Staying Ahead of Influenza: Cepheid’s Response to H3N2 Subclade K

As headlines swirl about the emergence of influenza A/H3N2 subclade K, many in the healthcare community are seeking clear, expert guidance on what this development means for diagnostic testing and patient care. To address the most pressing questions, we sat down with Dr. Mike Loeffelholz, Vice President of Scientific Affairs at Cepheid and an expert in infectious disease diagnostics. In this interview, Dr. Loeffelholz explains the science behind subclade K, dispels common misconceptions, and shares new data highlighting the reliability of Cepheid’s influenza testing solutions in the face of this new variant.

Dr. Loeffelholz, there’s a lot of buzz about the new influenza A/H3N2 subclade K. Is this a new virus, and should healthcare providers be concerned?

No, subclade K is not a new virus. It’s a variant within the existing seasonal influenza A/H3N2 lineage. While it has unique mutations and has contributed to vaccine mismatch and immune escape, it remains a form of seasonal flu. While there’s currently no evidence to suggest it poses a fundamentally new threat compared to other circulating H3N2 strains, we should always be prepared for the emergence of new influenza virus strains.  These new strains of influenza virus help to drive influenza virus infections and the intensity of each flu season.

Is it necessary to subtype H3N2 to identify subclade K for routine clinical management?

Subtyping H3N2, such as distinguishing subclade K from other variants, is not required for routine clinical care.¹ Antiviral medications, such as oseltamivir, are the standard treatment for the flu, particularly for those at high risk. These antivirals are effective against the H3N2 subclade K strain.² Therefore, the clinical management of a patient remains consistent regardless of whether their infection is identified as subclade K, another H3N2 lineage, or influenza A subtype H1N1, which is also circulating, but in lower numbers.

How does Cepheid ensure its influenza tests remain effective as the virus evolves?

Cepheid’s tests use a multi-target approach to detect influenza, providing redundancy across three gene targets for influenza A (matrix, basic polymerase, and acidic polymerase) and two for influenza B (matrix and non-structural). This design helps mitigate the impact of genetic drift and shift, ensuring reliable detection even as the virus evolves.

What do recent analyses show about Cepheid’s ability to detect subclade K and other emerging strains?

Our latest in silico analysis³ included over 10,000 influenza A sequences, with more than 4,000 H3N2 sequences—most belonging to J subclades and clade K. The sequences were obtained from the Global Initiative on Sharing All Influenza Data (GISAID)⁴ covering the period of June 1 to December 1, 2025. The predicted inclusivity for our Xpert® Xpress tests is ≥99.9% for H3N2 (including clade K) and ≥99.3% for all influenza A strains. For influenza B, overall predicted coverage is 100%. This means our tests are well-positioned to detect both contemporary and emerging strains.

What steps does Cepheid take to maintain broad strain coverage and outbreak preparedness?

We continuously monitor global influenza sequence data and perform both in silico and in vitro analyses. This proactive approach reflects our commitment to ensuring that our tests remain effective for broad strain coverage and future outbreak preparedness. Healthcare providers can trust that Cepheid’s solutions keep pace with viral evolution.

What’s your message to Cepheid’s customers who may be concerned about the new subclade?

While the emergence of H3N2 subclade K has generated concern in the news, Cepheid’s multi-target test design and ongoing surveillance provide confidence that your laboratory is equipped to detect this and other evolving influenza strains. No changes to your testing workflow are needed at this time, and our commitment to inclusivity and preparedness remains unwavering.

Download the new influenza inclusivity analysis here, or contact a Cepheid expert to learn more.