September 9, 2020Sherry Dunbar, PhD, MBA
Around this time each year, clinical lab managers must prepare for the vagaries of flu season—stocking test kits and reagents based on guesswork about flu prevalence, vaccine efficacy, and many other hard-to-predict factors. This year, though, planning for flu season is complicated by the ongoing COVID-19 pandemic. We will be faced with a simultaneous battle against two widely circulating respiratory infections that have overlapping symptoms, which poses a unique challenge, even for the most experienced in our clinical lab community.
For labs everywhere, it will likely not be possible to depend entirely on the usual flu tests. If the prevalence of COVID-19 cases is not significantly lower by the fall than it is now, laboratories in many regions of the US will have to incorporate SARS-CoV-2 testing for all patients with respiratory infections. This could be accomplished in a number of ways, such as through a new algorithm that indicates when to use a SARS-CoV-2 test versus when to use a flu test, or by testing every single patient with respiratory symptoms using both a flu test and a test for SARS-CoV-2. Given the potential for co-infection, combined tests covering both flu and SARS-CoV-2 have already been released by the Centers for Disease Control and Prevention and other diagnostic manufacturers.
Respiratory testing through the years
To consider how best to proceed, it’s helpful to get back to basics. Let’s start with influenza, which has seen some major shifts in testing recommendations in recent years. Substantial pressure for rapid results—driven in large part by efforts to prevent the unnecessary use of antibiotics—led to the widespread adoption of rapid antigen tests. Rapid antigen tests can produce results in 15 minutes, which initially made them ideal for use in a doctor's office. Unfortunately, those quick answers came at the cost of accuracy. Guidelines released last year by the Infectious Diseases Society of America (IDSA) advised against the use of rapid antigen flu tests because they have low to moderate sensitivities for influenza A/B. The IDSA now recommends rapid molecular tests—which can be run in a few hours to support same-day results for physicians—instead of viral culture, serologic tests, rapid antigen tests, and immunofluorescence tests.
Using highly accurate, rapid, molecular RT-PCR assays as the testing foundation can inform a clinical lab’s decisions about how to incorporate COVID-19 testing. Molecular tests come in a variety of formats, allowing users to tailor testing for the needs of their patient population. In an area with extremely low prevalence of COVID-19, for example, clinical labs might run a single assay covering influenza A/B and RSV for generally healthy patients with respiratory symptoms, while more comprehensive panels featuring the most common viral and bacterial pathogens associated with respiratory infections could be reserved for immunocompromised or other high-risk patients. In regions with high COVID-19 prevalence, labs might instead opt for a multiplex assay covering influenza A/B, RSV, and SARS-CoV-2 as their go-to test for most patients with respiratory symptoms.
Another benefit molecular tests offer is ease of use. They can be automated to handle everything from preparation through analysis without manual intervention—reducing hands-on time to just a few minutes for loading an initial sample. When flu season meets the pandemic, this functionality could be essential for allowing labs to scale up testing to meet spikes in demand, even if staffing levels change due to quarantine.
Finally, the adoption of multiplex tests covering many pathogens in a single assay could also be useful for easing supply chain problems. Running individual tests for influenza A, influenza B, RSV, and SARS-CoV-2 often requires four sets of test kits, four sets of reagents, and so on. A combination multiplex test that includes all of these pathogens would eliminate the need for multiple kits, reagents, nasal swabs, and other supplies. Since healthcare facilities have already experienced the increased need for these supplies due to COVID-19 testing, it is important that we plan now for supply shortages that may occur, should a bad flu season collide with the current outbreak.
Preparing for unknowns
Arriving in the midst of a pandemic, the upcoming flu season has the potential to add a new layer of complexity to respiratory testing in clinical labs. We cannot know how prevalent COVID-19 will be when flu season begins. We also have no idea how the pandemic might shape flu season—will flu transmission be reduced because more people are wearing masks, keeping their distance from each other, and staying home instead of traveling? Or will flu season be worse than usual if vaccination rates plunge because people want to avoid going to the pharmacy or doctor’s office?
With so many unknowns looming, clinical labs must plan ahead to give themselves as much flexibility and scalability as possible. Rapid, multiplex molecular tests can help address these needs and may be an important component in planning for the upcoming flu season.