Could COVID-19 and combined flu tests help overwhelmed hospitals?

In greater Kansas City, COVID-19 cases are on the rise. Raghu Adiga, the chief medical officer of Liberty Hospital, is worried and a little angry.

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

This is the worst scenario infectious disease experts in the United States have warned about. Flu season is colliding with COVID-19 in a country with a patchwork of restrictions, upcoming family vacations, and a shortage of rapid diagnostic tests 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 competed to produce multiplex tests that can quickly distinguish between COVID-19, influenza, and other respiratory diseases with a sample of patients. But there aren’t enough of these tests to meet the demand. Ask Adiga, who has perhaps a quarter of the multiplex tests she estimates she needs. When all coughs and fevers seem more or less the same, his staff must prioritize who gets those tests faster, while other patients wait hours upon potentially infectious hours to find out what they have.

“I’m afraid things will get really worse in the next 2-3 weeks,” says Adiga, her voice tense as she describes the situation. “We are paying the price for what the community hasn’t done.”

It remains to be seen how bad the US flu season will be. This is because COVID-19 has put knots, both positive and negative, in the Southern Hemisphere signaling system that epidemiologists use to predict the severity of the Northern Hemisphere flu season, says Ian Barr, Deputy Director of the Reference Center for Health. collaboration with the World Health Organization and influenza research in Australia.

The Australian government quickly blocked things in March, which is the start of the Australian flu season, and pushed people to get vaccinated. When the dust cleared and flu season was over, Barr says, there were so few flu infections and deaths that there wasn’t enough data to make any claims about how dangerous this year’s flu could be. But Charles Chiu, an infectious disease doctor at the University of California, San Francisco, says that even if the United States does not experience the dreaded “twindemic” of widespread flu and COVID-19, a small outbreak of influenza could cripple systems. sanitary.

“My concern is not that we will have an extremely virulent flu season. My concern is that even having a record low number of flu cases will put a strain on tests and hospitals both, ”Chiu says.

Multiplex tests are aimed at alleviating 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 the influenza A or B virus in the same test. Both are licensed for emergency use by 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 requires fewer technician hours, which could prevent human error. But the tests also require healthcare professionals to have specialized tools.

Roche’s high-capacity test results arrive in about 1 hour, but its Cobas lab-in-a-tube rapid test only takes about 20 minutes. A person’s nasal swab is inserted into a tube that is inserted inside Roche’s specialized machine. That tube has chambers, each of which contains different chemicals that process the sample when the seals break and the sample flows from one chamber to the next. When 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 the viral genetic material into a form that is repeatedly copied and detected by fluorescent molecules being added. as copies are made. Any signal above a certain threshold is a positive test.

“We really hope that the ability to squeeze multiple tests into a single tube will be a potential point of relief for the human element in lab testing,” says Valsamakis.

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

Roche validated its tests using 56 COVID-19 patient samples. All 56 tested positive. This detection rate is similar to the company’s comparable diagnostics for COVID-19 only. Different tests for different strains of influenza were all performed over 92%.

Viral genetics is a big driver of how diagnostics are done, says Dave Persing, chief medical and technical officer at Cepheid, a molecular diagnostics company that runs the multiplex test used by Liberty Hospital. Cepheid’s Xpert Xpress is also based on PCR and can distinguish between SARS-CoV-2, influenza A or B virus, and respiratory syncytial virus (RSV), which has similar respiratory symptoms. The Cepheid test produces results in approximately 35 min. And if healthcare professionals want to test for COVID-19 only, they can “turn off” the other parts of the test, says Persing. The company validated the diagnostics using 240 human samples carrying one of the viruses and compared the results to the individual diagnostic test for each. The combined diagnostics provided 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 the Cepheid test recognizes the envelope gene and the nucleocapsid gene, which produces a protein that clings to the virus’s RNA. Both genes are highly conserved among coronaviruses, something Persing says should make the test applicable to the next coronavirus outbreak. The RSV portion of the test covers two strains of that virus, while the flu portion detects current and potential future prevalent strains.

While hospitals like Liberty, which have the Cepheid machine, may choose to run tests separately, Persing says it’s easier and cheaper to have COVID-19 and the flu, at least, on the same cartridge. However, he says, supply will be an industry-wide problem.

And this is Adiga’s problem. It has about 150 multiplex tests a week, and it takes more than 600. This has forced hospital staff to make tough choices about who should get the limited supply. Meanwhile, Adiga joins 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 two years. We can’t have people gathering, “he says.” If we have to do something in the community to reduce the number of people who show up at our door, that’s what we need to focus on. “