A wait-and-watch season of respiratory viruses

Charna Albert

October 2022—Influenza incidence and what it will mean for testing in this respiratory virus season is a wild card, as is how SARS-CoV-2 will evolve. In early September, SARS-CoV-2 prevalence was declining in parts of the United States. “And if you believe in the theory of viral interference,” says Michelle Tabb, PhD, chief scientific officer at DiaSorin Molecular, “it’s leaving the door wide open right now for something else to step in. We’ll see if that’s RSV, or flu A, or if it’s a new COVID variant.”

Australia saw an early peak in influenza and the highest it has seen in about half a decade, simultaneous with COVID, says David Persing, MD, PhD, chief scientific officer at Cepheid. Public health advisors worry the same could happen in the Northern Hemisphere. “The concern is we’re going to have a surge in influenza and an ongoing level of COVID activity that will combine to create a pretty consequential respiratory season,” Dr. Persing says. Furthermore, with fewer exposed to influenza over the past two years, “the lack of natural immunity could create a condition in which we have more severe cases, or more cases overall, and that’s what everybody is afraid of.”

Australia’s statistics, while concerning, could reflect some amount of ascertainment bias, says Daniel Rhoads, MD, assistant professor and section head of microbiology at the Cleveland Clinic. “People are getting tested more now than they did pre-COVID when they have a respiratory virus,” he says. “So I think we’re going to detect more influenza, and we have to keep in mind that increased testing is going to lead to increased detection.”

What impact flu will have on the laboratory this season is uncertain, he says, because how many of those who become ill and don’t need hospitalization will seek a laboratory diagnosis for their respiratory disease is “an unknown variable.”

Nevertheless, he’s more confident about the upcoming respiratory season than he was in the previous pandemic years, thanks to experience. “We’ve learned a lot through the school of hard knocks,” he says. “And supply chain is in a much better place than it was a couple years ago.” Though there’s still the risk of severe outbreak in the vein of omicron this winter, “the challenge then isn’t so much the reagents. It’s having enough healthy people to take care of all the patients and do all the testing. So I think that remains a potential point of failure.”

Dr. Rhoads and others in late summer shared their predictions and plans for the upcoming season.

The Cleveland Clinic’s laboratory is implementing a testing strategy, honed over the past few pandemic years, that reflects the need to differentiate patients’ respiratory symptoms.

In the 2020–2021 flu season, Dr. Rhoads says, the Cleveland Clinic did not test adults for influenza routinely because of acutely limited resources. “We continued to test symptomatic children throughout that winter and essentially didn’t detect any influenza.” The following winter, he says, influenza A did circulate. “Interestingly, it was circulating and then omicron emerged. And during peak omicron, influenza dropped, and then as it waned, influenza came back. But we saw only H3N2 last winter, whereas typically we’ll see two influenza strains circulate sequentially in winter.” It may be that SARS-CoV-2 outcompeted flu, “but there are different opinions and thoughts,” he says. “I don’t know that we have good answers.”

This year at the Cleveland Clinic, he says, anyone who is symptomatic will receive multiplex testing for SARS-CoV-2 and influenza. “We will do stat testing if a patient is coming through the emergency department and might need hospitalization. We use the Cepheid Gene­Xpert platform for that.” Those platforms, he says, are installed in the main campus laboratory and distributed throughout the region at the Cleveland Clinic’s local hospitals.

For routine outpatient testing, they will run the Roche Cobas SARS-CoV-2 and influenza A/B test on the Cobas 8800 platform, which is performed as consolidated testing at the main campus. “And then for children, especially young children, we typically test for RSV in addition to influenza and SARS-CoV-2.” For routine turnaround time, that testing is performed on Hologic’s Panther using the Panther Fusion Flu A/B/RSV assay, which is RT-PCR, and the Aptima SARS-CoV-2 assay, which uses Hologic’s transcription-mediated amplification technology. “So those are our go-to workflows,” he says. Broad respiratory panel testing with the BioMérieux BioFire RP2.1 or Luminex NxTAG is used sparingly, he adds, typically on immunocompromised inpatients.

The Cleveland Clinic performed rapid molecular point-of-care testing for influenza on the Roche Cobas Liat (which can test for flu A/B and SARS-CoV-2 simultaneously, or A/B and RSV) in years past but stopped at the beginning of the pandemic, Dr. Rhoads says, and as of now has no plan to reinstate it. “We keep talking about it,” he says, “but there’s a few challenges with point-of-care testing in 2022. One is that it takes space and time to do the testing and we all know that staffing, in the laboratory but also at the front lines where people are seeing patients in primary care, is challenging.”

In addition, he says, some of the POC platforms are capable of testing for only one virus at a time, “or at least not all the viruses at one time. So now in addition to needing time, you sometimes need more than one sample, or more than one instrument. Or if the point-of-care testing is antigen testing and you don’t believe the result, if it doesn’t fit with the clinical syndrome, then maybe you’re collecting another sample and sending it for a nucleic acid amplification test. So where we’ve landed and what we’re planning for this season is to do lab-based testing.” The stat testing is done on site or at a local laboratory with a PCR platform, he says, and the routine outpatient testing in the main campus laboratory has a turnaround time of about a day.

New this year for the Cleveland Clinic is the SelfCheck Cobas SARS-CoV-2 + Flu assay, for which the laboratory received an EUA from the Food and Drug Administration. The test, which detects influenza A and B in addition to SARS-CoV-2, pairs an unsupervised, self-collected anterior nasal swab specimen with the Roche Cobas 8800 workflow, Dr. Rhoads says. Patients collect their specimen at home and deposit it in one of many drop boxes located throughout the Cleveland Clinic system. “It’s convenient for us in the laboratory because we can use it with our high-throughput testing systems.”