By Paul Nicolaus
March 17, 2020 | The coronavirus outbreak continues to wreak havoc as diagnostic developers scramble to come up with tools to combat the spread of disease.
As of Mar. 17, the number of people who have been infected has topped 180,000, including over 7,000 deaths since the outbreak began back in December, according to a virus tracker maintained by researchers at Johns Hopkins University.
The vast majority of cases—more than 80,000—have occurred in China, but over 100 countries have now reported laboratory-confirmed cases of COVID-19, including substantial numbers in Italy, Iran, Spain, and South Korea.
In the United States, there have been over 4,600 confirmed cases, although experts expect that figure to rise considerably as testing becomes more widespread following an initial response that critics have called both sluggish and flawed.
In the wake of the disease, Wall Street has witnessed historic sell-offs, and the U.S. has begun to shut down. Heading into mid-March, schools announced closures, businesses implemented telework, and sporting events have been cancelled or postponed.
Despite the troubling news piling up in recent weeks, there have been signs of innovative practices and possibilities along the way. The University of Washington’s UW Medicine began providing drive-through testing, for example, and the Gates Foundation announced plans to pursue at-home coronavirus test kits.
Beyond that, a flurry of recent announcements suggest that testing will continue to pick up in the days ahead.
New Policy to Expand Testing Capacity
On Mar. 16, the U.S. Food and Drug Administration (FDA) updated a policy originally issued on Feb. 29 in the hopes of achieving more rapid testing capacity in the U.S. The new guidance implements a policy for states to take responsibility for tests developed and used by laboratories within their borders and expands who the policy outlined in the initial guidance applies to.
Under the update, the agency indicated that—under certain circumstances—it does not plan to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an Emergency Use Authorization (EUA).
To date, over 90 test developers have sought assistance from the FDA with development and validation of tests they plan to bring through the EUA process, and more than 40 labs have notified the agency that they are testing or plan to begin testing soon.
“The number of products in the pipeline reflects the significant role diagnostics play in this outbreak and the large number of organizations we are working with to bring tests to market,” said FDA Commissioner Stephen Hahn in an announcement of an EUA recently issued to Thermo Fisher Scientific for its TaqPath COVID-19 Combo Kit.
The test is designed to provide results within four hours of a sample being received by a lab, the company explained. Thermo Fisher currently has 1.5 million tests available to ship to about 200 labs throughout the U.S. Moving forward, the company expects to ramp up to 2 million tests per week, and by the month of April expects to scale production up to 5 million per week.
The Roche cobas SARS-CoV-2 Test was the first commercially distributed diagnostic test to receive an EUA during the COVID-19 outbreak, FDA indicated. Hospitals and reference laboratories can run the test on Roche’s fully automated cobas 6800 and cobas 8800 Systems, according to the company, and test results are available in under four hours.
Most recently, FDA issued EUAs to Hologic for its Panther Fusion SARS-COV-2 Assay and to LabCorp for its COVID-19 RT-PCR test.
Hologic said the company can immediately begin shipping its product to labs across the United States, and beginning in April, expects to make nearly 600,000 tests per month. When LabCorp announced its test back on Mar. 5, the company indicated that after specimens are sent in from healthcare facilities, where patients are seen and the tests are ordered, results would be available within 3 to 4 days.
Prior to these latest commercial developments, the agency had issued EUAs to diagnostic tools put forth by the New York State Department of Public Health and the CDC.
In Pursuit of Faster Results
Others have emphasized the need for faster options.
The traditional testing process involves shipping samples from sick individuals to laboratories for processing, LexaGene’s CEO and Founder Jack Regan has explained. This inefficiency introduces a time-delay that can have serious consequences for disease spread.
While the development of new diagnostic tests are important, the challenge is bringing tests out of the specialized reference labs, which can take days to return results, and instead get them to settings like clinics, hospitals, and airports, where answers are needed quickly.
The company has announced its pursuit of a point-of-care genetic analyzer capable of detecting new pathogens on-site in one hour without the need for trained lab technicians. LexaGene says it is on track to deliver a next-generation pathogen detection system in Q3 of this year.
Salt Lake City, Utah-based Co-Diagnostics presented its new rapid diagnostic test for COVID-19 at the Molecular Medicine TriConference in early March. The test takes between one and two hours from blood sample collection to results and can be used as a companion, a confirmatory, or independent to the CDC’s test.
Physician-scientists at the University of California, San Diego (UCSD) are evaluating a new diagnostic testing system designed by start-up Fluxergy, which holds promise for identifying the SARS-CoV-2 virus in under an hour.
The evaluation is expected to be completed within a week, according to Davey Smith, a professor of medicine, head of the UCSD Division of Infectious Diseases and Global Public Health, and member of the Fluxergy Medical Advisory Board. If validated, the system will be used within UCSD clinical settings.
Hackensack Meridian Health's Center for Discovery and Innovation (CDI), meanwhile, launched a test that allows the network to quarantine and treat patients suspected of having COVID-19 with greater speed, and in the case of a negative result, keeps patients from spending unnecessary time in the hospital.
“The reason we feel that this is really critical for us and why we wanted to develop and put in place a rapid test is that we know that for coronavirus patients, especially ones that are critically ill, time is of the essence,” David Perlin, chief scientific officer of Hackensack Meridian Health's CDI, told Diagnostics World.
The test, which provides results in under four hours, is being used with patients who are presenting in the system’s tertiary care facilities and deemed to be high risk.
“We have to make rapid decisions, and that’s why we felt having a test locally, essentially point-of-care, which is within our hospital, would be really critical for patient management and in managing hospital resources,” Perlin added.
The health care network is able to test about 60 patients per day, and as of Mar. 16, Perlin said roughly 200 had been tested.
The detection aspect, which relies on real-time PCR, is not all that different from what is being used elsewhere. The difference-maker is that the tests can be processed without shipping them off and waiting on results.
Whether it’s LabCorp or Quest or other groups, Perlin said, the reason it takes a day or two—or several days—is due to the backlog of sampling.
High-throughput options like the Roche cobas system will be able to handle thousands of samples in an automated fashion, he noted, which is fantastic when it comes to screening large numbers of people who are either asymptomatic or mildly symptomatic. But those people can self-isolate for a day or two until results are received and a clinical decision can be made.
“The ones we’re more concerned about are the ones who are presenting to our emergency departments,” Perlin added. These are individuals who are critically ill and may need to be intubated. “We have to know what we’re dealing with, and that’s where we must have three or four-hour turnaround for those patients.”
Problems Hamstring Initial U.S. Testing Efforts
The actions taken to scale up testing have come amidst plenty of criticism of the initial U.S. response. Early efforts were hampered by faulty test kits sent out by the Centers for Disease Control and Prevention (CDC) and what critics say was overly narrow testing criteria.
Whereas the World Health Organization (WHO) adopted a test developed by German researchers, CDC pursued its own version that focused on a different set of the virus’s genes.
The CDC’s three-step test detects small amounts of the SARS-CoV-2 genome in a sample such as a nose swab. To ensure a test is working, kits included DNA unrelated to SARS-CoV-2.
As the agency began sending its test kits to state and local health labs in early February, though, some produced inconclusive results because of a failure of the negative control. A three-step replacement was promised but never arrived, according to a New York Times report, which meant testing was only carried out at the agency’s labs.
CDC eventually rolled out a two-step replacement and allowed some labs to continue using their tests, but it took days to get those results.
Beyond those initial test kits, part of the problem pertained to who could be tested. As infection rates appeared to remain low early on, some say the CDC’s initial criteria for who to test remained too narrow to effectively monitor and control the spread of the disease. Original criteria focused on those with symptoms and a travel history to an affected area or contact with a person known to have COVID-19.
But in northern California, an individual contracted the virus without recent international travel and without exposure to anyone known to be infected. While COVID-19 testing was requested, noted a Feb. 26 statement from University of California, Davis, “a test was not immediately administered” because the patient “did not fit the existing CDC criteria for COVID-19.”
The delayed discovery of this particular case, as well as community transmission elsewhere, highlighted the shortcomings of the early U.S. testing strategy.
Under increasing pressure to expand testing capacity, the FDA announced a policy in late February intended to expand the availability of diagnostics. Previously, only public health laboratories that could verify test kits issued by the CDC were allowed to test for the virus. The new guidance enabled some high-tech labs to create and use their own tests ahead of agency approval.
Shortly thereafter, projections soared. FDA commissioner Hahn anticipated “a substantial increase in the number of tests this week, next week, and throughout the month,” he said at a Mar. 2 press briefing. By the end of that week, he anticipated capacity could rise to approximately one million tests.
Others pointed out that it would take time to distribute vast quantities of test kits, and toward the end of that week the number of tests actually performed across the U.S. remained low, particularly when compared to the response efforts of other developed nations.
Ramping Up Testing Presents New Challenges
While testing is a crucial tool for understanding the epidemiology of an outbreak, it had become
increasingly difficult to determine just how many Americans had actually been tested once the effort moved from one handled by the CDC to one involving state public-health labs, university research labs, and eventually private labs as well.
After contacting the public-health departments of all 50 states and the District of Columbia, gathering data on websites, and corresponding with dozens of state officials, reporters at The Atlantic could only verify that 1,895 people had been tested, according to a Mar. 6 report. By comparison, the United Kingdom had tested nearly 20,000 people even though fewer than 200 cases had been detected there.
A week later, estimates indicated that roughly 16,000 had been tested for coronavirus in the United States, but by that point in its own COVID-19 outbreak, South Korea had tested over 100,000 people.
In a Mar. 10 media telebriefing, Nancy Messonnier, director of CDC’s National Center for Immunization and Respiratory Diseases, said 78 state and local public health labs across 50 states had the capacity to test up to 75,000 people for COVID-19 using the CDC lab kits. But the expectation within the next couple of weeks, she added, is that the majority of available testing would come from the commercial sector.
The following day, as WHO officially declared the outbreak a pandemic, some labs were running short on reagents for the RNA extraction process needed to determine whether samples confirm the presence of coronavirus. One crucial product in particular, made by QIAGEN (recently acquired by Thermo Fisher Scientific) was in short supply.
“We are deeply concerned that as the number of tests increases dramatically over the coming weeks, clinical labs will be unable to deploy them without these critical components,” The American Society for Microbiology noted. “Increased demand for testing has the potential to exhaust supplies needed to perform the testing itself.”
Serological Testing Could Help Reveal Scope of Outbreak
So what else is needed as the United States attempts to speed along its testing and curb the spread of disease?
Josh Sharfstein, a professor in the Department of Health Policy and Management at Johns Hopkins University who previously served as secretary of the Maryland Department of Health and Mental Hygiene and principal deputy commissioner of the FDA, pointed out that serology is one form of testing that is needed moving forward.
Unlike the tests used to diagnose active infection, serological tests could help reveal the scope of the outbreak by enabling researchers to test the blood of individuals who were not confirmed cases of COVID-19 and look for signs of immune response following exposure to the virus.
“Serology will help us to understand the spread of the virus through the population,” Sharfstein told Diagnostics World in an email, “since many people may be sick and recover without particularly noticing.”
There are efforts underway to come up this type of testing. During a Mar. 11 hearing, CDC director Robert Redfield told Congress that the agency has developed two serological tests that are being evaluated.
And in its updated policy announced on Mar. 16, the FDA provides recommendations for test developers who may wish to pursue serological tests for use during the coronavirus outbreak.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.