This Year’s Flu Season Has Largely Been Driven by a New Subclade. How Public Health Laboratories Have Responded

This flu season has been an intense one.

The US Centers for Disease Control and Prevention (CDC) estimates there have been at least 25 million illnesses, 330,000 hospitalizations and 20,000 deaths from flu so far this season.

And we’re still weeks away from late spring, when flu cases typically drop off.

What’s behind this active flu season? Experts point to the emergence of a new variant of influenza A(H3N2) known as subclade K.

What is subclade K?

Flu viruses constantly change over time—something scientists call “drifts” and “shifts.”

Small changes are known as antigenic drifts. Although the mutations change the virus, it can resemble other ones, which means the body may be able to recognize it and mount an effective immune response. When the change is significant and abrupt (called an antigenic shift), an entire new subtype of the virus—one most people will have little to no immunity against—can result.

CDC reports that subclade K is the result of an antigenic drift of influenza A(H3N2) that includes a number of significant mutations as compared with the vaccine strain.

Detecting flu variants like subclade K

Influenza viruses are classified based on their genetic and structural characteristics, which can be determined with routine diagnostic tests.

Tests that detect influenza, such as real-time PCR tests, are designed to detect a portion of the influenza genome that does not mutate readily, but is relatively stable, explained Jennifer Laplante, assistant director of the influenza group, Laboratory of Viral Diseases, Wadsworth Center, New York State Department of Health.

This first line of testing can determine whether an influenza virus is present in a patient sample, and if it’s an influenza A or an influenza B virus. Often this is done at a primary care clinic or urgent care. Some laboratories conduct further testing on influenza A viruses to characterize for subtype H1 or H3, which are the seasonal subtypes that typically infect humans. Once an influenza virus is detected, many public health laboratories will sequence a portion of the virus or the entire genome.

“This sequence is compared to other virus sequences, enabling us to see how different or similar the recently detected viruses are to each other and to those that have been detected in the past,” Laplante said. “When we sequence the virus, we can see the whole genetic code of the virus and track how it changes over time.”

How public health laboratories prepare for an active flu season

Given last year’s severe flu season, public health laboratories like the one in Wisconsin prepared far in advance for another challenging season.

“Our laboratory spent the summer validating higher‑throughput testing platforms and methods to meet any surge in testing,” said Erika Hanson, virology surveillance coordinator at the Wisconsin State Laboratory of Hygiene. “We focused on approaches that would expand our testing capacity while also providing flexibility in the event of reagent or supply shortages.”

To identify emerging strains, Hanson said her lab, like other public health laboratories, follows the CDC-APHL Influenza Virologic Surveillance Right Size Roadmap, which describes how much influenza testing is needed.

“Only a strategically selected subset of specimens must be fully characterized each season,” Hanson noted. “This approach can optimize surveillance data while reducing the overall burden and cost of testing. In Wisconsin, our influenza surveillance strategy already accounted for detecting variant strains in the population and did not require modification to identify the subclade K variant.”

Why flu surveillance is important—for now and later

Influenza is a highly mutable virus, and testing of specimens is the only way to determine which strains and subtypes are circulating. That information isn’t just essential for the detection of novel influenza viruses; it’s also essential for calculating the most accurate formula for next year’s flu vaccine.

“Subclade K was first identified in the US during the summer of 2025, after the influenza vaccine formulation for the 2025-26 season had already been chosen,” explained Hanson, who noted vaccine strains are selected up to nine months before the flu season begins. Because of this, the influenza A(H3N2) strain included in the vaccine is not a very good antigenic ‘match’ to subclade K. Additionally, this subclade had not previously circulated in the US, meaning the population had little existing immunity. Both its early-season introduction and its relative novelty likely contributed to its rapid spread this season.”

But flu testing doesn’t—and shouldn’t—stop after vaccine selection.

“If we detect a new virus or a surge in the spread of a virus that wasn’t chosen for the vaccine, there still may be time to make changes,” Laplante said. “Even if it’s too late to change the vaccine, we can continue to collect information that can inform public health policymakers or physicians on how to treat the virus now.”

Because subtyping of flu strains doesn’t directly impact patient care, the costs can’t be billed to insurance or passed on to the patient. That makes adequate funding of public health laboratories and the essential influenza testing they do critically important.

“The public health surveillance system exists to do battle with infectious microbes that can cause a great deal of death and sickness,” Michael Pentella, PhD, director of the Iowa State Hygienic Laboratory, emphasized. “Just like our military, public health workers need to be ready at a moment’s notice to defend and protect our communities. The public health workforce must be trained and ready for immediate action—our health and our lives depend on it. And just like our military, public health has to be funded so it is ready. We have seen a good number of emerging infectious agents in the last 50 years, from Legionella to HIV to Ebola to SARS-CoV-2. In each case, it has been the public health laboratory on the front line that has responded and protected people from getting sick. If we do our job, no one sees or hears about us. But we are here every day, doing everything we can to keep our communities healthy.”