestrial Animal Code). As a result, there are huge gaps in surveillance and reporting around the world. 

At the same time we've seen a growing number of studies - mostly out of Asia - warning of its growing adaptation to mammalian hosts (see EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids).

Our own CDC lists two lineages (A(H9N2) G1 and A(H9N2) Y280) as having at least some pandemic potential, and several candidate vaccines have been developed.

In terms of risk of emergence, the H9N2

Y280 lineage is ranked higher than H5N1

While there is still much to be learned about them, over the past couple of months we've seen 2 new lineages of LPAI H9N2 described in the literature.

EM&I: A new clade of H9N2 avian influenza virus circulating in Laos

Preprint: Outbreak of H9N2 Avian Influenza Viruses in Lesser Rhea in Peru, June-July 2025

Where H9N2 is endemic (Asia, Africa, the Middle East) attempts at controlling the virus with vaccines have been largely unsuccessful (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China).

While most human cases have been reported out of China (see below), this year Europe saw its first (imported) human infection with H9N2 in Italy (see WHO DON: Avian Influenza A(H9N2) - Italy (Ex Senegal)). 

Reports of LPAI H9N2 in European poultry have been rare, but in this latest report the EFSA describes an outbreak in 7 premises in Hungary.

Apart from these HPAI A(H5N1) outbreaks, Hungary reported the detection of A(H9N2) clade G5.5 virus back in April in 7 establishments keeping chickens (broilers), all of which were located in a single geographical area within one settlement. Increased mortality in one establishment initially raised suspicions of HPAI, however, the birds tested negative for HPAI A(H5) and A(H7) viruses. 

Tests for infectious bronchitis virus returned positive and pathological examinations revealed tracheitis, presenting with a clinical picture typical of a co-infection (Belkasmi et al., 2020; Regragui et al., 2025). This prompted testing for A(H9N2) virus.

As this specific clade had originally been restricted to countries outside the EU, such as those in the Middle East (Fusaro et al., 2024), poultry workers were interviewed about their travel history; however, no plausible link could be established. 

The source of introduction therefore remained unknown at the time of reporting. All affected establishments were stamped out, cleaned, and disinfected. After 2-3 weeks following repopulation, the birds will be tested again for A(H9N2) virus. Waterfowl flocks present in the affected county were tested for A(H9) virus prior to movement, but all these tests returned negative. 

The report goes on to describe the LPAI H9N2 virus:

Low pathogenic avian influenza A(H9N2) clade G5.5 (CDC, online-a) was identified in two genetically characterised samples collected from commercial poultry establishments in Hungary in April 2026. This clade is circulating in domestic birds in some countries in Africa, the Middle East and West Asia, and has previously never been detected in birds in the EU/EEA. 

Avian influenza A(H9N2) viruses belonging to clade G5.5 have also been reported in sporadic human cases, including Oman and Senegal in 2019, Ghana in 2024, and Italy in March 2026 in a patient who returned from West Africa (Pariani et al., 2026). 

The viruses that are most closely related to the Hungarian strains are A(H9N2) viruses of the same clade that had been circulating in the Middle East one or two decades ago. The long branches and time separating the Hungarian viruses from their progenitors suggest a significant gap of data, making it impossible to determine their origin.

Similarly to the majority of the A(H9N2) viruses of lineages G and B, they possess the HA-Q226L mutation (H3 numbering), which is associated with preferential binding to human-like α2-6-linked sialic acid (SA α2-6) receptors. 

The only recent reports of Clade G5.5 appear to have come from Oman, Senegal, and Ghana, although we are hindered by a general lack of testing, surveillance and reporting.

How it ended up in Hungary - some 4,000km from these locations - is a genuine mystery.  While migratory birds, imported exotic birds, or even human carriage are possible, there is scant evidence to support any conclusion. 

LPAI H9N2 may not be our biggest pandemic threat, but it is far from benign. The fact that H9 has successfully flown under the radar - only to turn up unexpectedly in central Europe - suggests we may want to consider expanding our testing and reporting systems beyond H5 and H7 viruses.  

Viruses: First Ecuadorian Pediatric Case of Multisystem and Neurological Involvement Associated with Influenza A—H5N1 Virus—Case Report

 

#19,239

In January of 2023 Ecuador reported its first (and as far as we know, only) human infection with H5N1; in a 9-year-old girl with reported contact with backyard poultry. 

The initial report included no details on when she was infected, her symptoms, or her current condition.

 

But the following day PAHO published a report stating : The patient is currently hospitalized in a pediatric intensive care unit, in isolation and with antiviral and supportive treatment.

A week later the WHO published a far more detailed report which stated:

The case is a nine-year-old girl, with no known comorbidities, from Bolívar Province, Ecuador. She developed symptoms of conjunctival pruritus and coryza on 25 December 2022. On 27 December, she was brought to a local health center for medical evaluation and treatment. On 30 December, due to the persistent symptoms including nausea, vomiting and constipation, she was admitted to a general hospital where empirical treatment for meningitis was started with antibiotics and antipyretics. On 3 January 2023, she was transferred to a pediatric hospital in critical condition where she was admitted to the intensive care unit (ICU) with septic shock and was treated with antivirals and mechanical ventilation due to pneumonia.

 Eight months later a report appeared in Travel Medicine which stated:

The patient was a 9-year-old girl without co-morbidities from Bolivar Province, who was admitted to a hospital due to severe flu symptoms in 30 December 2022. She was transferred to the ICU of a paediatric hospital on 3 January 2023 due to complications with septic shock and pneumonia. She received complex support antiviral treatment, including oseltamivir, managing to improve her critical condition; She continued in interdisciplinary management with favorable progress and was finally discharged from the hospital.

I mention these prior reports because today we have a new case report - published in the journal Viruses - which paints a far different picture of this patient's course of illness; one which had much more neurological involvement than previously acknowledged. 

Other than a vague mention that `empirical treatment for meningitis was started' during hospitalization in the WHO report, there was little to suggest this case presented as anything other than severe flu symptoms & pneumonia leading to septic shock. 

 Whereas, today's report states:

The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock. 

They also indicate that respiratory symptoms were minimal upon admission, instead citing `progressive neurological symptoms', which prompted urgent medical evaluation

Those early reports become problematic because clinicians require timely information on the full range of symptoms and/or presentation of novel flu infection, if they are to consider them in their differential.  

First, I've posted some brief excerpts from the case report, but the paper is very much worth reading in its entirety. After the break we'll look back at some other recent reports of severe neurological involvement from H5N1 infection. 

First Ecuadorian Pediatric Case of Multisystem and Neurological Involvement Associated with Influenza A—H5N1 Virus—Case Report
Frances Fuenmayor 1,*, Santiago Chávez 2, María de los Ángeles Costta 1, Mateo Carvajal 3, Denisse Benítez 3,Rommel Guevara 3, Erika Muñoz 3, Paúl Cárdenas 3,Marisol Carrillo 4 … Melanie Orellana 2
Viruses 2026, 18(7), 749;
https://doi.org/10.3390/v18070749

Abstract

Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry.

The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock.

Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state.

Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival.

Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry.

        (SNIP) 

(SNIP)

This case underscores the severity of multisystemic involvement in influenza A H5N1 in pediatric patients, as well as the importance of a structured follow-up protocol for managing neurological and metabolic sequelae. Our findings highlight the need for active surveillance in children exposed to avian-influenza risk factors and for protocols covering early identification, continuous monitoring, and rehabilitation after resolution of the acute illness. Given the magnitude of these clinical implications, primary prevention through zoonotic control remains a fundamental pillar for reducing the incidence of new cases.

(Continue . . . )

Although the `classic' presentation of H5N1 infection has been severe flu symptoms and fever leading to pneumonia, we've seen a number of atypical presentations over the years.   

Many recent cases - particularly from genotype B3.13 - have been mild, often with conjunctivitis and minor respiratory symptoms.  Some are even asymptomatic.  

But avian H5N1 also has a history of causing severe neurological manifestations both in humans, and in other avian and mammalian hosts.

• A 2009 PNAS study (Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration) found that the H5N1 virus was highly neurotropic in lab mice, and in the words of the authors `could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases’.

• Six years later - following the 2014 death of the first imported H5N1 case in Canada - we saw a study (see CJ ID & MM: Case Study Of A Neurotropic H5N1 Infection - Canada), where the authors wrote: `These reports suggest the H5N1 virus is becoming more neurologically virulent and adapting to mammals'.

• In a 2015 Scientific Reports study on the genetics of the H5N1 clade 2.3.2.1c virus - Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015 – the authors described its neurotropic effects, and warned that it could pose a ` . . . significant threat to humans if these viruses develop the ability to bind human-type receptors more effectively.'

Since 2022 we've seen a steady stream of reports of spillover of avian H5N1 into mammalian hosts, with many exhibiting severe (often fatal) neurological manifestations. A few of many recent blogs include:

Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans

PLoS Pathogens: Evolution of Highly Pathogenic H5N1 Influenza A Virus in the Central Nervous System of Ferrets

Emerging Microbes & Inf.: Neurotropic HPAI H5N1 Viruses with Mammalian Adaptive Mutations in Free-living Mesocarnivores in Canada

Pathogens: Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species

While severe neurological involvement from human H5Nx infection remains relatively rare:

In 2022 (see Clinical Features of the First Critical Case of Acute Encephalitis Caused by Avian Influenza A (H5N6) Virus), we reviewed the first known case of neuroinfluenza in an H5N6 patient; a 6-year-old girl who was admitted to a hospital with mild pneumonia - but severe encephalitis - in January of that year.

That was followed 15 months ago (April 2025) by a preliminary report on a neuroinvasive infection in an 8-y.o. girl (see Vietnam: Ho Chi Minh DOH Reports A Rare H5N1 Encephalitis Case In a Child), which reported:

As noted by infectious experts, this is a rare case in which the A/H5N1 avian influenza virus damages the central nervous system and does not attack the respiratory tract.

We followed up on that case last May in OFID: Central Nervous System Involvement by Novel Clade 2.3.2.1e H5N1 Avian Influenza Virus in a Paediatric Patient, where the authors warned:

Testing for IAV and  A(H5N1) virus should be considered in patients presenting with CNS infection with a history of exposure (e.g. dead poultry). Clinicians should be aware of meningoencephalitis associated with A(H5N1) infection in the absence of respiratory symptoms.

A reminder that while it can sometimes be mild, H5N1 isn't your father's influenza. 

J. Virology: Receptor profiling and growth assessment of influenza A virus in porcine mammary and non-mammary tissues and derived cells

 


#19,238

Until 28 months ago conventional wisdom held that cattle, sheep, goats and other mammalian livestock were not susceptible to HPAI H5Nx infection (see A Brief History Of Influenza A In Cattle/Ruminants). 

Isolated spillovers weren't impossible, but had never been confirmed outside of the lab, and thought highly unlikely.

All that changed abruptly in the spring of 2024 when we saw goats die from H5N1 in Minnesota, followed by a multi-state outbreak of H5N1 in dairy cattle. Since then more than 1,150 U.S. cattle herds in 20 states have been affected, and we've seen sporadic reports from the UK, Europe, and Asia. 

At first, the assumption was that only the B3.13 `Bovine' genotype of H5N1 could infect cattle, but in early 2025 genotype D1.1 was discovered in dairy cows in 3 states, and the European and Asia spillovers were from different genotypes as well. 

While we've seen evidence that cattle and other ruminants could serve as mixing vessels for avian influenza, the bigger concern has always been HPAI spillovers into pigs, which have a history of generating pandemic viruses. 

Although detections in swine have been limited, we've seen scattered evidence that H5N1 can infect pigs, albeit often asymptomatically. A few past reports include:

• WHO H5N1 detected in pigs in China (2004)
• EID Journal: Asymptomatic H5N1 In Pigs (2010)
• An Unusual Report Of H5N1 in Pigs (Indonesia 2016)
• Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria (2018)

In May of 2023, in Netherlands: Zoonoses Experts Council (DB-Z) Risk Assessment & Warning of Swine As `Mixing Vessels' For Avian Flu, we looked at growing concerns in Europe that avian H5N1 could increase its pandemic threat by spreading (and evolving) in farmed swine.

Followed only days later by a report out of Italy confirming an H5N1 spillover event at a `mixed species' farm (poultry & swine), and the subsequent seroconversion of the majority of the pigs tested on that farm (see Study: Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virus).

In late 2024, we saw two pigs infected with a new, recently emerged genotype (D1.2) in Oregon (see USDA Confirms 2nd Pig on Oregon Farm Tested Positive for H5N1).

And last fall, in Transboundary & Emerg Inf: Serological Evidence of HPAI (H5N1) in Invasive Wild Pigs in Western Canada, we looked at a study which found (limited) serological evidence of HPAI H5 infection in wild pigs in western Canada.

While the number of wild pigs in Canada is a matter of some debate, in the United States, estimates run in 6-9 million range, mostly clustered  across the Southern tier of states (see APHIS Map below).

Whether commercial or wild, swine are considered problematic when it comes to the spread and evolution of novel flu viruses. But how well adapted `bovine' strains of HPAI H5 might be to pigs is unknown. 

The lack of reports of HPAI H5 in pigs is comforting, but surveillance and testing for the virus in the United States is quite limited.

According to the USDA, as of Sept.1, 2025 there were 74.5 million hogs and pigs on U.S. farms, and according to their last published Influenza A Virus in Swine Surveillance report (Q4), in they tested 977 samples in 2025.

The USDA further notes:

Due to the voluntary nature of this surveillance, the information in this report cannot be used to determine regional and/or national incidence, prevalence, or other epidemiological measures, but it may help identify IAV-S trends.

The $64 question remains; are pigs - like cattle - more susceptible the newer HPAI viruses currently circulating in the United States? 

While it doesn't completely answer the question, today's study tested the infectivity and replication of 4 different influenza viruses (Bovine H5N1, LPAI H5N1, Swine H1N2, and Human H1N1) across an array of porcine cell lines (primary nasal turbinate, trachea, lung and mammary gland epithelial cells).

They report that porcine mammary epithelial cells contain both SA-α2,3 avian‑type  and SA-α2,6 human‑type receptor cells and can support replication of bovine H5N1 B3.13 to relatively high titers, suggesting lactating pigs are a plausible host for this genotype.

The caveat being, this study was done in vitro using tissues and cells from a  single porcine donor, tested against a limited array of (4) viruses. While it shows that pig udder cells can be infected, it's a long way from proving that infections are common in the field. 

That said, these results suggest that - given what we've already seen with cattle - we might be better served by escalating the surveillance and testing of swine - and increasing biosecurity on pig farms - before it becomes a bigger issue. 

Due to its length and technical details, I've only posted the abstract and a few excerpts.  Follow the link to read it in its entirety.

Receptor profiling and growth assessment of influenza A virus in porcine mammary and non-mammary tissues and derived cells

Ulises Barron-Castillo , Nathalie Berube1, Cynthia L. Swan1, M. Afzal Javed1, Lauren Aubrey1, Jill Trann1,2, Makenzie Gidych1, Sauhard Shrivastava1,2, Kaushal Baid1, Arinjay Banerjee ,2, Yan Zhou 

Received 17 April 2026 Accepted 8 June 2026 Published 6 July 2026

Address correspondence to Yan Zhou, yan.zhou@usask.ca.

Copyright © 2026 Barron-Castillo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

 
Highly pathogenic avian influenza (HPAI) virus clade 2.3.4.4b genotype B3.13 infected the mammary gland of dairy cattle; the new tissue tropism and host heightened concern about its ability to cross species barriers with zoonotic potential. Pigs play a key role in influenza A virus (IAV) adaptation, serving as a “mixing vessel” for the emergence of reassortants. The susceptibility of porcine mammary gland to HPAI infection remains unexplored.

In this study, we profiled IAV receptors in porcine mammary gland as well as respiratory tract tissues. Additionally, we evaluated the binding capacity of IAVs to these tissues. Furthermore, we isolated primary cells from porcine mammary gland and respiratory tract, and immortalized them. We examined the growth potential of IAV isolates from bovine, avian, swine, and human on these cells.

We showed that porcine mammary gland displays both SA-α2,3 and SA-α2,6, and that IAVs bind to mammary gland tissues with variable affinities. While bovine H5N1 virus replicates efficiently in mammary gland and respiratory tract cells, replication of other IAVs in mammary epithelial cells is moderate but is efficient in respiratory cells.

These findings suggest that porcine mammary gland could support the infection by HPAI 2.3.4.4b genotype B3.13.

(SNIP)

Pigs are known as mixing vessels for IAVs due to the presence of both SA-α2,3 and SA-α2,6 receptors in their respiratory tract, allowing co-infection by avian, human, and swine IAV strains (13, 14). The expression of both receptors facilitates viral reassortment, enabling the emergence of novel viruses with pandemic potential, such as the 2009 H1N1, a quadruple-reassortant strain (15).

Given the recent evidence of HPAI H5N1 replication in bovine mammary gland tissue, it is important to assess whether the porcine mammary gland could similarly support influenza viral infection. This will provide insights into whether it serves as a potential site for viral adaptation and reassortment. Meanwhile, it is also equally important to assess the potential replication of bovine H5N1 in porcine respiratory tract in comparison to other IAV strains.

Here, we characterized IAV receptors on porcine mammary gland and respiratory tract tissues. Additionally, we tested the binding capacity of IAV to these tissues. Furthermore, we isolated primary cells from both porcine mammary gland and respiratory tract tissues and immortalized them. The growth potential of a panel of IAV isolates from bovine, swine, human, and avian sources was examined in these cells.

We report that porcine mammary gland expresses both SA-α2,3 and SA-α2,6 receptors, and IAVs bind to mammary gland tissues with variable levels. HPAI H5N1 bovine isolate replicates efficiently in epithelial cells derived from the mammary gland and respiratory tract. In contrast, non-HPAI isolates exhibited moderate replication in mammary gland cells but efficient replication in respiratory tract cells. These findings suggest that porcine mammary gland tissues could support infection by HPAI H5N1 clade 2.3.4.4b genotype B3.13. 

        (Continue . . . )

 

PNAS (Referral): Genomic and structural evidence of SARS-CoV-2 and MERS-CoV in migratory birds

 
Tundra Swans Flyovers, Craig Strobeck, Public Domain,
https://www.fws.gov/media/tundra-swans-flyovers

#19,237

We've a surprising report to look at this morning in PNAS (most of which is behind a paywall) which describes the first detection of Betacoronaviruses (COVID & MERS-COV) in migratory birds in China. 

Coronaviruses are divided into 4 distinct genera: 

• Alphacoronaviruses
• Betacoronaviruses (i.e. SARS-CoV, MERS-CoV, etc.)
• Gammacoronaviruses
• and Deltacoronaviruses 

Alphacoronaviruses & Betacoronaviruses primarily infect mammals, while birds are mostly affected by Gammacoronaviruses, such as infectious bronchitis virus (AIBV) and occasionally by Deltacoronaviruses.

We've seen a few crossovers - particularly with Deltacoronaviruses - which have been detected mostly in birds and but occasionally in mammals (see Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus . . . . ). 

Numerous studies have tried (and failed) to infect birds with Betacoronaviruses, including: 

Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV

Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2

All of which has led researchers to long assume that birds aren't susceptible to either SARS-CoV-2 or MERS-CoV.  But today's report calls that into question.

In brief, George F. Gao et al. report finding:

• Three nearly full‑length SARS‑CoV‑2 genomes (2 Beta-like & 1 Gamma-like VOCs) in the feces of Tundra Swans collected in Jiangxi Province in 2021.

• They also report a ~70% complete MERS‑CoV genome was recovered from a Bar‑headed goose in Tibet in 2022. 

• While the original Wuhan Strain of SARS-COV-2 was unable to infect Swans (via tsACE2 receptors), some later variants appear to have acquired the ability to do so

Since I don't have access to the full report, I'll simply refer my readers to the link and abstract below.  I'll have a brief postscript after the break. 

Genomic and structural evidence of SARS-CoV-2 and MERS-CoV in migratory birds

Jian Cao, Sheng Liu, Chao Su, +4 , and George F. Gao gaof@im.ac.cn
Contributed by George F. Gao; received January 10, 2024; accepted May 15, 2026; reviewed by Jie Cui, Yi Guan, and Lin-Fa Wang
June 29, 2026 123 (27) e2400023123
https://doi.org/10.1073/pnas.2400023123

Copyright © 2026 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans.

These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes.

Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD–ACE2 complex, play key roles in virus–receptor engagement.

Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2.

In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

For years, the role of migratory birds in the spread of avian flu was bitterly contested, with many scientists insisting that birds were simply incapable of flying long distances while carrying the H5 virus (see 2011's Study: The Role Of Migratory Birds In Spreading Bird Flu).

Despite abundant evidence, it wasn't until the second half of the last decade that the role of migratory birds in spreading avian flu was generally accepted (see Migratory Birds & The Spread Of Highly Pathogenic Avian Flu).

While it isn't clear how important migratory birds might be in the spread of Betacoronaviruses, this study suggests we can no longer ignore their potential as carriers of SARS-CoV-2, MERS-CoV, and possibly other coronaviruses. 

A humbling reminder that anything we say with relative certainty about avian flu, novel coronaviruses - or any other infectious disease - today, is subject to future revision as these pathogens evolve and our knowledge base expands.  

Australia: WA Designates 5th Suspected H5N1 Case as `Presumed Positive'

 

#19,236

Four days ago Western Australia announced the discovery of a suspected H5N1 infected bird in Perth (collected 6/30). To date, more than 1,000 dead birds have been reported in WA alone, but collection and testing takes time, and so only a small percentage have been processed. 

And testing - particularly of bird or animal remains - can be difficult, as the ability to detect the virus can degrade over time. 

Normally, after a local lab detects the H5 virus, Australian samples are sent to the national CSIRO lab for confirmation.  In the case of the above mentioned Perth sample, after nearly a week - while they confirmed H5 - they were unable fully sequence the virus. 

However, WA's Chief Veterinary Officer Dr Katie Webb announced today,  “This case will be considered as ‘presumed positive’ based on the available test results, species involved, coastal location and the broader epidemiological picture.”

So far WA has received more than 1,000 reports of dead birds, but due to the high volume, the DPIRD has prioritized 172 for further investigation. Of those already processed in WA, 5 have tested positive and 64 have tested negative.   

As with any disease surveillance system - whether in birds, livestock, or people - confirmed cases will represent only the tip of the pyramid. 

In the case of H5N1 in birds:

• Only a percentage of birds will sicken and die (varies by species)
• Only a fraction of those birds will be seen, reported, and collected
• Of those, only a subset will be prioritized for testing
• And of that group, some may not have detectable levels of virus

While 7 cases detected across 3 Australian states may not sound like much, it is actually a pretty strong signal that multiple incursions of HPAI have likely occurred in recent weeks. 

This update from the Western Australian government website:

WA responding to ‘presumed positive’ H5 bird flu case in Perth
Media release

Additional testing of the previously reported migratory giant petrel found in the Whitfords - Mullaloo beach area has determined the case is a ‘presumed positive’ detection of the serious H5 bird flu strain.

Last updated: 6 July 2026

Additional testing of the previously reported migratory giant petrel found in the Whitfords - Mullaloo beach area has determined the case is a ‘presumed positive’ detection of the serious H5 bird flu strain.

Testing at CSIRO’s Australian Centre for Disease Preparedness has confirmed the petrel had an influenza virus of the H5 subtype.

The case has been classified as a presumed positive because viral sequencing to confirm the virus as H5 bird flu was not able to be achieved.

The inability to obtain a sequence may be due to a range of factors, including the level of decomposition of the carcass.

WA Acting Chief Veterinary Officer Dr Katie Webb said it was considered highly likely the bird was infected with H5 bird flu, but this could not be definitively proven at this stage.

“This case will be considered as ‘presumed positive’ based on the available test results, species involved, coastal location and the broader epidemiological picture,” Dr Webb said.

“This does not change our response in WA. We are treating this the same as a positive case based on the available epidemiological and laboratory evidence.”

This presumed positive case adds to the six confirmed positive detections of H5 bird flu nationally, including four in WA on the southern and south west coasts, one in South Australia and one in New South Wales.

Importantly, there is no evidence the virus has spread beyond these individual migratory seabirds, but we ask the community to be alert and follow advice about reporting sick or dead wildlife.

People should AVOID and not handle the animals, RECORD and take photos or a video and REPORT to the Emergency Animal Disease (EAD) Hotline on 1800 675 888.

There have been more than 1000 reports from WA to the EAD hotline since Friday 19 June. Of these reports, 172 have been prioritised by DPIRD for further investigation or testing based on the risk of H5 bird flu.

To date, a total of 64 negative test results have been recorded across the State.

More information is available on the Australian Government's Bird flu (avian influenza) website.

Watching Bird Flu in Nepal (H5N1)

 

#19,235

Nestled between India and China, Nepal is no stranger to HPAI H5N1 - including at least 1 human case in 2019 - along with sporadic outbreaks in poultry over the years.  

In recent months, however, FluTrackers has been following an increasing number of reports of outbreaks in both wild birds and poultry. 

Since early March, WOAH reports 66 outbreaks across the country, involving the loss of more than 500,000 domestic birds, and reports of die offs of wild birds (mostly wild house crows).  

While official government reports are infrequent and hard to access, local and international media have reported increasing concern over the spread of H5N1 in Nepal, with Nepal News reporting yesterday (Jul 4th) Health Ministry issues nationwide alert over spreading bird flu outbreak.

Ministry Joint Spokesperson Samir Mani Adhikari is quoted as urging `. . . the public to completely avoid direct contact with sick, dead, or infected poultry, to consume meat and eggs only after they are thoroughly cooked, and to report dead birds to nearby veterinary authorities.'

The subclade currently circulating in Nepal remains a bit of a mystery. I've not seen any recent mention, but we know that both clade 2.3.4.4b (the primary global subclade) and a more regional 2.3.2.1a have been reported in Nepal. 

A 3rd possibility exists, as eight months ago, in Viruses: Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a H5N1 Avian Influenza Viruses in Nepal in 2023, we looked at a report of a reassortment event which combined genetic elements from both subclades. 

This event was not unlike what we saw 3 years ago with the emergence of a new, more transmissible H5 Clade 2.3.2.1e virus in Cambodia & Vietnam that subsequently sparked an abrupt uptick in human infections between 2024-2026.

Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a H5N1 Avian Influenza Viruses in Nepal in 2023

Pragya Koirala 1, Manju Maharjan 2, Sharmila Chapagain 3, Barun K. Sharma 1,
Tirumala B. K. Settypalli 4, Charles E. Lamien 4 and William G. Dundon 4,*

Viruses 2025, 17(11), 1481; https://doi.org/10.3390/v17111481    

Abstract

Samples collected from two avian influenza outbreaks in Bagmati Province in central Nepal between January and March 2023 were positive for H5N1. Full genomes were generated for both viruses, which revealed that one of the viruses was very similar to clade 2.3.4.4b H5N1 identified in Bangladesh in 2021/2022.

The second virus was a reassortant H5N1 virus consisting of four genes (HA, NA, NP, and M) originating from a clade 2.3.2.1a H5N1 and the remaining four genes (NS, PB1, PB2, and PA) originating from a 2.3.4.4b H5N1. Notably, this second virus had a high identity with 2.3.2.1a clade viruses identified in humans and cats in India in 2024–2025.

These are the first full genome sequences of H5N1 avian influenza viruses from Nepal and given the recent human infections by 2.3.2.1a H5N1 viruses in the region, these data will be of interest to both public health and veterinary authorities. 

(Continue . . .)

The caveat here is, this study analyzed only two poultry isolates - taken from two different farms roughly 10 km apart in early 2023 - which tells us very little about prevalence or spread of variants the region. 

Regardless of the subclade involved, a large and escalating bird flu outbreak lying beneath the flyway between the two most populous countries (India & China) on the planet is very much worth our attention. 

Stay tuned.