Emerging subclade of H3N2 influenza drives cases of flu in northern hemisphere season for virus

A novel subclade of influenza A(H3N2), which was identified only after the 2025–2026 vaccine formulation was finalised, has become dominant in several countries, prompting close surveillance of disease severity, vaccine effectiveness and health system pressure

Global influenza surveillance has identified a novel strain of influenza A(H3N2) that has raised concern among public health experts during the northern hemisphere flu season. The virus – designated H3N2 subclade K – first appeared in international surveillance reports in June 2025, four months after the composition of the 2025–2026 seasonal influenza vaccine had been determined at a meeting the Crick Institute in London, UK. Since then, it has been associated with early waves of influenza activity across Canada, Japan and the UK.

Following a particularly severe influenza season in the USA in 2024, epidemiologists have intensified efforts to assess whether the emergence of subclade K could result in more severe illness or reduced vaccine effectiveness. However, evidence remains incomplete to date.

“It’s [still] too early to tell how severe the season is going to be,” said Dr. Shikha Garg, medical officer in the influenza clinical epidemiology and treatment team at the US Centers for Disease Control and Prevention (CDC).

Influenza A(H3N2) is a common cause of seasonal influenza alongside influenza A(H1N1) and influenza B viruses. However, the H3N2 lineage has drawn renewed attention because the newly identified subclade has accumulated a substantial number of genetic changes.

“It has changed enough [to get] its own subclade designation,” said Professor Jennifer Nuzzo of epidemiology and director of the Pandemic Center at Brown University School of Public Health.

Influenza viruses are known to undergo continual small genetic changes – the process of antigenic drift. The most recent changes have significantly altered the haemagglutinin surface protein of H3N2 subclade K with about 10 additional mutations in that haemagglutinin gene that now make it different from the earlier, representative virus that was in the development of this northern hemisphere season’s vaccine.

Although such drift is expected and underpins the need to update influenza vaccines each year, the growing global prevalence of H3N2 infections has heightened concern because this subtype is often associated with more severe disease.

Japan reported an unusually early influenza season, with officials declaring an epidemic in early October 2025. The UK has also seen an early rise in cases, with senior representatives in the NHS warning publicly of a difficult winter for the health service.

At the end of 2025, the UK’s influenza activity was at roughly three times the level observed at the same point in 2024. In the southern hemisphere, a 29 per cent increase in severe acute respiratory infections, including influenza, has prompted the Pan American Health Organization to call for strengthened preparedness to mitigate the impact of respiratory viruses.

“[However,] we have not yet seen any indication that the US is having a flu season like Japan,” said Nuzzo.

According to the weekly FluView report for the week ending 6 December 2025, H3N2 accounted for about 86 per cent of influenza A viruses reported by public health laboratories in the USA, with subclade K representing approximately 89 per cent of those.

Dr. Dan Weinberger, professor of epidemiology at the Yale School of Public Health, said the data suggested that H3N2 was the dominant strain so far this season and had become the primary driver of infections and spread.

Because H3N2 has historically been linked to more severe influenza seasons than H1N1 or influenza B, even a modest mismatch could have consequences. Past seasons dominated by H3N2 had been associated with higher rates of influenza-related hospitalisation and death, particularly among adults aged over 65 years and young children.

Vaccine uptake has become a particular concern this season. The US government shutdown that began in October and lasted 43 days limited access to public health data during the time in the year which would typically coincide with peak influenza vaccination. Although surveillance continued internally, public reporting was paused.

“For six weeks, if you looked at the CDC’s website, it was like there was no flu,” Nuzzo said, adding that the interruption may have undermined public awareness and confidence.

Early real-world data from the UK, where subclade K has become dominant, suggest that the 2025–2026 vaccine has reduced emergency department visits by 72 to 75 per cent in children and by 32 to 39 per cent in adults.

For further reading please visit: 10.1001/jama.2025.25205