To the Editor— The United States Food and Drug Administration (FDA) Emergency Situation Usage Authorization (EUA) and Guidelines for Usage (IFU) files describing the present approved virology tests for SARS-CoV-2 are largely unstandardized. There remains an urgent need for a searchable interface allowing expedition of standardized details reported in these EUA and IFU files. To acquire a better understanding of the existing testing landscape and to galvanize future test advancement, we provide here an online tool ( http://www.resiliencehealth.com/tests) that profiles existing and emerging virology tests for identifying SARS-CoV-2 (Figs. 1 and 2). We also call on the research community to react to an open COVID-19 XPRIZE competitors, OpenCovidScreen, seeking to determine inexpensive, top quality, scalable screening services.
NGS, next-generation sequencing; NAAT, nucleic acid amplification test; LFA, lateral flow assay; RT, reverse transcription; ddPCR, Bead Digital PCR; dPCR, digital PCR; qPCR, quantitative PCR.
a, Limit of detection (LoD) for tests that reported copies/ μL or copies/mL (provided in copies/ μL throughout). b, EUA virology test targets. SARS-CoV-2 5 ′– 3 ′ genome 4 on horizontal axis, with tests on the vertical axis and colors showing whether the test has one target (red) or numerous targets (brown) in the specified region. Each line indicates a test source (business or organization). If an EUA reported different LoDs for different targets, sample types or approaches, each is shown as a separate row. NGS, next-generation sequencing; NAAT, nucleic acid amplification test; LFA, lateral flow assay; RT, reverse transcription; ddPCR, Bead Digital PCR; dPCR, digital PCR; qPCR, quantitative PCR; RDRP, RNA-dependent RNA polymerase; DSP, diagnostic sample preparation; NP, nasopharyngeal; OP, oropharyngeal; rRT, real-time reverse transcriptase.
As of 27 July 2020, an analysis of the FDA data on EUA SARS-CoV-2 virology tests reveal a large range of limitation of detection (LoD), spanning > 5 orders of log10 differences. These metrics are of critical value due to the fact that each 10- fold increase in the LoD of a COVID-19 viral diagnostic test is anticipated to increase the incorrect unfavorable rate by 13% 1
Beyond this variable performance reported in IFUs for EUA tests, essential attributes of many tests, such as primer sequences, procedure steps or viral gene targets, are either uncertain or missing. Most authorized EUAs utilize big multipliers (2- to 200- fold) on their own LoD for contrived or medical samples to pass the minimum limit for approval, based on a 95%positive/negative portion agreement throughout at least 30 positive and 30 unfavorable samples. As submissions stand, it is tough to straight compare outcomes and even understand how a test will actually translate into real-world or scientific settings.
Furthermore, there has actually not been an independent assessment of these tests’ capabilities or a detailed benchmarking of their strengths and weak points in different scientific settings, nor a constant sample type (for instance, nasopharyngeal, nasal, saliva) used across the EUAs. Hence, a comprehensive benchmarking effort on all approaches on the market would be useful, comparable to ones performing head-to-head studies of serological tests 2 and other websites that annotate and analyze some of these tests, such as FindDx ( https://www.finddx.org/), the US National Institute for Standards and Technology (NIST)’s Quick Microbial Evaluating Techniques Consortium ( https://www.nist.gov/programs-projects/nist-rapid-microbial-testing-methods-consortium) and the COVID-19 Screening Project ( https://covidtestingproject.org/index.html).
However, even if all present EUA tests for the SARS-CoV-2 infection performed with >95%sensitivity and >95%specificity, their integrated capacities would still fall short of making it possible for massive, common temporal tracking (10s of millions each day), involving samples with varying viral load and substrates 3 Also, tests with a greater LoD would not be easily relevant to pooling methods, in which samples are by definition diluted before screening. Even the lower LoD tests, while assuring for pooling, have actually not had independent LoD evaluations. Genuinely city-scale or even national-level screening to decrease and manage infection rates would require quick turn-around times (test result in less than one day), simple processing, and a low cost (per test and capital cost), such that a customer, company or government body might easily pay for numerous tests a week for each individual.
To attend to the above issues, we have actually created the COVID-19 XPRIZE competition, OpenCovidScreen ( https://opencovidscreen.org/), to identify financially viable, high-quality, scalable screening choices (Fig. 3). After rivals are chosen on the basis of their outcomes, techniques, expense, scalability and speed, they will then be sent out blinded samples to analyze. Results will be published to the XPRIZE site and examined for general performance, LoD and incorrect positives. The finalists, based upon their general approaches, outcomes and development, will enter into the clinical recognition round, in which OpenCovidScreen will follow the techniques set out by the rivals to evaluate the reproducibility of their results. Top teams from this validation round will be awarded a prize and chosen to set up and release testing sites, in which OpenCovidScreen will help scale their tests and broaden them into more locations, along with to coordinate with government, industry and non-profit efforts (for instance, the NIH RADx Program and Testing for America; https://www.nih.gov/research-training/medical-research-initiatives/radx).
The OpenCovidScreen competition is meant to determine quickly, scalable, and inexpensive SAR-CoV-2 virology tests through a series of phases, starting with sending test and technique info (top), an efficiency test including blinded samples, and a scientific recognition stage (middle). The top rivals identified on the basis of their approaches, outcomes and scalability will then be picked for deployment to enable widespread usage of their tests (bottom).
We invite readers to send services for this XPRIZE, which is open to individuals from all around the world ( https://xprize.org/testing). This reward can work as a springboard for both brand-new and established technologies that can enable really worldwide viral testing and monitoring. Successful approaches will depend upon the accessibility of reagents, resources and automation, and as such, these metrics will also be utilized to recognize the finalists. Winning approaches will assist areas increase screening capabilities by orders of magnitude and therefore empower schools, businesses and cities to rapidly resume safely, as well as pioneer technologies and platforms that can be utilized for future outbreaks. It is vital to release rapid, scalable approaches efficient in tracking viruses to alleviate their detrimental effect on society. All are urged to help in this battle.
Recognitions
We thank Scott A. Jackson, Peter M. Vallone, and Kenneth D. Cole from the National Institute of Standards and Technologies (NIST). We thank Evaluating for America (501 c3) for their support, the OpenCovidScreen Foundation, Mayor Cory Mason, the Bert L and N Kuggie Vallee Structure, Igor Tulchinsky and the WorldQuant Foundation, Costs Ackman and Olivia Flatto and the Pershing Square Sohn Cancer Research Study Alliance, Ken Griffin and Castle, the US National Institutes of Health (R01 AI125416, R21 AI129851, R01 AI151059), and the Alfred P. Sloan Foundation (G-2015-13964). Research was supported by the DOE Workplace of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national labs focused on reaction to COVID-19, with funding supplied by the Coronavirus CARES Act.
Principles declarations
Competing interests
J.K. is cofounder and board member for Gingko Bioworks. G.C. has conflicts: http://arep.med.harvard.edu/gmc/tech.html
About this article
Cite this short article
MacKay, M.J., Hooker, A.C., Afshinnekoo, E. et al. The COVID-19 XPRIZE and the need for scalable, quick, and extensive screening.
Nat Biotechnol(2020). https://doi.org/101038/ s41587-020-0655 -4
-
Published:
Comments
Post a Comment