Taiwan CDC: Letter To Doctors on Locally Acquired H7N7 Case

 

#19,111 

Six days ago, in Taiwan CDC: Human Infection with a Novel H7 Avian Virus, we saw the first locally acquired human H7 influenza infection in Taiwan. The following day, that virus was further identified as H7N7.

While this appears to be an isolated incident, cases like this may happen more often than we are aware simply because the index of suspicion is generally low, infections can be mild or moderate, and most testing outside of the hospital doesn't identify the subtype. 

It often requires a bit of luck for these cases to be identified. Two years ago the ECDC issued guidance for member nations on Enhanced Influenza Surveillance to Detect Avian Influenza Virus Infections in the EU/EEA During the Inter-Seasonal Period.

In that summary, the ECDC pointed out:

Sentinel surveillance systems are important for the monitoring of respiratory viruses in the EU/EEA, but these systems are not designed and are not sufficiently sensitive to identify a newly emerging virus such as avian influenza in the general population early enough for the purpose of implementing control measures in a timely way.

While there's no quick fix for this problem, a reminder to doctors to be vigilant and to raise their index of suspicion when examining patients with acute respiratory symptoms, can increase the odds of detection. 

Today, in their first update on this case since last Friday, Taiwan's CDC has released the following (translated) letter to local doctors.  

I'll have a bit more after the break.

The Centers for Disease Control (CDC) has confirmed its first locally acquired case of H7N7 influenza A 

Doctors are urged to be vigilant and immediately report and test any suspected cases (CDC Circular No. 605 to the Medical Profession).
Release Date: 2026-04-08

Dear medical professionals nationwide,

the Centers for Disease Control (CDC) announced its first locally acquired case of H7N7 influenza A on April 3rd of this year (2023). The case involves a man in his 70s who works in poultry farming and has a history of chronic illness. He developed symptoms of runny nose, cough, and body aches on March 20th and sought medical attention at a hospital on March 22nd due to fever, where he was admitted to the hospital on the same day. Imaging examination revealed pneumonia.

Based on the clinical symptoms and the patient's contact history, the doctor reported the case as a novel influenza A virus and administered antiviral medication. Further testing by the CDC confirmed the patient's sample as H7N7 influenza A virus, a low pathogenic avian influenza virus (LPAI), which remained sensitive to antiviral drugs. The patient's condition improved, and two subsequent tests were negative. He was released from isolation on April 3rd of this year.

To prevent the spread of novel influenza A, physicians are urged to remain vigilant and conduct thorough "TOCC" inquiries during consultations (including travel history, occupation, contact history, and whether there has been any clustering).

If a case simultaneously presents with both "acute respiratory infection, with clinical symptoms possibly including fever (≥38℃), cough, etc." and "clinical, radiological, or pathological findings showing parenchymal lung disease," and has had close contact with a highly probable or confirmed case with symptoms within 10 days prior to symptom onset, has a travel or residence history in areas with novel influenza A outbreaks, or has had exposure to birds or pigs or visited bird or pig-related locations, then the case meets the reporting criteria for novel influenza A.

Reporting and specimen collection should be conducted as soon as possible according to the "Novel Influenza A Reporting Definition and Specimen Collection and Submission Procedures." Guidelines regarding the definition of novel influenza A cases and prevention measures are available on the Centers for Disease Control and Prevention website (http://www.cdc.gov.tw).

Thank you for joining us in protecting the health and safety of the public.

While perfectly reasonable given the current threat level - and the practical limitations of subtype testing in an outpatient clinical setting - this level of surveillance has a fairly low probability of picking up sporadic mild (or even moderate) novel flu cases in the community. 

Three years ago, in UK Novel Flu Surveillance: Quantifying TTD, we looked at the UKHSA's Technical Briefing #3, which found that it might take weeks - and hundreds of cases - before community spread of a novel flu could be confirmed using standard surveillance.

This is their `best case' R₀ 1.2 scenario

In response to the recent rise in spillovers of novel influenza A to humans, we've seen documents issued by the CDC (see CDC HAN: Accelerated Subtyping of Influenza A in Hospitalized Patients) and the ECDC (see ECDC: Updated Reporting Protocol for Zoonotic Influenza Virus) urging more aggressive testing; although these represent advisory - not regulatory - guidance.

Again last fall, in NAS : Diagnostic Tools, Gaps, and Collaborative Pathways in Human H5N1 Detection (Rapid Expert Consultation), we looked at many of the challenges inherent in detecting community cases of novel influenza. 

While it is certainly worth looking for, the reality is we'll have to get very lucky if we hope to detect the early spread of a novel flu virus in the community. 

Preprint: Bovine H5N1 Influenza Viruses Have Adapted to More Efficiently Use Receptors Abundant in Cattle

 

Positively selected mutations in the cattle H5N1 head domain
are reaching fixation as the virus continues to circulate.

#19,110

We've a fascinating, albeit somewhat technical preprint this morning, which identifies two HA mutations (D104G & V147M) that have become `fixed' and dominant in B3.13 H5N1 isolates (see graphic above) in the two years since the first spillover into Texas cattle. 

While these mutations (and others) have been previously elucidated (see Emergence of Antigenic Variants in Bovine H5N1 Influenza Viruses), today's paper links these changes to the virus's successful use of a different type of receptor cell (NeuGc); one that is not found in humans or birds, but is present in cattle and some other mammals. 

The authors write: 

Whilst humans and birds contain only a single type of sialic acid, N-acetylneuraminic acid (NeuAc), that is usable by influenza viruses 8-10, many mammalian species contain a second type of sialic acid, N-glycolylneuraminic acid (NeuGc). 

       (Snip) 

In several other influenza host species, such as pigs 14,15 and horses 16, high expression of CMAH in tissues results in the display of NeuGc on glycans.   

Most influenza viruses preferentially bind to sialylated glycans terminating in NeuAc, and, at best poorly use NeuGc-containing glycans as a receptor 17. However, a now extinct equine H7N7 virus showed a strong preference towards NeuGc 17,18.79 

While the B3.13 genotype still retains its strong affinity for NeuAc‑type (avian‑like α2,3‑linked sialic acid) receptors, it has found an alternative sialic acid in cattle it can bind to (NeuGc). 

Interestingly, these changes have not been observed in the D1.1 genotypes detected in cattle (see USDA APHIS Reports Wisconsin Dairy Herd Infected With Genotype D1.1). 

Today's study has an impressive pedigree, featuring such familiar names as Thomas Peacock, Wendy Barclay, and Ian H Brown.  I've only reproduced the abstract and a brief excerpt, so follow the link to read it in its entirety.

I'll have a bit more after the break.

Bovine H5N1 influenza viruses have adapted to more efficiently use receptors abundant in cattle
Jack A. Hassard,Jiayun Yang,Bernadeta Dadonaite, Jonathan E. Pekar, Jin Yu, Samuel A. S. Richardson, Rute M. Pinto, Kristel Ramirez Valdez, Philippe Lemey, Jessica L Quantrill, Jinghan Xue, Tereza Masonou, Katie-Marie Case, Jila Ajeian, Maximillian N.J. Woodall, Rebecca A. Ross, Nicolas Hudson, Kan Zhong, Hongzhi Cao, Samuel Jones, Hannah J. Klim, Brian R. Wasik, Desi N Dermawan, Jean-Remy Sadeyen, Dirk Werling,Dylan Yaffy, Joe James, Alessandro Nunez, Paul Digard, Ian H Brown, Daniel H. Goldhill, Pablo R. Murcia,Claire M. Smith, Yan Liu, Jesse D. Bloom, Munir Iqbal,Wendy S. Barclay, Stuart M. Haslam, Thomas P. Peacock

doi: https://doi.org/10.64898/2026.04.02.715584
This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF

Abstract

Sustained mammal-to-mammal transmission of high pathogenicity H5N1avian influenza viruses is reshaping the host range of these pathogens. One of the longest-running mammalian transmission chains involves the B3.13 genotype circulating in U.S. dairy cattle which was detected early in 2024. Genomic analysis revealed selection and rapid fixation of haemagglutinin mutations D104G and V147M. 

We demonstrate, via glycomic profiling, that bovine tissues, including the mammary gland, are enriched in N- and O-linked glycans capped with N-glycolylneuraminic acid (NeuGc), a sialic acid absent in humans and birds, which instead express only N-acetylneuraminic acid (NeuAc). 

Early cattle H5 viruses poorly recognized NeuGc, but D104G and V147M enabled efficient engagement of both NeuAc- and NeuGc-containing receptors. 

These mutations enhanced replication in bovine mammary tissue without major attenuation of replication in human lung and primary nasal epithelial cells. NeuGc-driven receptor adaptation therefore promotes viral fitness in cattle while potentially limiting immediate zoonotic risk. Deep mutational scanning further identifies alternative haemagglutinin substitutions that confer NeuGc usage and represent surveillance markers for emerging cattle H5 lineages.

       (SNIP) 

Together, these findings suggest that host-specific modifications of sialic acids can act as powerful evolutionary filters shaping influenza receptor usage during mammalian emergence. Incorporating this broader glycan diversity into surveillance frameworks may therefore improve our ability to anticipate host shifts and assess zoonotic risk as influenza viruses continue to expand into new mammalian reservoirs. 

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While the long-term impact all of this is difficult to predict, the glass-half-full interpretation is; the B3.13 lineage is currently adapting more towards bovine than human hosts.

So far, however, these mutations have only widened the ways that cattle can be infected, and haven't substantially reduced binding to NeuAc-containing receptors.  

The most remarkable thing is how quickly B3.13 has developed NeuGc compatible mutations and has turned them into a fitness advantage. We are witnessing active and robust viral adaptation in cattle, not just passive spillover from birds.

Yet surveillance and testing of livestock remains suboptimal, and in some regions, non-existent. 

While ignorance may be bliss in the short run, it can prove costly over time (see WPRO Table-Top Exercise Crystal: A `Bovine' Novel Flu Outbreak Scenario). 

The Lancet: Long COVID and Risk of Incident Cardiovascular Disease

Atrial Fibrillation 

#19,109

During the opening salvo of the COVID pandemic we saw an abrupt increase in out-of-hospital cardiac arrests; in early April 2020, the New York Fire Department reported a 400% increase in sudden cardiac arrest deaths (see NBC affiliate Massive Spike in NYC ‘Cardiac Arrest’ Deaths Seen as Sign of COVID-19 Under counting).

While most of these cases were never tested for COVID-19, this trend became so pronounced that the city ordered new Standards Of Care During A Pandemic: CPR & Cardiac Arrest, limiting the use of CPR in the field. 

Two months later, JAMA published an original investigation which found  10-fold increase in out-of-hospital cardiac arrests in New York City during the peak of their COVID-19 epidemic.

By mid-summer of that year, it was apparent that COVID was more than just a respiratory virus (see Nature Med. Review: Extrapulmonary manifestations of COVID-19), and can cause blot clots, along with severe cardiovascular damage. 

That first summer we saw this cautionary editorial published in JAMA.

Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter?
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575

Since then, studies showing post-acute impacts of COVID infection have exploded, with many citing repeated COVID infections as increasing the risk of long-term health damage. A few (of many) include:

EID Journal: Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection

Nature: Long-term Cardiovascular Outcomes of COVID-19

AHA: COVID-19 May Trigger New-Onset High Blood Pressure

NIH: Study Shows SARS-CoV-2 Infects Coronary Arteries, Increases Plaque Inflammation

EHJ: Accelerated Vascular Ageing After COVID-19 Infection: The CARTESIAN Study

While `Long COVID' and PASC (Postacute Sequelae of COVID) are now officially recognized conditions, researchers are still unravelling their impact.

Today we've a study from Sweden's Karolinska Institutet  which links `Long COVID' to new or emerging (incident) cardiovascular disease.

First the study, then a link and some excerpts from a press release, after which I'll return with a postscript.

Long COVID and risk of incident cardiovascular disease: a prospective cohort study using the Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) cohort

Pia Lindberga,b Pia.lindberg@ki.se ∙ Samuel Wiqvistg ∙ Maria Juszczykc,h ∙ Seika Leed ∙ Marta A. Kisield ∙ Caroline Wachtlere,f ∙ et al.  

Summary

Background

Long COVID has emerged as a global health challenge, with increasing evidence of cardiovascular sequelae. Most previous studies have focused on hospitalised cohorts, whereas cardiovascular risk in community-managed long COVID cases remains less explored. We aimed to investigate the incidence of major cardiovascular events in individuals with long COVID compared to those without long COVID in a large population-based setting.

Methods

Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) is a population-based cohort that covers all providers of healthcare for around 2.5 million residents in Stockholm County. Individuals aged 18–65 years with a physician-assigned long COVID diagnosis (ICD-10: U09.9) between October 2020 and January 2025 were identified. Exclusion criteria were hospitalisation for acute COVID-19 or pre-existing cardiovascular disease. Cox proportional hazards models estimated the effect of long COVID on a composite cardiovascular outcome (myocardial infarction, heart failure, cardiac arrhythmias, stroke, peripheral arterial disease), adjusting for demographic, lifestyle, and mental health factors.

Findings

Among 1,217,693 individuals, 8999 (0.7%) had long COVID diagnosis (66% women). Cumulative incidence of any cardiovascular event was higher in long COVID group (women 18.2%, men 20.6%) compared with control group (women 8.4%, men 11.1%). In a fully adjusted model, long COVID was associated with the composite cardiovascular outcome (women HR 2.06, 95% CI 1.92–2.22; men HR 1.33, 1.20–1.48), cardiac arrhythmia (women HR 3.11, 2.85–3.39; men HR 1.61, 1.41–1.85), and coronary artery disease (women HR 1.25, 1.04–1.52; men HR 1.26, 1.05–1.51). Heart failure incidence was elevated in women only (HR 1.25, 1.00–1.55), as also was peripheral artery disease (HR 1.25, 1.05–1.50). Long COVID was not associated with stroke in either sex.

Interpretation

Long COVID is associated with increased risk of incident cardiovascular disease, particularly cardiac arrhythmias, heart failure, and coronary artery disease. These findings underscore the need for systematic follow-up and integration of long COVID into cardiovascular risk assessment.

        (SNIP)

Discussion

This population-based cohort study demonstrates that individuals who developed long COVID after mild-to-moderate infection have an elevated risk of future cardiovascular disease analysed as a composite outcome. In particular, cardiac arrhythmias demonstrated markedly increased incidence in women with long COVID, although both sexes were affected. Risk of coronary artery disease was also elevated and in women and men, while heart failure and periphery artery disease were significant in woman patients with long COVID only. 

These findings are consistent with previous studies showing increased risk of cardiovascular sequelae in long COVID-19, including studies in non-hospitalised populations.2,4,17 The magnitude of excess risk for arrhythmias (HR ∼3.1 in women; HR ∼1.6 in men) is in agreement with earlier epidemiological and clinical research.3,7,18

These findings suggest an elevated burden of cardiovascular morbidity in individuals with long COVID, even in the absence of acute infection requiring hospitalisation.

        (Continue . . . )

 

Long COVID associated with increased risk of cardiovascular disease

People with long COVID are at increased risk of developing cardiovascular disease, according to a new study from Karolinska Institutet published in eClinicalMedicine. The results show that the risk of conditions such as cardiac arrhythmias and coronary artery disease is higher even among those who were not hospitalised during the acute infection.

(SNIP)

 During the follow-up period of around four years, people with long COVID were more likely to suffer from cardiovascular disease: 18.2 per cent of women and 20.6 per cent of men experienced some form of cardiovascular event, compared with 8.4 per cent of women and 11.1 per cent of men in the group without long COVID.

When the researchers then adjusted the results for factors such as age, socio-economic status and other known risk factors, the differences remained. Women with long COVID had just over twice the risk of receiving a cardiovascular diagnosis compared with women without long COVID. Men had approximately a third higher risk.

“We found that cardiac arrhythmias and coronary artery disease were more common among both women and men with long COVID. In women, there was also an increased risk of heart failure and peripheral vascular disease.

(Continue . . . )

Despite the preponderance of evidence enumerating the long-term negative health consequences of SARS-CoV-2 infection, much of the world now considers COVID be no worse than the catching `common cold', and that the real health risk lies in taking the vaccine.

As a result, uptake of the vaccine has plummeted, and few bother to take any precautions against infection. 

A recent study (see PLoS Med.: Association Between COVID-19 Vaccination and Sudden Death in Apparently Healthy Younger Individuals) found no evidence that COVID-19 vaccines increase the risk of sudden cardiac death in young healthy adults, but they did find a strong link between recent COVID infection and an increased risk of sudden cardiac death.  

But since they don't reflect popular opinion, these types of studies tend to be ignored by the media, and by the general public.

Emerg Microbes & Inf: Antiviral Activities of Multiple Antivirals Against HPAI H5N1 in Vitro and in Mice

CDC Influenza Antiviral Medications: Summary for Clinicians - Jan 2026

#19,108

For Americans (and indeed, for much of the world), our first line antiviral against severe influenza is oseltamivir (aka `Tamiflu'), an antiviral which was developed in the late 1990s.

There are other options (e.g. inhaled zanamivir, or 1-dose oral baloxavir, etc.), but they are not only more expensive, they are in far shorter supply. While the U.S. government doesn't release exact numbers, oseltamivir reportedly makes up well over 90% of all (SNS) stockpiled influenza antivirals.

None of these drugs are a panacea against influenza infection, but they are expected to reduce the severity and duration of infection; assuming they can be delivered to the patient in the first 24-48 hrs of infection.

How well they might work against a pandemic avian flu strain, like H5N1, isn't really known, particularly the standard 5-day (B.I.D) treatment course of oseltamivir or the 1-dose treatment with Baloxavir.  

We've seen concerns raised over the effectiveness of oseltamivir, including a year ago in St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk; excerpt below:

Our evidence suggests that it is likely going to be hard to treat people severely infected with this bovine H5N1 bird flu strain,” said corresponding author Richard Webby, PhD, St. Jude Department of Host-Microbe Interactions. “Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers’ exposures, for example, may be the most effective interventions.”

“In general, baloxavir [Xofluza] caused a greater reduction in viral levels than oseltamivir [Tamiflu], but neither was always effective,” said first author Jeremy Jones, PhD, St. Jude Department of Host-Microbe Interactions.

Last January, in Nature Comms: Oseltamivir and Baloxavir Monotherapy and Combination Therapy Efficacy Against Clade 2.3.4.4b A(H5N1) Influenza Virus Infection in Ferrets, we saw a CDC study which looked at both mono and combination therapy with oseltamivir and baloxavir in ferrets infected with H5N1 (genotype D1.1).

In short, they found:

• Ferrets infected with H5N1 D1.1 and treated with oseltamivir saw little or no clinical or virologic benefit compared to no treatment, with persistent high fevers, weight loss, and systemic viral replication.
• Ferrets treated with Baloxavir saw significantly less fever, weight loss, and viral replication. Some ferrets, however, saw a late rise in fever (after 4 days) and viral shedding, suggesting a viral rebound. 
• Ferrets treated with both drugs saw similar clinical protection to baloxavir alone, but did not show signs of rebound. 

Note: Ferrets are a good, but not perfect, proxy for humans in influenza research, so these results may not be 100% applicable to humans.  

A month later, we looked at a study (Nature Comms: Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice) by Webby & Jones et al. which suggests that baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating clade 2.3.4.4b (circa 2022) H5N1 avian viruses (in mice).

 

All of which brings us to a new study which raises additional doubts on the effectiveness of oseltamivir monotherapy against HPAI H5.

This is a lengthy, and technically dense, study. While many will want to read it in its entirety, the bottom line is that the existing 5-day course of oseltamivir appears inadequate to treat severe HPAI H5N1 infection (at least, in mice). 

The author report Baloxavir as being more potent, but even a 5-day B.I.D course (10 times the current dose) only saved 16.7% of treated mice.  Extending treatment to 7 days (14 doses), raised survival to 50%. 

While a 7-day course of Baloxavir (BMX) was strongest single-drug therapy, extended courses of MNP+BXM and OSP+BXM provided the most effective treatments.

Before everyone freaks out, due to their higher metabolic rate, the half-life of baloxavir is much shorter in mice than in humans. While it remains to be determined, an equivalent dose in humans might be more like 2 or 3 doses spread out over a week's time. 

First the link, abstract, and a brief excerpt. I'll have a bit more after the break.

Antiviral activities of multiple antivirals against highly pathogenic avian influenza A H5N1 in vitro and in mice

Danlei Liu ,Yujing Fan,Ka-Yi Leung,Ruiqi Zhang,Hoi-Yan Lam,Xiaochun Xie,Honglin ChenORCID Icon,Kwok-Hung Chan &Ivan Fan-Ngai Hung 

Article: 2645843 | Received 28 Jul 2025, Accepted 12 Mar 2026, Published online: 31 Mar 2026

https://doi.org/10.1080/22221751.2026.2645843 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated.

In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. 

Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. 

The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. 

Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

        (SNIP)

In summary, BXA, NHC, OSC, and RBV can significantly inhibit the replication of various H5N1 viruses in vitro. The combination treatments of NHC/BXA and OSC/BXA showed stronger antiviral effects. In mice, the 7-day BXM, MNP/BXM, and OSP/BXM treatments significantly increased survival rates.

Combination treatments significantly suppressed the viral replication in both the lungs and brains of mice. Therefore, extended BXM-based combination therapies could be considered as a first-line treatment for humans. The results provided a reference for clinical treatment.

        (Continue . . . )

 

Over the past couple of years we've seen increased calls for a shift in pandemic antiviral strategy towards Baloxavir (or combination therapy), but most countries have invested heavily in oseltamivir, making any change likely slow in coming.

Baloxavir is made only by Roche/Shionogi plants, while oseltamivir is now a generic drug manufactured around the world. The global supply of oseltamivir is probably 50 times greater than baloxavir, while the cost is roughly 1/10th.

The reality is, even oseltamivir will be hard to get - at least during the first critical first 24-48 hrs of infection - during a severe global influenza pandemic. It seems likely that `extended'  baloxavir or combination therapy will be limited to hospitalized patients with severe disease. 

Given our limited supply of antivirals and an expected wait of least 6 months before having any large quantities of vaccine, we will once again have to rely heavily on preventing infection; wearing face masks, hand washing, improved indoor ventilation, staying home while sick, and avoiding crowds.

Which is why I've already got my supply of masks, hand sanitizer, and OTC meds in the hall closet, and have stayed current with all of my vaccines.

If you aren't similarly prepared, you may want to revisit:

#Natlprep 2025: Personal Pandemic Preparedness

EID Journal: Tropism and Replication Competence of Cattle Influenza A(H5N1) Genotype B3.13 Virus in Human Bronchus and Lung Tissue

Flu Virus binding to Receptor Cells – Credit CDC

#19,107

Over the past 2 years we've seen 2 new genotypes of H5N1 emerge in North America  - `Bovine' B3.13 and D1.1 - both of which have infected thousands of  cattle, dozens of humans, and a huge (and largely uncounted) number of birds. 

While neither of these viruses have evolved into an easily transmissible strain, both have shown evidence of mammalian adaptation.  

Human cases have ranged from mild or asymptomatic (see JAMA Open: Asymptomatic Human Infections With Avian Influenza A(H5N1) Virus Confirmed by Molecular and Serologic Testing) to severe and even fatal (see Louisiana Department of Health Announces 1st H5N1-related Fatality).

Recent studies and preprints (using a variety of lung explant cultures, lung organoids, and human nasal epithelial cells) have found these new genotypes appear to be better adapted to the human respiratory system than older strains. 

A few recent examples include: 

Preprint: Bovine-derived Influenza A virus (H5N1) Shows Efficient Replication in Well-differentiated Human Nasal Epithelial Cells Without Requiring Genetic Adaptation

J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13

Pre-Print: A Cattle-derived Human H5N1 Isolate Suppresses Innate Immunity Despite Efficient Replication in Human Respiratory Organoids

While these studies utilize different methods and materials, they have constantly painted a picture of the recent emergence of a more `mammalian adapted' HPAI H5 viruses. 

To that list we can add a dispatch, published this week in the EID Journal by researchers from the University of Hong Kong and St. Jude Children's Hospital, which looks at two cattle derived H5 strains (from Ohio & TX) of the B3.13 genotype in human bronchus and lung ex vivo explants.

While today's study doesn't explicitly test the D1.1 genotype, they make note of previous studies (see above) which suggest - in some ways - it may be even better adapted than B3.13.

While relatively brief, much of this dispatch is technical in nature, and those with a keen interest will want to read it in its entirety.  

This study compares B3.13 to 3 other viruses; a Clade 0 H5N1 virus (Hong Kong 1997), an aggressive H5N6 isolate from China (2014), and a 2009 H1N1 virus from Hong Kong. Briefly, they report:

• Bovine H5N1 genotype B3.13 shows partial adaptation to human respiratory tissue. 

• B3.13 replicates in lung tissue on par with the 2009 H1N1pdm virus, albeit lower in the bronchus than either H1N1pdm and H5N6.

• Receptor binding tests suggest better adaptation to α(2–6)-linked SA, compared to the early H5N1 virus.

• B3.13 induced proinflammatory responses, but far less than avian H5N1 or H5N6, which likely accounts for its relatively mild presentation.

The link and some excerpts from today's study follow.  I'll have a bit more after the break.

Dispatch

Tropism and Replication Competence of Cattle Influenza A(H5N1) Genotype B3.13 Virus in Human Bronchus and Lung Tissue

Kenrie P.Y. Hui, John C.W. Ho, Ka-Chun Ng, Richard J. Webby, Malik Peiris, John M. Nicholls, and Michael C.W. Chan  

Abstract

In 2024, influenza A(H5N1) genotype B3.13 viruses emerged from cattle and caused mild spillover infections in humans. Using human bronchus and lung tissue, we evaluated tropism, replication, and pathogenesis of 2 cattle influenza isolates.

Those viruses showed moderate replication competence and induced robust proinflammatory responses, suggesting potential risk for human health.

 

Highly pathogenic avian influenza (HPAI) H5N1 viruses remain a major global health concern, particularly because of sporadic spillover into mammals (1). HPAI A(H5N1) clade 2.3.4.4b viruses entered the United States through a trans-Atlantic introduction in late 2021, after which extensive reassortment among migratory birds produced the B3.13 and D1.1 genotypes. Those variants have spread widely, driving outbreaks in livestock and causing occasional human infections (2,3).

Beginning in 2024, H5N1 clade 2.3.4.4b viruses were detected in dairy cattle across multiple US states, and those infections were linked to mild zoonotic cases in humans (4,5). To assess the health risks of emerging cattle-origin influenza viruses, we examined tropism, replication, receptor use, and innate immune responses of cattle H5N1 viruses in human respiratory tract explants.

        (SNIP) 

Conclusions

Viral titers and influenza NP-positive cells demonstrated that cattle-origin H5N1/439 and H5N1/98638 strains are better adapted to human upper airway tissues than avian H5N1/483 and have similar replication abilities as H1N1pdm/415742 in human lung explants.

The ability to bind α(2–6)-linked SA further indicates a shift of receptor affinities that are more compatible with upper respiratory tissues. Innate immune responses of H5N1/439 and H5N1/98638 viruses in human lung tissue fell between those triggered by H1N1pdm/415742 and H5N1/483 viruses, indicating that cattle H5N1 viruses could pose a human health risk.

Defining how these strains infect human tissues and shape immune responses is critical for anticipating outbreaks and reducing zoonotic transmission risks. Because influenza viruses continually evolve across diverse avian and mammalian hosts, sustained research and surveillance remain essential to prevent human infections.

Dr. Hui is an assistant professor in the School of Public Health at the University of Hong Kong, China. Her research interests include risk assessment, understanding the pathogenesis of emerging respiratory viruses, and the development of therapeutic options for severe influenza diseases and coronavirus infections.

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While it appears that neither B3.13 or D1.1 currently have the ability to spark a pandemic, H5N1 continues to set new records in infecting mammalian hosts (see ISIRV: Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year).

These genotypes won't be the last iterations of H5N1, and while the future trajectory of HPAI is unpredictable, recent trends should give us pause.

And if we get lucky - and HPAI H5 should prove incapable of making that evolutionary leap - rest assured there's no shortage of other viral contenders in the wild. 

Taiwan CDC Update: Novel H7 Infection Identified as H7N7

 

#19,106

We've an update this morning from Taiwan's CDC on yesterday's report (see Taiwan CDC: Human Infection with a Novel H7 Avian Virus) which identifies the novel virus as LPAI H7N7 and announces the recovery and discharge from the hospital of the patient. 

While this appears to be an isolated incident, this is a reminder that nature's laboratory is open 24/7, and new threats can emerge at any time.

Today's (translated) announcment follows:

The first locally transmitted case of H7 novel influenza A in China, whose sputum gene sequencing results identified H7N7, has been released from isolation today and is recovering at home.
 
Release Date: 2026-04-03

The Taiwan Centers for Disease Control (CDC) announced today (April 3) that the first case of local human infection with the H7 subtype of novel influenza A, which was detected recently, has been cured and discharged from isolation today after clinical treatment. The patient's condition has continued to improve and all tests have been negative. The patient will continue to be monitored until April 6.

The Taiwan Centers for Disease Control (CDC) stated that the sputum sample collected from the case on March 27th was genetically sequenced to identify the virus as H7N7, a low-pathogenic avian influenza virus (LPAI). No drug-resistant mutations were found, and the virus remains sensitive to antiviral drugs; the public need not panic. The CDC also today, in accordance with the International Health Regulations (IHR), notified the World Health Organization of this first locally acquired H7N7 influenza case through the IHR contact window.

The Taiwan Centers for Disease Control (CDC) explained that since 1959, more than 90 human cases of H7N7 have been reported globally, concentrated before 2003, mainly in Europe. Of these, only one case resulted in death, and the vast majority were mild cases of conjunctivitis. Subsequently, Italy reported three cases in 2013, also mild cases of conjunctivitis. No new human cases have been reported since 2013, but the virus continues to spread and evolve in birds.

The genetic analysis of the first H7 case in Taiwan showed that it was significantly different from the H7 cases in European human cases 10-20 years ago, and most similar to the H7 cases detected in wild birds in Taiwan over the years. No mutations related to enhanced bird-to-human transmission were found, and it is judged to be an isolated event with manageable risks.

The Centers for Disease Control (CDC) reiterates its reminder that workers in the poultry and livestock industries should adhere to disease prevention guidelines, including wearing protective equipment and proper disinfection after handling. If respiratory or eye symptoms develop, seek medical attention immediately and inform the animal contact history. The public should also follow the "5 Dos and 6 Don'ts" principle to avoid contact with or purchase poultry and livestock products from unknown sources, jointly safeguarding public health and safety. More information can be found on the CDC website (https://www.cdc.gov.tw/) or by calling the disease prevention hotline 1922.