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

Credit NIAID

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Although our primary seasonal influenza concern right now revolves around the newly emerging subclade (K) of H3N2, we continue to see sporadic reports of low - but increasing - resistance to the antiviral drug oseltamivir among H1N1 viruses.

While spontaneous `resistance' to oseltamivir (aka `Tamiflu') develops in roughly 1%-2% of treated patients, for the past 20 months we've been watching a slow rise in the number of antiviral resistant H1N1 viruses around the world.

In 2008 - before the arrival of a new, and still susceptible swine-origin H1N1 pandemic virus in 2009 - the old H1N1 virus had rapidly grown nearly 100% resistant to oseltamivir in less than a year (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs).

Although that crisis was averted, since then we've been closely watching for signs of increased antiviral resistance in seasonal flu - and while a few isolated pockets have occurred - none have managed to established a foothold.

But in March of 2024 we saw a worrisome report in The Lancet - 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.

Unlike the near total collapse of oseltamivir effectiveness in 2008 - which was due to a an H275Y mutation in the NA - this was due to I223V and S247N, and was not as profound of a loss in effectiveness.

Since then we've seen a number of studies (see Viruses: Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases and Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain) from around the world finding similar patterns.

While most of these increases have been modest, just over 2 months ago Taiwan's CDC reported that 6.5% of the H1N1 viruses they have characterized in 2025 have shown signs of oseltamivir resistance.

In recent days the Chinese press has been warning about an increase in oseltamivir resistant viruses, and the most recent influenza report (Dec 3rd) from China's National Influenza Center cites a 3.9% resistance rate in H1N1 since March 31st, 2025.

(Translation)

Overview of the Influenza Epidemic Situation in China (as of November 30, 2025 )

Monitoring data shows that influenza activity has increased in both southern and northern provinces this week. A total of 1,541 outbreaks of influenza-like illness have been reported nationwide .

The National Influenza Center conducted antigenic analysis on a subset of influenza virus strains collected between March 31, 2025 and November 30 , 2025 ( based on experimental dates) . The results showed that 98.0% ( 1054/1076 ) of the A(H1N1)pdm09 subtype influenza virus strains were similar to strain A/Victoria/4897/2022 ; 49.9% (415/832) of the A(H3N2) subtype influenza virus strains were similar to strain A/Croatia/10136RV/2023 ( chicken embryo strain), and 82.8% ( 689/832 ) were similar to strain A/District of Columbia/27/2023 (cell strain); and 97.5 % ( 313/321 ) of the B(Victoria) lineage influenza virus strains were similar to strain A /District of Columbia/27/2023 (cell strain) . () is a similar strain to B/Austria/1359417/2021 .

The National Influenza Center conducted drug resistance analysis on some influenza virus strains collected since March 31 , 2025. The results showed that 3.9% ( 31/792 ) of the A(H1N1)pdm09 subtype influenza virus strains had reduced or highly reduced sensitivity to neuraminidase inhibitors, while the remaining A(H1N1)pdm09 subtype influenza virus strains were sensitive to neuraminidase inhibitors; all A(H3N2) and type B influenza virus strains were sensitive to neuraminidase inhibitors; and all A(H1N1)pdm09 , A(H3N2) , and type B influenza virus strains were sensitive to polymerase inhibitors .

While not horrendous, this is roughly double the expected rate, making it a trend very much worth watching.

So far - based on 302+ H1N1 viruses tested since May - we aren't seeing signs of increased detections reported by the U.S. CDC (see FluView Week 47 Report below), but > 2/3rds of those tests (n=219) were conducted before the start of this fall's flu season

One A(H1N1)pdm09 virus had amino acid substitutions NA-I223V and NA-S247N and showed reduced inhibition by oseltamivir. One A(H1N1)pdm09 virus had PA-K34R amino acid substitution associated with reduced susceptibility to baloxavir.

High levels of resistance to the adamantanes (amantadine and rimantadine) persist among influenza A(H1N1)pdm09 and influenza A(H3N2) viruses (the adamantanes are not effective against influenza B viruses). Therefore, use of these antivirals for treatment and prevention of influenza A virus infection is not recommended and data from adamantane resistance testing are not presented.

While oseltamivir continues to be effective against the vast majority of seasonal flu viruses currently in circulation - and we don't appear to be anywhere near a repeat of the 2008 collapse - we are seeing some cracks in the veneer.