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Researchers and test developers continue to look for unique solutions to shorten the time for returning SARS-CoV-2 test results, as the virus’s aggressive march outpaces testing efforts, particularly in the U.S. Countless projects are underway to deploy rapid assays, at-home tests, and other innovations across the globe. On July 31, the National Institutes of Health’s (NIH) Rapid Acceleration of Diagnostic Technologies (RADx Tech) program reached an important milestone, awarding $248.7 million in contracts to seven biomedical companies to scale up and deploy accurate point-of-care (POC) tests across the country by fall, as influenza season begins.
The seven technologies, which competed alongside 600 completed applications, include next-generation sequencing (NGS), CRISPR, nucleic acid, and viral antigen platforms. They are:
- Mesa Biotech’s Accula SARS-CoV-2 hand-held real-time polymerase chain reaction (PCR) test that detects viral RNA and produces results in 30 minutes.
- Quidel’s Sofia SARS Antigen FIA test kit, which uses a lateral flow immunoassay in conjunction with an analyzer that delivers results in 15 minutes.
- Talis Biomedical’s Talis One COVID-19 POC test, which detects the virus in under 30 minutes through isothermal amplification of viral RNA and an optical detection system.
- Ginkgo Bioworks’ project to scale up high-throughput NGS technologies and produce 100,000 per day by year’s end.
- Helix OpCo’s project to ship standardized bulk test kits to various entities, ramping up nasal swab sample collections to 100,000 by the end of 2020.
- Fluidigm’s goal to produce thousands of new PCR tests per day, with a focus on saliva samples, through its Biomark HD microfluidics platform this fall.
- Mammoth Biosciences’s SARS-CoV-2 DETECTR assay, which uses CRISPR technology to produce a simpler workflow and greater turnaround time, which could significantly ramp up testing capacity in commercial labs.
The seven technologies were chosen from a pool of 100 “best concept” applicants. These will be the first technologies to go through RADx from scale up, manufacturing, and delivery to the marketplace. Scientists leading this effort detailed their strategy in the New England Journal of Medicine. “The RADx-tech program uses a rigorous, rapid-review process that provides independent evaluation of the technology and the potential to scale,” explained NIH Director Francis Collins, MD, and colleagues.
NIH, which received $1.5 billion from Congress to develop SARS-CoV-2 tests, has invested in several programs, including RADx, to promote and scale up SARS-CoV-2 testing. A year-end goal is to make tests available to 6 million Americans (2% of the population) on a daily basis. “This is only a start, and we expect that more RADx projects will advance in the coming months and begin scaling up for wide-scale use,” Collins wrote on his blog. In the longer term, RADx has its sights on developing diagnostics and making tests available to indigent and diverse populations.
NIH’s quest for quicker, more accurate tests feeds into the Rockefeller Foundation’s call for a national testing strategy to produce millions of screening tests within 3 months. This would involve ramping up POC tests and contact tracing, implementing widespread screening protocols, expanding support services for self-isolation, and ensuring that diagnostic tests are available to all Americans. Congress should commit $75 billion to make this happen, the foundation stated. As of now, millions of Americans can’t get quick access to testing, and test results from overburdened labs aren’t delivered quickly enough to support informed decisions for consumers, or larger contact tracing efforts.
Many test developers are eyeing home tests, a solution that could ease the testing lag in the United States, observed Paul E. Sax, MD, contributing editor of NEJM Journal Watch, in a recent blog post. PCR tests done on a nasopharyngeal swab are generally accurate, but they’re expensive and some would argue too sensitive—meaning they detect viral RNA fragments considerably after a person is no longer contagious, Sax wrote. In his view, “we need to lower the bar for accuracy and use one of the many rapid tests currently in development.”
The U.S. Food and Drug Administration (FDA) has been slow to approve home tests, likely because they’re less sensitive than PCR. “This is a legitimate concern, but one that should not block their urgent approval anyway. We should welcome these tests, even if less accurate, and broadly adopt them for widespread community use,” asserted Sax. The reasons: They would be cheap, done easily via saliva, and could be conducted every day. They’ll also answer a key question: “Am I contagious to others,” Sax added.
The Johns Hopkins Center for Health Security echoed this sentiment in a recent analysis. Home tests could improve availability of testing options to consumers while reducing transmission risk, authors of the analysis stated. However, this should not be treated as a stand-alone solution. Clinical testing strategies and public health surveillance should accompany this method, the authors added. This means collecting symptom and travel history of at-home test users. Federal government bodies should also take steps to fund and review and support development of at-home tests to increase testing and surveillance capacity.
The FDA to date has issued emergency use authorizations (EUA) for a handful of home tests manufactured by LabCorp; startups Vault Health and hims & hers; and direct-to-consumer genetic testing companies LetsGetChecked and Vitagene. Some tests collect saliva from tubes or immerse samples into chemical cocktails that light up in the presence of COVID-19 genes. The FDA on August 15 issued an EUA for a saliva test developed by the Yale School of Public Health and used by the National Basketball Association that does not require any special swab or collection device and that does not require a separate nucleic acid extraction step.
Another test delivers results in minutes, ideal for low-resource areas, according to one news report. Other approaches are using loop-mediated isothermal amplification or NGS technologies to rapidly identify the virus. Some mass testing approaches using DNA sequencing could potentially read up to 100,000 samples in a single run. Many of these tests are months from being available in clinics. A sample of innovative tests in development underscores the depth of this effort:
- The sVNT test developed by scientists from Duke-NUS Medical School identifies functional neutralising antibodies that block the binding of the coronavirus spike protein to the angiotensin-converting enzyme 2 host receptor in an hour with high sensitivity and specificity.
- A clinical trial underway in London will use a rapid PCR-based testing system with the capacity to process up to 100 samples a day in care homes.
- Researchers at Virginia Tech are pursuing a patent on a droplet biosensing method that can analyze the contents of a microdroplet sample and identify the virus in minutes.
- A rapid, easily scalable blood test identifies positive cases in 20 minutes through agglutination.
- Clinician-scientists at Nanyang Technological University, Singapore’s Lee Kong Chian School of Medicine have refined the PCR diagnostic test method to achieve results in 36 minutes through a single-tube reaction process.
- Israeli scientists are conducting a pilot program on a rapid test that leverages artificial intelligence technology to identify and classify evidence of a virus in blood or saliva samples in less than a second.