Respiratory infections: Flexibility is key to managing increased seasonal testing burdens

Acute respiratory infections are one of the leading causes of death and disability in the world._1,2 During ‘flu season’, which spans the Autumn and Winter months, viruses circulate and spread at a high rate, impacting healthcare systems with increased office visits, hospitalizations, and deaths.³ Many of these infections are caused by viruses with which we are all familiar, such as influenza A and B, respiratory syncytial virus (RSV), and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, there are many pathogens that can cause similar symptoms, including other viruses, such as rhinovirus, enterovirus, and parainfluenza viruses.³

With many respiratory illnesses displaying highly similar signs and symptoms, such as cough and runny nose, it is difficult for clinicians to diagnose specific respiratory infections based on symptoms and physical examination alone. In primary care settings, empiric treatment with antibiotics is frequently initiated—even when a viral infection is a strong possibility, leading to unnecessary or inappropriate prescribing of antibiotics, which contributes to antimicrobial resistance.^4,5 An early and accurate diagnosis is essential to identifying the cause of a respiratory infection to ensure appropriate treatment and effective use of resources.

It is reported that there are approximately 32 million patient visits for influenza-like illnesses in the US annually. During the past 20 years in the US, only a small percentage of those presenting with influenza-like illness were tested and, of those tested, only 23% to 43% during peak activity were associated with a positive test for influenza.^6,7 Therefore, while testing has a clear role to play in the accurate diagnosis of respiratory illness, it is not always utilized. Reasons for this discrepancy can be related to funding, access to appropriate tests, and even perception of the dangers of respiratory viruses.⁸

Some laboratory-based techniques, such as viral culture, immunofluorescence assays, and single-target RT-PCR, can be laborious and complex, comprising many steps to process, requiring the use of special instruments, and utilizing skill sets that may challenge the capacity of clinical laboratories. Alternatively, rapid antigen tests are less complex and require fewer skills, but compromise on sensitivity.⁹

There is also a challenge for the clinician, as each presenting patient may require a different set of tests.¹⁰ For example:

• An otherwise healthy patient with less severe symptoms may require only evaluation for SARS-CoV-2 and influenza A/B
• A hospitalized patient with more severe symptoms may benefit from a broader panel of tests 
• A pediatric patient presenting with moderate symptoms warrants tests in addition to SARS-CoV-2 and influenza A/B, such as RSV

With many reasonable analytes to consider, it can be difficult for the clinician to determine what testing algorithms to follow, whether or not to test for individual pathogens, a targeted subset of pathogens, or broad syndromic panel testing, which may not be tailored to each scenario and can be costly if not all tests are necessary.¹⁰ The challenge of balancing diagnostic stewardship and laboratory capacity comes with the risk of important respiratory infections or co-infections being missed, potentially resulting in delays in appropriate patient management.

While conventional methods require multiple tests to be ordered individually, multiplex testing enables laboratory professionals to run a single test, necessitating only one sample from patients. With comprehensive, but also flexible multiplex testing, challenges associated with testing algorithms can be mitigated, reducing the burden on physicians and laboratory staff. This helps to reduce repeat testing for respiratory infections in the laboratory and frees up the laboratory staff’s already reduced capacity, particularly important during the busy flu season.¹¹

When considering the benefits of flexible multiplex testing, which can provide laboratory leaders with rapid and accurate results, it is important to consider features such as:^9,11,12

• Wide coverage across a range of pathogens, including viruses and bacteria, where appropriate, and co-infection detection
• A small sample volume to allow for any additional results beyond those originally ordered
• Rapid results, as more information per test can lead to more effective patient management 
• Tailored approach allowing clinicians to order tests specific to their patients 
• Cost-effectiveness through tailored testing delivering only the results needed 
• Sustainability through fewer tests and therefore fewer consumable parts being required  

These features can be of great benefit to laboratories in easing pressure at busy times, such as during flu seasons, while quicker and more accurate results benefit patients by enabling timely and appropriate treatment.

Progress in this area is ongoing. Typically, a single PCR test used on a centralized lab platform differentiates up to five targets, such as viruses, with each target identified by a different fluorescent color. Current innovation has led to ways of measuring additional targets in a single fluorescence channel, further increasing the capacity of high throughput multiplex testing.¹³

Following the COVID-19 pandemic, ‘flu season’ is more complex and unpredictable. Laboratories need to be agile in order to support clinicians who are faced with the challenge of deciding what pathogens to test for each patient, which includes justifying the cost of these decisions. By utilizing flexible, multiplex testing for respiratory infections, laboratories can manage costs and enable clinical decisions for timely, appropriate treatment.