The 2023-2024 H1N1 Dual Mutant Flu Virus Has Further Evolved is Possibly Driving Severity in 2026
Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 22, 2026 53 minutes ago
Dual Mutant H1N1 Remains Under Surveillance
Influenza A(H1N1)pdm09 viruses carrying the neuraminidase substitutions I223V and S247N, first detected internationally in 2023, remain an important antiviral-surveillance target in 2026. However, evidence that these viruses are directly responsible for increased clinical severity has not yet been established, making genomic and clinical investigations crucial.
The original multi-country study identified 101 dual-mutant viruses across five continents between May 2023 and February 2024. Laboratory testing showed approximately 13-fold reduced inhibition by oseltamivir, with individual isolates demonstrating roughly 13- to 16-fold reductions. Importantly, susceptibility to other tested influenza antivirals remained normal.
Evolution Did Not Stop in 2024
Genomic analysis showed that the mutants separated into two phylogenetic groups. Nine viruses in Group 1 additionally carried R257K, a substitution previously associated with restoration of neuraminidase activity in another resistance background. The much larger Group 2 contained 92 viruses, with many acquiring hemagglutinin from the 5a.2a.1_C.1.1.1 lineage through reassortment, potentially improving the functional HA-NA balance and viral fitness.
More recent surveillance confirms continued circulation. By the week ending May 23, 2026, the U.S. CDC had identified 19 H1N1pdm09 viruses carrying I223V plus S247N that showed reduced oseltamivir inhibition. No decreased susceptibility to baloxavir was detected among 4,491 influenza viruses tested during that surveillance period.
Why Further Sequencing Matters
As highlighted in this
Thailand Medical News report, newer research also indicates that S247N detections increased substantially from summer 2025, particularly in Europe, emphasizing that neuraminidase evolution is continuing. Detailed sequencing and clinical correlation will therefore be needed before mutations detected in circulating strains can be linked convincingly with unusually severe disease.
The emerging picture is one of an H1N1 lineage capable of retaining transmission fitness while accumulating changes affecting antiviral susceptibility. The critical unanswered question is whether newer genomic combinations alter pathogenicity, immune escape or treatment outcomes. Until patient-level severity data and contemporary sequencing establish such associations, increased disease severity should remain a hypothesis rather than an attributed effect of the dual mutants.
References:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11210663/
https://wwwnc.cdc.gov/eid/article/30/7/24-0480_article
https://pmc.ncbi.nlm.nih.gov/articles/PMC11614803/
https://www.authorea.com/doi/full/10.22541/au.176100323.38119769/v1
https://www.mdpi.com/1999-4915/18/2/210
99-4915/16/7/1109">https://www.mdpi.com/1999-4915/16/7/1109
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