J. Virology: Risk assessment of avian influenza A(H5N5) virus from the first human case using the ferret model

Credit: Multiple transatlantic incursions of HPAI
clade 2.3.4.4b A(H5N5) virus into North America
and spillover to mammals

#19,290

Last November we saw the first, and as far as we know - only - human infection with emerging H5N5 subtype of avian flu in a resident of Washington State who had contact with backyard poultry and/or wild birds. 

We've been following HPAI H5N5's spread in birds and small mammals - first in Europe, then in Canada and the United States - for several years, including a report last month; Preprint: HPAI H5N5 in a Polar Bear and Atlantic Walrus, Svalbard, 2026, with Widespread Seroconversion in Polar Bears.

In late July we saw a Preprint: A lethal human H5N5 influenza virus isolate exhibits low pandemic risk traits, which somewhat reassuringly found the virus displayed relatively low pandemic risk traits:

• It replicated relatively poorly (compared to seasonal H1N1) in upper respiratory cell cultures, 
• It has a more avian-like pH inactivation point (about 5.5)  compared to human-adapted flu strains
• And - unlike in the Erdelyan et al. study (which reported rapid 100% mortality and some transmission in ferrets) - they reported that  infected ferrets did not infect healthy co-housed ferrets.

Today we've a study published in the Journal of Virology by researchers at the CDC's Influenza Division, NCIRD, which is slightly less reassuring. 

• While they still found no evidence of airborne transmission in the ferret model, they report limited direct-contact transmission in 2 of 3 co-housed ferrets. 

• And while the preprint reported moderate disease severity in ferrets, today's study reports uniformly severe/fatal disease, with rapid systemic spread. 

• And where the preprint characterized WA/2148 as having reduced replication in human bronchial epithelial cultures, the CDC study instead found robust replication in polarized Calu-3 airway cells at both 33°C and 37°C. 

There were differences in both the methods and materials used in these two studies, which could account for these disparities. Today's study even notes that primary human airway cultures or organoids would provide a more physiologically relevant comparison than the proxies used by these two studies.

And as always, the caveat remains that we can only draw limited conclusions from the evaluation and characterization of a single isolate, since even minor differences between strains or genotypes can make significant changes to its behavior.

Due to it length, and technical nature, I've only reproduced the abstract and some excerpts from the study below.  Follow the link to read it in its entirety.  I'll have a brief postscript after you return.

Risk assessment of avian influenza A(H5N5) virus from the first human case using the ferret model
Authors: Joanna Pulit-Penaloza , Jessica A. Belser, Nicole Brock, Troy J. Kieran, Claudia Pappas, Hui Zeng, Xiangjie Sun, Juan A. De La Cruz, Yasuko Hatta, Han Di, C. Todd Davis , Taronna R. Maines 
https://doi.org/10.1128/jvi.00856-26
 
PDF/EPUB

ABSTRACT

The incursion of Eurasian-origin genotype A6 A(H5N5) virus into North America expanded the genetic diversity among North American highly pathogenic avian influenza viruses and heightened concern about zoonotic risk. Following a fatal human infection with the A(H5N5) virus A/Washington/2148/2025, viral replication was assessed in polarized human bronchial epithelial cells, and pathogenicity, transmissibility in direct contact and respiratory droplet models, and airborne virus shedding were evaluated in ferrets to inform pandemic risk assessment.

A(H5N5) displayed robust replication in Calu-3 cells at 33°C and 37°C, showing kinetics and peak titers comparable to those of contemporary genotype B3.13 and D1.1 A(H5N1) viruses. In ferrets, A(H5N5) replicated efficiently in the respiratory tract, disseminated to extrapulmonary tissues, and caused fatal disease in all inoculated animals. Airborne transmission was not observed, and infrequent, low-level detection of virus in air samples paralleled that of A(H5) viruses that are not transmissible via air in ferrets.

In a direct contact model, limited transmission was detected within 4 days of exposure, with evidence of lower respiratory tract replication in contact animals. These findings indicate that the A(H5N5) virus has the capacity for robust replication in an airway epithelial cell line and can cause severe systemic infection and mortality in ferrets but has not acquired adaptations for airborne spread in mammals. Collectively, these results underscore heterogeneity among clade 2.3.4.4b A(H5Nx) viruses in North America and the need for genotype-by-genotype evaluation of newly emerged viruses to understand public health risk.

IMPORTANCE

The emergence of Eurasian-origin genotype A6 highly pathogenic avian influenza A(H5N5) virus in North America has increased viral diversity and raised concerns about zoonotic and pandemic risk. In this study, we evaluated the replication kinetics, pathogenesis, and transmission of A/Washington/2148/2025 A(H5N5) virus, which was isolated from the first reported human infection with this influenza virus subtype, using polarized human bronchial epithelial cells and the ferret model. 

The A(H5N5) virus replicated efficiently in vitro at temperatures representative of the upper and lower respiratory tracts and caused fatal systemic disease in inoculated ferrets. Limited transmission was observed during 4 days of direct contact. Airborne virus detection was infrequent and did not result in airborne transmission. These findings show that A(H5N5) virus can replicate robustly in mammalian cells and cause severe disease but lacks adaptations supporting efficient airborne spread, informing assessment of the pandemic risk posed by genotype A6 influenza viruses.

        (SNIP)

DISCUSSION

The rapid expansion of clade 2.3.4.4b A(H5N1) influenza viruses into novel mammalian hosts has necessitated comprehensive risk assessments of representative viral isolates from different genotypes associated with human infection and detections in mammalian hosts (19, 20).

Collectively, these studies have revealed that clade 2.3.4.4b A(H5N1) viruses can replicate efficiently in a diversity of mammalian epithelial cell types derived from the human respiratory tract (21–23), cause severe and fatal disease in animal models, and have varied capacity for airborne transmission to susceptible contacts (4–6, 18, 24).

 

The detection of A(H5N5) virus associated with fatal human disease in 2025 underscores the confounding unpredictability of A(H5) viruses, and their continued threat to human health.

       (SNIP) 

Overall, the WA/2148 A(H5N5) virus showed the capacity to cause severe, systemic mammalian infection and robust replication in polarized human airway epithelial cells, characteristics similar to those of other contemporary A(H5Nx) viruses. However, the virus lacked clear adaptation for efficient airborne spread, indicating limited adaptation to a mammalian host. Our findings underscore substantial heterogeneity in pathogenesis and transmission among clade 2.3.4.4b A(H5Nx) viruses, supporting continued genotype-by-genotype evaluations.

       (Continue . . .)

As a pandemic virus, H5N5 may not be ready for prime time, but as a zoonotic threat it already appears to be capable of robust replication in human airway cells and causing severe systemic disease in mammals.

All of which makes it a virus very much worth our continued attention. 

Kent County MI Health Department Bulletin on Swine Flu (in pigs) at Local Fair

Credit Wikipedia


#19,289

We've seen an unusually quiet year of reporting on Swine Variant Influenza, with only 2 H1N2v (human) cases reported since October 1st of 2025; a far cry from the average of 36 human infections per year since tracking began in 2011 (n=581). 

The CDC describes swine influenza viruses as: 

• Swine influenza is a respiratory disease of pigs caused by type A influenza viruses that regularly cause outbreaks of influenza in pigs.
• Influenza viruses that commonly circulate in swine are called “swine influenza viruses” or “swine flu viruses.”
• Like human influenza viruses, there are different subtypes and strains of swine influenza viruses.
• The main swine influenza viruses circulating in U.S. pigs in recent years have been, swine triple reassortant (tr) H1N1 influenza virus, trH3N2 virus, and trH1N2 virus.

When a swine influenza virus spills over into a human, it is called a swine-variant virus. The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018]  Jul   2019   5.8  5.7 Moderate

H3N2 variant [A/Ohio/13/2017]          Jul   2019   6.6  5.8 Moderate

H3N2 variant [A/Indiana/08/2011]      Dec 2012   6.0  4.5 Moderate

While no additional cases have been confirmed, this week the Kent County Health Department announced the closure of their county fair's swine barn after the sudden death of a pig, and `several other pigs developed signs of illness'. 

KCHD is reportedly investigating reports of `influenza-like' illness among individuals who had contact with pigs at the fair, but no confirmed human infections have been reported at this time.

They are urging the public:

“Anyone who develops flu-like symptoms after having contact with pigs at the fair should contact the Kent County Health Department and let their health care provider know about their exposure.”

So far, we've no indication of the subtype involved or the severity of the human `influenza-like' illnesses they are investigating. Typically, swine variant infections are mild or moderate in humans, with only a couple of deaths reported since 2011. 

The bulletin advises that the Kent County Fair has ended, but attendees who had contact with pigs at the fair should monitor for flu-like symptoms for 10 days.  They then go on to list the precautions other fair-goers in Michigan should take when attending agricultural events. 

First, the Health Department announcement, after which I'll have a bit more.

Health Officials Raise Awareness Following Swine Flu Detection in Pigs at the Kent County Youth Fair

 

GRAND RAPIDS, MI. (August 10, 2026) — The Kent County Health Department (KCHD), in partnership with the Michigan Department of Health and Human Services (MDHHS) and the Michigan Department of Agriculture and Rural Development (MDARD), is advising people who may have had contact with pigs at the Kent County Youth Fair to monitor for influenza-like symptoms due to a detection of swine influenza.

On Friday, August 7, a pig at the Kent County Youth Fair died suddenly, and several other pigs developed signs of illness. The sick pigs were isolated, and the swine barn was immediately closed to the public. However, as a precaution, the KCHD is investigating reports of influenza-like illness among individuals who had contact with pigs at the fair.

“While we do not have confirmation of human infection at this time, we are taking this situation seriously and want people who may have been exposed to know what symptoms to watch for and what to do next,” said Kent County Health Department Health Officer Dr. Adam London.

“Anyone who develops flu-like symptoms after having contact with pigs at the fair should contact the Kent County Health Department and let their health care provider know about their exposure.”

Signs and Symptoms in Humans

Symptoms of swine flu can be similar to the seasonal flu and may include:

• Fever
• Lethargy (tiredness)
• Lack of appetite
• Coughing
• Runny nose
• Sore throat
• Eye irritation
• Nausea
• Vomiting
• Diarrhea

Anyone who had contact with pigs at the fair should monitor for these symptoms for 10 days. Those who develop symptoms should contact their healthcare provider or their local health department for testing. The KCHD Communicable Disease Unit can be reached at 616-632-7228.

Protecting Animal and Human Health at the Fair

While the Kent County Youth Fair has ended, people who plan to attend other agricultural fairs or have contact with animals should take the following precautions to reduce the risk of influenza and other diseases that can spread between animals and people:

• Avoid interacting, touching, or petting animals if you have an increased risk for severe influenza complications.
• Don't eat, drink, or put anything in your mouth in areas with animals.
• Don't take toys, pacifiers, cups, baby bottles, strollers, or similar items into areas with animals.
• Wash your hands with soap and water before and after exposure to pigs or other animals, using hand-sanitizer if water and soap are not available.
• Change and wash clothing and clean footwear or equipment after visiting animal areas, particularly if you have livestock at home.
• Avoid close contact with animals that appear sick, including animals showing loss of appetite, fever, tiredness, eye redness, discomfort, coughing, or a runny nose.
• If you must come in contact with animals that may be ill, then wear personal protective equipment (PPE). This includes protective clothing, gloves, and a well-fitting mask that covers your mouth and nose and immediately contact the fair veterinarian. Parents and caregivers should review considerations for specific groups of people when selecting a respirator or mask for children.
• Stay home and away from others, including animals, if you are experiencing flu-like symptoms

Pork Remains Safe to Eat 

Swine flu in pigs is not a food safety concern, and people cannot contract influenza by eating properly handled and cooked pork or pork products. Consumers should continue to follow standard food-safety practices when handling and preparing pork.

For more information about preventing swine flu, please visit the Centers for Disease Control and Prevention (CDC) website.

This isn't just an American problem, as there is much diversity among swine flu viruses around the globe, with China's EA H1N1 `G4' virus often cited as the biggest pandemic threat. We've also followed repeated spillovers in Brazil, and last year the Eurasian 1C Swine Influenza A Virus was labeled a `high pandemic risk'.

The reality is, surveillance and testing for swine influenza A viruses is notoriously sub-optimal, and many strains circulate under the radar.  

For more on the risks of exposure to influenza infected pigs, you may wish to revisit:

Preprint: Occupationally Exposed & General Population Antibody Profiles to Influenza A Viruses Circulating in Swine as an Indication of Zoonotic Risk

 

Virology: Acquisition of specific human respiratory tract binding by 2.3.4.4b H5N1 hemagglutinins requires multiple mutations

 

#19,288

There remains much interest in exactly what changes the HPAI H5Nx virus would need in order to become a more `humanized' virus - like seasonal H3N2 and H1N1 - which have a strong affinity for the alpha 2,6 receptor cells most commonly found in the human respiratory system.

While it seems likely that it would require multiple concurrent mammalian adaptations to create a pandemic strain, the ability of avian flu viruses to bind to human α2-6 receptor cells is considered one of the biggest obstacles the virus must overcome in order to successfully spread in humans.

Complicating matters, as we've discussed previously (see here, here, and here), HPAI H5 viruses encompass a large and growing array of closely related - but genetically distinct subclades, subtypes, and genotypes - and a mutation that might impact one strain might not have the same effect on another. 

In December of 2024, a study in Science: A Single Mutation in Bovine Influenza H5N1 Hemagglutinin Switches Specificity to Human Receptors, suggested a single HA amino acid change (Q226L) could switch H5N1 B3.13 from binding preferentially to avian-type receptor cells to human-type receptor cells.

The authors wrote:

“Our experiments revealed that the Q226L mutation could significantly increase the virus’ ability to target and attach to human-type receptors,” explains Paulson. “This mutation gives the virus a foothold on human cells that it didn’t have before, which is why this finding is a red flag for possible adaptation to people.”

The shift alone, however, may not be enough to enable human-to-human transmission. Other genetic changes—such as mutations in polymerase basic 2 (E627K) that enhance viral replication and stability in human cells—would likely be necessary for the virus to spread efficiently among people.

The following month, in Preprint: The Q226L Mutation Can Convert a Highly Pathogenic H5 2.3.4.4e Virus to Bind Human-type Receptors, another study (later published in PNAS) found that adding Q226L to an older clade 2.3.4.4e H5N6 virus could switch receptor binding from avian to human-type receptors. 

While concerning, we've not seen any evidence of efficient or sustained spread of H5N1 in humans, suggesting there are additional enhancements required. 

Today we've a new study that offers an update on impact of the Q226L mutation in H5N1 B3.13, which finds that its impact varies between HPAI H5 strains. 

While Q226L did shift binding in laboratory tests towards human-type glycans, those glycans were not found on the human tracheal tissues tested, and the Q226L mutant failed to bind human trachea.

The addition of another HA mutation, N224K, increased human-tracheal binding, but only sparsely and mainly to goblet cells. All of which reinforces the notion that  receptor adaptation to humans in HPAI H5 is neither simple nor uniform.

Q226L appears to be decisive in some H5 strains, but the current bovine 2.3.4.4b H5N1 virus likely requires additional changes before it can efficiently bind to human receptors in the upper airway.  

I've only posted the link, abstract, and some excerpts from the study. Follow the link to read it in its entirety. 

Acquisition of specific human respiratory tract binding by 2.3.4.4b H5N1 hemagglutinins requires multiple mutations

Authors: María Ríos Carrasco, Mafalda F. Guerreiro Cabana, Eszter Kovács, Zoé Ducarne, Cindy G. J. Cleypool , Geert-Jan Boons, Robert P. de Vries  r.vries@uu.nlAuthors Info & Affiliations

https://doi.org/10.1128/jvi.01065-26

ABSTRACT

It has been suggested that the hemagglutinin of the human-infecting cattle-derived 2.3.4.4b virus A/Texas/34 H5N1 (H5TX) requires only one mutation, namely Q226L, to switch from binding avian-type to human-type receptor preference. In this study, we examined the binding of H5TX Q226L, along with other key mutations, to sections of human trachea. We conclude that, while H5TX Q226L can bind human-type receptors, more than a single mutation is required for this protein to bind to human respiratory tract tissue.

We also report changes in receptor-binding specificity of another 2.3.4.4b HA mutant, H5FR Q226L (from A/duck/France/161108/16 H5N8), associated with the presence of a multibasic cleavage site. This study offers insight into the determinants of evolution toward human-type receptor binding in currently circulating H5Nx viruses. It also emphasizes the importance of testing individual strains using additional methods, including tissue-based approaches, alongside synthetic glycans.

IMPORTANCE

Currently, H5N1 influenza A viruses are responsible for numerous zoonotic spillover events, from infecting birds to other mammals, including dairy cattle. Although no human-to-human transmission has been observed, several people have been infected. This host range expansion is typically linked to changes in one of the viral surface proteins, hemagglutinin, which can switch its preference from avian-type to human-type receptors. To better understand the potential of the currently circulating H5N1 virus to transmit among humans, we evaluated the effects of the Q226L mutation, in combination with other amino acid substitutions, on binding to the human trachea. We also studied the effect of the multibasic cleavage site, a specific motif present in highly pathogenic influenza strains, on receptor-binding properties. These findings provide insight into the role of receptor binding in influenza infections.

        (SNIP)

We conclude that more than a single mutation is required for the hemagglutinin of the currently circulating 2.3.4.4b viruses to bind human respiratory tissue. This aligns with previous work showing that multiple amino acid changes are required to switch from avian- to human-type receptors in H5 strains (3). One key takeaway from this study is the significance of glycan architecture. H5TX mutants, similarly to other HAs, distinguish not only between SIA linkage but are also selective according to glycan branch length and sialylation (31).

More research is needed on the presence of asymmetrical glycans in the human respiratory tract and their role in influenza A virus hemagglutinin attachment to cells. Moreover, we emphasize the importance of not underestimating the MBCS’s influence on hemagglutinin’s receptor-binding properties.

       (Continue . . . )

JAMA Peds: Effectiveness of Oseltamivir in Hospitalized Children With Laboratory-Confirmed Influenza, 2014-2023

 

#19,287

While the timing and severity of the next flu season is uncertain, we are already seeing reports of increased flu activity in Asia (see HK DH investigates case of severe paediatric influenza A infection), making the following JAMA Pediatrics  study on the effectiveness of Oseltamivir in hospitalized children both timely and reassuring.

One of the popular memes on the internet and in tabloid media has been that the influenza antiviral drug oseltamivir (Tamiflu ®) is either A) Ineffective or B) Ineffective and Dangerous.

A cherry picking of data, along with hyperbolic media reports – like the Daily Mail’s Ministers blew £650MILLION on useless anti-flu drugs - have helped to drive these beliefs. 

Admittedly, antivirals are not a panacea against influenza infection, but when administered early in an infection, they can significantly reduce the severity and duration of illness.

The addition of an FDA warning in 2008 - based on primarily on media reports from Japan - warning of rare `Neuropsychiatric events' (particularly among pediatric patients), further drove public opinion.  

A 2018 report, however (see Study Finds No Relationship Between Suicide & Oseltamivir In Pediatric Patients), strongly refuted those claims, but the stigma remains. 

As a result, oseltamivir is often underused, even though we've seen repeated studies showing their worth (see CID Journal: Under Utilization Of Antivirals For At Risk Flu Patients and  CDC Study: Early flu Antiviral Treatment Can Shorten Hospital Stays in Children With Flu).

   

CDC Influenza Antiviral Medications: Summary for Clinicians - Jan 2026

All of which brings us to a new investigative report, published yesterday in JAMA Pediatrics, which finds that oseltamivir treatment was associated with a 31% lower hazard of ICU admission and shortened hospital LOS (Length of stay) in hospitalized pediatric patients with lab confirmed influenza.

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

Original Investigation

Effectiveness of Oseltamivir in Hospitalized Children With Laboratory-Confirmed Influenza, 2014-2023

Kacie Rytlewski, MD1; Angela Dunn, MS2; Alissa O’Halloran, MSPH3 et al
Published Online: August 10, 2026
doi: 10.1001/jamapediatrics.2026.3376

 Key Points

Question  Does oseltamivir treatment reduce risk of intensive care unit (ICU) admission and hospital length of stay among pediatric patients hospitalized with influenza?

Findings  Using a cohort study from a population-based surveillance network in 13 states across 8 influenza seasons, oseltamivir treatment was found to decrease both the likelihood of ICU admission and hospital length of stay among pediatric patients hospitalized with laboratory-confirmed influenza.

Meaning  These findings support the current national recommendations from the American Academy of Pediatrics, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America that recommend antiviral treatment for children hospitalized with laboratory-confirmed influenza.

Abstract

Importance  National organizations recommend antiviral treatment for hospitalized children with influenza; however, use in this setting has recently declined. Studies of oseltamivir effectiveness in children are limited by misclassification bias, unknown symptom onset date, and incomplete capture of antiviral use prior to admission.

Objective  To assess the association between oseltamivir receipt and intensive care unit (ICU) admission and hospital length of stay (LOS) among pediatric influenza-associated hospitalizations.

Design, Setting, and Participants  This cohort study used data that were obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET), which conducts US population-based surveillance for laboratory-confirmed influenza hospitalizations for all ages across 13 states. The study data include seasons 2014 to 2015 through 2022 to 2023, excluding 2020 to 2021. Participants included children aged younger than 18 years who were hospitalized with laboratory-confirmed influenza and for whom a respiratory symptom onset date was available. These data were analyzed from October 2024 through May 2026.

Exposures  Oseltamivir receipt as a time-dependent exposure.

Main Outcome(s) and Measure(s)  The primary outcome was time from symptom onset to ICU admission. Secondary outcome was time from admission to discharge (LOS). Adjusted Cox proportional hazard models (aHR) with oseltamivir receipt as a time-dependent exposure were used.

Results  After exclusions, 6044 influenza cases were included in the primary ICU analysis, of whom 4240 (70.2%) received oseltamivir, and 7103 cases were included in the secondary LOS analysis, of whom 5746 (80.9%) received oseltamivir. In the ICU analysis, the median (IQR) age was 3 (1-7) years, 3382 (56%) were male and 3721 (44%) were female, and 2937 (49%) had 1 or more medical comorbidity—the most common of which was asthma in 1547 children (26%). In adjusted models, compared with untreated children, oseltamivir treatment reduced the hazard of ICU admission (aHR, 0.69; 95% CI, 0.60-0.80) and shortened LOS (analyzed as hazard of hospital discharge; aHR, 1.13; 95% CI, 1.06-1.21).

Conclusions and Relevance  In this cohort of children hospitalized with influenza, oseltamivir treatment was significantly associated with a reduced risk of ICU admission by 31% and decreased hospital LOS. These findings demonstrate the benefits of oseltamivir receipt and support current national recommendations for oseltamivir treatment as soon as possible in children hospitalized with suspected or laboratory-confirmed influenza.

        (SNIP)

Our main finding was a significant decrease in ICU admission risk among hospitalized children with laboratory-confirmed influenza treated with oseltamivir compared with those not treated. The association persisted after excluding patients who received oseltamivir prior to admission. The association of oseltamivir with decreased odds of ICU admission has been shown in prior retrospective cohort studies in children.7 Importantly, our additional analyses of age, underlying medical comorbidity, and timing of oseltamivir initiation from symptom onset showed consistent benefit for all hospitalized pediatric patients with influenza.

Our analyses also demonstrated a significant decrease in the hospital LOS among those receiving oseltamivir, reflected as an increased hazard of discharge; this is notable particularly given that cases had a relatively short LOS (median, 3 days). This finding persisted in our sensitivity analyses. There was no evidence of effect modification by age or medical comorbidity. We observed the reduction in LOS most prominently with early treatment, which has been observed previously.5,7 Our findings suggest that health care professionals should encourage caregivers of children to seek care early in the course of influenza-like illness and also urgently consider oseltamivir treatment for all children and adolescents hospitalized with suspected or confirmed influenza.

       (Continue . . . )

 

A Summer Snapshot Of U.S. Wild & Captive Mammals With Confirmed HPAI H5

 

#19,286

The USDA maintains a public database of wild and captive mammals (excludes livestock) infected with HPAI H5 across the country since its arrival in 2022; one which is highly dependent upon investigations and submissions by individual states and/or veterinarians. 

Last December, in Declining Mammalian Spillover Submissions To USDA Over Past 8 Months, we looked at a 90% drop in reported infections of HPAI H5 to mammalian wildlife during the 2nd half of 2025, despite increased detections in wild birds.

What the above chart did not reflect was the existing backlog, and gaps (between collection and confirmation dates) and/or delays in reporting cases (see chart below). Delays of 2 to 3 months are common (see graph below), and delays of 6 to 8 months are not unheard of. 

Graph created by Gemini using USDA data

Since April of this year, only 3 cases (2 skunks and 1 domestic cat from Utah) have been confirmed by the USDA.  While there may be as-yet unpublished data in the pipeline, the decline in case reports appears to be ongoing. 

Graph created by Gemini using USDA data

Reporting varies considerably by state (see chart below), with New Mexico reporting the highest total.

Graph created by Gemini using USDA data

But after 4 years, there are still 8 states which have yet to report a single detection.

• Alabama
• Arkansas
• Hawaii
• Maryland
• Mississippi
• New Hampshire
• South Carolina
• West Virginia

These disparities may come down to differences in climate and terrain (swamps vs. forests vs. deserts), varying activity by migratory flyways, and the fact that infected wildlife quite often die in remote, difficult to access places where their carcasses are quickly scavenged by other animals, making them unlikely to be discovered or tested.

But it is also possible that some states are simply more proactive in investigating, and reporting suspected cases, than others.

As far as host range is concerned, there are 54 different species listed in the USDA database, with the top 3; Domestic cat (155), Red fox (126), and House mouse (111) make up nearly half (48.0%) of all reported mammal submissions.

• There are, altogether, 16 different feline species (wild/captive/domestic) - which combined account for 238 submissions or (29.2%) of confirmed cases.

• Marine mammals make up another large chunk of the data accounting for 13.7% of all submissions (n=112), led by Northern Elephant Seal (57), Harbor seal (27), and Bottlenose dolphins (11)

(Excludes 22 one-off single detections)

Graph created by Gemini using USDA data

All of these numbers are presumed to represent a small fraction of the actual number of infections, as limited seroprevalence studies have found antibodies in a large array of wildlife species (see Virology: Susceptibilities & Viral Shedding of Peridomestic Wildlife Infected with Clade 2.3.4.4b HPAI Virus (H5N1).

Meanwhile, the public remains largely oblivious to the threat of HPAI (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), while some state and local governments appear not to have prioritized surveillance, testing, and reporting. 

Although the decline in reported wildlife infections to the USDA may turn out to be a good sign, a lack of evidence is not evidence of lack.

WHO: Risk assessment of the introduction, spread, and zoonotic spillover of MERS-CoV Clade B in camel populations of the Nile Basin and Across Africa

 

#19,285

While the number of human MERS-CoV cases reported over the past six years has fallen dramatically, this high morbidity/mortality coronavirus continues to pose a significant public health threat ((Referral) Nature: Human MERS-CoV cases are falling but pose an ongoing pandemic threat) as it spreads and evolves in camels in the Middle East and Africa.

Some of this decline may be due to difficulties in identifying cases, while some Middle Eastern countries have shown past reluctance to report cases. It also seems likely that cases are being missed in North and Central Africa as well (see EID Journal: Geographic Distribution of MERS-CoV among Dromedary Camels, Africa). 

As of 11 June 2026, the WHO had reported a total of 2,637 laboratory-confirmed human cases have been reported - mostly from countries in the Arabian Peninsula - with an estimated case fatality ratio (CFR) of approximately 37%.   

But both the  EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016 and Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al., suggest that far more MERS-CoV cases have occurred than have been reported.

  

MERS-CoV clade B is most common on the Arabian peninsula, while Africa is dominated by clade C, which is thought to be less well adapted to human physiology.  Clade A hasn't been reported in humans or camels since 2015, and is now considered extinct. 

But over the past year at least two studies have reported evidence that clade B-like viruses (or clade B/C recombinants) may be circulating in Africa. Today's risk assessment cites:

• In Egypt, phylogenetic analyses of a camel-derived sample identified genome fragments clustering with clade B viruses from the Arabian Peninsula, circulating alongside endemic African clade C viruses (Gomaa, Edwards, Wang, Taweel, et al., 2025).

• In a separate study (Hassan et al., 2025), metagenomic sequencing of nasal swabs from camels imported from Sudan also detected MERS-CoV genome fragments clustering with clade B human and camel strains

In both cases, the available sequences were limited and less than 100% complete, and so they must be regarded as preliminary, and will require full-genome confirmation.

The 24-page  FAO–WHO–WOAH GLEWS+ assessment (below) reached three primary conclusions; the first two question only deal with the impact on dromedaries, while the third deals with the public health risk.

Confidence in the two camel specific answers is low, while the confidence in the public health question is moderate. 

The section discussing question 3, provides the following rationale (excerpt):

Once introduced into camels in the Nile Basin countries, the likelihood of MERS-CoV clade B spillover to occupationally exposed humans is assessed as very likely, reflecting the intensity of human-camel contact, weak and uneven implementation of biosecurity and hygiene measures and constraints in surveillance and early detection systems.

The consequences are assessed as moderate. MERS-CoV Clade B can cause severe disease in humans and is associated with a high case fatality ratio, particularly among those with underlying medical conditions, and immunocompromised individuals. 

In the absence of licensed vaccines for the general population or widely available specific treatments, spillover events have the potential to result in severe clinical outcomes, especially in settings with limited access to advanced healthcare. Healthcare-associated outbreaks also remain a concern where infection prevention and control measures are insufficient. However, despite its high replication competence, a substantial proportion of MERS-CoV infections are asymptomatic or mild.

Furthermore, sustained human-to-human transmission is generally limited and typically requires close and prolonged contact. Consequently, widespread community transmission is not expected. Overall, the public health risk of MERS-CoV clade B spillover from camel populations to humans exposed to camels or their products in the Nile Basin countries is assessed as high.

The level of confidence in the assessment is considered moderate, reflecting evidence of frequent human–camel contact and known zoonotic potential of MERS-CoV clade B, but also important uncertainties regarding the frequency of spillover events, the role of specific exposure pathways, and gaps in surveillance and epidemiological data from the Nile Basin region.

The full risk assessment is well worth reading in its entirety.