COVID-19 Testing: Which Tests, Where, and Why? [with a special FOCUS on the USA]

In order to contain the COVID-19 pandemic in any country, healthcare systems need to be able to rapidly diagnose patients for treatment and public health officials should realistically calculate the percentage of the population that has been exposed and can safely return to work.

Thus, accurate and well-placed testing to detect and differentiate between active and cleared infection is one of the main cornerstones to formulating both isolation and isolation re-emergence strategies.  This creates an almost insatiable market for testing solutions, but strategic deployment of testing based on attributes rather than number could greatly accelerate countries’ plans to contain viral spread. 

Alcimed analyzes the different approved COVID-19 tests and highlights what kinds of tests can be deployed where to maximize information and resources regardless of where in the outbreak cycle a country currently is.

Current Testing Methods: Strengths & Limitations

Tests vary widely in turnaround time, number & type of personnel required to administer, and expense of the test and test system.
Consequently, some tests will be more useful than others in stopping the pandemic at different stages of its progression.

For diagnostics, the standard remains nucleic acid amplification, including PCR and rapid molecular point-of-care (POC) tests. Antibody tests are also essential for detecting previous exposures and cleared infections.

Another variable is test accuracy. Due to the critical need, regulatory agencies in granting emergency use authorization have set a low bar for test accuracy. Few studies have compared the accuracy of different COVD-19 tests. As a result, positive and negative results need to be considered provisional, and retesting may be needed.

Nucleic Acid Molecular Detection

PCR Tests allow for a yes/no determination for COVID-19 infection, but there are significant drawbacks.

First, there is the time lost: 24 hours or more for shipping, 6 hours for processing, and results communication.
This may be a good testing method for surveying an asymptomatic population or testing mildly ill patients self-quarantining at home, but clearly is far too slow to help hospitals direct positive patients to a special area of the hospital for isolation or quickly determine if they are eligible for experimental treatments.

Shipping time can be saved by in-house hospital testing.
Several examples of tests designed to run in hospital labs are Abbott’s SARS-Cov-2 test that can run on its m2000 Realtime analyzer, and BD’s joint test with BioGX designed to run on BD’s MAX system. The Abbot m2000 can process 470 of the tests a day and provide results in 6.5 hours, but only larger hospitals tend to have such equipment. Smaller hospitals still rely on governmental reference labs, commercial labs, and even university labs have been deputized for testing.

Rapid Molecular Point-of-Care (POC) Tests

Rapid Molecular Point-of-Care (POC) Tests reduce turnaround time to minutes, allowing quick separation of COVID-19 patients and allow regular HCP screening.

POC tests require minimal hands-on involvement and run on small, easily portable machines that can be used in nursing homes, urgent care facilities and other locations.
On the downside, healthcare providers still need to take the sample from patients to apply to the test cartridges, potentially exposing themselves and using up PPE.

Cepheid GeneXpert® Xpress SARS-CoV-2

Cepheid’s test was the first rapid point-of-care test to receive emergency use authorization (EUA) by the FDA, on March 20^th.

The test takes about 45 minutes to provide results and runs on the company’s GeneXpert systems, 5,000 of which are already in use in US hospitals and medical facilities.
Although not a high-throughput machine, the system can process 96 tests in 24 hours. Cepheid based its SARS-CoV-2 test on the same cartridge technology as its current flu/RSV test which targets multiple sections of the viral genome to detect current and possible future variants of the pathogen.

The GeneXpert system can run 24/7 and does not require any special training to run.
Cepheid’s Dr. David Persing says the tests should be limited to in-hospital use for patient isolation and management to reduce strain on the testing supply. However, the test could also be useful in outpatient settings as production ramps up.

Price could be an issue for mass testing, with each test cartridge reportedly costing $35 in the US although Médecins Sans Frontiéres (MSF) has been pushing for a $5 price. Although similar to the price of commercial reference lab tests, hospitals may have to purchase the materials themselves whereas reference lab tests are billed directly to the patient’s health insurer.

The GeneXpert platform itself costs ~$17,000 and may be especially useful in Africa where there are already many GeneXpert devices due to prior investment in TB testing by The Global Fund and others.

Mesa Biotech Accula™ SARS-CoV-2 Test

Mesa Biotech was second to receive an EUA from the FDA for its rapid point-of-care test, on March 23^rd, and can deliver results in 30 minutes.

Mesa Biotech has focused specifically on developing diagnostics well-suited for combatting pandemics (including SARS & Ebola) and anticipates that its SARS-CoV-2 test will decentralize testing from hospitals and commercial labs to primary care offices, nursing homes, and mobile screening facilities.

The test uses similar PCR technology to its test for flu and RSV, using the same palm-sized “dock” to receive test cartridges and sample.

Abbott ID Now COVID-19 Test

This test uses isothermal nucleic acid amplification to provide a yes/no answer to whether the virus is present and is the fastest test to be announced so far, taking 5 minutes for a positive result, and 13 minutes for a negative result.

It runs on Abbott’s ID NOW^TM platform—a toaster-sized box weighing 6.6 pounds which is also used for flu and strep tests and is the most common molecular point-of-care test platform in the USA according to Abbott, with about 18,000 in circulation.
Many of these are in non-hospital locations such as physicians’ offices and urgent care centers where tests could be done on all patients to identify COVID-19 cases.

Abbott says they will be able to deliver 50,000 tests per day in April which is about half the total daily number of COVID-19 tests currently run in the USA.

Antibody Tests

Antibody tests detect the presence of antibodies to SARS-COV-2 signaling prior infection, which can take several weeks to rise in response to initial infection.
These tests are needed to understand how much of the population has been exposed and developed immunity, and how much of the population remains at-risk.

The CDC (Center for Disease Control and Prevention) has already begun to conduct these serology studies in COVID-19 hotspots like NYC and will launch a national study this summer, as well as a study of US healthcare workers.

These tests are less urgent than tests for active infections making reference labs well-suited to process these tests.
However, rapid point-of-care tests using minimal sample can make collection and reporting quicker and easier and facilitate their use at convenient locations like doctors’ offices and mobile testing facilities.

BD and BioMedomics’ require minimal equipment and takes only 15 minutes. Healthcare providers collect a few droplets of blood and apply to the test cartridge with a few drops of buffer. Additionally, Scanwell Health is seeking an emergency use authorization for their at-home test in which patients answer an online questionnaire to receive a test kit by mail, take a simple blood sample via finger prick, scan the results with an app and receive an explanation by a healthcare provider online.
Unlike all the tests discussed so far, this test can be ordered by a non-healthcare provider and when paired with spit test collection give a better picture of the infectious burden and level of immunity for those still in isolation.

In brief, as cases are mounting in a new location, rapid molecular POC tests can be deployed to quickly isolate COVID-19 patients reporting to hospitals while at-home spit tests can be deployed on populations sheltering in place to allow for contact tracing and rapid assessment of the viral burden in the population. This maximizes social distancing, reduces the number of HCPs and PPE required for widespread testing, and can equally distribute the processing burden across all available labs (government, commercial, and academic).
Test results can be consolidated online for more efficient reporting and connected directly to electronic medical record systems where they exist.
Even in countries without significant online populations, SMS reporting, and door to door reporting would still significantly reduce the number of HCPs required to monitor whole populations, while cycling up their antibody testing capacities. 

Countries mid-outbreak can also begin rapidly deploying a mixture of POC and at-home molecular and serology tests to speed the rate at which deciphering active infections and developed immunity exist at a population level to estimate re-opening risks and actively monitor those still at risk with the more efficient contact tracing and targeted quarantine, as well as create efficient border screening to prevent new imported cases as travel restrictions are also eased. 

About the authors

Ephraim, Senior Consultant in Alcimed’s Healthcare team in the USA