OFFLU: Global Overview of Spread & Impact of H5 Clade 2.3.4.4b HPAI virus in Wildlife, 2020-2024

#19,074

Offlu has just published a 77-page overview on the impact of the  HPAI H5Nx virus on global wildlife during the opening years (2020-2024) of this ongoing, and unprecedented, epizootic.  

As you can see by the table of contents (below), there is far too much to adequately detail in this blog.  

While the data largely tells us where we've been, this document also  makes recommendations on where we need to be going, if we hope to limit the damage from this virus. 

Download it both as a reference, and as a guide going forward. 

Vaccines: Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential

 

#19,073

Last week Spain reported a rare human infection with H1N1v swine influenza in a patient in Catalonia with no known history of exposure to pigs, or to a contaminated environment. 

While reports like this are not common, it is assumed that these cases are largely underreported, since symptoms are likely to be mild-to-moderate, and most people don't get tested for uncomplicated flu.

We've seen estimates that perhaps 1 in 100 swine variant cases here in the United States are actually picked up by surveillance (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought. 

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

But 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. 

While swine influenza A viruses share the same HA and NA types as seasonal influenza (H1N1v, H1N2v, H3N2v, H3N1v, etc.) they are often antigenically distinct, making the value of deploying existing seasonal flu vaccines in the opening months of a swine flu pandemic unknown. 

In today's study, researchers from the Francis Crick Institute in London, and Italy's WOAH Reference Laboratory for Swine in Influenza tested 5 European lineages of swine influenza (see table below) against components of recent seasonal flu vaccines.

What they found was seasonal flu boosters offered moderate protection against some European swine flu strains (notably, 1C.2.1), but little or no protection against others, like 1A.3.3.2. 

I've reproduced the abstract, and some excerpts, from the study.  Follow the link to read it in its entirety.  I'll have a brief postscript after the break.

Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential
Alice Lilley1,*, Chiara Chiapponi2, Alice Prosperi2, Ana Moreno2, Laura Soliani2, Nicola Lewis1 and Ruth Harvey1

Vaccines2026, 14(3), 211;https://doi.org/10.3390/vaccines14030211

Academic Editor
Published:25 February 2026

Abstract

Background/Objectives: Influenza A viruses cause seasonal epidemics of respiratory infections in humans, the severity of which can be mitigated by influenza vaccine use. Influenza A viruses circulating in pigs continue to pose a pandemic threat, as evidenced by the influenza virus that caused the 2009 pandemic, which originated in pigs. To understand the relative risk of emergence of influenza A viruses from pigs and to assess the potential role of the seasonal influenza vaccine in mitigating this risk, we evaluate the potential cross-protection afforded by the seasonal influenza vaccine against different clades of recently circulating swine influenza A viruses.

Methods: The presence of cross-reactive antibodies in pre- and post-vaccination human serum samples was measured in haemagglutination and microneutralisation assays. Representative H1 swine influenza A viruses from different genetic lineages were tested against sera collected after administration of the seasonal influenza vaccine in healthy adult volunteers over a 6-year time-period.

Results: Although a clade-dependent boosting of post-vaccination antibody titres was observed, protective titres often failed to be reached. There was heterogeneity in recognition by sera for the contemporary swine influenza A viruses, with the 1C.2.1 clade virus being well recognised in both assays, whilst very low pre- and post-vaccination antibody titres were observed against the 1A.3.3.2 clade (which emerged in pigs following the reverse zoonotic introduction from humans of the A/H1N1 pdm09 virus) by both assays.

Conclusions: Seasonal influenza vaccines produce cross-reactive antibodies against some clades of influenza A viruses circulating in pigs, but not all. Depending on the lineage and clade of the virus, the seasonal influenza vaccine might have utility in the event of a swine variant outbreak in humans, whilst a specific vaccine against the outbreak strain is developed.

       (SNIP)

A systematic review found that post-influenza vaccination antibody levels waned within six months but remained higher than pre-vaccination titres [31]. The administration of a booster dose of vaccine in the event of a swine influenza outbreak in humans is likely to help boost antibody titres in those who have previously been vaccinated, except for the 1A.3.3.2 virus.

However, only two time points (almost one year apart) are represented here, and therefore, conclusions about antibody titres at other time points cannot be made. Additionally, volunteers did not report influenza infections occurring during this time period, which could reduce the appearance of waning immunity in the cohort.

These results suggest that the seasonal vaccine does not induce cross-reactive antibodies against all lineages, or even all clades within a lineage, of swine H1 influenza A viruses.

The value of the seasonal vaccine in the event of a swine influenza outbreak will be dependent on the strain of virus, as will the benefit of administering a booster dose to those who have already been vaccinated. However, due to the availability of the seasonal vaccine, its use should be considered in response to a swine influenza outbreak while a strain-specific vaccine is produced.

Continued surveillance of SwIAV and development of candidate vaccine viruses is vital due to low population immunity in humans. Moreover, these results highlight the need for the continued promotion of influenza vaccination due to its ability to induce cross-reactive antibodies against some H1 swine influenza viruses.

       (Continue . . . )

 
While not a home run, there is enough evidence here to consider seasonal flu boosters in the opening months of a swine flu pandemic, at least against some European lineages. 

Whether the same benefits might be expected against other strains - from North America, Asia, or South America - isn't clear.  

But as the authors point out, this is yet another reason to get the seasonal flu vaccine each year, as it might provide some degree of baseline immunity against a swine flu pandemic. 

And any amount of protection in a pandemic beats none at all. 

J.I.D.: Development & Characterization of Candidate Vaccine Viruses against HPAI A(H5) Viruses for Rapid Pandemic Response

 
WHO H5 CVV list (n=46)

#19,072

Two days ago, in WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026, we looked at the latest WHO recommendations for CVVs (Candidate Vaccine Viruses) against zoonotic influenza viruses.

While no new H5 CVVs were recommended,  antigenic characterization of several recent isolates were pending, and H5 continues to evolve. 

Less well known is that the CDC also maintains their own list of  HPAI H5 CVVs - and while there are some overlaps with the WHO's list - there are some differences (see How The WHO & CDC Are Developing Candidate H5N1 Vaccines).   

On the same day that the WHO released their semi-annual zoonotic vaccine update recommendations, the Journal of Infectious Diseases published the following CDC review of 25 existing H5 CVVs, and how well they might work against current (U.S & Cambodian) H5N1 strains. 

CVVs are `seed viruses' which have been antigenically matched to various legacy strains of H5 - and were determined to grow reasonably well in an egg medium - which means they could be quickly used to begin vaccine manufacturing. 

The big caveat is that antigenic matching is done using HI assays in ferrets, which may not fully predict its effectiveness in humans. And - as this report cautions - even tiny changes in the virus can have major impact on its antigenic profile. 

In one of their studies, researchers looked at two clade 2.3.2.1e viruses collected from humans in Cambodia in 2023. The two isolates were:

• A/Cambodia/NPH230032/2023
• A/Cambodia/NPH230776/2023

Despite their genetic similarity, they reacted quite differently.  

• Encouragingly, the A/Cambodia/NPH230032/2023 virus showed broad cross-reactivity against several legacy CVVs. 

• A/Cambodia/NPH230776/2023, however, showed reduced cross-reactivity against many of those same CVVs, with only a specific 2.3.2.1 lineage CVV showing strong inhibition.

While it is possible that an interim vaccine might be developed early in the next pandemic based on an existing CVV - potentially shaving weeks or even months off the manufacturing process - a lot of things would have to go `right'. 

But since a targeted strain-specific vaccine could take 6 months or more to develop, having an existing library of CVVs to draw from might  save a lot of lives. 

I've only posted the abstract, and a few excerpts from the results and discussion. Follow the link to read it in its entirety. 

Development and Characterization of Candidate Vaccine Viruses against High Pathogenicity Avian Influenza A(H5) Viruses for Rapid Pandemic Response  

Li Wang , Jieru Wang , Jaber Hossain , Hans C Cooper , Cindy Adolphus , Michael Currier , Ginger Atteberry , Chenchen Feng , Marie K Kirby , Han Di ... Show more

The Journal of Infectious Diseases, jiag132, https://doi.org/10.1093/infdis/jiag132
Published: 28 February 2026

PDF

Abstract

High pathogenicity avian influenza A(H5) viruses pose a pandemic threat. These viruses have rapidly evolved in birds and frequently crossed species barriers, resulting in over 1,000 confirmed human infections, with a case fatality proportion of approximately 50%. In response, the U.S. CDC has developed dozens of A(H5) candidate vaccine viruses (CVVs) over the past two decades, primarily targeting clades known to infect humans. This report summarizes the development and characterization of the CVVs, with a particular focus on their antigenic relationships with clades 2.3.2.1e and 2.3.4.4b A(H5N1) viruses, which have been responsible for the majority of recent human infections.

 

(SNIP)

Given the ongoing A(H5N1) outbreaks in birds and mammals, along with zoonotic transmission to humans caused by clades 2.3.4.4b and 2.3.2.1e, we aimed to evaluate the ability of antibodies raised against these CVVs in ferrets to inhibit hemagglutination of representative strains from these two clades. 

Three recent human A(H5) isolates were tested in the HI assay: A/Texas/37/2024(TX37), a clade 2.3.4.4b virus representing the first human case of the 2024 U.S. dairy cattle A(H5)outbreak; A/Cambodia/NPH230776/2023 and A/Cambodia/NPH230032/2023, both clade2.3.2.1e viruses isolated in 2023.

Seven out of 16 heterologous ferret antisera inhibited the TX37 virus with HI titers within a 2-fold difference compared to the homologous HI titer (Table 2). Out of those seven antisera, four were raised against CVVs belonging to genetic clades different from TX37.

Similarly, eight ferret antisera raised against these A(H5) CVVs inhibited A/Cambodia/NPH230032/2023 (2.3.2.1e) despite seven of the CVVs being from heterologous genetic clades. Interestingly, only two ferret antisera inhibited A/Cambodia/NPH230776/2023, though it belongs to clade 2.3.2.1e, the same clade as A/Cambodia/NPH230032/2023 (Table 2).

Twelve amino acid differences within HA1, including substitutions in the receptor-binding domain and antigenic site B, are likely responsible for the observed difference in cross-reactivity of CVV antisera against these two viruses (Supplementary Table 3).

DISCUSSION

In this study, we provided a comprehensive overview of 25 A(H5) CVVs developed at the CDC over the past two decades, including detailed information on their HA titers, EID₅₀ values, and viral protein yields. These CVVs have been distributed to government agencies, vaccine manufacturers, academic institutions, and other stakeholders to facilitate laboratory characterization, regulatory evaluation, and vaccine manufacturing. 

 (SNIP)

While ferret antisera provide a valuable surrogate model for antigenic characterization, it is important to acknowledge their limitations. Species-specific differences in immune responses between ferrets and humans are well-documented for seasonal influenza viruses [13]. Human serological data for clades 2.3.2.1e and 2.3.4.4b viruses remain limited, although a recent study has begun to address this gap [14]. Future efforts should prioritize evaluating antibody responses in individuals vaccinated with A(H5) vaccines or previously infected with A(H5) viruses to better assess the potential for cross-protection against emerging zoonotic strains.

In conclusion, maintaining a diverse and regularly updated A(H5) CVV library is critical for global readiness as avian influenza viruses continue to evolve. The demonstrated cross-reactivity of several heterologous CVVs with current zoonotic strains underscores the importance of antigenic breadth in CVV selection and suggests that some stockpiled or previously developed candidates may provide adequate protection and enable rapid vaccine production, offering valuable lead time during outbreak response.

(Continue . . .)

 

Nature Comms: The Risk of Kidney Disease Increases Following SARS-CoV-2 Infection Compared to influenza

 

Nature Med. Review: Extrapulmonary manifestations of COVID-19

#19,071

Now that 90% of the world's nations are no longer reporting COVID infections, hospitalizations, and deaths (see No News Is . . . Now Commonplace), the current health burden of COVID infection is largely obscured.  

Estimates put the number of U.S. daily infections at > 90K (see Estimated Burden of COVID-19 Illnesses, Medical Visits, Hospitalizations, and Deaths in the US From October 2022 to September 2024), but with limited testing, no one really knows.  

Even though COVID has lost much of its initial lethality, the above study suggests it caused 1.1 million hospitalizations, and 101 300 deaths in the U.S. during the study period.

Also not reliably counted are the long-term impacts of (often repeated) COVID infection.  `Long-COVID' - or Post COVID Syndrome - has been estimated to affect up to 20% of survivors. 

Research also suggests that with each SARS-CoV-2 reinfection, the risks of complications or developing Long COVID increase. With fewer people getting vaccinated/boosted, and fewer still bothering with NPIs, multiple reinfection's are increasingly commonplace. 

While world governments (and the general public) seemingly don't want to hear about it, the evidence of long-term harm from repeated (even mild) COVID infection continues to mount.  

A few (of many) recent studies include:

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

Referral: JAMA - COVID-19 in Pregnancy Linked With Risk of Neurodevelopmental Disorders in Early Childhood

European Society of Cardiology: Major Consensus Statement Released on Long-Term Cardiovascular Impact of COVID Infection

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

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

To this growing preponderance of evidence we can add a new study, just published in Nature Comms, which finds increases in both acute kidney injury (AKI) and chronic kidney disease (CKD) following COVID infection. 

Those with long memories will recall that we first saw evidence of COVID infection's impact on the kidneys more than 5 years ago (see JASN: Acute Kidney Injury In Hospitalized Patients With COVID-19).

This wasn't entirely surprising, since the SARS-CoV-2 virus enter cells via ACE2 receptors, which are particularly abundant in numerous renal tubules in human kidneys. Many early studies reported a high rate of AKI and CKD following COVID hospitalization. 

Since the full edited version of this study hasn't been posted, I'll simply post the following abstract and summary.  Follow the link to read it in its entirety. 

I'll have a bit more after the break.

The risk of kidney disease increases following SARS-CoV-2 infection compared to influenza

Yue Zhang,  Nasrollah Ghahramani, Vernon M. Chinchilli & Djibril M. Ba

Communications Medicine , Article number: (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Background

Although case reports and observational studies suggest COVID-19 increases the risk of kidney diseases, real-world evidence comparing it with influenza is limited. Our study aims to assess the association between COVID-19 infections and subsequent kidney diseases, using influenza as a positive control and incorporating a negative control to establish clearer associations.

Methods

A large retrospective cohort study with strata matching was conducted using the MarketScan database with records from Jan. 2020 to Dec. 2021. We used the ICD-10 codes to identify individuals and build three cohorts: (1) COVID-19 group, (2) Positive control group: Influenza but no COVID-19, and (3) Negative control group: no COVID-19 / Influenza. The outcomes were acute kidney injury (AKI), chronic kidney disease (CKD), end-stage renal disease (ESRD), and glomerular diseases. Multivariable stratified Cox proportional hazards regression analyses were performed.

Results

The study includes 939,241 individuals with COVID-19, 1,878,482 individuals in the negative control group, and 199,071 individuals with influenza. COVID-19 is significantly associated with increased risks of AKI (adjusted hazards ratio, aHR: 2.74; 95% CI, 2.61-2.87), CKD (aHR: 1.38, 1.32-1.45), ESRD (aHR: 3.22, 2.67-3.88), and glomerular diseases (aHR:1.28, 1.09-1.50), while influenza has no impact on CKD, ESRD, and glomerular diseases. Time-specific analyses indicate that COVID-19 has stronger effects on AKI in the short term but has stable long-term effects on CKD.
Conclusions

In this large real-world study of working-age, commercially insured adults in the United States, COVID-19 infection is associated with a 2.3-fold risk of developing AKI, a 1.4-fold risk of CKD, and a 4.7-fold risk of ESRD compared to influenza. Greater attention to kidney diseases post-COVID-19 is essential to prevent future adverse health outcomes.

Plain Language Summary

COVID-19, caused by the SARS-CoV-2 virus, has been linked to multiple organ complications, with emerging evidence suggesting effects on kidney diseases. However, it is unclear how the risk of kidney disease after COVID-19 compares with influenza, another common viral infection. In this study, we analyzed commercial health insurance data from over three million working-age adults in the United States to compare individuals with COVID-19, those with influenza, and those with neither infection. We found that individuals who had COVID-19 were more likely to develop kidney problems, including short-term injury and long-term chronic disease. These findings suggest that COVID-19 may have a stronger impact on kidney diseases than influenza, highlighting the need for greater attention and monitoring of kidney function after COVID-19 infection.

For a variety of economic, societal, practical, and political reasons the world decided more than 3 years ago that COVID should be treated as a `mild, almost trivial flu-like' illness. 

And while it is true that > 99 out of every 100 COVID cases survives, disability claims have skyrocketed (see CSIRO Pub: Impacts of Long COVID on Disability, Function and Quality of Life for Adults Living in Australia), and chronic illnesses are increasing.

Based on limited data, the WHO estimates that 1 in 6 people who contract COVID will develop some degree of `Long COVID'. Globally, that suggests > 400 million people, and > 20 million in the United States.

Which is one of the reasons why, as recently as late December, we saw a WHO Statement: COVID-19 Still Causes Severe Disease & Renewed Vaccination Recommendations.

 But it is unclear, at this late stage, whether anyone is still listening. 

WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026

Credit NIAID

#19,070

In addition to deciding which influenza viruses to include in the next seasonal flu vaccine (see WHO Recommendations for Influenza Vaccine Composition for the 2026-2027 Northern Hemisphere Influenza Season), twice each year flu researchers are asked by WHO to advise on the development of new CVVs (Candidate Vaccine Viruses) for zoonotic influenza.

While our attentions are primarily focused on the clade 2.3.4.4b H5N1 virus, there are literally dozens of other zoonotic influenza A viruses circulating around the world (see CDC IRAT list), all of which are believed to have some degree of pandemic potential.

Each year new variants - subclades, subtypes, or genotypes - emerge, and the WHO must decide if they warrant the creation of a CVV. Since H5 viruses evolve rapidly, many older CVVs no longer match circulating strains.

Having a proven CVV already tested and approved can save valuable time if  rapid production and distribution of a pandemic vaccine are ever required.

And over the past two decades, the WHO has recommended a lot of them (see list below). Forty-six are approved and available, and 6 are pending. And that's just for H5 subtypes.

They WHO has also approved 22 H7 CVVs (20 available, 2 pending), and 11 H9 CVVs (8 available, 3 pending), along with a smattering of other subtypes (H1, H3, H10, etc.).

This week the WHO published a 13-page update which contains background information on a wide range of novel avian and swine flu viruses detected over the past 6 months.  

While they cite ongoing antigenic changes - particularly among the H5Nx panoply of viruses - in the end only one new CVV was recommended for development; a new A/Hunan/40087/2025-like H9N2 CVV.

We've been following concerning antigenic changes in H9N2 viruses for quite some time (see China CDC Weekly: Epidemiological and Genetic Characterization of Three H9N2 Viruses Causing Human Infections — Changsha City, Hunan Province, China, April 2025).

While no new H5 CVVs were recommended, antigenic characterization is still pending on a number of recent human H5 infections, including last September's H5N2 case from Mexico, and several recent  H5N1 cases in Cambodia (clade 2.3.2.1e), along with a number of poultry isolates collected from Egypt, Laos, and Brazil. 

This report also finds that the recent H5N5 virus isolated from a human in Washington State showed reduced reactivity to existing CVVs.

The HA1 of the A(H5N5) virus from the human case in the United States of America had five amino acid substitutions relative to the A/Astrakhan/3212/2020 CVV, including a gain of a potential glycosylation site. Post-infection ferret antisera raised against clade 2.3.4.4b A/American Wigeon/South Carolina/22-000345-001/2021, A/Ezo red fox/Hokkaido/1/2022 and A/Astrakhan/3212/2020 CVVs showed reduced reactivity to the A(H5N5) virus.

For now, however, the WHO has decided the threshold has not been met to justify recommending the creation of an H5N5 CVV.  

I've only posted the summary, follow the link to read it in its entirety. I'll have a bit more after the break. 

Genetic and antigenic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness

February 2026

The development of influenza candidate vaccine viruses (CVVs), coordinated by the World Health Organization(WHO), remains an essential component of the overall global strategy for influenza pandemic preparedness.

Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes. Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs.

This document summarizes the antigenic and genetic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals1 that are relevant to CVV updates. Institutions interested in receiving these CVVs should contact WHO at gisrs@who.int or the institutions listed in announcements published on the WHOwebsite2.

       (Continue . . . )

While having a closely-matched CVV might shave weeks or even months off the time it would take to develop, manufacture, and deploy a pandemic vaccine, there are still many obstacles to overcome.  

Any flu jab would likely require 2 shots - 30 days apart - and even under the best case scenarios, it would likely take 6 months or longer before substantial quantities of vaccine are available to the public. 

Some past blogs on some of the logistics of developing a pandemic vaccine include:

Referral: SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1

NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States

How The WHO & CDC Are Developing Candidate H5N1 Vaccines

Manufacturing Pandemic Flu Vaccines: Easier Said Than Done

FluView Week 7: Influenza Remains Elevated & Additional Reports of Antiviral Resistance

 

https://www.cdc.gov/fluview/surveillance/2026-week-07.html

#19,069

Three months into this year's influenza season and flu activity remains elevated across much of the country (see map above), although we are seeing a decided shift from influenza A (primarily H3N2) to influenza B (see chart below).

While the big story of this year's flu season has been the emergence of a `drifted' H3N2 subclade K virus, another aspect we've been following have been sporadic reports around the world of reduced oseltamivir effectiveness against H1N1 due to NA-I223V and NA-S247N amino acid substitutions.

A few blogs include:

Eurosurveillance: Expansion of influenza A(H1N1)pdm09 NA:S247N Viruses with Reduced Susceptibility to Oseltamivir, Catalonia, Spain, and in Europe, July to October 2025

China: National Influenza Center Reporting Increased Oseltamivir Resistance in Seasonal H1N1

Taiwan CDC Statement On Increased Antiviral Resistance in Seasonal H1N1 Cases in 2025

Since 2009, global resistance to oseltamivir has run < 1%, although we've seen sporadic community clusters of H275Y mutations (see here, here, and here) and low‑levels of  I223V/S247N reported (see here and here). 

Over the entire 2024-2025 flu season - out of 1697 H1N1 viruses tested - only one carried the NA-I223V and NA-S247N amino acid substitutions.

Reassuringly, during the first 13 weeks of the 2025-2026 flu season (Oct - Dec) the CDC reported zero elevated resistance among the first 193 H1N1 viruses tested (see screenshot from FluView Wk 53).  

On January 10th (Fluview Wk 1), however, the CDC reported 2 (out of now 224) H1N1 viruses (0.2%) tested showed `reduced inhibition by oseltamivir' due to amino acid substitutions NA-I223V and NA-S247N. 

Two weeks ago, in FluView Week 5: Influenza Remains Elevated & Slight Uptick In Antiviral Resistance, we saw that count had increased to 7 reduced inhibition and 3 highly resistant (due to the more worrisome H275Y mutation).

Yesterday's FluView (week 7) - based now on 517 H1N1 isolates tested since October - reports 3 more reduced inhibition (n=10) and a 4th with highly reduced inhibition.

Four A(H1N1)pdm09 viruses had NA-H275Y amino acid substitution conferring highly reduced inhibition by oseltamivir and peramivir. Ten A(H1N1)pdm09 viruses had amino acid substitutions NA-I223V and NA-S247N and showed reduced inhibition by oseltamivir. Two B viruses had amino acid substitution NA- M464T and showed reduced inhibition by peramivir.

The impact of the H275Y mutation on oseltamivir resistance is far greater than I223V/S247N, but the stacking of H275Y with either I223V or S247N can greatly enhance the effect.

Although elevated above the historic baseline, these latest numbers still remain fairly low, and should not affect clinical decisions regarding antiviral treatment. 

But as a trend, they are very much worth noting.  

Which is why we'll be watching future reports to see if these numbers plateau, or continue to rise.