In the wake of the COVID-19 pandemic, the landscape of respiratory virus testing has evolved rapidly, driven by burgeoning diagnostic solutions like multiplex testing, highlighting the need for more informed public health strategies and diagnostic stewardship.
By Andy Lundin
Summary: The landscape of respiratory virus testing has rapidly evolved due to the COVID-19 pandemic and the rise in RSV and influenza cases, leading to diverse testing options and new guidelines emphasizing diagnostic stewardship and multiplex testing.
Takeaways:
- Evolving Testing Landscape: The ADLM’s new 2024 guidance highlights the broad variety of testing solutions for respiratory viruses, reflecting the significant changes in diagnostic approaches since the COVID-19 pandemic.
- Importance of Diagnostic Stewardship: The new guidelines stress the need for careful test selection and management, promoting diagnostic stewardship to ensure accurate results and effective resource utilization.
- Rise of Multiplex Testing: Multiplex testing, which can simultaneously diagnose COVID-19, RSV, and influenza, has become increasingly prevalent, offering rapid, comprehensive testing but also raising concerns about cost and appropriate usage.
In just a few short years, the landscape of respiratory virus testing has changed significantly. Spurred by the COVID-19 pandemic, followed by a surge in RSV cases in 2022(1), and the ongoing prevalence of influenza, solutions for respiratory virus testing abound, both at the point of care and for home use.
Recognizing how much diagnosing respiratory viruses has evolved since 2020, the Association for Diagnostics & Laboratory Medicine (ADLM) published a new guidance document in 2024 on laboratory diagnosis of respiratory viruses (2).
A Wide Range of Testing Solutions
A prominent theme of the new ADLM guidance is the recognition of how diverse the respiratory testing landscape has become. According to the guidance document, the options to test for respiratory viruses COVID, RSV, or influenza “vary widely in terms of the number of viral pathogens included, viral markers targeted, regulatory status, and turnaround time to results, as well as their analytical and clinical performance.”
Ensuring that modern testing solutions can accurately detect currently circulating respiratory pathogens is an ongoing priority for companies in the diagnostic field. This is particularly important considering the ever-evolving diagnostic landscape, marked by unpredictable pathogen surges, the emergence of new virus variants, and the co-circulation of respiratory viruses.
“COVID-19 remains a significant concern due to the potential emergence of new variants that can evade immunity, prompting an anticipated rise in hospitalizations and the importance of booster vaccinations,” says Jack Feng, CEO of iHealth, a company that provides a three-in-one, rapid home test for COVID-19 and Influenza A&B. “The flu season is projected to be substantial, possibly larger than usual due to lower population immunity from reduced circulation in previous years, highlighting the need for early vaccination and timely testing. RSV is likely to follow normal seasonal patterns, with new vaccines and immunizations aimed at reducing severe cases in vulnerable populations.”
To address these challenges, new diagnostic technologies, such as multiplex testing, are becoming increasingly ubiquitous.
The Rise in Multiplex Testing
Indeed, multiplex (or syndromic) tests to diagnose COVID, RSV, and influenza have become increasingly prevalent in the diagnostic space. The rise in this type of testing modality is in response to previous surges in COVID and RSV cases, as well as an increase in instances where patients suffer from these respiratory viruses simultaneously. This kind of testing is particularly critical for aging, already ill, and/or immunocompromised patients, according to the ADLM guidance
A number of companies have announced and launched their own multiplex testing solutions to help clinicians and labs accurately diagnose these co-circulating respiratory illnesses.
Roche is one company that has entered the multiplex testing space for cases of COVID-19, RSV, and influenza. The company’s cobas SARS-CoV-2, Influenza A/B & RSV nucleic acid test for the cobas liat system is designed to detect and differentiate between the respiratory pathogens within 20 minutes. It has an EUA and is approved for use in point-of-care or CLIA-waved settings, says Alesia McKeown, scientific partner, medical and scientific affairs at Roche.
McKeown noted the significance of having multiplex testing available given the complexity of testing to diagnose any one of these co-circulating respiratory illnesses since the pandemic.
“The lack of consistent seasonality and an increase in cases, along with the unpredictability of respiratory pathogen prevalence, leads into the biggest value for multiplex testing because we know that all of these symptoms overlap,” McKeown says.
However, utilization of multiplex testing can be costly for health care organizations, making it crucial to avoid its application in low-impact situations. To prevent the overutilization of rapid multiplex viral panels, the ADLM guidance document recommends incorporating restrictive or guided test ordering within electronic medical records. This approach requires clinicians to select an approved indication from a list of appropriate use criteria before ordering a rapid multiplex viral panel, ensuring that such testing is used only when necessary.
Significance of Diagnostic Stewardship
Indeed, the ADLM guidelines emphasize the importance of maximizing the value of the diagnostic tests by choosing the right test for the right patient in the appropriate context. This approach, referred to in the new ADLM guide as “diagnostic stewardship,” ensures that “accurate and clinically relevant results are delivered at the right time, guiding necessary clinical actions while conserving healthcare resources.”
According to ADLM’s guidance document, diagnostic stewardship “involves the evaluation of test performance, testing volume, laboratory feasibility, cost vs value, and the overall impact on clinical outcomes. Provider education efforts and guidance in the form of algorithms and policies can be useful tools to guide appropriate test selection.”
Diasorin is another company that provides a multiplex testing solution for respiratory illnesses and also commends the tenets of diagnostic stewardship.
Diasorin’s latest solution is the FDA 510(K)-cleared Liaison Plex system and Liaison Plex Respiratory Flex Assay. The Respiratory Flex Assay tests for 19 pathogens commonly associated with respiratory infections, including 14 viral and five bacterial targets detected from nasopharyngeal swabs.
Michelle Tabb, chief scientific officer, for Diasorin Molecular and Luminex noted that clinicians should be considerate of the patient’s symptoms when selecting panels to run. For example, she suggests clinicians consider whether the patient is suffering from a long-term cough illness or if they are experiencing acute symptoms of a respiratory viral infection. Understanding the specifics of the illness can significantly aid in making informed decisions about which tests to utilize.
“Testing for the right targets is an important part of diagnostic stewardship. Or else you run the risk of getting false-positive test results,” says Tabb. Tabb also highlighted that multiplex and syndromic testing can minimize the need for repeat or unnecessary tests, helping to reduce health care spending.
Additionally, effectively utilizing syndromic testing can enhance the lab’s financial standing through improved reimbursement opportunities, which the Flex Testing solution offers by allowing labs to decide how many and which targets to test for within the panel and pay proportionally, says Giulia Amicarelli, vice president, global molecular marketing and marketing services, for Diasorin Molecular and Luminex.
“Keeping an eye on reimbursement and cost savings by avoiding larger syndromic panels in cases when they are not clinically appropriate and, therefore, not fully covered by insurance policies is critical as hospitals face economic challenges,” she notes.
Further reading: Routine Lab Tests Can’t Reliably Diagnose Long COVID
Continuing At-Home Testing
As the respiratory testing landscape continues to evolve, Feng of iHealth anticipates that the co-circulation of these respiratory viruses will persist, placing ongoing pressure on health care systems, especially during peak seasons. This underscores the importance of staying informed about the various testing options available on the market, including at-home tests, which remain crucial for the public to have access to.
“Laboratorians should remain alert and involved to provide guidance on managing testing and the information obtained from a wider range of testing settings,” according to the ADLM guidance. This includes POCTs and at-home testing, both antigen-based and molecular tests.
The ADLM guide emphasizes the importance of using nucleic acid amplification tests (NAATs) for molecular detection of respiratory viruses, highlighting their superior sensitivity and specificity compared to other methods. However, the guide also recognizes the advantages of rapid antigen testing, particularly in situations where access to a centralized lab is limited or where quick results could influence management decisions. Most antigen tests provide results in 10 to 15 minutes on average, making them valuable in these contexts.
Jeremy Stackawitz, CEO of Senzo, an in-vitro diagnostics company focused on developing innovative, accurate, and accessible testing products, highlights a key advantage of having readily available at-home tests: they can reduce the number of mildly ill patients seeking professional testing, as these individuals can obtain the same results more quickly through self-administered tests. With the recent introduction of multiplex solutions for home use, consumers now have more options than ever before.
Meanwhile, Alex Mohacs, Senzo’s CMO, underscores the vital importance of surveillance in managing respiratory viruses, while also noting that the cost of tests plays a significant role in determining the scope and extent of these surveillance efforts.
“Diagnostics only work when they are accessible, and accessibility often means affordability,” says Mohacs. “If tests are too expensive, they won’t be widely used, which undermines the goal of widespread surveillance and early detection.”
Senzo is also developing a respiratory multiplex test for both point-of-care and at-home use, noted Stackawitz. This affordable retail test offers high accuracy with results in under 10 minutes and would be the first home-test authorized by FDA for COVID, Flu (A and B) and RSV.
Other Public Health Considerations
The ADLM guidance document notes that the decision to test patients for respiratory viruses is influenced by several factors—which include the identification of cases during an outbreak and for infection control in hospitalized patients (i.e., surveillance testing), as well as the identification of immune responses (i.e., antibody testing)—but also emphasizes timely treatment and management.
Indeed, an increased focus on the test-to-treat approach in respiratory virus management has become increasingly crucial in tandem with advancements of multiplexing and at-home testing.
“That’s especially important for respiratory because there’s a pretty narrow window by which antivirals can be dispensed and still be efficacious,” says McKeown. “And so the faster that you get that test and that treatment to your symptom onset, the more likely you will be able to get antiviral medication and hopefully alleviate those symptoms as soon as possible.”
Looking ahead, Feng anticipates AI will play a significant role in the diagnostic space, particularly in light of the ongoing developments and innovations in respiratory testing.
“Integration (of testing) with digital health platforms and the use of AI for trend analysis have further improved public health responses. These advancements have led to earlier detection and intervention, targeted treatments and better-informed public health strategies, although challenges such as cost and accessibility disparities remain,” he says.
Andy Lundin is CLP’s associate editor.
References:
- Adams G, Moreno GK, Petros BA, et al. Viral Lineages in the 2022 RSV Surge in the United States. New England Journal of Medicine. Published online February 22, 2023. doi:https://doi.org/10.1056/nejmc2216153
- Berry GJ, Jhaveri TA, Larkin PMK, Mostafa H, N Esther Babady. ADLM Guidance Document on Laboratory Diagnosis of Respiratory Viruses. The Journal of Applied Laboratory Medicine. 2024;9(3):599-628. doi:https://doi.org/10.1093/jalm/jfae010
