PCORI Biweekly COVID-19 Scan: Next-Generation Sequencing Assays, Point-of-Care Breath Test (August 6-August 19, 2020)
The Briefing provides an at-a-glance view of some important developments in the information universe surrounding COVID-19. The views presented here are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders.
Two types of coronavirus tests are worth noting: tests that detect coronavirus itself and tests that detect antibodies to coronavirus (ie, evidence of the body’s immune response against coronavirus). The first is slow, expensive, and precise. These tests can return an actual diagnosis—according to the CDC’s definition—of COVID-19. The second is fast, less expensive, less precise, and is typically used to detect past exposure to the coronavirus. While these tests might indicate if a person has been exposed to virus, they cannot return a definitive diagnosis of an active infection. However, some experts, after weighing the balance of evidence, think widespread deployment of antibody tests might help bring some normalcy back to our lives.
In this issue of the Biweekly COVID-19 Scan, we report on 2 tests (see Topics to Watch) that aim to upend this dichotomy. Both purportedly detect the actual virus but do so faster than the polymerase chain reaction (PCR) tests that are currently the gold standard. These new methods of rapid testing might help bring the power of definitive diagnosis to more people in less time. Although accuracy must always be balanced with speed and cost, the potential for more effective testing in the United States is growing.
In addition to the topics reported here, ECRI Horizon Scanning is monitoring 15 screening and diagnostics topics that might have an impact on the US health care system relative to COVID-19 in the coming year (see the first issue of the Horizon Scanning COVID-19 Supplement Status Report).
ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.
Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.
Next-Generation Sequencing Assays to Diagnose COVID-19
At a Glance
- Next-generation sequencing (NGS) assays use deep sequencing and computational methods to diagnose COVID-19, distinguish between different infectious diseases, track the spread of the coronavirus, and expedite broad screening of large populations for coronavirus exposure.
- NGS assays can purportedly test between 2000 and 3000 samples simultaneously. They may only be performed at laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
- The Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to 2 NGS assays and is evaluating other assays.
Many central laboratories performing nucleic acid-based tests to confirm a diagnosis of COVID-19 are backlogged, and some have shortages of testing supplies from spikes in COVID-19 cases in the United States. NGS assays have been developed to diagnose COVID-19. These tests include COVIDseq (Illumina, Inc, San Diego, California), CleanPlex SARS-CoV-2 panel (Paragon Genomics, Inc, Hayward, California), COVID-19 NGS test (Fulgent Genetics, Inc, Temple City, California), and Helix COVID-19 NGS test (Helix OpCo, LLC, San Mateo, California). The assays must be performed at CLIA-certified laboratories, including central laboratories and some laboratories at hospitals, research institutions, and academic institutions.
These assays employ deep sequencing (ie, a genetic sequencing technique that requires only a very small sample) and computational methods to detect nucleic acids of the coronavirus. The tests can amplify and detect sequences from the whole viral genome (ie, a string of about 30 000 nucleic acids) or several genomic regions. NGS assays purportedly offer high throughput, enabling 2000 to 3000 samples to be processed in about 12 hours. These assays might also be used in epidemiology studies to track the spread of coronavirus or to broadly screen individuals who are planning to return to work or school.
Implementing NGS testing might help guide patient management. NGS assays can purportedly process thousands of samples within 12 hours, thereby potentially decreasing the burden on central laboratories with a backlog of patient samples. NGS might also enable simultaneous identification of multiple infectious agents in a single patient sample and exclude suspected infectious agents.
Early feedback from ECRI internal stakeholders suggested that NGS might help clinicians triage infected and uninfected patients, isolate COVID-19 cases, and identify patients with viral infections other than coronavirus. They thought that NGS might also enable large-scale testing and improve public health efforts to contain coronavirus spread by confirming COVID-19 cases, detecting variants in nucleic acid sequences, and identifying transmission patterns. However, stakeholders raised concerns about a high rate of false-positive or false-negative test results—consistent with other molecular diagnostics—and delaying factors, such as sample transportation and testing in large batches, which call into question the reliability of NGS assays for diagnosing coronavirus.
- Area of Potential Impact: Patient outcomes, population health, health care delivery and process, health care costs
- Category: Screening and diagnostics
Rapid Point-of-Care Breath Test to Detect Coronavirus
At a Glance
- A point-of-care test for detecting coronavirus in breath samples based on the detection of viral particles using terahertz spectroscopy is being developed by researchers at Ben-Gurion University of the Negev in Israel.
- The test purportedly takes less than a minute to perform, and initial studies demonstrated about 90% agreement with results generated by gold-standard nucleic acid testing.
- Test developers estimate that the test could be commercially available as early as the fall of 2020 and cost between $50 and $100 per kit.
Researchers at Ben-Gurion University of the Negev (Beer-Sheva, Israel) are developing a point-of-care test that purportedly detects coronavirus in breath samples from both symptomatic and asymptomatic carriers in less than 1 minute. The test is designed to detect electro-acoustic properties specific to coronavirus viral particles using an investigational method called terahertz spectroscopy, which has been proposed for the rapid and accurate detection of various microbial agents.
To initiate the test, a person breathes into a whistle-like tube that holds an electronic chip containing thousands of electro-optical sensors. After breath sample collection, a removable capsule containing the sensors is placed in a small spectrometer connected to a laptop computer that transmits data for cloud-based analysis. Results are automatically recorded in a database that public health authorities can use to monitor coronavirus spread. In preliminary tests, the breath test matched PCR-based swab test results in more than 90% of tests performed. Researchers estimate that test kits will cost between $50 and $100 and could be commercially available by the fall of 2020.
A simple, high-throughput, point-of-care breath test to detect coronavirus might allow rapid testing in high-traffic public areas and facilitate widespread economic reopening. The availability of a simple and effective breath test could provide reassurance as part of ongoing public health efforts during the pandemic response. If the test can identify more asymptomatic coronavirus carriers, it might help improve contact tracing and self-isolation practices to slow the spread of coronavirus.
Early feedback from ECRI internal stakeholders suggested that a rapid breath test for coronavirus could be a “game changer” if it is scalable, inexpensive, and reasonably accurate. Stakeholders also thought that more people might willingly be subjected to a breath test rather than a more invasive and more uncomfortable nasal swab test. A rapid turnaround test might also make scheduling of elective surgical procedures easier than current laboratory testing allows. However, stakeholders cautioned that automated data transfer to public servers could pose privacy issues.
- Area of Potential Impact: Patient outcomes, population health, health care costs
- Category: Screening and diagnostics
Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes
The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.
In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.
The HCHSS COVID-19 supplement produces 3 main outputs:
- Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
- Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
- High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.
Commentary in this COVID-19 Scan reflects preliminary views of ECRI Horizon Scanning and internal ECRI stakeholders.
The information contained in this document has not been vetted by other stakeholders.
We welcome your comments on this Scan. Send them by email to [email protected].
Posted: August 26, 2020
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