Book:COVID-19 Testing, Reporting, and Information Management in the Laboratory/Diagnostic testing of COVID-19 and other coronaviruses/Current test methods and their differences

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2.4 Current test methods and their differences

NOTE: Information shown here may rapidly become outdated given how quickly response to pandemic testing can change. A full attempt to keep the content relevant will be made.

2.4.1 Background on the laboratory testing environment

Before continuing, it should be noted that many elements of the prior-mentioned COVID-19 testing guidance have governmental public health laboratories in mind. However, as the scale of the epidemic grew in 2020, and into 2021, the need for commercial laboratories and assay developers to get involved with efforts towards increasing analytical testing throughput—through a more rigorous public-private partnership—became abundantly clear.[1][2][3][4] At times during the pandemic, laboratory turnaround times have been slow due to a variety of factors, from lack of in-house laboratory resources to handle high test volumes and a slower-than-expected ramping up of test kit production[1][3][4], to actually getting diagnostic assays that are more rapid (yet still accurate) in their diagnosis, simpler to use, and useable at the point of care.[5][6] The good news is these rapid point-of-care molecular test kits are now becoming more readily available around the globe, including the United States, thanks in part to the U.S. Food and Drug Administration's Emergency Use Authorization (EUA) process.

Despite at-home kits becoming more available, quick and effective laboratory-based testing remains important, particularly as the delta variant continues to put strains on some U.S. states and their testing efforts into the late summer of 2021.[7][8] As such, it remains important to compare the U.S. laboratory testing environments of public health and large commercial testing labs with those of small, in-office clinical labs. In the U.S., all but research-based laboratory testing of human specimens is regulated under CLIA, including public health laboratories. Of the more than 297,000 non-exempt CLIA-registered labs in the U.S., only 38,742 or 13.0 percent of them are certified to perform moderate- and high-complexity testing as of August 2021.[9] Your public health labs and commercial diagnostic labs fall into this category, with investments in the personnel, training, certifications, and equipment to conduct those sorts of tests. Contrast this with the small yet numerous physician office laboratories (POLs) and how they operate. As of August 2021, some 42.4 percent of non-exempt CLIA-certified laboratories in the United States are POLs.[9] Located in an ambulatory or outpatient care setting, these labs test specimens from human patients to assist with the diagnosis, treatment, or monitoring of a patient condition. Testing in the clinical lab generally depends on three common methodologies to meet those goals: comparing the current value of a tested substance to a reference value, examining a specimen with microscopy, and detecting the presence of infection-causing pathogens.[10]

These POL's operate in a different environment than your average public health laboratory or reference lab that receives, processes, and reports on specimens en masse. The POL is typically a smaller operation, performing simple laboratory testing that can produce useful diagnostic data cheaply and rapidly. Rather than performing advanced pathology and molecular diagnostic procedures that require specific equipment and expertise, the POL typically focuses on blood chemistry, urinalysis, and other testing domains that don't require significant resources and provide rapid results. This can be seen in Centers for Medicare and Medicaid Services statistics reported in August 2021 that show 69.3 percent of non-exempt POLs in the U.S. are certified to provide CLIA-waived tests[9], "simple tests with a low risk for an incorrect result."[11]

As of September 2021, with 1. all but several handfuls of the current EUAed molecular in vitro diagnostic COVID-19 test kits being limited to moderate- and high-complexity CLIA labs[12] (the FDA claims that EUAed SARS-CoV-2 tests authorized for "use at the point of care" are considered CLIA-waived tests[13]), and 2. serology testing still being considered moderate- to high-complexity in nature[12], a significant majority of clinical laboratories are left with only a handful of CLIA-waived options for assisting with the effort to test the U.S. population for SARS-CoV-2 infection. Given the rapid rate of change at multiple levels of government and society and the continual spreading of misinformation[14][15][16], it's important to remember these fundamental differences in laboratories when trying to explain to someone why even in September 2021 they will still find it challenging to go to their primary care physician and get tested for SARS-CoV-2 in the doctor's office. Should researchers develop and the FDA provide EUAs for more CLIA-waived point-of-care assays, these differences may become less noticeable, and more people will be able to be tested.

2.4.2 PCR-based methods

As of September 2021, the U.S. Food and Drug Administration (FDA) has issued 260 EAUs for all types of molecular in vitro diagnostic test kits. Two hundred and eight of those 260 are only authorized to be used in CLIA-certified high-complexity laboratories, and 19 are rated for both moderate- and high-complexity. When looking at the makeup of the EUAs, a huge majority of those tests use some form of RT-PCR methods, with most using real-time or qualitative versions of RT-PCR (qRT-PCR). CLIA-waived RT-PCR tests are still rare, however. Eight PCR-based kits from five manufacturers have an additional authorization for point-of-care (POC) use (and thus CLIA-waived use) when used with their authorized POC devices[12]:

  • BioFire Diagnostics' BioFire Respiratory Panel 2.1-EZ
  • Cepheid's Xpert Omni SARS-CoV-2
  • Cepheid's Xpert Xpress SARS-CoV-2
  • Cepheid's Xpert Xpress SARS-CoV-2/Flu/RSV
  • Mesa Biotech's Accula SARS-Cov-2 Test
  • Roche Molecular Systems' cobas SARS-CoV-2
  • Roche Molecular Systems' cobas SARS-CoV-2 & Influenza A/B
  • Visby Medical's COVID-19 Point of Care Test

Of course, there are many more test kits than those approved in the United States. The Foundation for Innovative New Diagnostics (FIND) is currently "collating an overview of all SARS-CoV-2 tests commercially available or in development for the diagnosis of COVID-19."[17] As of September 2021, their site shows nearly 280 commercialized manual NAAT tests around the world (most being RT-PCR), with 30 in development. The AdVeritasDx test and controls database is also useful.[18]

2.4.3 LFA and isothermal amplification methods

LFAs are currently rare, but due to their advantages of being quick and useable at the point of care, some healthcare professionals have suggested that as a format for antigen and antibody (serology) testing, they could positively change the testing landscape.[19][20][21] As of September 2021, 25 of 88 serology tests that have received EUAs by the FDA are explicitly labeled as being LFAs, with 12 of those 25 being approved for POC/CLIA-waived use.[22] An article by Sheridan in Nature Biotechnology highlights a handful of others developed around the world (see their Table 1).[19] FIND shows more than 400 commercialized rapid diagnostic immunoassay tests around the world, though it's not clear how many of them actually LFAs (from their list, only 14 are explicitly stated as being LFA).[17] While LFAs have increasingly been approved around the world in 2021[22][17], it remains a question whether or not we continue to see more of them, at least in the United States.[20]

Also of note are isothermal amplification methods. Abbott's ID NOW and Cue Health's Cue COVID-19 and Cue COVID-19 Test for Home and OTC tests (the latter being the first isothermal amplification test approved for home use) are described by the FDA as using "isothermal nucleic acid amplification technology for the qualitative detection of SARS-CoV-2 viral nucleic acids."[23][24][25] Isothermal amplification tends to be an easier process to manage due to being able to keep amplification at a constant temperature.[26] In fact, Abbott has stated its EUAed ID NOW COVID-19 test can be completed within five minutes.[27] However, May 2020 findings by New York University put the test's accuracy into question. On July 1, 2020, an FDA spokesperson allegedly indicated receipt of 126 reports of "adverse events" concerning the test.[28] In 2020, some 393 complaints were reported to the FDA, with 1,492 complains being reported in 2021 (through July 31) according to an FDA MAUDE (Manufacturer and User Facility Device Experience) search.[29] The FDA was reportedly investigating the data and working with Abbott to have additional studies performed on the test's accuracy in 2020.[30] In October 2020, Abbott released additional study data showing overall sensitivity of 93.3% and specificity of 98.4%, emphasizing the ID NOW's best use with samples taken within seven days of symptom onset.[31] On August 27, 2021, the FDA re-issued its EUA for the ID NOW with updated in silico inclusivity analysis results (among other things)[32], but it's not clear if the FDA is continuing to work with Abbott on the test's accuracy claims.

Specific isothermal amplification techniques called loop-mediated isothermal amplification (LAMP) and reverse transcription LAMP (RT-LAMP) are beginning to emerge as options for COVID-19 testing. For example, Talis Biomedical is developing the Talis One COVID-19 system for point-of-care testing. It has received National Institutes of Health's Rapid Acceleration of Diagnostics (RADx) funding[33] and, should it receive its EUA (as of August 2021, it was still awaiting FDA authorization[34]), is expected to be among the first U.S.-approved RT-LAMP tests for COVID-19.[35] In November 2020, the first LAMP-based, prescription "collect and test" at-home kit—the Lucira COVID-19 All-In-One Test Kit—was approved by the FDA for emergency use.[36] Globally, examining FIND's list of nearly 280 commercialized manual NAAT tests around the world, five of them are explicitly shown to be some form of LAMP test. Multiple preprints on medRxiv and bioRxiv, as well as published papers, suggest that RT-LAMP could provide rapid results for SARS-CoV-2 testing.[37][38][39][40][41] However, it's apparent that adoption of LAMP as a COVID-19 test technique has been slow at best overall.

2.4.4 Blood serum

Blood in tubes (9617266704).jpg

Blood serum or serology assays come in three common varieties: LFA, enzyme-linked immunosorbent assay (ELISA), or neutralization assay.[42] As discussed prior, LFAs are intended to be rapid point-of-care tools for qualitatively testing body fluids for patient antibodies or viral antigen. The ELISA is, in contrast, a more lab-bound method which produces results that are qualitative or quantitative. In the context of COVID-19 testing, ELISA tests for the presence of patient antibodies in a given specimen based upon whether or not an interaction is observed with the viral proteins present on the test plate. However, even if antibodies are present, ELISA isn't able to tell a clinician if those antibodies are able to protect against future infection. Neutralization assays are the lengthiest to complete, taking from three upwards to five days.[42] This is largely due to the fact that the assay depends on culturing cells that encourage growth of the target virus. Afterwards, introduced patient antibodies, if present, will fight to prevent viral infection of cells. This process is performed in decreasing concentrations, giving the clinician an opportunity to "visualize and quantify how many antibodies in the patient serum are able to block virus replication."[42] In contrast to ELISA, a neutralization assay is able to determine if a patient's antibodies are actively fighting against the target virus, even after recovering from the infection. In November 2020, the FDA granted an EUA to the first ELISA-based serology test to detect nuetralizing antibodies from recent or prior SARS-CoV-2 infection.[43]

Johns Hopkins' Center for Health Security appears to be tracking serology-based COVID-19 tests that are in development or have been approved in various parts of the globe. However, for the most up-to-date list of serology tests that have received EUAs in the United States, the FDA's EUA list appears to be the best source. As of September 2021, the FDA shows 88 serology assays approved for diagnostic use in the U.S. Of those 88, sixteen are explicitly listed as being ELISA-based.

A review of Johns Hopkins' tracking list showed more LFA-based tests among those approved in other parts of the world. Among their list of those still in development, an LFA stands out for integrating CRISPR detection.[44] CRISPR (clustered regularly interspaced short palindromic repeats) represents bacterial and archaeal DNA sequences derived from DNA fragments of previous infection. This genetic material can then be used as an activator of biomarkers when attached RNA "guides" find a match with target viral RNA in patient specimen.[45] This CRISPR-based LFA, called DETECTR, was further described in a paper published in October 2020, with the authors concluding it could be used "as a complementary technically independent approach to qRT-PCR, thereby increasing the testing capacity of medical microbiological laboratories and relieving the existent PCR-platforms for routine non-SARS-CoV-2 diagnostic testing."[46]

2.4.5 Antigen tests

An antigen is a substance—often a protein but may also be an environmental like a virus—that provokes the immune system to produce an antibody against it.[47] As such, another approach to testing for the presence of a virus in a specimen is to test for the antigen rather than the antibody. An antigen test is useful as a repeated surveillance test, but it has drawbacks as a one-time diagnostic test.[48][49][50] For COVID-19 and other viral infections, an antigen test has the advantage that specimen collection can typically be done with a simple nasal swab rather than a more invasive nasopharyngeal swab. Another advantage, on one hand, is that antigen testing is more rapid and convenient because the extraction and amplification steps of PCR are not used. On the other, antigen testing is less sensitive for the same reason: you test only what's there (rather than amplifying the amount for greater sensitivity).[49][51]

A theory increasingly gaining traction, however, is that "[a] higher frequency of testing makes up for poor sensitivity.”[49][50][52] Several researchers have shared pre-print and published research suggesting this outcome[49]:

Larremore and his colleagues have modeled the benefits of more frequent tests, even ones that are less accurate than today’s. Fast tests repeated every three days, with isolation of people who test positive, prevents 88% of viral transmission compared with no tests; a more sensitive test used every two weeks reduced viral transmission by about 40%, they report in a 27 June preprint on medRxiv. Paltiel and his colleagues reached much the same conclusion when they modeled a variety of testing regimes aimed at safely reopening a 5000-student university. In a 31 July paper in JAMA Network Open, they found that, with 10 students infected at the start of the semester, a test that identified only 70% of positive cases, given to every student every two days, could limit the number of infections to 28 by the end of the semester. Screening every seven days allowed greater viral spread, with the model predicting 108 infections.

As such, the utility of antigen testing, despite its lower sensitivity, appears to be surveillance situations where a large group of individuals who are at risk can be screened at regularly scheduled intervals of two to four days. The end result, in theory, would be few people who are target-positive would be missed, positives could be isolated and verified with a more sensitive test, and more target-positive people would be identified and isolated before reaching peak infectivity.[49][53] To be clear, it's not a perfect solution, but as Harvard epidemiologist Michael Mina and Boston University economist Laurence Kotlikoff suggest, "[w]e need the best means of detecting and containing the virus, not a perfect test no one can use."[53] In August 2020, a coalition of six U.S. state governors bought into that concept and agreed to work together with the Rockefeller Foundation, as well as the Quidel Corporation and Becton, Dickinson and Company, which had received FDA EUAs to market antigen tests for SARS-CoV-2.[52][54] As of September 2021, thirty-four FDA EUAs for antigen tests have been issues; 28 of those 34 include allowances for CLIA-waived testing, and 10 were authorized for home use.[55]

2.4.6 Testing alternatives and challenges

We’ve never faced this before, where clinical labs needed to very quickly be able to ramp up a test so fast.[56]
- Jennifer Doudna, Executive Director of the Innovative Genomics Institute, University of California, Berkeley

Though the dismantling and fund-cutting (proposed and real) of government programs designed to protect the populace from pandemics—as well as shortfalls in funding overall[57]—have likely hobbled local, national, and global response to COVID-19[58][59][60][61], it should be recognized that this pandemic may arguably represent a once-in-a-century type of event.[62][63] That said, even the most well-prepared governments would still face challenges in quickly learning about, controlling, and developing therapies for a novel disease agent. Shortages in supplies, workers, funding, and other resources are inevitably caused with a pandemic as people across all types of infrastructure fall ill.[57][64] This requires the additional human elements of adaptability, drive, and shared knowledge to find new and alternative solutions to fighting the challenges inherent to fighting against a novel disease.

See for example a non-peer-reviewed paper published on bioRxiv in early April 2020, where Schmid-Burgk et al. pointed out that though RT-PCR methods are the most common for currently testing for SARS-CoV-2, "global capacity for testing using these approaches, however, has been limited by a combination of access and supply issues for reagents and instruments." They proposed "a novel protocol that would allow for population-scale testing using massively parallel RT-LAMP by employing sample-specific barcodes." They claimed that a single heating step, pooled processing, and parallel sequencing with computational analysis would allow for the testing and tacking of "tens of millions of samples." Though the protocol was not validated with clinical samples, and concerns about sensitivity levels of RT-LAMP (an isothermal nucleic acid amplification technique that allows for RNA amplification) have been raised, the authors' work exemplifies the immediacy and ingenuity that has gone into finding workable solutions to a once-a-century problem.[37]

Another example of ingenuity in the face of difficult circumstances can be found at the University of California, Berkeley. At the beginning of the pandemic, its Innovative Genomics Institute (IGI) rapidly repurposed a 2,500-square-foot scientific lab into an automated diagnostic laboratory that could initially process more than 1,000 patient samples per day, with the ability to ramp up to 3,000 per day thanks to robotics and a streamlined workflow. Partnering with dozens of people from Thermo Fisher Scientific, Salesforce, Third Wave Analytics, and Hamilton Corp., the lab focused on not only turnaround time but also accuracy of results through automation. Their continued success, of course, still relies on a steady supply of reagents and related supplies from Thermo Fisher.[56][65]

Since the pandemic's start, others have also expressed concerns about the global supply of reagents necessary to test for SARS-CoV-2. Successful testing using RT-PCR requires two different enzymes: reverse transcriptase, for converting RNA to DNA, and polymerase, for amplifying the converted DNA. These enzymes and other reagent components may be instrument-specific, and at least one component has to be sympathetic to detection of the target virus' RNA. Little of this can be prepared without a proper sequence of the virus in question. Dr. Ronald Leonard, president and medical director of Cytocheck Laboratory and medical director of the Labette Health hospital, expressed the difficulties associated with reagent manufacturing thusly[66]:

With the instant demand for SARS-CoV-2 testing, the manufacturing process had to start from scratch for the SARS-CoV-2 specific components, and this did cause a lag time before reagents were available. The increased demand coupled with the decision to only allocate reagents to two national laboratories, some state health departments, and to "hot spots" has compounded the difficulty for laboratories like ours to obtain the necessary reagents to perform the testing.

Reports of COVID-19 test reagent shortages from various sources have appeared since March 2020.[67][68][69][70][71][72][73][54][53][74][75][76] Over time, those shortages even extended to supplies for non-COVID-19 tests such as those for strep throat, bronchitis, mycobacterial infections, urinary-tract infections, fungal infections, and sexually transmitted infections.[74][75][76] In the face of these supply challenges, some have taken matters into their own hands. Noting Irish laboratories' difficulties sourcing lysis buffer (for isolating molecules of interest and keeping them stable), Cork Institute of Technology's Dr. Brigid Lucey worked with several other virologists and microbiologists early in the pandemic, as well as with pharmaceutical company Eli Lilly, to produce a custom-formulated yet high-quality lysis buffer for not only Irish laboratories but also other countries can take advantage of. "We are happy to share what we found with other countries and it’s important our scientists retain their skills to make this kind of formulation because we may need to do this again in the future if we get other pandemics," she said.[70]

Another challenge lies in the accuracy of serology-based antibody tests, let alone how much they actually tell us about immunity. FierceBiotech's Conor Hale touched upon this in late April 2020[77]:

Compared to molecular tests—which sequence and match the RNA of the novel coronavirus to produce a result—the FDA has described antibody tests that gauge the body’s immune system response as a less-complicated endeavor that could proceed without review, dubbed “regulatory flexibility” by Commissioner Stephen Hahn. This policy shift has led to confusion, with some antibody test developers falsely claiming their tests are FDA-approved or could diagnose COVID-19 at home. Still others have sold outrightly fraudulent tests online.

At least in the U.S., these problems are compounded by company participation in test validation of EUAs being voluntary.[77] As a late April 2020 memorandum from Congress put it: "FDA is unable to validate the accuracy of antibody tests that are already on the market, and companies are ignoring requests from the Department of Health and Human Services (HHS) to voluntarily submit their tests for validation ... FDA has failed to police the coronavirus serological antibody test market, has taken no public enforcement action against any company, and has not conveyed any clear policy on serological tests..."[78] The entire memorandum is revealing in the challenges of attempting to relax social distancing measures under the pretense of the effectiveness of antibody testing. Entities such as the University of California - San Francisco[79] and the University of California - Berkeley[80] early on emphasized the importance of elements such as sensitivity, specificity, proper training, and the unknowns of the predictive ability of the test. Even assays running under trusted platforms such as PCR can reveal issues. For example, Thermo Fisher Scientific's TaqPath COVID019 Combo Kit, approved for EUA in March 2020, received scrutiny and updates to address issues with false-positive and -negative results[81][82], highlighting the difficulty of, at least early on in the pandemic, balancing the need for rapidly approving test kits for emergency use while also maintaining some semblance of oversight regarding their effectiveness and proper use. This has been further hampered by an August 2020 decision that stated the FDA could not require laboratory developed tests (LDTs) to be submitted for an EUA. As the Pew Charitable Trust's Liz Richardson argued in September 2021, reversing this decision "would enable labs to continue bringing innovative and effective new tests to market quickly while empowering FDA to protect the public from faulty products that allow infection to spread."[83]

Finally, while point-of-care testing, including at-home testing, has made strides in 2021[55], their need remains apparent. Dozens of at-home tests remained in development (many of them antigen tests) at the end of 2020, and even now a major barrier is found in making them both accurate and easy for untrained people to understand and use.[84][85] And as more at-home tests continue to receive EUAs in 2021, they are still not without concern, particularly in regards to ensuring that at-home test results get reported properly and rapidly.[84][86] One such early example at the end of 2020 was Lucira Health's LAMP-based Lucira COVID-19 All-In-One Test Kit, which was approved as a prescription-based at-home test, but with the stipulation that the prescribing healthcare provider would be responsible for reporting results.[36] Such a requirement arguably can and should be put in place for at-home antigen-based testing as well.[84]

As the pandemic churns through its second year, it's more important than ever for leaders across government, healthcare, and the media to continue to not spread misinformation and not make decisions based on poor scientific evidence. It will take organized efforts from multiple stakeholders—such as that found with a June 2020 NIH workshop on expanding and improving COVID-19 antibody tests[87]—to continue to find responsible solutions to the challenges we still face with this pandemic.


  1. 1.0 1.1 Madrigal, A.C.; Meyer, R. (31 March 2020). "Private Labs Are Fueling a New Coronavirus Testing Crisis". The Atlantic. Retrieved 07 April 2020. 
  2. Hale, C. (17 March 2020). "FDA opens the gates to commercial coronavirus testing without agency review". FierceBiotech. Retrieved 07 April 2020. 
  3. 3.0 3.1 Appleby, J. (28 March 2020). "Why It Takes So Long To Get Most COVID-19 Test Results". NPR - Health Shots. Retrieved 07 April 2020. 
  4. 4.0 4.1 Ryan-Mosley, T. (5 April 2020). "Why some covid-19 tests in the US take more than a week". MIT Technology Review. Retrieved 07 September 2021. 
  5. Nguyen, T.; Bang, D.D.; Wolff, A. (2020). "2019 novel coronavirus disease (COVID-19): Paving the road for rapid detection and point-of-care diagnostics". Micromachines 11 (3): 306. doi:10.3390/mi11030306. PMID 32183357. 
  6. Yang, T.; Wang, Y.-C.; Shen, C.-F.; Cheng, C.-M. (2020). "Point-of-care RNA-based diagnostic device for COVID-19". Diagnostics 10 (3): 165. doi:10.3390/diagnostics10030165. 
  7. Scott, D. (1 September 2021). "Why can’t America fix its Covid-19 testing problems?". Vox. Retrieved 06 September 2021. 
  8. Zoga, D. (3 September 2021). "NBC 5 Responds: Searching for a COVID-19 Test? You're Not Alone". NBC DFW. Retrieved 06 September 2021. 
  9. 9.0 9.1 9.2 Centers for Medicare and Medicaid Services, Division of Clinical Laboratory and Quality (August 2021). "CLIA Update - August 2021" (PDF). Retrieved 07 September 2021. 
  10. Garrels, M.; Oatis, C.S. (2014). Laboratory and Diagnostic Testing in Ambulatory Care: A Guide for Healthcare Professionals (3rd ed.). Elsevier Health Sciences. pp. 368. ISBN 9780323292368. Retrieved 09 April 2020. 
  11. Centers for Disease Control and Prevention (6 August 2018). "Clinical Laboratory Improvement Amendments (CLIA): Test complexities". Retrieved 09 April 2020. 
  12. 12.0 12.1 12.2 "In Vitro Diagnostics EUAs - Molecular Diagnostic Tests for SARS-CoV-2". U.S. Food and Drug Administration. 7 September 2021. Retrieved 07 September 2021. 
  13. U.S. Food and Drug Administration (25 March 2021). "FAQs on Diagnostic Testing for SARS-CoV-2". U.S. Food and Drug Administration. Retrieved 07 September 2021. 
  14. Simonite, T. (24 March 2020). "The Professors Who Call ‘Bullshit’ on Covid-19 Misinformation". Wired. Retrieved 09 April 2020. 
  15. Suciu, P. (8 April 2020). "During COVID-19 Pandemic It Isn't Just Fake News But Seriously Bad Misinformation That Is Spreading On Social Media". Forbes. Retrieved 09 April 2020. 
  16. Soucheray, S. (15 July 2021). "Surgeon General warns of COVID-19 misinformation". CIDRAP. University of Minnesota. Retrieved 07 September 2021. 
  17. 17.0 17.1 17.2 Foundation for Innovative New Diagnostics (23 April 2024). "SARS-CoV-2 Diagnostic Pipeline". Foundation for Innovative New Diagnostics. Retrieved 18 November 2020. 
  18. AdVeritasDx (2020). "The SARS-CoV-2 Test & Controls Database". Retrieved 18 November 2020. 
  19. 19.0 19.1 Sheridan, C. (23 March 2020). "Fast, portable tests come online to curb coronavirus pandemic". Nature Biotechnology - News. doi:10.1038/d41587-020-00010-2. Retrieved 08 April 2020. 
  20. 20.0 20.1 Bistricean, C. (1 April 2020). "COVID-19 Testing for the Physician Office Laboratory (POL) -". Medium. Retrieved 10 April 2020. 
  21. Dickens, J.F. (3 April 2020). "Coronavirus testing: How it works – Questions answered". Reaction. Retrieved 10 April 2020. 
  22. 22.0 22.1 "In Vitro Diagnostics EUAs - Serology and Other Adaptive Immune Response Tests for SARS-CoV-2". U.S. Food and Drug Administration. 3 September 2021. Retrieved 07 September 2021. 
  23. Hinton, D.M. (27 March 2020). "ID NOW COVID-19" (PDF). U.S. Food and Drug Administration. Retrieved 10 April 2020. 
  24. Hinton, D.M. (10 June 2020). "Cue COVID-19 Test" (PDF). U.S. Food and Drug Administration. Retrieved 08 July 2020.  }}
  25. Hinton, D.M. (5 March 2021). "Cue COVID-19 Test for Home and Over The Counter (OTC) Use" (PDF). U.S. Food and Drug Administration. Retrieved 07 September 2021. 
  26. Zanoli, L.M.; Spoto, G. (2013). "Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices". Biosensors 3 (1): 18–43. doi:10.3390/bios3010018. PMC PMC4263587. PMID 25587397. 
  27. "Detect COVID-19 in as Little as 5 Minutes". Abbott. 27 March 2020. Retrieved 10 April 2020. 
  28. Devine, C. (3 July 2020). "Coronavirus test used by White House has questionable accuracy". CNN Politics. Retrieved 08 July 2020. 
  29. "MAUDE - Manufacturer and User Facility Device Experience". U.S. Food and Drug Administration. Retrieved 07 September 2021. "Search for "ID NOW COVID-19" in Brand Name" 
  30. Perrone, M. (14 May 2020). "FDA probes accuracy issue with Abbott’s rapid virus test". Associated Press. Retrieved 19 May 2020. 
  31. Taylor, N.P. (7 October 2020). "Abbott, on defense, details embattled rapid COVID-19 test results". MedTechDive. Retrieved 18 November 2020. 
  32. Hinton, D.M. (27 August 2021). "ID NOW COVID-19" (PDF). U.S. Food and Drug Administration. Retrieved 07 September 2021. 
  33. National Institutes of Health (31 July 2020). "NIH delivering new COVID-19 testing technologies to meet U.S. demand". News Releases. National Institutes of Health. Retrieved 12 August 2020. 
  34. O'Connor, L. (11 August 2021). "Despite MDx Product Delays, Talis Biomedical Expecting 'Meaningful Revenue Ramp in 2022'". 360 Dx. Archived from the original on 11 August 2021. Retrieved 07 September 2021. 
  35. "The Talis Advantage". Talis Biomedical. Retrieved 13 August 2020. 
  36. 36.0 36.1 Romo, V. (17 November 2020). "FDA Approves 1st At-Home Coronavirus Test". NPR. Retrieved 18 November 2020. 
  37. 37.0 37.1 Schmid-Burgk, J.L.; Li, D.; Feldman, D. et al. (2020). "LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding". bioRxiv. doi:10.1101/2020.04.06.025635. 
  38. Lamb, L.E.; Barolone, S.N.; Ward, E. et al. (2020). "Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification". medRxiv. doi:10.1101/2020.02.19.20025155. 
  39. Kellner, M.J.; Ross, J.J.; Schnabl, J. et al. (2020). "A rapid, highly sensitive and open-access SARS-CoV-2 detection assay for laboratory and home testing". bioRxiv. doi:10.1101/2020.06.23.166397. 
  40. Yu, L.; Wu, S.; Hao, X. et al. (2020). "Rapid Detection of COVID-19 Coronavirus Using a Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) Diagnostic Platform". Clinical Chemistry 66 (7): 975–77. doi:10.1093/clinchem/hvaa102. PMC PMC7188121. PMID 32315390. 
  41. Park, G.-S.; Ku, K.; Baek, S.-H. et al. (2020). "Development of Reverse Transcription Loop-Mediated Isothermal Amplification Assays Targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)". Journal of Molecular Diagnostics 22 (6): 729–35. doi:10.1016/j.jmoldx.2020.03.006. PMC PMC7144851. PMID 32276051. 
  42. 42.0 42.1 42.2 Center for Health Security (26 August 2021). "Serology tests for COVID-19". Johns Hopkins University. Retrieved 06 September 2021. 
  43. Food and Drug Administration (6 November 2020). "Coronavirus (COVID-19) Update: FDA Authorizes First Test that Detects Neutralizing Antibodies from Recent or Prior SARS-CoV-2 Infection". Food and Drug Administration. Retrieved 18 November 2020. 
  44. "A protocol for rapid detection of the 2019 novel coronavirus SARS-CoV-2 using CRISPR diagnostics: SARS-CoV-2 DETECTR" (PDF). Mammoth Biosciences. 2 March 2020. Retrieved 09 April 2020. 
  45. "CRISPR’s powers unleashed for disease detection". Nature - Research Highlights. 16 February 2018. Retrieved 09 April 2020. 
  46. Brandsma, E.; Verhagen, H.J.M.P.; van de Laar, T.J.W. et al. (2020). "Rapid, sensitive and specific SARS coronavirus-2 detection: A multi-center comparison between standard qRT-PCR and CRISPR based DETECTR". The Journal of Infectious Diseases In Print: jiaa641. doi:10.1093/infdis/jiaa641. PMC PMC7665660. PMID 33038252. 
  47. "Antigen". MedlinePlus. U.S. National Library of Medicine. Retrieved 07 August 2020. 
  48. Anderson, K. (6 August 2020). "5 Investigates: Concerns about current use of rapid antigen tests for COVID-19". WCVB 5 ABC. Retrieved 07 August 2020. 
  49. 49.0 49.1 49.2 49.3 49.4 Service, R.F. (2020). "Radical shift in COVID-19 testing needed to reopen schools and businesses, researchers say". Science. doi:10.1126/science.abe1546. 
  50. 50.0 50.1 Kremer, R. (7 August 2020). "UW System Orders 350,000 COVID-19 Tests". Urban Milwaukee. Retrieved 07 August 2020. 
  51. Guglielmi, G. (2020). "The explosion of new coronavirus tests that could help to end the pandemic". Nature 583: 506–09. doi:10.1038/d41586-020-02140-8. 
  52. 52.0 52.1 Clark, C. (6 August 2020). "COVID Antigen Tests: Coming to Case Counts Near You?". MedPage Today. Retrieved 07 August 2020. 
  53. 53.0 53.1 53.2 Courage, K.H. (31 July 2020). "Should we be testing fewer people to stop the spread of Covid-19?". Vox. Retrieved 05 August 2020. 
  54. 54.0 54.1 Mervosh, S.; Fernandez, M. (4 August 2020). "‘It’s Like Having No Testing’: Coronavirus Test Results Are Still Delayed". The New York Times. Retrieved 05 August 2020. 
  55. 55.0 55.1 "In Vitro Diagnostics EUAs - Antigen Diagnostic Tests for SARS-CoV-2". U.S. Food and Drug Administration. 7 September 2021. Retrieved 07 September 2021. 
  56. 56.0 56.1 Terry, M. (30 March 2020). "CRISPR Pioneer Jennifer Doudna Expects Automated COVID-19 Test Lab to Begin Testing Next Week". BioSpace. Retrieved 10 April 2020. 
  57. 57.0 57.1 Sands, P.; Mundaca-Shah, C.; Dzau, V.J. (2016). "The Neglected Dimension of Global Security — A Framework for Countering Infectious-Disease Crises". The New England Journal of Medicine 374 (13): 1281–87. doi:10.1056/NEJMsr1600236. PMID 26761419. 
  58. Morris, C. (26 February 2020). "Trump administration budget cuts could become a major problem as coronavirus spreads". Fortune. Retrieved 10 April 2020. 
  59. Specter, M. (17 March 2020). "The Coronavirus and the Gutting of America’s Public-Health System". The New Yorker. Retrieved 10 April 2020. 
  60. Roos, R. (25 May 2007). "Congress cut pandemic funds before passing spending bill". CIDRAP - News & Perspective. Retrieved 10 April 2020. 
  61. Schnirring, L. (20 December 2007). "Congress slashes pandemic preparedness funding". CIDRAP - News & Perspective. Retrieved 10 April 2020. 
  62. Gates, B. (2020). "Responding to Covid-19 — A Once-in-a-Century Pandemic?". The New England Journal of Medicine. doi:10.1056/NEJMp2003762. PMID 32109012. 
  63. Shontell, A. (10 April 2020). "Melinda Gates: This is not a once-in-a-century pandemic. 'We will absolutely have more of these.' The billionaire philanthropist predicts a timeline for going back to normal". Business Insider. Retrieved 10 April 2020. 
  64. Madhav, N.; Oppenheim, B.; Gallivan, M. et al. (2017). "Chapter 17: Pandemics: Risks, Impacts, and Mitigation". In Jamison, D.T.; Gelband, H.; Horton, S. et al.. Disease Control Priorities: Improving Health and Reducing Poverty (3rd ed.). The World Bank. ISBN 9781464805288. 
  65. Sanders, R. (30 March 2020). "UC Berkeley scientists spin up a robotic COVID-19 testing lab". Berkeley News. Retrieved 10 April 2020. 
  66. Nolting, R. (10 April 2020). "Local testing delayed by lack of reagents". Parsons Sun. Retrieved 10 April 2020. 
  67. Herper, M.; Branswell, H. (10 March 2020). "Shortage of crucial chemicals creates new obstacle to U.S. coronavirus testing". STAT. Retrieved 10 April 2020. 
  68. Hale, C. (18 March 2020). "Qiagen aims to more than quadruple its COVID-19 reagent production in 6 weeks". Fierce Biotech. Retrieved 10 April 2020. 
  69. Mehta, A. (3 April 2020). "Mystery surrounds UK claim of Covid-19 test reagent ‘shortage’". Chemistry World. Retrieved 07 September 2021. 
  70. 70.0 70.1 Roche, B. (8 April 2020). "Irish scientists develop reagent in effort to ease Covid-19 testing delays". The Irish Times. Retrieved 10 April 2020. 
  71. Padma, T.V. (13 May 2020). "Efforts to combat Covid-19 in India hit by imported reagent shortages". Chemistry World. Retrieved 19 May 2020. 
  72. David, E.; Farber, S.E. (20 June 2020). "Survey shows resources for COVID-19 diagnostic testing still limited months later". ABC News. Retrieved 08 July 2020. 
  73. Johnson, K. (2 July 2020). "NC Labs Facing Shortages In COVID-19 Testing Chemicals". Patch. Retrieved 08 July 2020. 
  74. 74.0 74.1 American Society for Microbiology (9 November 2020). "Supply Shortages Impacting COVID-19 and Non-COVID Testing". American Society for Microbiology. Retrieved 18 November 2020. 
  75. 75.0 75.1 Abbott, B.; Krouse, S. (9 November 2020). "Covid-19 Testing Saps Supplies Needed for Other Medical Tests". The Wall Street Journal. Retrieved 18 November 2020. 
  76. 76.0 76.1 Williams, S. (21 April 2021). "Supply Shortages Hit Life Science Labs Hard". The Scientist. Retrieved 07 September 2021. 
  77. 77.0 77.1 Hale, C. (27 April 2020). "Congress urges FDA to better police, evaluate COVID-19 antibody tests". Fierce Biotech. Retrieved 01 May 2020. 
  78. Subcommittee on Economic and Consumer Policy (24 April 2020). "Preliminary Findings of the Subcommittee’s Coronavirus Antibody Testing Investigation" (PDF). U.S. House of Representatives. Retrieved 01 May 2020. 
  79. Farley, P.; Sanders, R. (27 April 2020). "Testing the Tests: COVID-19 Antibody Assays Scrutinized for Accuracy by UCSF, UC Berkeley Researchers". UCSF News. Retrieved 01 May 2020. 
  80. Sanders, R. (27 April 2020). "What COVID-19 antibody tests can tell us, and what they can’t". Berkeley News. Retrieved 01 May 2020. 
  81. Whooley, S. (17 August 2020). "FDA warns on false results for Thermo Fisher TaqPath COVID-19 testing kit". + Mass Device. WTWH Media LLC. Retrieved 23 August 2020. 
  82. Taylor, N.P. (18 August 2020). "Thermo Fisher COVID-19 test flagged for false positive and negative results". MedTechDive. Retrieved 23 August 2020. 
  83. Richardson, L. (2 September 2021). "With Delta Surging, FDA Needs Authority to Ensure Accuracy of COVID-19 Tests". Pew Charitable Trust. Retrieved 07 September 2021. 
  84. 84.0 84.1 84.2 Wan, W. (24 October 2020). "Home tests could help in the fight against the coronavirus. So where are they?". The Washington Post. Retrieved 18 November 2020. 
  85. McDermott, A. (2020). "Inner Workings: Researchers race to develop in-home testing for COVID-19, a potential game changer". PNAS 117 (42): 25956-25959. doi:10.1073/pnas.2019062117. PMC PMC7584891. PMID 32999063. 
  86. Crear-Perry, J. (5 November 2020). "The hidden public health hazard of rapid Covid-19 tests". STAT. Retrieved 18 November 2020. 
  87. National Institutes of Health (23 June 2020). "Experts identify steps to expand and improve antibody tests in COVID-19 response". News Releases. Retrieved 08 July 2020. 

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Citation information for this chapter

Chapter: 2. Diagnostic testing of COVID-19 and other coronaviruses

Edition: Fall 2021

Title: COVID-19 Testing, Reporting, and Information Management in the Laboratory

Author for citation: Shawn E. Douglas

License for content: Creative Commons Attribution-ShareAlike 4.0 International

Publication date: September 2021