Preprint: Dairy Cows Infected with Influenza A(H5N1) Reveals Low Infectious Dose and Transmission Barriers

 

Credit EID Journal

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Today we have a preprint that suggests that a long-held belief about how HPAI H5 has been transmitting between dairy cows may be flawed, or at least incomplete. 

In the 15 months since dairy cattle were first reported to be infected with HPAI H5N1 in Texas, the USDA has confirmed 1,073 infected herds across 17 states, although limited testing and a focus almost solely on lactating dairy cows suggests the impact may be higher (see Nature: A Mathematical Model of H5N1 Influenza Transmission in US Dairy Cattle).

The assumption by the USDA has long been that the B3.13 genotype entered dairy cattle via a single spillover from birds - in the spring of 2024 in Texas - and was then spread to other states by the interstate transport of infected cattle.

Cow-to-cow transmission within these herds was quickly hypothesized to be due to contaminated milking machines, although other routes of infection could not be ruled out (see EID Journal: Persistence of Influenza H5N1 and H1N1 Viruses in Unpasteurized Milk on Milking Unit Surfaces).

Over the past year we've also seen sporadic spillovers of H5N1 into goats, alpacas, pigs, and most recently to sheep in both the UK and in Norway. Despite very limited surveillance,  hundreds of peridomestic animals (cats, foxes, mice, etc.) have been infected in and around dairy farms and in the wild.

Complicating matters further, last February, two states (Nevada & Arizona) reported dairy herds infected with a new H5N1 genotype (see APHIS Statement On HPAI Genotype D.1 In Arizona Dairy Cattle). 

APHIS described this as a `third spillover' and that it `. . . may indicate an increased risk of HPAI introduction into dairies through wild bird exposure.'

Today we have a preprint (albeit sporting an excellent pedigree, including Andrew Bowman & Richard Webby), which challenges the current hypothesis that bovine  HPAI is being spread primarily by contaminated milking equipment. 

While they confirmed that Bovine (B3.13) H5N1 efficiently infects the bovine mammary gland at very low infectious doses - and produces clinical disease and reduced milk production - they were unable to duplicate the spread of the virus via contaminated milking equipment under controlled experimental conditions.

 The authors wrote:

While contaminated milking equipment is strongly hypothesized to be the primary route of exposure on-farm5,6, our experimental findings did not confirm this, falling short of an explanation for the apparently frequent on-farm transmission.

While small sample sizes in experimental settings may limit the ability to observe transmission, this also raises important questions about whether real-world farm conditions present higher risks than can be reproduced in high-containment facilities.

Other agent, host, and environmental cofactors that might contribute to transmission cannot be ruled out and must be explored as this study demonstrates critical gaps in our understanding of transmission. 

While I've posted the abstract and a few excerpts, this is a fascinating report, and deserves to be read in its entirety.  I'll have a postscript after the break.

Dairy cows infected with influenza A(H5N1) reveals low infectious dose and transmission barriers

Andrew Bowman1, Carolyn Lee2, Natalie Tarbuck1, Hannah Cochran1, Bryant Foreman1, Patricia Boley1, Saroj Khatiwada1, Alok Dhakai1, Khadijat Adefaye1, Jennifer chrock1, Mohammad Jawad Jahid1, Thamonpan Laocharoensuk1, Raksha Suresh1, Olaitan Shekoni1, Erika Stevens1, Sara Dolatyabi1, Christina Sanders1, Elizabeth Ohl1, Devra Huey1, Juliette Hanson1, Renukaradhya Gourapura1, Richard Webby3, Cody Warren4, Scott Kenney1

This is a preprint; it has not been peer reviewed by a journal. https://doi.org/10.21203/rs.3.rs-6900680/v1

This work is licensed under a CC BY 4.0 License

Abstract

The discovery that highly pathogenic avian influenza A(H5N1) virus exhibits a strong tropism for the bovine mammary gland1–4 represents a major shift in our understanding of influenza A virus host range and tissue specificity.

We conducted a comprehensive series of experimental studies with influenza A(H5N1) B3.13 genotype in lactating dairy cattle to address several key questions related to the viral dose required to establish infection, routes of exposure that lead to transmission, and factors contributing to the morbidity and mortality observed on farms. We demonstrate that intramammary exposure to as few as 10 TCID50 is sufficient to establish robust infection, shedding of high viral titers in milk, and clinical mastitis.

Despite evidence of such a low infectious dose, we were unable to recapitulate transmission to sentinel cows via contaminated milking equipment and close contact with infected animals under experimental conditions. High-dose intramammary exposure to influenza A(H5N1) drives severe clinical outcomes and mortality observed in dairy cows on-farm, while respiratory and oral exposure are less likely to establish productive infection and associated morbidity.

This study challenges current hypotheses of influenza A(H5N1) transmission on dairy farms5,6, raising important questions about potential agent, host, or environmental cofactors that contribute to the spread of the virus.

        (SNIP)

DISCUSSION

In this study, we demonstrate that a low dose of virus is sufficient to establish robust intramammary infection, which may underlie the widespread and efficient transmission of influenza A(H5N1) in dairy herds.

However, sentinel cows repeatedly exposed to contaminated milking equipment and cohoused with infected cows did not become infected, indicating that cow-to-cow transmission observed on dairy farms may depend on factors that are not easily replicated under experimental conditions in high biocontainment research settings. 

(SNIP)

Although human-to-human transmission of influenza A(H5N1) virus has not been reported, the persistence of the virus in dairy cattle and evidence of mammalian adaptation, coupled with the broad and unprecedented host range, are alarming from a public health perspective. A second, separate introduction of the D1.1 genotype virus, primarily circulating in wild birds, was reported in dairy cows in early 2025. 

Unlike the B3.13 virus circulating in cattle, this D1.1 genotype has been associated with severe disease in humans, resulting in two deaths31–33—a highly concerning feature should this genotype continue to spread unfettered.

Further, the co-circulation of B3.13 and D1.1 viruses in dairy cows increases the risk of reassortment and viral evolution and complicates efforts to control the influenza A(H5N1) outbreak. Additional studies are needed to characterize the immune response and assess the level of protection following re-exposure to both homologous and heterologous influenza A(H5N1) viruses. The mechanism of transmission within and between dairy herds is a critical question that remains and urgently needs to be answered.

        (Continue . . . )

The fact that we are now 15 months into this crisis and still don't have a solid understanding of how the HPAI virus is transmitting among dairy cattle should give all of us pause.   

Testing of cattle remains limited, and is often at the discretion of the farm owner, many of whom are reluctant to cooperate over fears of economic losses, and the stigma of quarantine.

We've also seen farm workers reluctant to report illnesses, or refuse to be tested, over fears of losing their jobs (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA) or of an encounter with immigration officials. 

Reporting has slowed to a glacial pace, making it very hard to know exactly where the risks from H5N1 currently stand. 

While we've been lucky so far - and bovine H5N1 hasn't sparked a large-scale human outbreak - these viruses continue to evolve along numerous pathways, and what emerges tomorrow, or next year, may not be so constrained. 

Should that day ever come, we'll rue all of the days we squandered while we optimistically waited for the virus to `burn itself out'.

Aging Neurosci: Review - Infections with Chlamydia pneumoniae and SARS-CoV-2 and Alzheimer’s Disease Pathogenesis

 
 Potential neuroinflammatory outcomes following infection.

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In the decade following the 1918 influenza pandemic the world saw a secondary global rise of neurodegenerative diseases - including Parkinson's and what we would describe today as Alzheimer's Disease (AD) - that was dubbed Encephalitis lethargica (EL) (aka "sleeping sickness").

While some scientists believed (EL) was a rare sequelae of the 1918 pandemic virus, the exact cause remains unknown. A post-viral infection, however, remains a likely culprit (see Evidence for an enterovirus as the cause of encephalitis lethargica).

Regardless, millions died, or were institutionalized. 

 

Throughout history, there have been reports of other neurological outbreaks following severe epidemics, including febris comatosa which sparked a severe outbreak in London between 1673 and 1675, and following the 1889–1890 influenza (?) pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") was described in Italy.

Although the exact cause of the 1889-1890 pandemic remains unknown (candidates include H3N8, H2N2, and potentially, a SARS-like coronavirus), it is often cited as causing unusual neurological manifestations.

This history of post-pandemic neurological sequelae sparked discussions early in the COVID pandemic (see J. Neurology: COVID-19 As A Potential Risk Factor For Chronic Neurological. Disorders), and we continue to see worrisome signs today (see Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients).

Increasingly, we see concerns that neurodegenerative diseases may be caused - or at least, exacerbated - by past bacterial or viral infections (see Alzheimer's Society Infections and the risk of dementia)

A study published a little over two years ago in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, found statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.

Today we have an article published this week in Aging Neuroscience which reviews the evidence linking two respiratory pathogens (Chlamydia pneumoniae and SARS-CoV-2) to Alzheimer’s disease (AD) development and progression.

With the very strong caveat that the exact cause of Alzheimer's, Parkinson's, and other neurogenerative diseases are not yet known - and all are likely the result of multiple genetic and environmental factors - the role of infectious diseases is a hypothesis under serious investigation.

The author's of today's review paper offer a plausible hypothesis on how some types of viral and bacterial infections could potentially contribute to the pathogenesis of Alzheimer's Disease.

I've posted the link, and some excerpts, but you'll want to read review in its entirety.  I'll have a brief postscript after the break.

Infections with Chlamydia pneumoniae and SARS-CoV-2 and Alzheimer’s disease pathogenesis

Alexa Romanella, 1Maegan McCall2, Rachel Corwin1, Alaha Abdul Faruq1, Emily Lingo1, Sanya Bhambhani1, Christine J. Hammond3,

Introduction: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the world, but our understanding of causation is still lacking. A current evidence-based hypothesis proposes that certain infectious agents initiate the neurodegeneration consistent with AD. Two infectious agents correlated to AD pathogenesis are Chlamydia pneumoniae (Cpn), a respiratory obligate intracellular bacterium, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the COVID-19 pandemic. Both organisms may predispose susceptible populations to disease manifestations, such as AD.

Methods: This review focused on peer-reviewed original research and review articles evaluating the potential association of Cpn and SARS-CoV-2 with AD. Our focus included: genetic risk with expression of APOEε4 and other biomarkers common to AD including interleukin-6 (IL-6), chemokine ligand 2 (CCL2), neuropilin-1 (NRP1), and structural/functional aspects of the infectious processes and resultant neuroinflammation.

Results: Both Cpn and SARS-CoV-2 may infect the neuroepithelium of the olfactory system to enter the brain. Cpn binds to heparan sulfate proteoglycans for entry into mucosal cells. SARS-CoV-2 infects epithelia after binding to ACE2 receptors. Once inside the neuroepithelium, the pathogens may traffic to the olfactory bulbs. NRP1, an abundant receptor in AD, also potentiates SARS-CoV-2 infection. Furthermore, both pathogens may enter the systemic circulation for eventual entry through the blood brain barrier. The SARS-CoV-2 spike protein, in conjunction with CCL2, co-stimulates macrophages, resulting in IL-6 cytokine release. Likewise, Cpn infection leads to an increase of CCL2 and IL-6 cytokine release. The primary infection of either organism may lead to chronically elevated levels of IL-6 and secondary infection(s). Additionally, host APOEε4 expression appears to increase susceptibility to Cpn and SARS-CoV-2 infections.

Discussion: Cpn and SARS-CoV-2 may enter the brain through olfactory neuroepithelial cells and/or through the blood brain barrier. SARS-CoV-2 utilizes specific receptors for infection, while Cpn utilizes binding of proteoglycans. Neuroinflammation may be an outcome of infection with one or both organisms as observed by increased levels of CCL2 and IL-6 leading to AD pathogenesis. Genetic risk is noted for infection with both organisms with expression of APOEε4. Ongoing and future studies will further dissect mechanisms of infection with SARS-CoV-2 and Cpn as they may inform on causation and diagnostic factors for AD.

       (SNIP)

Infection with SARS-CoV-2 or Cpn may contribute to AD pathogenesis

While the exact pathology of AD is unclear, there is evidence to suggest that its development may be linked to inflammation of neuronal tissue, specifically in the limbic system.

There are many situations that can cause neuroinflammation, one being infection with microbes that are able to gain entrance to the CNS. We have described a few pathways by which Cpn and SARS-CoV-2 can gain entry to the CNS and proceed to promote inflammation via modulation of an inflammatory cascade.

We therefore propose that in certain settings, such as with aging and genetic predisposition, that infection with these pathogens may be a risk factor for the development or modulation of AD.

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As an EMT/Paramedic in the 1970s who saw a lot of senile dementia patients - and whose grandfather died of Parkinson's in the 1960s - I've often wondered about the potential link between the 1918 pandemic (when most of my patients would have been young adults or teenagers) and neurodegenerative diseases. 

Whether that question will be definitively answered before I exit this mortal coil remains to be seen.  

But recent studies suggest the fewer viral or bacterial assaults you endure, the less likely you are to develop a neurodegenerative disease. Which is one of the reasons why - in 2025 - I continue to mask up when in crowded public spaces and stay current with my flu and COVID vaccines. 

And quite honestly, I can't imagine changing that anytime soon. 

Virology: Assessment of the Public Health Risk of Novel Reassortant H3N3 Avian Influenza Viruses That Emerged in Chickens

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Although H5 and H7 viruses have sparked relatively small epidemics over the past two decades, over the past 130+ years, only H1, H2, and H3 viruses are known to have caused human influenza pandemics (see graphic above).  

While it is possible other subtypes reigned supreme before 1890, the assumption today is that H1, H2, and H3 viruses have a competitive edge against others like avian H5 and H7 (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).

This one of the reasons why we pay so much attention to zoonotic swine (H1, H2 & H3) flu viruses (see Emerg. Microbes & Inf.: Eurasian 1C Swine Influenza A Virus Exhibits High Pandemic Risk Traits).

But twice in my lifetime we've also seen avian influenza viruses reassort and spill over into humans, sparking deadly pandemics. 

• The first (1957) was H2N2, which According to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'

• In 1968 a novel H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 56 years later.

Over the past few years we've seen a number of concerning studies coming out of China (see EID Journal: Evolution of Avian Influenza Virus (H3) with Spillover into Humans, China) regarding the expansion of multiple H3Nx viruses in Chinese poultry (and occasional spillovers into humans).

A study published in late 2023 (see Emerg. Microb & Inf.: Emergence of Novel Reassortant H3N3 Avian Influenza viruses, China 2023), described a new reassortant H3N3 virus in Chinese poultry which included an HA gene from H3N8, an NA gene from H10N3, and internal genes from H9N2 (all zoonotic subtypes).

Despite this impressive pedigree, initially this reassortant H3N3 virus was reportedly not pathogenic in mice, bound preferentially to avian receptor cells, and lacked a number of key mammalian adaptations.

A study published a year later (see BMC Genomics: Evidence of an Emerging Triple-reassortant H3N3 Avian Influenza Virus in China) painted a far more concerning picture, finding it had acquired mutations that may` . . . increase viral resistance, virulence, and transmission in mammalian hosts.'

Last March, in Vet. Research: Emergence of a Novel Reassortant H3N3 Avian Influenza Virus with Enhanced Pathogenicity and Transmissibility in Chickens in China, the authors reported that H3N3 could:

• `infect and replicate in the upper and lower respiratory tract of BALB/c mice without prior adaptation'
• replicate `vigorously' within the chicken respiratory & digestive tracts and transmit efficiently and swiftly among chickens through direct contact
• `exhibited high and moderate stability in thermal and acidic conditions and efficient replication capabilities in mammalian cells'

While obviously still not ready for prime time, H3N3 appears to be making steady progress towards mammalian adaptation. Whether it is a true contender, or just another in a long-line of evolutionary stepping stones, remains to be seen. 

Today we have a risk assessment on this emerging subtype, which finds that this genetically diverse and continually evolving subtype already `. . . exhibits abundant genetic markers for mammalian host adaptation'.

This is a lengthy and detailed review of what is currently known about this subtype, and many will want to read it in its entirety.  I've only reproduced the abstract and a few excerpts below.  

I'll have a postscript after the break.

Assessment of the public health risk of novel reassortant H3N3 avian influenza viruses that emerged in chickens

Authors: Han Li , Qi Tong , Mengyan Tao, Jixiang Li, Haili Yu, Qiqi Han, Jiancheng Wu, Show All (19 Authors) , Honglei Sun

PDF/EPUB

ABSTRACT

Influenza A (H3N2) viruses are historically responsible for the 1968 Hong Kong flu pandemic. Since then, H3N2 has continued to circulate as a seasonal influenza virus in humans. Public health concerns were raised in 2022 when human infections with novel reassortant H3N8 influenza viruses originating from chickens were first reported in China.

Here, we conducted a systematic surveillance of H3 avian influenza viruses (AIVs) circulating in poultry and assessed the public health risk of emergent H3 reassortants. We found that H3 AIVs were prevalent in both ducks and chickens. Notably, in December 2022, a novel chicken-derived H3N3 subtype virus was identified, which gradually replaced the previously predominant H3N8 virus and became prevalent in chickens.

Genetic analysis demonstrated that the novel H3N3 virus is a triple-reassortment strain with the H3 gene segment from chicken H3N8 virus, the N3 gene segment from the H10N3 virus, and internal gene segments derived from H9N2 viruses.

Compared with chicken H3N8 and duck H3N3 viruses, the novel chicken H3N3 viruses produced higher yields and induced greater pathogenicity in human respiratory epithelial cells and mammalian models (mouse and ferret). Importantly, the chicken H3N3 viruses could be transmitted efficiently between ferrets through direct contact.

The polymerase activity of the chicken H3N3 viruses in mammalian cells was markedly increased by the PA gene originating from the H9N2 virus. Our findings indicate that the circulation of novel chicken H3N3 viruses poses a threat to both the poultry industry and human public health.

IMPORTANCE

The H3Ny subtype influenza A virus can infect a wide range of hosts. In addition to circulating among wild birds and poultry, the virus can also infect humans and a variety of mammals. Here, we found that H3Ny subtype AIVs were widely prevalent in domestic chickens and ducks.

Novel H3N3 reassortant viruses emerged as a result of the genetic reassortment of the chicken-derived H3N8 AIVs with H10N3 and H9N2 AIVs. The novel H3N3 subtype AIVs are gradually displacing H3N8 AIVs and becoming prevalent in chickens. Furthermore, these novel H3N3 AIVs exhibited enhanced infection ability and efficient transmissibility in mammalian models, indicating a growing potential public health risk.

 (SNIP)

In summary, our study revealed the emergence and increasing prevalence of H3N3 viruses in chicken populations, highlighting their enhanced transmissibility and pathogenicity in human respiratory epithelial cells and mammalian models compared to chicken H3N8 viruses.

Notably, H3N3 viruses demonstrated efficient direct-contact transmission in ferrets, indicating their potential for cross-species transmission.

Collectively, these findings suggest that H3N3 viruses might pose a risk to public health, emphasizing the urgent need for comprehensive surveillance and control of the spread of H3Ny reassortant viruses in poultry.

       (Continue . . . )

As always, H3N3 isn't a single viral threat, but rather a diverse and evolving array of similar viruses all sharing the same HA/NA gene types. The H3N3 viruses that have been collected and analyzed to date represent only a subset of what is likely circulating in the wild.  

While many of the findings cited above are of obvious concern, perhaps the biggest red-flag is just how much attention Chinese scientists are giving this novel subtype, and how quickly we are seeing reports published. 

This emerging subtype has obviously caught the Chinese scientific community's attention, which suggests we would do well to keep it on our radar as well. 

Viruses: The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023

 

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Over the summer of 2023 we saw two high-profile H5N1 outbreaks in domestic cats; one in Poland and the other in South Korea. Unlike the Polish outbreak - where details were slower to emerge - the South Korean outbreak was quickly linked to contaminated cat food. 

Both outbreaks occurred nearly a full year before the USDA added domestic cats to their Mammals With H5N1 list, which now contains 139 domestic cats, and scores of other wild and captive felines.

While felines had long been considered poorly susceptible to influenza A viruses (IAVs), in 2004 we saw the deaths of dozens of captive tigers who'd been fed H5N1 contaminated chicken. Since then we've learned that cats are susceptible to a wide range of IAVs (see A Brief History Of Avian Influenza In Cats).

In the Polish outbreak both indoor - and indoor/outdoor cats - across a wide swath of the country were affected (see map above). The authors of today's report summarized that outbreak:

The epizootic in Poland in 2023 was unprecedented in scale, with HPAI H5N1 virus infection confirmed in 29 domestic cats, one captive caracal, a few pet ferrets, and a dog [3,4,14,15]. However, the number of affected animals was likely higher, with cases reported nationwide.

The authors noted: All sequences carried mammalian-adaptive mutations in the polymerase gene, specifically PB2-E627K and PB2-K526R, associated with enhanced replication at lower temperatures [2,3,4,14,15].

 We've previously looked at these cases, including in:

Eurosurveillance: Two Papers On HPAI H5N1 clade 2.3.4.4b virus in cats, Poland, June to July 2023

Viruses: Natural Infection With HPAI H5N1 In Pet Ferrets - Poland, 2023

Microorganisms: Case Report On Symptomatic H5N1 Infection In A Dog - Poland, 2023

While some experts suspected H5N1 contaminated poultry had entered the food chain, Poland's MOA vigorously denied the claim (see Poland : Ministry of Agriculture Statement On H5N1 & Food Safety). In the end no single route of infection was ever identified. 

Instead, a combination of 3 different routes was suggested:

• Contaminated poultry meat

• Direct contact with infected birds

• Environmental contamination

Today we have a seroprevalence study of felines which was launched in the wake of the 2023 outbreak, that reviewed 835 cat serum samples submitted for routine bloodwork during June of 2023 and from cats not exhibiting influenza symptoms. 

Out of those 835 cat serum samples - 68 cats (8.1%) tested positive for influenza A virus antibodies in the primary screening (with 3 more suspected).  Of those 68 IAV positive samples, 23 were positive for H5-specific antibodies.   

Intriguingly, 2/3rds of the IAV positive samples were of a non-H5 origin, but further identification was beyond the scope of this study, and so we don't know if they were human or avian IAVs. 

While most documented feline H5N1 infections have proved fatal, a seroprevalence of 3% of H5 antibodies is significant, because it suggests these felines are survivors of a past H5 encounter.  

Which means that some mild, perhaps even subclinical, feline infections with the H5 virus are likely going unreported.  Due to its length, I've just posted the link, abstract, and a few excerpts.  

Follow the link to read the study in its entirety.  I'll have a postscript after the break. 

The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023

Anna Golke 1,,Tomasz Dzieciątkowski 2,Olga Szaluś-Jordanow 3,Michał Czopowicz 4,Lucjan Witkowski 4,Monika Żychska 4,Ewa Domańska 5,Dawid Jańczak 6,Tomasz Nalbert 4,Stephanie Lesceu 7,Marzena Paszkowska 8,Justyna Giergielewicz 8 and Tadeusz Frymus 3 D

Viruses 2025, 17(6), 855; https://doi.org/10.3390/v17060855

Published: 16 June 2025

Abstract

Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional epidemiological study to assess the seroprevalence of IAV, especially H5Nx, infections in domestic cats.

Eight hundred thirty-five serum samples collected in June 2023 were tested using a competitive ELISA for antibodies to IAV nucleoprotein. Positive or doubtful samples were further screened for H5-specific antibodies. The overall seropositivity for IAV was 8.5% (CI 95%: 6.8%, 10.6%; 71/835 cats), and 23/68 IAV-seropositive cats (33.8%) were also seropositive for H5 antigen. Multivariable analysis identified young age (≤8 years) and male sex as significant risk factors for H5 seropositivity, while non-H5-IAV seropositivity was more common in cats aged ≥12 years. 

These findings suggest different exposure pathways and host risk profiles for H5 and non-H5 IAVs and underscore the importance of enhanced surveillance in cats, particularly in regions affected by HPAI outbreaks. Given the susceptibility of cats to both avian and human IAVs, including subclinical infections, there is a theoretical risk for viral reassortment. Preventive measures, including vaccinating humans and restricting outdoor access for cats, should be considered in endemic areas.

(SNIP)

The observed anti-H5 seroprevalence in Polish domestic cats raises essential questions about the likely sources of exposure, which we cannot definitively answer. It is possible that outdoor cats encounter infected birds or other wild animals. Since well-fed domestic cats often leave their prey uneaten, owners may remain unaware of such interactions [29].

Our findings suggest a need to reconsider the role of companion animals as potential intermediate hosts in the ecology and evolution of IAVs. The U.S. CDC’s Influenza Risk Assessment Tool (IRAT) and the WHO’s Tool for Influenza Pandemic Risk Assessment (TIPRA) estimate a low pandemic risk for H5N1 clade 2.3.4.4b [39]. However, these tools assess only the current risk and do not predict the virus’s future evolutionary trajectory or reassortment potential. Considering that on March 24, the UK Department for Environment, Food & Rural Affairs and the Animal and Plant Health Agency issued a statement confirming that the Chief Veterinary Officer had identified a case of avian-origin influenza (H5N1) in a sheep in Yorkshire, it is likely that we will soon have to contend with new routes of virus transmission in Europe [40].

We now have more information about the global distribution, host range, and genetic diversity of the H5N1 virus than for most other zoonotic pathogens. So far, most surveillance systems remain biased toward symptomatic or dead animals. In contrast, the COVID-19 pandemic has underscored that subclinical infections play a substantial role in pathogen transmission and contribute to maintaining epidemics at the population level [41].

In light of the above, future research should prioritize the following: (i) including feral and free-roaming cat populations in serological studies; (ii) confirming ELISA results with other methods to determine subtype-specific exposure; and (iii) investigating behavioral risk factors and their relation to infection dynamics through case–control or cohort designs. These steps will help address current methodological limitations and enhance our understanding of IAV ecology in companion animals.

        (Continue . . . )

While the CDC continues to rank the risk to general public from avian flu as low, they do provide very specific guidance to pet owners on how to limit their risk of infection from the virus.

Bird Flu in Pets and Other Animals

Key points

• Avian influenza viruses, which can cause bird flu illness, mainly infect and spread among wild birds and domestic poultry. However, some avian influenza viruses can infect and spread to other animals, including pets.
• While it is unlikely that you would get sick with bird flu from direct contact with your infected pet, it is possible.
• If your pets (including pet birds, cats or dogs) go outside and eat or are exposed to sick or dead birds, dairy cows, or other animals infected with avian influenza viruses, they could become infected.
• Prevent pets from interacting with wild birds, backyard poultry, cows, or other outdoor animals.
• Keep pets away from clothes, surfaces or environments that could potentially be contaminated with avian influenza viruses.
• Do not feed pets raw pet food or unpasteurized (raw) milk.

Prevention measures for people

• As a general precaution, people should avoid direct contact with wild birds and observe wild birds only from a distance.
• Pet owners should prevent their pets (including pet birds, dogs, and cats) from interacting with potentially infected dairy cows, backyard flocks, and wild animals.
• Pet owners should not let their pets consume raw pet food or raw (unpasteurized) milk.
• Pet owners should prevent their pets from touching clothes or other surfaces or environments that could potentially be contaminated with avian influenza viruses.
• Do not touch sick or dead birds, their feces, litter, or any surface or water source (ponds, waterers, buckets, pans, troughs) that might be contaminated with their saliva, feces, or any other bodily fluids without wearing PPE.

BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients

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In the opening months of the COVID pandemic we looked at a study (see JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease) which reported more than 1/3rd of a study group (n=214) hospitalized in Wuhan, China showed signs of neurological involvement.

Neurological manifestations ranged from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.). 

While this early report from Wuhan indicated an unusually high percentage of patients with neurological symptoms, it isn't unheard of that a severe respiratory infection can cause neurological complications. 

Two years previously, in Neuroinfluenza: A Review Of Recently Published Studies, we had looked at rare instances of neurological manifestations associated with with seasonal (and avian) influenza infection.

Credit CDC 2018 COCA Call On Severe Influenza

Over that first summer we saw a number of studies on neurological manifestations in COVID patients - with some warning of potential long-term sequelae - including an enhanced risk of Parkinson's disease.

• In mid-June, in The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?, we revisited the mysterious neurological epidemic that began around the time of the 1918 pandemic, and continued on for a decade.
• A couple of weeks later, in The Lancet: Yet Another Study On Neurological Manifestations In Severe COVID-19 Patients, we looked at report published in The Lancet Psychiatry, that described 153 COVID-19 cases treated in UK hospitals which found a wide range of neurological and psychiatric complications affecting both younger and elderly patients.
• In July I blogged on a 63-page report from the Journal Brain called The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.
• In August, in J. Neurology: COVID-19 As A Potential Risk Factor For Chronic Neurological. Disorders, we revisited the growing concerns over the long-term neurological impacts of COVID-19 infection.
• Also that month (see Parkinsonism as a Third Wave of the COVID-19 Pandemic?) we looked at a Review Article, published in the Journal of Parkinson's Disease, that examined the parallels between COVID-19 and epidemics of the past, and the potential for seeing a new wave of neurological disorders.

By November of 2020 it had become apparent that COVID caused more than just a nasty respiratory infection; that it could affect many other parts of the body, and sometimes leave behind a wide range of post-covid symptoms (see CDC: Late Sequelae of COVID-19 (Long COVID).

Although the degree of impairment can vary widely, and many of these impacts may lessen or resolve over time, we've seen studies suggesting that as many as 1 in 5 adults (20%) experience some type of `Long-COVID' sequelae.

Studies suggest that Post-COVID sequelae also includes increased cardiac risks, increased new onset hypertension, an increased risk of developing diabetes, strokes, and kidney disease/injury. 

None of this information was exactly welcomed by governments eager to `move past' the pandemic - and a public desperate for a return to `normalcy' - so much of the research over the past 4 years has been dismissed or ignored.

Despite the accumulating evidence to the contrary - to most people - COVID is now regarded as little more than a `bad cold'.

COVID vaccine uptake has plummeted, despite research showing it can provide significant protection against both severe outcomes and `Long COVID' (see ECDC Rapid Review: Does COVID-19 Vaccination Reduce the Risk and Duration of Post COVID-19 Condition?).

While I could wax apoplectic for hours on this topic, today we've an impressive Systematic Review & Meta-analysis based on more that 4 million patients, which finds that neurological symptoms are both common and persistent in COVID-19 survivors.

This is, as you might imagine, an extensive review and its 16-page PDF deserves careful reading. But briefly, they report fatigue affecting over 40% of patients and memory disorders affecting nearly 30%, at least 6 months post infection. 

There is obviously a great deal to take in, so follow the link to read this review in its entirety.  I'll have a brief postscript when you return. 

Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients
Toka Elboraay, Mahmoud A. Ebada, Maged Elsayed, Heba Ahmed Aboeldahab, Hazem Mohamed Salamah, Omar Rageh, Mohamed Elmallahy, Hadeer Elsaeed AboElfarh, Lena Said Mansour, Yehia Nabil, Ahmed Khaled Abd Eltawab, Hany Atwan & Souad Alkanj

BMC Neurology volume 25, Article number: 250 (2025) Cite this article

Abstract

Background

Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

Methods

A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.

Results

The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.

Conclusions

Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.

Registration and protocol

This meta-analysis was registered in PROSPERO with registration number CRD42024576237.

       (SNIP)

Conclusion

In conclusion, this meta-analysis highlights the significant prevalence of long-term neuropsychiatric symptoms associated with COVID-19, including fatigue, depression, anxiety, cognitive impairment, sleep disturbances, and headaches.

These persistent issues underscore the need for healthcare systems to prioritize mental health and cognitive care for post-COVID-19 patients. Comprehensive, multidisciplinary strategies that address both physical and mental health are essential to improve patient outcomes and quality of life. Such efforts will support the development of targeted treatments, mitigating the pandemic’s enduring impact on mental health and enhancing overall wellbeing.

        (Continue . . . )

Although this review focuses on observed (or reported) post-COVID neurological manifestations, the authors do discuss the potential for seeing neurodegenerative diseases develop over a longer time period.

Our findings indicated that 27.8% of 1,299,214 patients experienced memory problems, a prevalence significantly higher than the 17.5% reported by Zeng et al. (2023) among 7,322 patients. This elevated prevalence may stem from multiple interconnected mechanisms, including neuroinflammation, disrupted neurotransmitter activity, and irregular sleep patterns, all known to impair hippocampal function. The hippocampus is vital for memory consolidation, learning, and neurogenesis, specifically through the production of neural stem cells in the dentate gyrus.

However, this brain region is particularly vulnerable to neurodegenerative processes and psychiatric disorders, which may be amplified by SARS-CoV-2 infection. Evidence suggests that the hippocampus is a primary target of the virus’s effects, contributing to post-infection memory loss through mechanisms such as oxidative stress, cytokine-driven inflammation, and vascular damage [160, 165, 180].

Two years ago we looked at a study (see Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks), which found statistical linkage between viral illnesses and developing neurodegenerative diseases in the future.

Even if these worst-case neurodegenerative impacts from COVID never materialize, there are other viruses with pandemic potential - including H5N1 - which have been repeatedly linked to neurological impacts (see here, here, here, and here).

Making it imperative that we take the lessons from COVID seriously, else we risk far more damage from the next global health crisis.

Washington DOH Reports 25-fold Increase In Pertussis Cases in 2024 over 2023

 

#18,758

Pertussis, or `whooping cough’ was once a major childhood scourge in the United States, with more than a million cases reported between 1940 and 1945, resulting in thousands of deaths.

All that began to change with the introduction of a whole cell Pertussis vaccine (DTP) in the mid-1940s.  By 1960, the number of Pertussis cases in the United States had dropped to about 15,000 cases a year – a 95% reduction over 20 years. 

Rates dropped another 70% over the the ensuing decade (see chart above), and throughout the 1970's, 1980's and 1990's remained relatively low. 

The DTP vaccine, while highly effective, was blamed for a variety of adverse reactions, prompting a move away from whole cell pertussis vaccines to safer – but less broadly protective  - acellular vaccines in the 1990s (DTaP). 

Up until the early 2000's, Pertussis - very much like measles - was well controlled in the United States due to a high uptake of childhood vaccines. But faith in vaccines has eroded over the past 20 years - largely due to the power of social media - and as a result both diseases have made a come back. 

Although yearly outbreaks are highly variable, in 1992 the U.S. reported 4,082 cases while 20 years later (2012) they reported 48,277; the worst year since 1955. In 2019 - before COVID - the U.S. reported > 18,000 cases. 

While social distancing and PPE use during COVID slowed spread of Pertussis, since 2023 it has been rising again. On Friday the Washington State DOH released the following report, citing a 25-fold increase in Pertussis cases in 2024 (over 2023), and early indications that 2025 is on target to exceed last year's numbers. 

For immediate release: June 13, 2025 (25-082)

Washington sees 25-fold increase in whooping cough cases in 2024 compared to previous year 

Contact: DOH Communications 

 
Vaccination coverage rates among 19–35-month-olds decreased from 73% in 2019 to 65% in 2024

OLYMPIA – Washington state experienced a dramatic surge in whooping cough cases in 2024, with 2,261 confirmed and probable cases reported – a staggering 25-fold increase from 87 cases recorded in 2023, according to preliminary data released in the Washington State Department of Health (DOH) Annual Pertussis Summary. Additionally, as of May 31, there have already been 1,314 cases reported statewide this year.

What is Whooping Cough?

Pertussis, commonly referred to as whooping cough, is a bacterial disease which can cause cold-like symptoms that can turn into severe coughing spells. Severe complications can include apnea (temporarily stopping breathing), pneumonia, convulsions, collapsed lungs, rib fractures, and brain damage.

The disease is most dangerous for infants under a year of age who may struggle to breathe and can turn very pale, or even blue from not getting enough air. In severe cases, infection lead to death. Tragically, in 2024, the state reported its first whooping cough-related death since 2011— a reminder of the disease’s potential severity.

Whooping cough symptoms usually start 5 to 21 days after exposure. Whooping cough is generally treated with antibiotics. It’s important to start treatment as soon as possible to help keep the disease from spreading to others. Early treatment can also make the symptoms end sooner and be less severe.

Vaccination is the best defense against whooping cough

DOH strongly encourages everyone to stay up to date on their whooping cough vaccinations, especially those at higher risk of serious illness or those who are in close contact with them. This includes:Infants under 1 year old. Pregnant people, especially those in the third trimester. Families and caregivers of infants and young children. People with weakened immune systems or chronic respiratory illnesses. Older adults, especially those 65 and older who are more susceptible to pneumonia.

For more information, visit DOH’s Pertussis (Whooping Cough) web page where answers to frequently asked questions are also available.

Two weeks ago PAHO.org reported:

In the United States of America, between EW 1 and EW 18 of 2025, 10,062 confirmed and probable cases of pertussis, including five deaths (11), have been reported. This is the second year with the most cases reported since 2020, after 2024 in the country (2, 11).

Of the states with confirmed and probable cases of pertussis, those with the highest number in 2025 are Washington (n= 1,067 cases), Oregon (n= 723 cases), and California (n= 590 cases) (11).

The most affected age groups are among the 11 to 19 years of age, representing 31% and the 1to 6 years of age representing 24%. Deaths were mainly reported in children under 1 year of age (n= 4 fatal cases) (11).

Since Pertussis tends to spread most effectively during the warm weather months (June-Nov), we could be on track for beating last year's tally (n=35,493).

While reliable numbers are hard to find, globally tens of millions of cases occur every year, with hundreds of thousands of lives lost. 

Two years ago, as part of my Personal Pre-Pandemic Plan, I updated my (long overdue) Tdap vaccine. While most people think of whooping cough as only a concern for infants and toddlers, it can be quite debilitating (and persist, often for weeks) for anyone of any age.

Make sure you and your family are up to date with whooping cough vaccination to help protect against this disease.

 
As a child of the 1950s I sometimes find myself yearning for the `good old days', but there are some aspects of life 70 years ago (e.g. polio, measles, whooping cough, smoking, drunk driving, driving without seatbelts, etc.) that are not worth reviving.