#Natlprep 2026: Pandemic Planning At Both Ends of the Spectrum

 

Note: This is the 16th day of National Preparedness Month. Follow this year’s campaign on Twitter by searching for the #NatlPrep #BeReady or #PrepMonth hashtags.

This month, as part of NPM26, I’ll be rerunning some updated preparedness essays, along with some new ones.

#19,336

Next week (Sept 25th) the U.N. will host a meeting for world leaders in New York City for the purposes of pandemic planning, which will be broadcast live on UN Web TV.  

As this is a 1 day meeting, and it comes amid headwinds from several directions, it isn't clear exactly what will come from it.

Earlier this month, The Lancet published a comment (excerpts below) on this upcoming meeting, which discussed some of the many challenges it faces.

From commitment to governance: what should the 2026 UN high-level meeting on pandemic preparedness deliver?

Nelson Aghogho Evaborhenea,b Send email to nelsone@ruc.dk ∙ Maureen Lubac,d ∙ Hawi Getnet Degue ∙ Marc Bosonkief ∙ Douglas Muthinji Wanjag ∙ Pimchanok Ratanapisesh ∙ et al.  Article Info

Published September 4, 2026
DOI: 10.1016/j.langlo.2026.104070 External Link Also available on ScienceDirect External Link
Copyright: © 2026 The Author(s). Published by Elsevier Ltd.
 
Download PDF 

In September, 2026, world leaders will convene in New York for the second UN high-level meeting on pandemic prevention, preparedness and response (PPPR).1 The first high-level meeting produced a political declaration that reaffirmed commitments to strengthen pandemic preparedness and advance equity, catalysed the WHO Pandemic Agreement negotiations, and emphasised a whole-of-government and society approach to PPPR.1 Since then, member states have amended the International Health Regulations, adopted the Pandemic Agreement, expanded preparedness financing mechanisms, and proposed reforms to the broader global health architecture.

These developments represent substantial progress. However, the environment in which they must now operate has changed profoundly.

Geopolitical competition has intensified, multiple crises have diverted political attention and financial resources, official development assistance and multilateralism have come under increasing pressure, and the withdrawal of the USA from WHO has accelerated a turn towards nationalism and bilateral approaches to pandemic preparedness,2 adding another layer to an already complex architecture.

Meanwhile, regional institutions have assumed greater responsibilities for PPPR.3 In Africa, for example, the revised statute of Africa Centers for Disease Control and Prevention (CDC) adopted in 2022 expanded the Africa CDC’s mandate and gave it authority to declare a Public Health Emergency of Continental Security, a power Africa CDC exercised during the 2024 mpox outbreak and again during the ongoing Ebola outbreak, alongside WHO’s declaration of a Public Health Emergency of International Concern. Without meaningful coordination, parallel initiatives risk creating overlapping mandates, fragmented financing, and competing expectations relating to surveillance, pathogen sharing, data governance, and equitable access to medical countermeasures.4

Against this backdrop, the credibility of the high-level meeting should not be measured on the basis of yet another ambitious political declaration, but instead, on the basis of whether the meeting delivers a credible governance framework that aligns ongoing reforms, strengthens their coherence, and translates political commitments into sustained preparedness. We outline three priorities.

       (Continue . . . )

The expectation is that these world leaders will adopt a non-binding "political declaration" on preventing and preparing for future pandemics which was drafted over the summer. While long on good intentions, this document lacks much in the way of `teeth' (enforcement mechanisms, dedicated funding, or even a detailed roadmap).

Meanwhile, public health entities and researchers around the world continue to sound the alarm. A few (of many) examples: 

• In April of 2025 the ECDC published ECDC Guidance: Recommendations for Preparedness Planning for Public Health Threats

• In July 2025 Switzerland Unveiled a New Pandemic Plan

• Also in 2025, Canada announced plans to Purchase 500,000 doses Of H5N1 Vaccine and the EU announced plans to purchase up to 27 million doses. 

• Last December the ECDC published Pre-pandemic Guidance: Strategies to Fight Avian and Swine flu in Humans

• And just last month we looked at Referral: Two Related Papers (PNAS & The Lancet) on Preparing for The Next Pandemic

Whether these plans - or the vaccines and antivirals being stockpiled - will be adequate or appropriate for the next global health crisis remains to be seen. As we've seen before, No Pandemic Plan Survives Contact With A Novel Virus.

But having a framework for dealing with a crisis, and running realistic exercises, can be invaluable when the next pandemic strikes.

Most of these pandemic plans are created by - and for - national governments.  What planning may be going on at state/province/or local levels - or for the private sector - is harder to discern. 

But as many people learned to their cost during the last pandemic, it is just as important to be prepared on the individual, family, and neighborhood level.

Sadly, over the past few years much of the public guidance that was once heavily promoted by the CDC and HHS on pandemic preparedness has been expunged from their websites. 

It's as if the first rule of pandemic preparedness in the 2020's is . . . we don't talk about pandemic preparedness.

Buried in the CDC's archives, however, are a number of useful documents, including these from 2017 (download them while they are still available):

• Get Your Household Ready For Pandemic Flu {PDF - 16 pages]
• Get Ready for Pandemic Flu: Educational Settings [PDF – 16 pages]

• Get Ready for Pandemic Flu: Workplace Settings [PDF – 16 pages]  

In addition to the advice offered in these (and other) guidance documents, I'd like to offer 5 things you can do today to prepare for a possibility of seeing another pandemic sometime in the reasonably near future.

1. Get, and become, a `Flu Buddy'

The first item is one we've discussed often (see Yes, We Have No Pandemic . . . But Line Up A Flu Buddy Anyway). I first fleshed out the idea in a 2008 blog called Lifelines In A Pandemic.

A `Flu Buddy’ is simply someone you can call if you get sick, who will then check on you every day (by phone, social media, or in person), make sure you have the food and medicines you need (including fetching prescriptions if appropriate), help care for you if needed, and who can call for medical help if your condition deteriorates.

Those people who care for others, like single parents, also need to consider who will take care of their dependents if they are sick.

2. Avail yourselves of the vaccines that are available now.

While the evidence is limited, there are some studies suggesting that getting the seasonal flu vaccine may give you some small degree of protection against the H5N1 virus. Even if it doesn't, it may reduce your chances of having a dual infection, which could either be more serious, or even lead to a reassortant virus.

COVID remains a threat, and a dual COVID-flu infection can be worse than either one alone, so if you can get one - keeping current with that vaccine makes sense as well.

Since bacterial co-infections are common with influenza, getting the latest appropriate pneumonia vaccines can also a smart move. In 2023, I also updated my Tetanus shot (Tdap), and those over 75 will want to consider the RSV vaccine.

3. Get a Dr. Checkup, Renew Rx Meds, & Handle any Medical Issues

Over the past 3 years I've endured two 21-day scalp and face field treatment (Fluorouracil) following my skin cancer surgery in 2024 (and again in 2026). 

I also got my Rx meds renewed, and have laid in a stock of any OTC meds I might need.

4. Stock up on PPEs or other supplies you might need

I went into COVID with an existing supply of N95 masks and gloves, and I refreshed my stocks in 2022, but if you don't already have all the N95/KN95 or other personal protective gear you would want or need during a pandemic, now is the time buy them.

Once a crisis begins, it is often too late to stock up. And that goes for any preparedness supplies or gear you might desire in an emergency (Hand Sanitizers/OTC meds/etc.)

5. Be prepared to Shelter in Place

If there was one lesson from the opening months of COVID, it is that many of us may elect - or be forced - to stay home, and avoid public places. Supply chains may be compromised, and there may be runs on `necessities' leaving some store shelves bare.

We see this every year before blizzards and hurricanes, and so it makes sense - whenever possible - to keep a stocked pantry, along with the other staples of life.

 
Last winter, in The Gift of Preparedness 2025 we looked a number of items that might make life more bearable during an extended `bug-in' situation.The good news is, much of what you need to do now to prepare for a pandemic would hold you in good stead for any prolonged emergency or disaster. Frankly, there is not much here I wouldn't do to be prepared for hurricanes, blizzards, or earthquakes.

And if we get lucky, and no pandemic (or other emergency) occurs in the near term, I'll count my blessings - and sleep much better at night - knowing I'd done everything I could to be prepared.

And as a wise man once said:

“Everything you say in advance of a pandemic seems alarmist. Anything you’ve done after it starts is inadequate." - Michael Leavitt, Former Secretary of HHS

Taiwan CDC: Both influenza and the COVID-19 epidemic are currently in their peak season, with influenza cases continuing to rise

 

#19,335

A little over 2 weeks ago (Aug 28th), Japan announced the earliest start to their influenza season since the 2009 H1N1 pandemic (see Japan MHLW Reports Unusually Early Start to the Fall Flu Season), while last week Taiwan reported  `. . . emergency room visits reached 11.2%, exceeding the epidemic threshold (11.0%), indicating the start of the epidemic period.'

Four days ago (Sept 11th) South Korea announced the early start to their flu season, and recent reports from China suggest flu is gaining ground in their southern provinces. 

While all of this is unusually early flu activity, Hong Kong - which often sees a biphasic (summer & winter) flu season - continues to report substantial flu (see Update on cluster of Influenza A cases in TWGHs Wong Tai Sin Hospital) as well. 

Today Taiwan's CDC has updated their flu report, and is urging the public to take precautions and to be aware of early warning signs of severe illness. 

        (translation)

Both influenza and the COVID-19 pandemic are currently in their peak season, with influenza cases continuing to rise

The public is urged to implement self-protective measures such as frequent handwashing and wearing masks, and to be aware of the risk signs of severe illness.  

Release Date: 2026-09-15 The Centers for Disease Control (CDC) stated today (September 15th) that both influenza and the COVID-19 pandemic are currently in their epidemic season, and the influenza epidemic continues to rise. The public should strengthen their precautions against influenza and COVID-19, and practice good handwashing, cough etiquette, and wear masks when entering crowded or poorly ventilated places. If symptoms appear, people should wear masks, seek medical attention, and rest at home to reduce the risk of transmission.

The CDC pointed out that the domestic influenza epidemic is rising and in its epidemic season. In the 36th week (September 6th-12th), there were 136,796 outpatient and emergency room visits for influenza-like illnesses, an increase of 16.5% compared to the previous week.

Additionally, last week (September 8th-14th), there were 92 new cases of severe influenza complications (79 H1N1, 5 H3N2, and 8 untyped A cases) and 21 deaths (18 H1N1, 2 H3N2, and 1 untyped A case).

Laboratory monitoring data shows that the influenza virus currently circulating in the community is mainly type A, with type A H1N1 accounting for 82.2%. This flu season (114-115), there have been 1,421 cumulative severe cases (800 H1N1, 503 H3N2, 28 untyped A, 90 B) and 274 deaths (149 H1N1, 104 H3N2, 9 untyped A, 12 B), with most severe cases occurring in people over 65 (65.0%) and those with chronic conditions (82.7%), and 68.3% had not received this season’s flu vaccine.

According to data from the Taiwan Centers for Disease Control (CDC), the COVID-19 epidemic in Taiwan is declining, but it is still in its epidemic period. In week 36 (September 6-12), there were 17,847 outpatient and emergency room visits related to COVID-19, a 13.3% decrease compared to the previous week (August 30-September 5). Last week (September 8-14), there were 53 new locally transmitted severe cases and 18 local deaths. Since October 2025, there have been a cumulative total of 675 locally transmitted cases of COVID-19 complicated by severe illness, of which 124 have died. Severe cases are predominantly among those aged 65 and above (73.3%) and those with a history of chronic diseases (82.8%). 83.6% of these cases have not received the COVID-19 vaccine this season. In the past four weeks, the most prevalent local variants have been NB.1.8.1 and PQ.16.1.1.

The Centers for Disease Control (CDC) reminds the public to pay attention to their health as temperatures gradually cool in autumn. Those who are at high risk of influenza, including themselves and their families, should be especially vigilant. If they experience flu-like symptoms such as fever or cough, they should wear a mask, seek medical attention promptly, or rest at home. If they experience any warning signs (such as shortness of breath, difficulty breathing, cyanosis, bloody sputum, chest pain, altered consciousness, or low blood pressure), they should seek medical attention immediately. A doctor will assess whether they meet the eligibility criteria for publicly funded antiviral influenza medication to ensure timely treatment and reduce the risk of severe complications.

Whether any of this translates to an early flu season for North America or Europe remains to be seen.  The most recent data from the CDC suggests that influenza and RSV activity remains very low, and COVID is only slightly elevated.

 
While it is impossible to predict exactly what kind of winter respiratory season we'll see, past experience suggests it isn't something we should take lightly.  Last year's `moderately severe' flu season is estimated to have caused:

Which is why I'll be rolling up my sleeve again in the next few weeks for both my flu and COVID shots, and I won't hesitate to wear a face mask this winter in crowded indoor public places. 

EID Journal: Characteristics and Superspreading Potential of Andes Virus Person-to-Person Transmission

R0 (pronounced R-nought) or Basic Reproduction Number.

Essentially, the number of new cases in a susceptible population
likely to arise from a single infection. With an R0 below 1.0, a virus
(as an outbreak) begins to sputter and dies out. Above 1.0, and
an outbreak can have `legs’.

Rt represents the actual transmission of a disease in a population
where some people may be immune and control measures are in place

 #19,334

Four months ago the big infectious disease story was an unusual outbreak of Andes Hantavirus (ANDV) aboard a cruise ship out of Argentina, which resulted in 13 identified cases (12 laboratory-confirmed and 1 probable) and 3 fatalities.

The incubation period for ANDV can run up to 6 weeks, with a 42-day monitoring period generally recommended. Some cases can be mild, or even asymptomatic, but the CFR (case fatality rate) can reach 30%-60%.

Although outbreaks of ANDV are fairly rare, and generally limited in size, we've followed several outliers over the years. 

Including, most famously, a 2019 outbreak in Argentina - where, over a period of 3 months - a total of 34 laboratory-confirmed cases of Hanta Pulmonary Syndrome (HPS) - including 11 deaths - were reported in Epuyén, Chubut Province.

The WHO DON report stated:

The index case had environmental exposure prior to symptom onset on 2 November, and subsequently attended a party on 3 November. Six cases who also attended the party experienced the onset of symptoms between 20-27 November 2018.

An additional 17 cases, all of whom were epidemiologically-linked to previously confirmed cases, experienced symptom onset between 7 December 2018 and 3 January 2019 (Figure 1). Potential human-to-human transmission is currently under investigation.

Following the above outbreak, the NEJM published “Super-Spreaders” and Person-to-Person Transmission of Andes Virus in Argentina, which warned: ANDV Epuyén/18−19 strain shows a facility (R>2) for sustaining continuous chains of transmission if no control measures are enforced. 

The idea that 20% of those infected may be responsible for 80% of the forward transmission of a virus has been around for decades, but gained momentum after the 2003 SARS outbreak. 

During that first SARS outbreak, studies found most patients would typically only infect 1 or perhaps 2 additional people, and often none at all. 

But a small percentage of patients proved unusually efficient at spreading the virus, with some responsible for 10 or more secondary infections (see MMWR Severe Acute Respiratory Syndrome --- Singapore, 2003).

A decade later, we'd see the same phenomenon repeated with MERS-CoV (see Superspreaders & The Korean MERS Epidemiological Report) where one Korean MERS patient (#14) is believed to have infected as many as 85 people, while two others (#1 & #16) appear to have infected more than 50 others between them.

 

According to Stein’s excellent 2011 review Super-spreaders in infectious diseases: 

Super-spreading events are shaped by host, pathogen, and environmental factors. Often, more than one factor may be implicated in the same outbreak.

Superspreading events aren’t limited to coronaviruses, as they have been documented with measles, HIV, TB, S. aureus, Ebola, and various STDs . . .among others (cite) 

In January of 2013, in Influenza Transmission, PPEs & `Super Emitters’ we looked at research that found five patients (19 percent) in their study were "super-emitters" who emitted up to 32 times more flu virus than did the rest. Patients who emitted a higher concentration of influenza virus also reported greater severity of illness.  

While the host and the pathogen are important parts to the equation, environment and opportunity also play a pivotal role in exacerbating these superspreader events.

All of which brings us to an EID Journal Dispatch which finds that the 20/80 rule also applies across a larger sampling of ANDV clusters reported over the years, and while the pooled average Rt remains at a reassuring .74, in some outbreaks (including the NEJM report) that number approached or exceeded 1.0. 

I've only reproduced the Abstract and a few excerpts from the dispatch, so you'll want to follow the link to read it in its entirety.  I'll have a brief postscript when you return.

Dispatch
Characteristics and Superspreading Potential of Andes Virus Person-to-Person Transmission

Zihao Guo1 , Kailun Pan1, Yu Zhao, Sheikh Taslim Ali, Kai Wang, Lirong Cao, Zhuang Cui, Shengqiang Liu, Ka Chun Chong, Daihai He, Shi Zhao , and Yuantao Hao2

Abstract

By using historical contact tracing data, we estimated that 23.4% of case-patients caused 80% of Andes virus (ANDV) person-to-person transmission. We demonstrated a low but nonnegligible probability of observing a large-scale ANDV infection outbreak in a rodent-free setting consisting of close contacts, despite the historically self-limited person-to-person transmission of ANDV.

(SNIP)

On May 2, 2026, an ANDV outbreak aboard the MV Hondius cruise ship was reported to the World Health Organization (WHO), with the first case illness onset on April 3 (10). Subsequent epidemiologic investigations proposed a working hypothesis that person-to-person transmission originated from a seed case in a person who probably acquired infection through environmental exposure during travel in Argentina before boarding the ship on April 1 (10). By July 2, a total of 13 ANDV cases had been identified, including 12 laboratory-confirmed and 1 probable case; 3 of those cases were fatal (10). 

According to the initial WHO notification for the outbreak on May 2, public health and control measures, including contact tracing, case isolation, clinical care, and medical evacuation of symptomatic passengers, had been implemented onboard the ship (11). By using historical contact tracing data, we aimed to estimate key epidemiologic characteristics of person-to-person transmission of ANDV, including the serial interval (SI) distribution and transmission heterogeneity, given that those traits strongly shape outbreak size.

(SNIP) 

We identified a total of 88 case-clusters from the included studies, among which 50 (56.8%) were not associated with any secondary person-to-person transmission events. After accounting for variations across lineages or strains, the pooled estimate of Rt was 0.74 (95% credible interval [CrI] 0.28–1.29) and the estimate of k was 0.64 (95% CrI 0.36–1.16). Apart from inherent differences among ANDV lineages or strains, the substantial variation in Rt across lineages or strains could also be attributed to differences in study settings and individual-level heterogeneity in reproduction numbers (5).

We estimated that 23.4% (95% CrI 15.1%–30.3%) of the cases generated 80% of the transmission events, suggesting the person-to-person spread of ANDV exhibited relatively high heterogeneity, although it appeared lower than that observed for other pathogens known for superspreading events, including SARS-CoV, SARS-CoV-2, Middle East respiratory syndrome coronavirus, and Ebola virus (13,14).

(SNIP)

Conclusions

In summary, our results provide insights into the person-to-person transmission potential of ANDV, which exhibited substantial heterogeneity. We found a low but significant chance of observing a relatively large-scale ANDV outbreak in a rodent-free setting consisting of close contacts, which might be eradicated across a few generations of person-to-person transmission. Because no vaccine or antiviral treatment for ANDV infection is currently available, continuous surveillance of person-to-person transmission risk of ANDV is essential for preparedness against future outbreaks.

Dr. Guo is an associate professor in the School of Public Health, Tianjin Medical University, Tianjin, China. His primary research interests include epidemiology and transmission dynamics of emerging infectious diseases.

Simply put, while most ANDV outbreaks are likely to sputter out relatively quickly, there is enough variability in the transmission of the virus that occasional larger outbreaks are possible. 

For more on superspreader events you may wish to revisit:

MMWR Early Release: COVID-19 Superspreading Event In A Church Choir

CDC Update: Rapid Assessment Of COVID Outbreak At 2023 EIS Conference

Ziad Memish: Two MERS-CoV Hospital Super Spreading Studies

The Lancet: Mapping The Korean MERS-CoV Superspreading Event

Australia Reports 1st Sea Lion Death From H5N1

 

YouTube Video ABC News

#19,333

While the last posted update on South Australia's bird flu status appears to be 3 days ago, on Sept 10th, SA's environment minister Emily Bourke announced the death of an endangered Australian sea lion due to H5N1 in the press conference above.

The sea lion recovered from Seal Bay on Kangaroo island - which was being cared for after a shark attack - reportedly died from the virus.

Location Kangaroo Island - Credit Wikipedia

 

Kangaroo Island is home to a number of marine mammals which are known to be susceptible to avian flu (see Preprint: Mass mortality of southern elephant seals during multi-species outbreak of HPAI H5N1 on sub-Antarctic Heard Island), including:

• Australian sea lion.

• Australian fur seal.

• New Zealand fur seal.

• Bottlenose dolphin and common dolphin. 

While Australia's reporting on avian flu has changed; counting events rather than individual H5-positive tests, the numbers continue to rise steadily. 

So far, the virus has not been reported in poultry or other livestock, but the risks to australia's fauna remains high, and only a fraction of the nearly 42,000 hotline reports have been investigated. 

Canada: CFIA Reports 1st HPAI Poultry Outbreak SInce May

Screenshot CFIA

#19,332

While HPAI H5 no longer completely retreats each summer, the warmer months of the year usually see far less activity than the fall and winter.  And each fall, as we await the arrival of the annual southbound migration of birds, we ponder what changes that might bring (see H5Nx: Reassort & Repeat).

In the 2023-2024 avian flu season, we famously saw the emergence of a `bovine' H5N1 genotype B3.13, which has since infected (at least) 1,179 cattle herds across 20 states. 

Avian flu's return in the fall of 2024 brought with it a far more aggressive poultry/wild bird strain (D1.1) (which can also infects humans), along with a spate of oseltamivir resistant outbreaks in Canada. 

Abrupt Shift in H5N1 Genotypes in Wild Birds in US/Canada

Nature https://www.nature.com/articles/s41591-026-04300-1

Last fall - while both D1.1 and B3.13 continued to dominate - we saw the first known human infection with HPAI H5N5 in a backyard bird keeper in Washington State.  

While each fall doesn't guarantee a new wrinkle in the avian flu story, we often first notice big changes in the makeup and behavior of avian flu when migratory birds return from their high latitude roosting spots (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

We've already witnessed a noticeable uptick in outbreaks in commercial and backyard poultry in the United States over the past couple of weeks (see USDA dashboard below).

To this we can add Canada's first poultry outbreak since May 16th, a poultry farm in the rural municipality of De Salaberry, in Manitoba.  

Canada's first poultry outbreak of the new season comes at roughly the same time as last year (Sept 9th), and considerably earlier than the first Canadian outbreak of fall 2024 (Oct 21st).

Whether this fall brings anything substantially different remains to be seen, and unfortunately, we probably won't learn about any genetic changes for several months. As we saw last year, in Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID, the average delay in submitting sequences to GISAID was 7 months (228 days), with some countries taking nearly 2 years.

  

And genetic sequences - even when they are submitted to GISAID - are often devoid of crucial metadata (i.e. collection date, exact location, host-specific information, etc.), limiting their value to the scientific community.

For now, we'll have to content ourselves with less specific data; where, when, the size, and the type of outbreak (commercial poultry, backyard flocks, livestock, peridomestic mammals, or even humans). 

In the meantime, if you raise backyard birds, or frequent live markets, now is a good time to familiarize yourselves with the risks of avian flu, and the things you can do to reduce those risks.

UF/IFAS Extension: What Backyard Flock Owners Need to Know about Bird Flu (Influenza H5N1)

Eurosurveillance: Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026

 

#19,331

Regular readers know that we've been following an uptick in reports of  `reduced susceptibility' of the seasonal H1N1 flu virus to the antiviral drug oseltamivir (aka `Tamiflu') around the globe for the past 3 years.

In March 2024 The Lancet published - Global Emergence of Neuraminidase Inhibitor-Resistant Influenza A(H1N1)pdm09 Viruses with I223V and S247N Mutations - which reported a much higher incidence of oseltamivir resistance among samples tested in Hong Kong in 2023. 

Instead of the H275Y mutation which caused nearly total resistance in 2008, these viruses carried dual I223V/S247N mutations which together produced a ≈ 10-fold reduced inhibition by oseltamivir.  

Concerning, but not enough of a hit to invalidate the clinical use of the drug. 

This was followed up 3 months later by EID Journal: Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023–February 2024 which reported a ≈ 13-fold reduced inhibition by oseltamivir

In July of 2025, Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain, we looked at a study that found a sharp increase in detections of the NA:S247N mutation beginning in 2024, but not including I223V.

Last December, in Eurosurveillance: Expansion of influenza A(H1N1)pdm09 NA:S247N Viruses with Reduced Susceptibility to Oseltamivir, Catalonia, Spain, and in Europe, July to October 2025. a Rapid Communications reported on another dramatic surge in H1N1 viruses carrying the NA:S247N mutation in Catalonia Spain, and other parts of Europe.

Abrupt rise in resistance in Catalonia, Spain - fall 2025

Some weeks (see above graphic), as many as 100% of viruses tested showed this NA:S247N mutation. 

The good news, however, was that once again, a second permissive mutation - NA:I223V - was not detected in these recent Catalonia isolates. 

As for detections in the United States (see Feb 2026 blog), 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.

And 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 FluView Wk 53).  

But shortly after the New Year we began to seen an uptick in reduced inhibition detections in the United States. By late February (FluView week 7) - based on 517 H1N1 isolates tested since October - the CDC reported 10 isolates with reduced inhibition and 4 with highly reduced inhibition (due to NA:H275Y).

In early June we looked at the last full FluView report of the 2025-2026 flu season, which reported a total 20 reduced inhibition results, and 11 highly reduced results:

Nine A(H1N1)pdm09 viruses had NA-H275Y amino acid substitution conferring highly reduced inhibition by oseltamivir and peramivir. Nineteen A(H1N1)pdm09 viruses had amino acid substitutions NA-I223V and NA-S247N and showed reduced inhibition by oseltamivir. One A(H1N1)pdm09 virus had amino acid substitutions NA-I223T and NA-S247N and showed reduced inhibition by oseltamivir. Two A(H3N2) viruses had amino acid substitution NA-E119V conferring highly reduced inhibition by oseltamivir. Three B viruses had amino acid substitution NA-M464T and showed reduced inhibition by peramivir.

While the number of S247N+I223V mutations remains low (2.1%), this was more than a 35-fold increase over the previous year. And equally concerning - after an extended absence - the tag team of S247N+I223V was being reported again in a newer NA-clade H1N1 virus.

All of which brings us to this week's Eurosurveillance dispatch, which reports on a similar rise of S247N+I223V in the Netherlands; first in 2024 and then - after a brief absence - again in 2026.

Due to its technical nature, I've only posted some excerpts. Those seeking a deeper dive will want to follow the link to read it in its entirety.   I'll have a postscript after the break.

Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026 

Zandra Felix Garza1 , Dirk Eggink1 , Mariam Bagheri1 , Sharon van den Brink1 , Gabriel Goderski1 , Mark Pronk2 , Pascal Lexmond2 , Mariëtte Hooiveld3 , Rianne van Gageldonk-Lafeber1 , Björn Koel2 , Ron Fouchier2 , Adam Meijer1

In 2023/24, a neuraminidase (NA)-clade of A(H1N1)pdm09 influenza viruses carrying the NA-I223V amino-acid substitution emerged, followed by acquisition of NA-S247N [1-3]. Both substitutions individually increase the 50 per cent inhibitory concentration (IC50) by oseltamivir but the resulting IC50-fold-increase remains below the threshold for reduced inhibition (RI) (IC50-fold-change > 10 compared with median IC50 of wildtype (WT) viruses [4]). In double-mutant viruses, the substitutions act synergistically, causing phenotypically RI by oseltamivir, but not by zanamivir [1,2].

In late 2025, Saubi et al. [5] reported re-emergence of A(H1N1)pdm09 viruses carrying NA-S247N in Spain and elsewhere in Europe. Here, we show the re-emergence of A(H1N1)pdm09 NA-I223V and NA-S247N double-mutant viruses in 2025/26 in the Netherlands and assess their phenotypic susceptibility, global spread and evolution from 2023 to 2026.

Discussion

The recent expansion of A(H1N1)pdm09 influenza virus clusters carrying either NA-I223V (2023/24) or NA-S247N (2025/26) was followed in both seasons by the emergence and spread of double-mutant viruses combining these substitutions, causing RI by oseltamivir. This pattern suggests a fitness advantage of single and double mutants [2], although they have not become permanently dominant. The appearance of double mutants is likely independent of antiviral selection, as NA inhibitors are only sporadically used in several countries reporting high proportions of these viruses and such viruses have not been reported from Japan, where NA inhibitor use by capita is highest [14,15], in publicly available GISAID data.

NA-I223V and NA-S247N, alone or in combination, have been proposed as changes that compensate for the fitness cost of NA-H275Y, which confers highly RI by oseltamivir [16]. Both substitutions individually, and especially together, further drastically reduce inhibition by oseltamivir in NA-H275Y mutants [16,17].

During the study period, NA-S247N together with NA-H275Y was detected 33 times and once as a triple mutant including NA-I223V, confirming that such variants showing very high RI can arise and are of concern. Phenotypic data for Dutch viruses show that the 2025/26 NA-I223V combined with NA-S247N double mutant display oseltamivir RI while retaining normal inhibition by zanamivir, similar to the 2023/24 double-mutant and reports elsewhere [1,2,17]. The shown impact of different reference IC50 values on fold-change calculations highlights the need for caution in using WT data and interpreting IC50 values near the 10-fold RI threshold, given the arbitrary nature of the defined threshold values [11]. Synergistic IC50 increases in double mutants should nonetheless be carefully monitored and reported. The impact of these double mutants on clinical management of influenza patients is unknown and should be part of future studies.

Dominance of double mutants within defined HA/NA-subclusters, with gradual accumulation of additional changes, suggests global dissemination from one or several initial emergence(s) or introduction(s), although occasional detection of double mutants in other NA-clades indicates that parallel evolution of similar A(H1N1)pdm09 variants showing oseltamivir RI is also possible. Awareness is therefore warranted whenever NA-I223V or NA-S247N become fixed in spreading subclusters. The recent emergence and spread of NA-S247N in NA-clade D.1 on an HA-clade D.3.1.1 background should be closely monitored during the progressing 2026 southern hemisphere and coming 2026/27 northern hemisphere seasons. Similar to the abundancy of NA-clade D.3 with NA-S247N in HA-clade D.3.1.1 background, HA-clade D.3.1.1 viruses could provide a favourable context for the expansion of such viruses carrying NA of clade D.1 with NA-S247N.

Our global assessment is limited by reliance on non‑embargoed sequences and metadata in GISAID. Country and regional representativeness depends on local laboratory capacity to sequence at least the HA and NA gene segments, and on whether data are submitted to GISAID or other databases (e.g. GenBank, Pathoplexus). While WHO Collaborating Centres partly compensate for gaps at NICs by sequencing of representative viruses shared by NICs and submitting these sequence data to GISAID, our analysis may still over‑estimate mutant presence in some regions and under‑estimate it in others. Our study outcomes should therefore be interpreted in light of these sampling and database‑related limitations.

Conclusion

Our findings highlight the need for continued surveillance on the evolution of A(H1N1)pdm09 influenza viruses and the possible emergence of mutants, especially double and triple ones, with antiviral (highly) RI. The capacity to phenotypically evaluate the impact of individual and combinations of amino-acid substitutions associated with antiviral (highly) RI remains a critical component of this surveillance.

        (Continue . . . )

In 2024 we saw sporadic reports of I223V+S247N in H1N1 NA-Clade C.5.3.3 viruses which produced a 12-13 fold reduction in oseltamivir susceptibility. By 2025 they had largely disappeared, replaced by reports of less impactful single S247N mutations spreading in Europe.

Fast forward to 2026 and we find that the I223V+S247N combo has reappeared in a genetically different NA-clade (D.3) H1N1 virus, suggesting the earlier appearance was more than just a fluke. 

Where this story goes from here is anyone's guess, but should the I223V+S247N combo team up with additional permissive mutations (including H275Y) - and also become more prevalent in seasonal H1N1 - it could compromise the clinical effectiveness of our primary influenza antiviral drug; oseltamivir.   

A lot of `ifs', but given the stakes, this is a story very much worth following. 

The CDC should resume reporting on antiviral mutations in October, and hopefully we'll be getting similar reports out of Europe later this fall.