Respiratory season panels, subtypes, and a new Survey

Charna Albert

December 2025—Most assessments of respiratory virus season linger on the unknowns. How severe will the season be? Where will the impact be most felt? Which virus will be the primary driver of the disease burden?

Traditionally, though, there are knowns too: information on circulating strains, made available by the Centers for Disease Control and Prevention through its surveillance data.

Not so this season. Before the government shutdown put an end to the CDC’s regular surveillance activities, the agency in late August predicted a respiratory season comparable to last year’s, the first since 2017–2018 to be classified as high severity for influenza. Northwestern Memorial Hospital in Chicago at one point last season saw a 17 percent positivity rate for influenza, says Chao Qi, PhD, D(ABMM), director of the clinical microbiology laboratory. At its peak, the laboratory ran 500 tests a day. “We were busy,” she recalls. “Very busy.”

Alesia McKeown, PhD, scientific partner of medical and scientific affairs at Roche Diagnostics, sizing up this respiratory virus season in mid-October, didn’t feel the medical community was “going into it blind” without the CDC, which on Sept. 25 stopped reporting data. On the other hand, she concedes, “I think right now we may have a false sense of security. We know things are boiling, based on regional public health surveillance data, but they’re not completely out of our control.”

Before the government reopened in mid-November, CAP TODAY spoke with those on the frontlines of preparing and testing for the seasonal viruses and responding to emerging viral and bacterial threats. Shortly before the reopening, Canadian researchers reported a vaccine-mismatched variant, influenza A(H3N2) subclade K, based on early data from Japan and the U.K., that they concluded is projected to predominate among A(H3N2) viruses in the 2025–2026 season in the northern hemisphere (Sabaiduc S, et al. J Assoc Med Microbiol Infect Dis Canada. Published online Oct. 31 2025. doi:10.3138/jammi-2025-0025). And in November the first ever human case of H5N5 avian flu was confirmed in Washington State.

Even in ordinary times, “Respiratory virus season is so much about the prediction business, and we just don’t know,” says Michelle Tabb, PhD, chief scientific officer at Diasorin, speaking in late October.

“Other things going on now, though, make me more concerned about severity. One is the government shutdown and the reporting ability for surveillance reasons, which is linked to preparedness. The other is messaging about vaccinations, especially the COVID vaccine,” Dr. Tabb says.

Diasorin has its own procedures for determining how often it should track circulating viral strains and for gathering information used to monitor assay performance and inventory needs. Like others, it relies too on the academic medical centers that add their sequences to the publicly available databases. “We have sequencing capabilities internally to keep us going,” she says, “but certainly there might be an impact on how much data is available.”

“Between the clinical labs serving patients, the government and what they do for monitoring and surveillance, and the manufacturers, we are super tightly connected,” she continues, “maybe more so than people realize. We need to be doing this together.”

SARS-CoV-2 cases were declining nationally in late September, the last time such data were released. But the CDC Advisory Committee on Immunization Practices’ changes to vaccine guidance could add to the complexity of the season. “The U.S. isn’t great at vaccinations already,” Dr. McKeown says, “and now that we’re seeing all of this confusion, which is driving a decrease in uptake, I’m concerned what that’s going to mean for the severity of COVID as it hits our population, and what that’s going to mean for our health systems.”

It isn’t clear how the new guidance will affect uptake of the flu vaccine, Dr. Tabb says, especially for those typically vaccinated for both in the same visit. “Maybe they don’t go at all. I’m just not sure.”

What does all this portend for clinical laboratories?

“I don’t think the messaging changes,” Dr. McKeown says. “Being as prepared as possible is always going to be our mantra.” A more immediate concern for hospitals, laboratories, and patients: “We have payers and policymakers who are changing our reimbursement landscape. Moving into respiratory season, everybody should double-check their policies.”

Dr. Tabb notes the appeal of large syndromic panels in respiratory season. “Everyone wants to know what’s infecting my patient,” she says. “However, when it’s expensive and sometimes not actionable, then you have to start thinking, exactly which patients should I run this on? With health care costs skyrocketing and these panels hundreds of dollars, ‘do I need to run this panel on this patient’ is a big question.”

At Northwestern, use of the BioMérieux BioFire RP2.1 was limited prepandemic to immunocompromised inpatients, says Dr. Qi, professor of pathology at Northwestern Medicine. But over time, restrictions on the test loosened, first because it was difficult to differentiate the immunocompromised population from general inpatients, then because outpatient use was permitted during the pandemic and never reversed. Last season, she says, physicians used the extended panel at a daily volume of almost 300.

“From the live lab workflow viewpoint, we felt the large panel was being overused,” she says. The laboratory discussed with physicians why the smaller Cepheid fourplex panel wasn’t meeting their outpatient needs, hoping to determine if they would object to limits on the extended panel. The feedback they received from physicians was that they want answers. “Whether or not the answer is actionable, it gives them peace of mind,” she says. It can also make a sick patient less uneasy about walking away without a prescription when it isn’t needed.

The laboratory suggested adding a comment to the order, something that would encourage thinking twice without complete prohibition. “I understand both sides,” she says. “But without a hard stop restriction, it’s very hard to control its use.”

Then, months after respiratory season concluded, the hospital learned its payers would provide no reimbursement for use of the extended panel in outpatients, leaving the hospital to foot the bill. Now, when an outpatient order is placed this season for the extended panel, the orderer has to answer two questions. The first is whether the patient meets severely immunocompromised status (defined by one of the following: organ or stem cell transplant, undergoing chemotherapy for cancer, HIV with a CD4 T lymphocyte count less than 200, combined immunodeficiency disorder, or receiving a prednisone dose of greater than 20 mg for at least 14 days). The second question is whether the patient has had a severe acute cough for two weeks or more and is pregnant or is a person who has regular contact with infants under age one or is an infant under age one.

If neither one is checked, the order defaults to the smaller panel. The order form also notes insurers are unlikely to cover the cost of the extended panel. “We use the location to tailor the order behind the scenes,” Dr. Qi says.

Some physicians voiced concerns about differentiating pertussis from the seasonal respiratory viruses without the extended panel. In response, one laboratory in the Northwestern system will offer this season a new pertussis-specific PCR test. Dr. Qi is aware physicians may routinely order the fourplex plus pertussis, given the option. “My concern is it’s going to be overused. We pulled the data from last season,” when only 22 people tested positive, six of whom were coinfected with a respiratory virus. The laboratory may build controls eventually, she says, but for now they’re sticking to the plan to offer the test with the smaller panel.

“For this season, we want to see how people will use the test,” she says.

As the need to balance clinical value and cost becomes more important and more difficult, Roche and Diasorin have begun to offer syndromic panels that allow for customization.

Roche this year received 510(k) clearance for its Cobas Respiratory 4-Flex, a SARS-CoV-2, influenza A/B, and RSV panel that allows the user to design a custom panel menu from the four targets. The test, which runs on the Cobas 5800/6800/8800 systems and consolidates the four targets into a single assay, includes an optional digital reflex (available for now on the 5800 system) for use when the first targets chosen are negative.

The goal is to tailor the test to the patient, which could be valuable, Dr. McKeown says, when testing for RSV in different patient populations. For example, this technology would allow the laboratory to test average-risk patients for influenza A/B and SARS-CoV-2, and if those are negative, automatically reflex to RSV.

Roche next year plans to launch an updated 12-target version of the assay. Like the fourplex, the test will employ temperature-activated generation of signal (TAGS), a newer technology that uses color, temperature, and data processing to triple the number of targets that can be detected in a patient sample with a single diagnostic test. “We’re moving this more multiplex technology onto a more high-throughput system,” Dr. McKeown says, for greater cost-effectiveness and use in a broader population. “We’re building on the [TaqMan] technology we already have. We’ve just changed the dynamics of the probes.”

Diasorin’s solution is the Liaison Plex Respiratory Flex Assay, a customizable 19-target sample-to-answer respiratory panel that includes 14 viral and five bacterial targets, among them Mycoplasma pneumoniae and Chlamydia pneumoniae. (It can also perform influenza A H1 and H3 subtyping.) It received 510(k) clearance in 2024.

Users of the Diasorin assay can prioritize the “top slice” of respiratory pathogens, Dr. Tabb says. “From there, depending on what’s circulating, labs can select additional targets.” Users pay only for the tests they run.

If the first targets selected are negative, “you can go back to the system and have it analyze more targets on the panel” without rerunning the patient sample. “The raw data is stored in the system,” she says. Another benefit: If a patient has already been tested with a standalone fourplex from Diasorin or another manufacturer, and all targets were negative, “you can use our system to run all panel targets except for those four you’ve already run with the other test. You don’t have to repeat test those targets.”

Diagnostics companies are aware hospitals and laboratories need to cut back. “Manufacturers are listening,” Dr. Tabb says. “We understand we have to do something—otherwise we might see less and less usage of our full panel.” Also at play is the tendency to “swing back the other way,” she says, now that the pros and cons of larger syndromic panels are fully understood. “We’ve seen people argue for and against the big panels. Maybe now we’re coming back to the middle, and manufacturers need to adapt.”

On that note, she continues, Diasorin also is putting out new targeted testing. The Simplexa COVID-19/Flu A/B, and RSV Direct kit, for the Liaison MDX instrument, received 510(k) clearance at the end of October. “It’s a new chemistry and a 45-minute sample-to-answer assay,” she says. The company is also making its foray into molecular point-of-care testing, with a new platform called the Liaison Nes, now awaiting FDA clearance. “There’s a [respiratory] fourplex on that system as well, with a sample-to-answer of less than 20 minutes.”

In theory, flexible panels like those from Roche and Diasorin could allow laboratories to select the target by epidemiologic trend.

One tool Dr. Qi uses to track trends at Northwestern is BioMérieux’s Fireworks system, which gives BioFire users insight into assay performance and utilization and can be used for pathogen surveillance at the institutional and national levels. At the local level, the Illinois and Chicago public health departments publish pathogen surveillance data, she says.

With uncertainty at the federal level, will clinical laboratories this season turn more to state and local public health laboratories for data and guidance?

“I think that’s a difficult thing to predict,” says Randal Fowler, PhD, D(ABMM), deputy director of laboratory services at the Tennessee Department of Health. “We already have close communication and partnerships with a lot of our clinical labs.” Dr. Fowler and his colleagues share information with the community through a public-facing dashboard that tracks the statewide weekly percentage of emergency department visits and hospital admissions with respiratory illness discharge diagnosis codes for influenza, SARS-CoV-2, and RSV. “It shows a comparison to what you’re seeing in Tennessee, but also to what you’re seeing nationally,” Dr. Fowler says. It also shows the weekly percentage of ED visits and hospital admissions by age group, and a yearly comparison dating back to 2022.

The Tennessee public health laboratory also regularly communicates with the Laboratory Response Network of sentinel laboratories, he says. Historically, that communication has focused on sample submission but also general public health information. “We could use it for sharing more public health data,” he says.

Does sharing state-level surveillance data help clinical laboratories strategize about which tests to run or testing methods to employ?

“My hope is yes,” Dr. Fowler says. “I’ve worked in clinical and public health labs, and I know that as a decision-maker I would find it useful.”

“It’s thinking through what we are able to share and how to share it,” he adds, “so it gets to the appropriate people to make the appropriate decisions.”

The health department in Washington State confirmed in late autumn that a resident of Grays Harbor County, on the Pacific Coast, is the first person to be diagnosed with avian flu in the U.S. since February and the first human ever known to be infected with the H5N5 strain.

The patient, an older adult with underlying health conditions, became severely ill and remained hospitalized as of late November. The source of viral exposure was thought to be a mixed backyard flock of domestic poultry at the patient’s home that had exposure to wild birds.

The H5N1 threat, meanwhile, appears this year to have lessened. There were 67 confirmed human cases of H5N1 in 2024. As of mid-November this year, the U.S. had seen three confirmed human cases.

Benjamin Bradley, MD, PhD, medical director of high consequence pathogen response, virology, and molecular infectious diseases at ARUP Laboratories, hasn’t fully exhaled yet. “I think it’s safest to say there is still potential threat for this virus to spill over into humans,” he says. “It’s still something we need to keep track of, though it does appear the acuity may have changed.”

Dr. Bradley, a member of the CAP Microbiology Committee and assistant clinical professor in the Department of Pathology at the University of Utah School of Medicine, isn’t aware of any single trend or event that has prevented further spread of H5N1. “Some of it could be due to some immunity now existing within the dairy cattle population,” he says. “It’s part of the natural ebb and flow of this virus as well. Typically, we wouldn’t expect to see as much activity over the summer. Coming into flu season, coming into this time of year when migratory birds are moving through the U.S., is another point where we need to be on alert to see what happens this year.”

October recorded more than twice the number of poultry flocks infected compared with September, affecting 66 flocks, according to Brown University’s Pandemic Center Tracking Report. The total number of livestock herds infected in October remained at one, in Idaho. “If it’s relatively quiet over the fall and winter months,” Dr. Bradley says, “that may be a sign the H5 threat has lessened.”

Laboratories seeking to develop or onboard an H5 assay have more options now than they did last year, Dr. Bradley says, including ARUP’s own H5 assay, which is available there and at several other reference laboratories and clinical laboratories. Commercial sources for inactivated H5 virus validation material are now available, he says, and some commercial laboratories have developed primer probe sets for purchase. The literature has also grown. “We have more resources now than we did a year ago, such that if H5 were to flare up again, our diagnostic options have expanded,” he says. (There’s more flexibility, too, with the FDA final rule on laboratory-developed tests having been rescinded.)

New from the CAP this year is the H5N1 Influenza A Detection and Subtyping Survey. “We’re looking to give laboratories that are doing influenza subtyping, especially testing for H5, an opportunity to see how their assay is performing against that of other groups,” Dr. Bradley says. The program was available for order in July of this year. Dr. Bradley and others hope to observe in the first year how laboratories use the Survey. “Some may not be running an H5-specific test, but some other PCR where they would like to see the performance of this analyte, so they may subscribe in those situations.”

The long-term aim, in his view, is to look beyond H5 to influenza A subtyping as a whole. “While this last year or two we’ve been focused on this one specific strain of H5N1, there are highly pathogenic strains of H7. There are other emerging subtypes of influenza. It’s impossible to predict the future, even more so when it comes to influenza because of how much this virus can mutate, because of how many different HA subtypes are out there. So what we would like the Survey to eventually do is serve as a flexible platform for laboratories doing subtype identification to be able to compare against peers,” he says.

Influenza A subtyping is a public health need, Dr. Bradley says, and something more laboratories may need to take on in the future. “Having a Survey that can be adaptable is important too, and that’s what we’re looking at building. That is, not just answering the question for the pathogen we’re worried about now, but how we can be ready in the future too.”

Manufacturers also have their eyes on the future. Their focus in the past four to five years has been on the “big four,” as Dr. McKeown calls them—SARS-CoV-2, influenza A/B, and RSV. “We’ve gotten good at providing those testing solutions,” she says.

“Now we have even more threats.” Next could be a push to fold bacterial targets into the standard testing strategy, “as we look toward a complete respiratory package, not just focusing on the viruses.”

In development at Roche is the Cobas Eplex Respiratory Pathogen Panel 3, an update to the 20-plus target RP2 panel. The plan is to include more bacterial targets—Bordetella pertussis and parapertussis, for example. Roche also is considering next steps for the forthcoming 12-target Respiratory Flex, Dr. McKeown says. “Does it need a companion bacterial panel too? And if we were to provide that, how would that disrupt or complement testing strategies? Who would be tested and why?” Expansion is a given, she says. The difficulty, as usual, is in anticipating need. An educated guess can be made, of course, but anticipating the need is not unlike “a flip of the coin,” she says.

The CDC drew attention to one troubling development on the bacterial side in a report published this fall. The report describes, from 2019 through 2023, a dramatic increase in rates of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacterales. The age-adjusted incidence of NDM-CRE increased 461 percent over that period, the agency reported. The age-adjusted incidence of carbapenemase-producing CRE, meanwhile, increased 69 percent (Rankin DA, et al. Ann Intern Med. Published online Sept. 23, 2025. doi:10.7326/ANNALS-​25-02404).

“The exact reasons for the increase are still being elucidated,” says Tiffeny Smith, PharmD, scientific partner, infectious diseases, medical and scientific affairs at Roche. An increase during the pandemic in the use of broad-spectrum antibiotics selecting for resistance and the high number of patients hospitalized likely caused some of the transmission, Dr. Smith says, particularly when personal protective equipment and other resources were in short supply and infection control efforts were reprioritized. “NDM probably wasn’t at the top of the list at that time.”

Dr. Smith argues for heightened antimicrobial stewardship efforts in respiratory season, when antibiotic usage typically rises. “With, say, a multiplex test, which can quickly rule in or out a viral cause, clinicians can decrease the use of empiric broad-spectrum antibiotics.”

To detect CP-CRE, Roche offers the Cobas Eplex blood culture identification Gram-negative panel. “It will detect the most common Gram-negative organisms and the five different carbapenemases. The clinician gets not only identification of organisms such as Klebsiella or E. coli, but also a rapid screening of whether the resistance marker is present,” she says.

Though most laboratories don’t do carbapenemase typing in-house, “with the awareness that there has been an increase in NDM, I hope that will shift,” Dr. Smith says. Like other forms of surveillance, it is not reimbursable.

The Tennessee public health laboratory belongs to the CDC’s Antimicrobial Resistance Laboratory Network. “The model has been to regionalize testing,” Dr. Fowler says, with Tennessee providing comprehensive antimicrobial resistance testing, including for CP-CRE, for other states in the region. The network is educating laboratories at the state and local levels, too, to provide testing for their jurisdictions.

Dr. Fowler stops short of calling the current situation an outbreak. “But what I would say is, if you look back over the last five years, back to 2020, we have seen a slow uptick in the number of cases we’re seeing that are NDM-producing organisms. We’re also seeing the same thing for other carbapenemase genes such as blaOXA-23.” Other carbapenemases (for example, KPC) and metallo-beta-lactamases (for example, IMP), on the other hand, are still consistently detected. “We’re not seeing any changes,” he says.

Is it reasonable to say NDM gained more of a foothold during the pandemic?

“It’s hard to say,” he says, but a likely explanation is that “we’ve been able to establish testing that allows us to not only detect but to characterize and distinguish between different carbapenemases.” And as submissions are encouraged, “we’re starting to get more and more people to submit isolates.”

From Dr. Smith’s perspective, now could be the right moment to get buy-in from the hospital to bring carbapenemase typing in-house, especially if NDM is detected.

“This is an opportunity to speak with the antimicrobial stewardship program and the infection control team and say, ‘We’ve seen this trend. How we can we evaluate this to ensure we’re taking the best care of our patients and not contributing to the transmission?’”

“It starts there, in the hospital, where the patients are,” she says.

Charna Albert is CAP TODAY senior editor.