Perspectives on influenza A(H3N2) subclade k virus

Editor's Note
As the flu season continues in the United States, concerns regarding a mutated form of Influenza A(H3N2) known as “subclade k” spreading globally was discussed in a December 18 JAMA perspective article. The authors described the risk with this recent emergence of the A(H3N2) variant, which they noted will likely cause reduced effectiveness of this year’s influenza vaccines and potentially another severe season. They also provided historical perspective on Influenza A(H3N2) since it first emerged in 1968 when it caused a pandemic associated with an estimated 100,000 deaths in the US and 1 million deaths worldwide, per the article.

They noted that relative to other seasonal strains, influenza A(H3N2) has the highest evolutionary rate and usually causes more severe epidemics with greater excess mortality and morbidity, especially in older adults and risking children, as well.

For example, in the US, the 2024 to 2025 influenza season, caused predominantly by a mix of A(H3N2) and A(H1N1) viruses, caused severe impact across all age groups, including children. This was despite estimated vaccine effectiveness of 63% to 78% in children and adolescents and 41% to 55% in adults in reducing influenza-associated hospitalizations.

They added that inadequate vaccine uptake, delays in seeking health care, and failure to make timely use of available antivirals were likely contributory factors.