By Paul Nicolaus
November 2, 2020 | As the coronavirus pandemic overlaps with flu season, some experts say early detection will be especially crucial for battling this double threat. And in recent months, new diagnostic tests have emerged to help distinguish one from the other.
SARS-CoV-2, the virus that causes COVID-19, has clearly proven to be deadly. The global fatality count has already surpassed 1 million as the pandemic continues. Year in and year out, meanwhile, seasonal influenza has proven lethal as well. The World Health Organization (WHO) estimates that seasonal flu leads to roughly 290,000 to 650,000 annual deaths due to respiratory diseases.
Every year, the flu virus has a mutation, explained Amit Roy, an internal medicine physician in New York. While scientists continue to learn more about the novel coronavirus as time goes on, some aspects remain mysterious for now. “We do not know yet if such rapid mutation would take place with the coronavirus,” he told Diagnostics World.
With flu season already underway in the northern hemisphere yet peak flu season still to come, public health officials and infectious disease experts have expressed concern about the prospect of facing exposure to both of these potentially deadly viruses during the same stretch.
One key challenge is that the symptoms of COVID-19 and influenza are so similar. It can be challenging for clinicians to distinguish one from the other based on signs alone, which can include fever, chills, body aches, sore throat, runny nose, cough, or gastrointestinal issues like diarrhea, nausea, or vomiting.
There are some differences. COVID-19 can, in some patients, cause a sudden loss of smell or taste. But that’s not enough to make a definitive diagnosis, Sandy Schneider of the American College of Emergency Physicians said during a Sept. 19 podcast episode hosted by the Infectious Diseases Society of America (IDSA).
Another worrisome aspect is that flu and COVID-19 could conceivably occur in the same individual at the same time. “From an emergency physician point of view, what we’re probably going to need to do is rely a lot on testing,” Schneider said.
But this does pose some challenges. While flu tests are generally good at picking up patients who have influenza, false negatives can occur for various reasons, ranging from poor sample acquisition to the test itself. And the same goes for COVID-19. If the test comes back positive, the patient probably has COVID-19. If the results are negative, on the other hand, it doesn’t necessarily rule out infection.
And while many are focused on the flu and COVID-19 in particular, some infectious disease experts have pointed out that other respiratory illnesses circulate during flu season and can present similarly, which can add to this sense of uncertainty.
Experts Say Prepare for the Worst
During the IDSA talk, Edward Michelson highlighted this year’s flu season in the southern hemisphere, which was surprisingly mild. The reason behind this dramatic decline in cases and hospitalizations is probably due to the protective actions taken against COVID-19, explained Michelson, a professor in the Department of Emergency Medicine at Texas Tech University’s Health Sciences Center.
Although a mild flu season in the southern hemisphere is often an indication of a mild season in the northern hemisphere, some experts have pointed out the lingering unknowns in a country like the United States, where there are high COVID-19 case numbers as well as a strong sense of independence and reluctance, by some, to follow prevention measures such as social distancing or wearing a mask.
Speakers at a Sept. 10 briefing hosted by IDSA suggested Americans prepare for the worst-case scenario as people are exposed to multiple dangerous viruses at the same time. There is concern about college campuses, for instance, where students appear to be a significant source of COVID-19 outbreaks, explained Jeanne Marrazzo, director of the division of infectious disease at the University of Alabama at Birmingham.
And it isn’t clear that state labs have the supplies needed to process both COVID and flu tests, she added, or that public health authorities at the state and local levels have adequate staffing to support surveillance during this year’s flu season.
Combination testing could offer some advantages. Taking just one sample from a patient could lead to quicker, more comprehensive results, and require fewer consumable supplies, like swabs, which could help ease pressure on the supply chain.
During the spring months, the US Food and Drug Administration (FDA) issued emergency use authorization (EUA) to Salt Lake City, Utah-based BioFire Diagnostics LLC for its BioFire Respiratory Panel 2.1 and to German company QIAGEN GmbH for its QIAstat-Dx Respiratory SARS-CoV-2 Panel—both of which produce test results within about an hour. And later, in July, the agency issued EUA authorization to a test developed by the Centers for Disease Control and Prevention (CDC), which provides results in roughly four hours but is not commercially available.
Marrazzo pointed out that these types of tests would require a lab with the ability to conduct genetic testing, however, and (as of the Sept. 10 briefing) indicated there was still no widely available diagnostic tool that could test for both COVID-19 and the flu.
More Tests Arrive, Some Trim Turnaround Time
Throughout the months of September and October, other developers continued to announce the arrival of combination tests.
Austin, Texas-based Sonic Healthcare USA launched a multiplex RT-PCR assay that combines testing for SARS-CoV-2 and Influenza A/B with a single specimen collection. And GenMark Diagnostics, based in Carlsbad, Calif., announced its ePlex Respiratory Pathogen Panel 2 (RP2). The molecular test provides results in under two hours for more than 20 viruses and bacteria that cause common respiratory infections, including COVID-19, influenza A and B, respiratory syncytial virus (RSV), and rhinovirus.
New Jersey-based BioReference Laboratories, Inc., an OPKO Health company, indicated it is now accepting specimens for a new multiplex COVID-19 and influenza test intended for use by healthcare providers, clinics, and health systems throughout the United States to help diagnose COVID-19 and Influenza A or B.
The availability of a CE-IVD marked test for the simultaneous detection of SARS-CoV-2, Influenza A, Influenza B and RNA was announced by BioGX BV, the European subsidiary of Birmingham, Alabama-based BioGX. The test has a time-to-result of under 2 hours for 24 samples but is not available for sale or use in the United States, according to a late September statement.
Other tests, meanwhile, could reduce the turnaround time needed to gather a result. Sunnyvale, Calif.-based Cepheid’s Xpert Xpress SARS-CoV-2/Flu/RSV, for instance, is a four-in-one rapid molecular diagnostic test intended to detect the viruses causing COVID-19, Flu A, Flu B, and RSV infections from a single patient sample and can deliver results in under 40 minutes.
Roche’s rapid version of its Cobas SARS-CoV-2 & Influenza A/B test is designed to run on the Swiss company’s benchtop Cobas Liat system. It offers results for single samples in under 20 minutes and provides the option of conducting rapid testing in either point-of-care or clinical lab settings. (Roche had previously announced a combination test designed to run on its 6800/8800 systems, which is capable of providing up to 96 results in about three hours.)
Quidel Corporation, based in San Diego, Calif., announced its Sofia 2 Flu + SARS Antigen FIA rapid point-of-care test that delivers three results from one sample in about 15 minutes. The test is designed to be used with the Sofia 2 Fluorescent Immunoassay Analyzer for the simultaneous detection and differentiation of the antigens from SARS-CoV-2, influenza A, and influenza B in nasopharyngeal and nasal swab specimens.
Still other developments are in the works.
Abacus Diagnostica, a Finnish company specializing in rapid molecular diagnostics, has been working toward a four-in-one test kit for detecting influenza A, influenza B, RSV, and SARS-CoV-2. According to a statement released earlier this fall, the company anticipates a November market launch.
And while LabCorp has already launched a multiplex for COVID-19, flu, and RSV, the Burlington, N.C., company has indicated that it has its sights set on providing an at-home combination test, too.
Availability Needs to Pick Up
Because COVID-19 and influenza symptoms overlap, in patients with symptoms or severe disease it will be important to determine the cause in order to provide effective therapy, explained Gerald W. Fischer, CEO of Longhorn Vaccines & Diagnostics, a molecular tool, assay, and vaccine development company.
Fischer also noted that with multiple respiratory viruses circulating during the fall and winter, patient co-infection with COVID-19 and another respiratory virus (such as influenza) could lead to more severe illness and an increase in hospitalizations.
Tests that detect both SARS-CoV-2 and influenza will be helpful for physicians seeing symptomatic patients, he told Diagnostics World, because a rapid and specific diagnosis may enable not only improved treatment for the patient but also influenza prophylaxis for individuals at high risk of infection and for those who are exposed to an infected patient.
One key challenge, however, “will be providing enough tests once the population becomes fully involved with flu and cold season,” Fischer added.
Because similar symptoms characterize COVID-19 and flu, a significant concern is that the flu season will cause confusion and put further strain on healthcare systems that are already overwhelmed by the pandemic, according to Arvind Kothandaraman, general manager of specialty diagnostics at Massachusetts-based PerkinElmer.
“A single test that can accurately detect and differentiate between COVID-19 and flu will be vital to manage this situation,” he explained.
The company’s PKamp Respiratory SARS-CoV-2 RT-PCR Panel, which has received clearance to be marketed as an in vitro diagnostic (IVD) device in over 30 countries, enables differential diagnosis between COVID-19, flu, and RSV infection. It is built off PerkinElmer’s SARS-CoV-2 assay, which has been established as the most sensitive test kit in the market, according to the FDA’s reference panel comparative data.
“Accurate and timely differential diagnosis will drive informed decisions to prevent panic and enable careful allocation of precious medical resources,” he told Diagnostics World, and suppliers of the more sensitive COVID-19 tests are likely to have the expertise needed to come up with multi-target assays without sacrificing quality.
Labs are preparing to provide healthcare professionals with these test results, he explained, and reducing turnaround time will remain crucial.
While combination tests are “trickling in” as of early fall, Kothandaraman said availability will need to pick up to meet global demand. That’s no small feat considering the pandemic has led to supply shortages of many materials needed for testing, and the surge in test samples during flu season will only heighten existing demand.
Labs will be looking to address this issue, he added, by working with reliable manufacturers who can supply the equipment, reagents, and consumables needed for testing.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.