Leveraging the flexible future of respiratory diagnostics

Unpredictability has become a defining challenge for laboratories preparing for the annual respiratory season. With fluctuating seasonal severity, overlapping viral and bacterial threats, and emerging pathogens with pandemic potential, laboratories continue to be challenged in their ability to develop a testing strategy that meets all of these needs. The 2024–2025 respiratory season embodied all of these uncertainties. It was characterized by an especially severe influenza burden, the first high-severity season in more than seven years, along with the highest rates of hospitalizations and outpatient visits for respiratory illnesses observed in the last fifteen years.^1,2 Additionally, rising cases of Mycoplasma pneumoniae³ and Bordetella pertussis⁴ further demonstrated the need to include bacterial pathogen detection within the diagnostic toolkit. Lastly, heightened surveillance of the human burden of influenza A(H5N1) challenged testing strategies, demanding many institutions to adopt additional measures for influenza A subtyping in their inpatient populations.⁵

The dynamic nature of the annual respiratory burden must be met with options that offer flexibility. Customizable and flexible molecular solutions now represent a critical tool for aiding in the development of a fit-for-purpose respiratory testing strategy. These solutions, which are being developed on CLIA-waived and moderate complexity systems, now offer unprecedented ease in designing a personalized strategy that empowers institutions to maximize the diagnostic yield of each test to uniquely meet their regional needs. 

Building a robust testing strategy

Designing a respiratory testing strategy is anything but prescriptive. Labs must balance clinical needs, operational realities, and resource constraints to find the right fit. The Association for Diagnostics & Laboratory Medicine’s document on laboratory diagnosis of respiratory viruses, released in 2024, provides a framework and guidance, but real-world implementation varies.⁶ While there is no one-size-fits-all approach, there are several key factors for laboratories to consider when developing testing strategies: 

• Seasonality and current trends: Factor in the unpredictable timing and prevalence of viral and bacterial respiratory pathogens.
• Patient populations: Consider age, demographics, immune status, and comorbidities.
• Care setting: Tailor testing approaches to the unique demands of inpatient versus outpatient environments and access to CLIA-waived and moderate complexity systems.
• Time to result and turnaround time: Ensure results are delivered quickly enough to guide clinical decisions effectively.
• Actionability of results: Focus on tests that will meaningfully influence patient management and public health decisions.
• Access/reimbursement: Evaluate whether the test is both medically necessary and accessible to the target patient population.

Given all of these considerations, many laboratories have turned to multiplex testing platforms for the diagnosis of respiratory infections. Defined as a syndromic approach to diagnosis, these tests are designed to provide simultaneous results for multiple pathogens that cause similar symptoms, all from a single patient sample. Targeted multiplex tests that detect influenza A, influenza B, SARS-CoV-2, and RSV (often referred to as a respiratory 4-plex) have risen in popularity in the post-pandemic era and are becoming the standard of care for diagnosis of respiratory infections for the general population. Expanded multiplex panels that typically detect 20-plus viral and bacterial pathogens have also gained traction for their role in defining treatment plans for inpatients and high-risk individuals. However, challenges still remain in determining how best to leverage these standardized solutions within diverse patient care pathways, especially in the face of changing seasonal dynamics.

The promise of flexibility

Flexible, customizable diagnostic solutions are a promising tool for laboratorians looking to evolve their testing strategies to better meet their specific needs. Potential impacts of a flexible solution include the following:

• Higher diagnostic yield: Customizable panels allow laboratorians and providers to design tests that detect only what is medically necessary for their patient population. One study showed that tailoring panel composition based on local pathogen prevalence, patient age, and epidemiologic trends can greatly increase diagnostic yield.⁷ Another study found that adding high-prevalence targets, such as rhinovirus, to a standard 4-plex respiratory panel improved diagnostic yield from 12.5% to 26% during the study period.
• Improved diagnostic stewardship: Some flexible solutions also offer digital reflex testing, which allows a two-step approach for results reporting, all from a single test run. Clinicians can first request a subset of targets and, if those are all negative, the instrument will automatically provide results for a predefined list of additional pathogens. Manual release of additional targets may also be possible if results are requested within a pre-defined time window. Digital reflex supports diagnostic stewardship by reducing duplicate testing and decreasing reagent costs.⁸
• Increased access: Flexible respiratory testing technologies are now being designed for high-throughput platforms, enabling laboratories to process larger volumes more efficiently. Expanded multiplex panels on these systems have the potential to cut costs, streamline workflows, and make comprehensive respiratory testing more affordable, increasing access for a broader patient population.

Respiratory season readiness

As laboratories prepare for another season marked by both familiar and unpredictable respiratory threats, the ability to adapt strategies to specific needs while maintaining vigilance for unexpected changes will be critical. Flexible, customizable testing technologies offer a way forward, helping networks expand access, refine stewardship, and respond efficiently to shifting patterns of disease. 

Is your institution ready for a change? Consider these questions when evaluating how these solutions may be implemented in your network:

• Does our current testing strategy provide enough flexibility to adapt to unexpected shifts in circulating pathogens?
• Which patient populations or care settings in our network would benefit most from customizable respiratory panels?
• How could implementing digital reflex or flexible panel options support stewardship and cost efficiency?
• What partnerships across clinical teams (e.g., infection prevention, pediatrics, emergency medicine) would strengthen adoption of these solutions?

By asking these questions now, laboratorians can build a foundation of preparedness that balances flexibility, stewardship, and personalized patient care. 

References

1. Dugan V. 2024-25 Influenza season update and seasonal influenza vaccine recommendations for the 2025-26 U.S. influenza season. CDC/NCIRD. June 26, 2025. Accessed October 3, 2025. https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/04-dugan-influenza-508.pdf.
2. Lewis T. Why this year’s flu season is the worst in more than a decade. Scientific American. March 6, 2025. Accessed October 3, 2025. https://www.scientificamerican.com/article/why-this-years-flu-season-is-the-worst-in-more-than-a-decade/.
3. Same RG, Gerber JS. Walking (pneumonia) down memory lane: Mycoplasma pneumoniae returns. J Pediatric Infect Dis Soc. 2025;14(2):piaf006. doi:10.1093/jpids/piaf006. 
4. Hanna S, Samies N. Clinical progress note: Pertussis. J Hosp Med. 2025;20(8):862-865. doi:10.1002/jhm.70080. 
5. CDC. Technical Report: June 2024 highly pathogenic avian influenza A (H5N1) viruses. CDC. June 5, 2024. Accessed October 3, 2025. https://www.cdc.gov/bird-flu/php/technical-report/h5n1-06052024.html.
6. Berry GJ, Jhaveri TA, Larkin PMK, Mostafa H, Babady NE. ADLM guidance document on laboratory diagnosis of respiratory viruses. J Appl Lab Med. 2024;9(3):599-628. doi:10.1093/jalm/jfae010.
7. Gonzalez K, Amicarelli G. Age-stratified epidemiology of respiratory pathogens and the value of customizable syndromic testing using the LIAISON PLEX respiratory flex assay. J Mol Diagn. 2025;27(9):809-818. doi:10.1016/j.jmoldx.2025.05.009.
8. Norton JM, Dashler G, Klein E, Mostafa HH. The utility of syndromic respiratory pathogen panels: the premise of flexible and customizable approaches. J Clin Microbiol. 2025;63(7):e0031325. doi:10.1128/jcm.00313-25.