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Combined COVID-19 and flu tests could help overwhelmed hospitals

The tests are fast, are easy to perform, and require only one patient sample. But some hospitals are saying there are just not enough to go around

by Megha Satyanarayana
November 18, 2020 | A version of this story appeared in Volume 98, Issue 45


A health-care worker wearing a mask, face shield, and gloves holds a swab sample.
Credit: Jon Nazca/Reuters/Newscom
Tests that can distinguish between COVID-19 and the flu with one patient sample could reduce testing burdens and the use of critical supplies.

In greater Kansas City, COVID-19 cases are climbing. Raghu Adiga, the chief medical officer at Liberty Hospital, is worried—and a little bit angry.

He has neither the staff nor the testing capacity to manage the respiratory illnesses that are increasingly coming through the door. It’s flu season. The Thanksgiving holiday is coming. He fully expects people to gather, probably without masks, as there are no mandates in this part of the Midwest, where prevention fatigue mixes with a strong undercurrent of preserving individual rights. He sees hospitals in his corner of Missouri that will soon be overwhelmed.

This is the worst-case scenario that infectious disease experts in the US have been warning about. The flu season is colliding with COVID-19 in a country with a patchwork of restrictions, upcoming family holidays, and a dearth of rapid diagnostic testing for SARS-CoV-2. Knowing whether people have the flu or COVID-19 affects not only the treatment they receive but also whether they would be isolated if hospitalized.

Several companies have raced to produce multiplex tests that can quickly distinguish between COVID-19, the flu, and other respiratory diseases with one patient sample. But there just aren’t enough of these tests to meet demand. Ask Adiga, who has maybe one-quarter of the multiplex tests he estimates he needs. When all coughs and fevers seem about the same, his staff has to prioritize who gets those faster tests, while other patients wait hours upon possibly infectious hours to find out what they have.

“I’m afraid things are going to get really worse in the next 2–3 weeks,” Adiga says, his voice strained as he describes the situation. “We are paying the price for what the community hasn’t done.”

How bad the US flu season will be remains to be seen. That’s because COVID-19 has put kinks, both good and bad, in the Southern Hemisphere reporting system that epidemiologists use to predict the severity of the Northern Hemisphere’s flu season, says Ian Barr, the deputy director of the World Health Organization Collaborating Centre for Reference and Research on Influenza, in Australia.

My worry is that even having a record low number of flu cases is going to put a strain on testing and hospitals both.
Charles Chiu, professor, University of California, San Francisco

The Australian government locked things down quickly in March, which is the start of Australia’s flu season, and pushed people to get vaccinated. By the time the dust cleared and the flu season ended, Barr says, there were so few flu infections and deaths that there weren’t enough data to make assertions about how dangerous this year’s flu might be. But Charles Chiu, an infectious disease doctor at the University of California, San Francisco, says that even if the US doesn’t experience the feared “twindemic” of widespread flu and COVID-19, a small flu outbreak could cripple health-care systems.

“My worry is not that we are going to have an extremely virulent flu season. My worry is that even having a record low number of flu cases is going to put a strain on testing and hospitals both,” Chiu says.

Multiplex tests are meant to alleviate these strains, says Alexandra Valsamakis, the chief medical officer of Roche Molecular Diagnostics. Roche has two products that can detect the COVID-19 coronavirus and influenza A or B virus in the same assay. Both have emergency use authorizations from the US Food and Drug Administration. Combining multiple infectious diseases into one test means using only one set of reagents, some of which are in short supply, and it requires fewer technician hours, which could prevent human errors. But the tests also require health-care providers to have specialized instruments.

Results from Roche’s higher-capacity test arrive in about 1 h, but its Cobas lab-in-a-tube rapid test takes only about 20 min. A person’s nasal swab is placed in a tube that is put inside Roche’s specialized machine. That tube has chambers, each of which contains different chemicals that process the sample as seals break and the sample flows from one chamber into the next. By the time the sample reaches the bottom of the tube, Valsamakis says, it encounters the enzymes and buffers needed to perform the polymerase chain reaction (PCR) that converts viral genetic material into a form that is copied repeatedly and detected by fluorescent molecules that are added as the copies are made. Any signal above a certain threshold is a positive test.

“We are really hoping that the ability to collapse multiple tests into a single tube will be a potential relief point for the human element in laboratory testing,” Valsamakis says.

Roche’s tests use multiple viral targets for the flu and COVID-19, a strategy Valsamakis says prevents the test from becoming obsolete as these viruses change genetically over time. The COVID-19 targets are the SARS-CoV-2 gene that makes the envelope protein that protects the virus, and a section of the virus’s RNA called open reading frame 1ab, the proteins of which may be involved in signaling and the expression of other viral genes. The flu targets are matrix genes and a nuclear export protein gene.

Roche validated its tests using 56 samples from COVID-19 patients. All 56 tested positive. This detection rate is similar to the company’s comparable diagnostic for COVID-19 only. Several assays for different strains of flu all performed above 92%.

Thanksgiving can’t really happen like every other year. We can’t have people gathering.
Raghu Adiga, chief medical officer, Liberty Hospital

Viral genetics is a big driver of how diagnostics are made, says Dave Persing, chief medical and technical officer at Cepheid, a molecular diagnostics firm that makes the multiplex test that Liberty Hospital uses. Cepheid’s Xpert Xpress also relies on PCR, and it can distinguish between SARS-CoV-2, influenza A or B virus, and respiratory syncytial virus (RSV), which has similar respiratory symptoms. Cepheid’s test produces results in about 35 min. And if health-care workers want to test for only COVID-19, they can “turn off” the other parts of the test, Persing says. The company validated the diagnostic using 240 human samples carrying one of the viruses and compared those results with the single diagnostic test for each. The combined diagnostic gave only one false negative for COVID-19 and two false positives for influenza B; there were no false results for influenza A.

The SARS-CoV-2 part of Cepheid’s test recognizes the envelope gene and the nucleocapsid gene, which makes a protein that clings to the virus’s RNA. Both genes are highly conserved between coronaviruses, something Persing says should make the test applicable to the next coronavirus outbreak. The RSV part of the test covers two strains of that virus, while the flu portion detects current prevalent strains and potential future ones.

While hospitals like Liberty, which have the Cepheid machine, could opt to run tests separately, Persing says it’s easier and cheaper to have COVID-19 and the flu, at least, on the same cartridge. Still, he says, supply is going to be an issue industry-wide.

And this is Adiga’s problem. He has about 150 multiplex tests per week and needs more than 600. This has forced hospital staff to make difficult choices about who should get the limited supply. In the meantime, Adiga is joining other hospital administrators in greater Kansas City to plead with elected officials and public health authorities for social restrictions.

“Thanksgiving can’t really happen like every other year. We can’t have people gathering,” he says. “If we are going to have to be doing something in the community to reduce the number of people showing up at our door, that’s what we really have to be focusing on.”


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