Fall traditionally kicks off flu season, when microbiology and core lab workloads jump with added volume and provider questions about tests. This year, however, flu season and the raging COVID-19 pandemic are converging, presenting an unprecedented planning challenge.
“We don’t know exactly what flu season will look like with the pandemic,” said Joel E. Mortensen, PhD, director of the diagnostic infectious diseases testing laboratory at Cincinnati Children’s Hospital Medical Center in Ohio.
“We’ve been so focused on COVID, there’s not been much time to plan for flu season,” added Elizabeth Palavecino, MD, medical director of clinical microbiology at Wake Forest Baptist Health in Winston-Salem, North Carolina.
The crunch is on. Laboratorians now have important, complicated considerations about choosing respiratory virus tests, refining testing algorithms, and delineating how they expect to use tests.
Volume and Supply Challenges
Similar clinical presentations of influenza A, influenza B, COVID-19—the illness caused by the novel coronavirus—and other respiratory diseases mean that clinicians will order far more tests, which all “hit the same supply chain,” noted Amy Mathers, MD, associate professor of medicine and pathology and associate director of clinical microbiology at University of Virginia School of Medicine in Charlottesville. She spoke with CLN this summer as her lab faced a severe shortage of reagents.
“We’ve never tested for flu at the level we’re testing for COVID,” added Frederick S. Nolte, PhD, director of clinical laboratories and professor of pathology and laboratory medicine at Medical University of South Carolina (MUSC) in Charleston.
Public adoption of social distancing and masks might make flu less prevalent this fall, especially in areas where children do not return to school, according to experts. Cincinnati Children’s Hospital saw its test positivity rate drop to 0 within 45 days of a mask mandate, said Mortensen and Jennifer L. Kasten, MD, a staff pathologist. Kasten hopes this measure and others keep the institution’s respiratory illness rates in check but cautioned that she is “not sure what will be the most likely respiratory illness this year.”
Test Choices and Algorithms
During an interview this summer, Nolte said costs and his available resources would ultimately drive his test choices. He was considering the BioFire Respiratory 2.1 Panel with SARS-CoV-2. This large panel tests for 22 respiratory pathogens including influenza A and influenza B. Nolte also was watching development of the Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV test, which would detect SARS-CoV-2, flu A, flu B, and respiratory syncytial virus (RSV). In June, Cepheid said it intended to pursue Food and Drug Administration (FDA) emergency use authorization for the test.
Nolte predicted that MUSC’s 1,500 daily COVID-19 results would soon rise to 3,000. He noted that the BioFire panel detects more pathogens, while Cepheid’s panel is automated and high throughput. He expects to use multiple tests and platforms to test for both flu and COVID-19, with a large panel test reserved for inpatients, the immunocompromised, and the very young, who need quick diagnoses.
Various guidelines recommend testing for flu only if a positive result will change how a case is managed, Nolte noted. But COVID-19 testing guidelines from the Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America “are so loose that everyone who wants a test gets a test.” He wants more specific criteria for COVID-19 testing.
Reagent, Platform, and Staffing Considerations
At University of Mississippi Medical Center in Jackson, Patrick Kyle, PhD, anticipates a fall surge in respiratory virus test orders from emergency medicine physicians especially. Kyle, director of clinical chemistry, serology, and toxicology, made test choices based on available platforms and reagents. He plans to use a Cepheid flu test with a 35-minute turnaround, plus three polymerase chain reaction (PCR) tests for SARS-CoV-2. They include the Cepheid Infinity, the Abbott m2000 Realtime system, and the CDC assay as a lab-developed test. He’s interested in using Cepheid’s Xpert Xpress SARS-CoV-2/Flu/RSV to diagnose influenza A, influenza B, RSV, and COVID-19, if it receives FDA emergency use authorization. However, he’s concerned about the supply of reagents for the test. Kyle was evaluating costs of Cepheid multianalyte products versus separate flu and COVID tests. When flu and COVID-19 are ruled out, Kyle expects to use the BioFire FilmArray RP2 Panel with 21 viral and bacterial targets.
Palavecino was considering the BioFire panel including SARS-CoV-2. Other panels with both flu and COVID-19 now in development might not be as automated as BioFire, and her lab currently doesn’t have enough staff with molecular diagnostics expertise to run them. The full BioFire respiratory panel might not be covered for outpatients, she added.
“I want more alternatives. I want something that detects flu A, B, and COVID that I can use on both outpatients and inpatients,” Palavecino said. Reagent shortages could force her to use SARS-CoV-2 rapid antigen tests approved for emergency use in certain patients. Antigen tests are not as sensitive and specific as molecular tests, and negative results must be confirmed.
At Boston Medical Center (BMC), epidemiology, lab, and pharmacy staff want to streamline platforms for respiratory viruses because they anticipate patients will present with co-infections, said Cassandra M. Pierre, MD, MPH, hospital epidemiologist and medical director of public health programs. The BioFire Respiratory 2.1 Panel with SARS-CoV-2 is a likely, efficiency-improving choice under consideration for ambulatory and inpatient area use. However, with 499 beds and many patients who continue to require SARS-CoV-2 tests pre-procedure or prior to convalescing in other facilities, Pierre anticipates resource constraints. If necessary, BMC might consider anterior nasal testing, with lower sensitivity, for some patients.
Kasten and Mortensen are discussing separate algorithms for SARS-CoV-2 tests for specific sites, the medically fragile, and the symptomatic. Asymptomatic patients will be tested only for SARS-CoV-2.
Initial discussions about the other algorithms have explored combinations of tests for flu A and flu B, SARS-CoV-2, and RSV in specific populations. Kasten and Mortensen are considering various PCR tests that target flu A, flu B, and SARS-CoV-2, either separately or in combination. A large panel—such as BioFire Respiratory 2.1 Panel with SARS-CoV-2—and parsing out data points for specific populations is another option. Other contenders include the Cepheid GeneXpert system and the rapid Abbott ID Now, said Mortensen. For each patient, he foresees getting 2-3 swabs and running tests on 2-3 of his half-dozen analyzers. But he would prefer a quick, single swab commercial test for multiple pathogens.
Kasten noted Cincinnati Children’s internal debate about specimen pooling—a potentially efficient way to evaluate low-prevalence populations and reserve reagents—for screening asymptomatic outpatients. Mortensen pointed to logistical questions about bar-coding individual specimens for batched testing and retesting, data flow to track all results, and the prospect of diluting pathogens targeted for detection. Dilution means less sensitivity and more false negatives.
Many hospital labs have ramped up communications with other parts of their institutions amid the pandemic, a trend that will only increase during flu season. Nolte and others have devised channels for close, frequent communication among the lab, administration, and key players in care.
Decisions about COVID-19 testing “require ten times more communication than making changes to sexually transmitted infection tests,” Mortensen said. He is gathering feedback and input from upper management, the emergency department, and various pediatric specialties. After using that information to make key lab decisions, he communicates the decisions back to these groups. He expects to involve more groups as flu season progresses.
Some workarounds devised during COVID-19-related shortages might serve institutions well during flu season. For example, Kyle has been validating assays via nasopharyngeal swabs in saline because he has not received shipments of viral transport medium since February.
Kyle hopes to increase the number of collection swabs on hand by ordering 5,000 to 10,000 at a time. He recommends that other labs also increase their swabs, collection kits, and collection media for the coming flu season. Mortenson noted the tall stacks of boxes in his office and his plan to both increase COVID-19 testing tenfold and have enough supplies for 20,000 flu tests by October.
At BMC, Pierre wearing her epidemiologist hat is focused on reducing strain on the hospital through more preventive flu shots for healthcare workers—including lab personnel—and the public. She worries about transmission from patients who skipped routine physician visits and vaccines. BMC is devising a new vaccination strategy for healthcare workers and a public campaign aimed at early-season flu vaccines for adults and children. It will rely on vaccinations outside of usual settings, perhaps in mobile health clinics and satellite facilities.
For now, change will be the new normal. “Past years’ experience cannot be a crib sheet for flu in autumn,” Kasten noted. “In a word, the approach for respiratory testing this fall will be flexibility,” Mathers added.
Deborah Levenson is a freelance writer in College Park, Maryland. +Email: [email protected]