LII:COVID-19 Testing, Reporting, and Information Management in the Laboratory/Adding COVID-19 and other virus testing to your laboratory
- 1 3. Adding COVID-19 and other virus testing to your laboratory
- 1.1 3.1 What methodologies will you use?
- 1.2 3.2 What kind of space, equipment, and supplies will you need?
- 1.3 3.3 What other considerations should be made?
- 2 References
- 3 Citation information for this chapter
3. Adding COVID-19 and other virus testing to your laboratory
Maybe you've been running an environmental health laboratory and want to expand into clinical health testing. Perhaps you're in charge of an academic research lab but want to expand to the clinical diagnostic side. Or maybe you're running a physician office laboratory (POL) and are wondering if it's even possible to expand your waived testing efforts to COVID-19. Where the previous chapter discussed the "what" of COVID-19 and viral testing, this chapter aims to help you with the "how" of adding it to your laboratory offerings.
Naturally, many questions come with the "how":
- Does using one method make the most sense, or will your lab turn to multiple methods for virus testing? This may be determined by current equipment, space considerations, and budget.
- What type of lab are you running? A POL is going to have fewer options available than a CLIA moderate- or high-complexity lab.
- How interoperable are you existing laboratory and clinical informatics solutions? Research laboratories face more challenges in integrating their systems with EHRs and other clinical systems.
- What vendors and consultants are out there to help get equipped? Some vendors have very specific solutions, whereas others may have a broader range of offerings.
These questions and more are addressed this chapter.
3.1 What methodologies will you use?
3.1.1 PCRCOVID-19 and other coronaviruses were discussed in detail. The prevailing method (often called the "gold standard") among them all is real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for testing. Broadly speaking, PCR is useful in pharmaceutical, biotechnology, and genetic engineering endeavors, as well as clinical diagnostics. As such, labs in those industries that already have PCR infrastructure in place have a theoretical step-up over a lab that doesn't.
PCR technology has advanced to the point where it is more efficient and user-friendly than prior, yet "the high cost of the instruments, servicing contracts, and reagents pose major challenges for the market, especially to the price-sensitive academics." Writing about the thirty-fifth anniversary of PCR in 2018, science writer Alan Dove not only highlighted these cost issues but also the size and energy requirements for running the equipment. "As a result, one of the defining techniques of modern molecular biology has remained stubbornly inaccessible to educators and unusable in many remote locations." Various efforts have been made over the years to bring costs down by modifying how heating and temperature control are performed, but many of those system aren't typically optimal during a pandemic when turnaround time is critical.
Amidst the pandemic, additional challenges also exist to those wanting to conduct PCR testing for COVID-19 and other viruses. As was discussed at the end of the previous chapter, supplies of reagents and consumables are not particularly robust mid-pandemic, with shortages being reported since March 2020. These shortages may eventually work themselves out, but they highlight the need for other varying methods that don't necessarily depend on the same reagents and consumables that are in short supply.
For those labs wishing to adopt PCR testing of viruses—particularly COVID-19—into their workflow while providing reasonable turnaround times, all is not lost. However, careful planning is required. For example, you'll want to keep in mind that some PCR machines require vendor-specific reagents. If you're going to acquire a particular instrument, you'll want to do due diligence by verifying not only the supported reagents but also those reagents' overall availability (real and projected). You'll also want to consider factors such as anticipated workload (tests per day), what your workflow will look like, and how to balance overall investment with the need for reasonable turnaround times.
As of August 2020, an increasing body of research is being produced suggesting ways to improve turnaround times with PCR testing for COVID-19, with many research efforts focusing on cutting out RNA extraction steps entirely. Alcoba-Florez et al. propose direct heating of the sample-containing nasopharyngeal swab at 70 °C for 10 minutes in place of RNA extraction. Adams et al. have proposed an "adaptive PCR" method using a non-standard reagent mix that skips RNA extraction and can act "as a contingency for resource‐limited settings around the globe." Wee et al. skip RNA extraction and nucleic acid purification by using a single-tube homogeneous reaction method run on a lightweight, portable thermocycler. Other innovations include tweaking reagents and enzymes to work with one step, skipping the reverse transcription step, and using saliva-based molecular testing that skips RNA extraction.
Saliva as a specimen
The saliva molecular tests in particular are intriguing. Talk of the potential utility of using saliva as a specimen for COVID-19 was occurring as early as April, and the first saliva-based COVID-19 test, produced by Spectrum Solutions in cooperation with RUCDR Infinite Biologics Laboratory and Vault Health, was given an FDA EUA in April. On August 15, Yale School of Public Health was given an EUA for it SalivaDirect molecular test. Although still PCR-based (and a CLIA high-complexity test), SalivaDirect is being touted as a means to improve specimen collection safety, consume fewer reagents, prove compatible with high-throughput workflow, and cut overall turnaround time. Not only is saliva easier to collect and safer for healthcare staff, the test is essentially "open sourced," not requiring proprietary equipment from Yale, making the test more flexible by being validated to reliably function with a wider array of reagents and instruments. When compared to using a nasopharyngeal swab specimen using the ThermoFisher Scientific TaqPath COVID-19 combo kit, results were comparable 94.1% of the time. While sensitivity and specificity may be slightly less comparable to other PCR options, the overall advantages during reagent shortages and a definitive need for broader testing likely outweigh the slightly lesser sensitivity and specificity.
3.1.2 Pooled testing
Another method some labs are taking to speed up turnaround time is using pooled testing. The general concept involves placing two or more test specimens together and testing the pool as one specimen. The most obvious advantage to this is that the process saves on reagents and other supplies, particularly when supply chains are disrupted. This methodology is best used "in situations where disease prevalence is low, since each negative pool test eliminates the need to individually test those specimens and maximizes the number of individuals who can be tested over a given amount of time." However, it's best left to situations where expectations are that less than 10 percent of the population being tested is affected by what's being tested for.
The downside of pooled testing comes with the issues of dilution, contamination, and populations with 10 or more percent infected. A target-positive specimen that comingles with other target-free specimens is itself diluted and in some cases may cause issues with the limit of detection for the assay. Additionally, if the pool tests positive, target-free specimens may become contaminated by a target-positive specimen. This may cause issues with any individual specimen assays that get ran. And the workflows involving pooling must be precise, as a technician working with multiple specimens at the same time increases the chance of lab errors. Finally, at least in the U.S., a Food and Drug Administration (FDA) emergency use authorization (EUA) for a validated pooled testing method is required. (Validation of pooled methods may differ in other countries.) The U.S. Centers for Disease Control and Prevention (CDC) has published interim guidance on pooled testing strategies for SARS-CoV-2.
3.1.3 Rapid antigen testing
As mentioned in the previous chapter, the benefits of antigen testing For COVID-19 and other viral infections are 1. specimen collection can typically be done with a simple nasal swab rather than a more invasive nasopharyngeal swab, 2. testing is more rapid and convenient, and 3. it takes some pressure off the PCR supply chain. However, antigen testing only tests what's there, rather than amplifying the amount, resulting in generally lower sensitivities. As such, the real 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. If your lab is able to support this sort of testing, then this type of testing may be an option. However, as of August 2020, only three vendors have EUAs for antigen diagnostic tests: Quidel Corporation; Becton, Dickinson and Company; and LumiraDx UK Ltd. With six U.S. states already contracted to purchase hundreds of thousands of two of those companies' test kits, it's not clear how well they'll manage to meet demand.
3.1.4 LAMP and CRISPR
Early on in the pandemic, while PCR was getting most of the attention, reverse transcription loop-mediated isothermal amplification (RT-LAMP), an isothermal nucleic acid amplification technique that allows for RNA amplification, was also quietly being discussed, and it has since gained more attention. The University of Oxford, for example, is in the process of getting a rapid, affordable, clinically-validated RT-LAMP test approved for the European market. Oxford also notes that "[a]n advantage of using LAMP technology is that it uses different reagents to most laboratory-based PCR tests." Thi et al. have tested a two-color RT-LAMP assay with an N gene primer set and diagnostic validation using LAMP-sequencing, concluding that the pairing of the two "could offer scalable testing that would be difficult to achieve with conventional qRT-PCR based tests." And California-based Color Genomics have set up their own proprietary RT-LAMP system, capable of handling up to 10,000 tests per day.
In most cases, LAMP-based testing is much simpler than PCR, lacking the requirement of specialized instruments. Despite LAMP generally being thought of as less sensitive than PCR, the recent explosion of research into RT-LAMP methods for testing for the presence of SARS-CoV-2 seems to gradually indicate that "under optimized conditions," RT-LAMP methods may actually be able to rival the sensitivity and specificity of many RT-PCR COVID-19 tests. Esbin et al. add:
These methods allow for faster amplification, less specialized equipment, and easy readout. LAMP methods also benefit from the ability to multiplex targets in a single reaction and can be combined with other isothermal methods, like [recombinase polymerase amplification] in the RAMP technique, to increase test accuracy even more. These techniques may be particularly useful for rapid, point-of-care diagnoses or for remote clinical testing without the need for laboratory equipment.
CRISPR methods are also being used in conjunction with RT-LAMP. RT-LAMP creates complementary double-stranded DNA (cDNA) from specimen RNA and then copies (amplifies) it. Then CRISPR methods are used to detect a predefined coronavirus sequence (from a cleaved molecular marker) in the resulting amplified specimen. Though as of August 2020 approved assays using CRISPR-based detection of SARS-CoV-2 are limited to a handful of companies, the technology has some promise as an alternative testing method. It has the additional advantage of being readily coupled with lateral flow assay technology to be deployed in the point-of-care (POC) setting.
3.1.5 Point-of-care and other alternative testing Addressing POC testing, the WHO recommends that such assays:
- have a sensitivity (true positive rate) or at least 70 percent;
- have a specificity (true negative rate) of at least 97 percent;
- provide results in less than 40 minutes;
- require diagnostic machines that cost less than $3,000 U.S.;
- individually cost less than $20 for the patient;
- be simple enough that only a few hours of training are required to run the test; and
- operate reliably outside a clean laboratory environment.
While few of the available test systems can meet all these requirements, it's clear the push to expand COVID-19 testing to the point of care is accelerating. The U.S. National Institutes of Health's Rapid Acceleration of Diagnostics (RADx) funding program has sought to speed up innovation in COVID-19 testing and promote "truly nontraditional approaches for testing that have a slightly longer horizon." As of August 2020, RADx has chosen to fund seven biomedical diagnostic companies making new lab-based and POC tests that could significantly ramp up overall testing in the U.S. into September 2020. Four offerings are lab-based (from Ginkgo Bioworks, Helix OpCo, Fluidigm, and Mammoth Biosciences) and three are POC tests (from Mesa Biotech, Quidel, and Talis Biomedical), all using varying technologies and methods such as next-generation sequencing, CRISPR, microfluidic chips, nucleic acid testing, antigen testing, and saliva testing. Both Mesa Biotech's rapid, cartridge-based RT-PCR Accula System and Quidel's rapid Sofia SARS Antigen FIA test are already EUAed and CLIA-waived, with Talis' Talis One LAMP-based lateral flow immunoassay kit still awaiting EUA and CLIA status approval. Whether or not these POC and lab-based tests make it to the average physician office laboratory remains to be seen, however.
- a method of DNA nanoswitch detection of virus particles;
- a dual biomarker-based finger-stick test for acute respiratory infections;
- a rapid breath test to detect volatile organic chemicals from the lungs;
- an affordable, hand-held spectral imaging device to detect virus in blood or saliva in seconds;
- an ultrahigh frequency spectroscopic scanning device to see virus particles resonating;
- a method that combines optical devices and magnetic particles to detect virus RNA;
- an RNA extraction protocol that uses magnetic bead-based kits;
- the additional use of an artificial intelligence (AI) application to better scrutinize test results; and
- the miniaturization of PCR technology to make it more portable and user-friendly.
Of course, most of these are largely experimental technologies, and realistically getting them into the lab may be far out. But they represent out-of-the-box ideas that have some kind of chance at playing a greater role in the clinical laboratory or in point of care settings in the future.
3.2 What kind of space, equipment, and supplies will you need?
3.2.1 Laboratory space arrangements
Whether adding PCR to your existing laboratory, modifying existing PCR workflows, or starting from scratch, preventing contamination is a top priority. As PCR can effectively amplify even the tiniest of quantities of DNA and RNA, the risk of amplifying a contaminant and ruining the validity of an assay is very real. Contamination typically comes from non-amplified environmental substances such as aerosols, and from carryover contamination of amplicons from earlier PCR cycles. As such, not only do best-practice processes and procedures (P&P) need to be followed (e.g., unidirectional workflow, thorough cleaning procedures, proper preparation and disposal), but also where to place PCR-related equipment must be carefully considered.
When possible, separate rooms for sample preparation, PCR setup, and post-PCR activities, each with their own airflow control, are encouraged. However, the laboratory attempting to add PCR to an already small clinical diagnostic lab may not have the luxury of having multiple rooms. In that case, a single-room setup may suffice, if the workflow areas remain demarcated or physically partitioned. Additionally, a single-room setup must also have stricter P&P and design controls to offset the space constraints. For example, the sample preparation area of the room should have a laminar flow hood with UV light that is regularly cleaned, and post-PCR analysis may need to occur later in the day after cleanup from prior steps. Of course, always maintaining unidirectional workflow—regardless of number of rooms—is also critical to minimizing contamination. For example, technicians shouldn't be transporting amplified materials into the DNA extraction area.
Although dated, Roche Diagnostics' 2006 PCR Applications Manual provides a detailed breakdown of setting up the laboratory for PCR. Das et al. and Dr. Jennifer Redig provide additional valuable insight. The World Health Organization (WHO) also provides guidance for setting up molecular testing in the lab.
Isothermal amplification considerations
Similarly, because DNA and RNR amplification is involved, contamination concerns exist with isothermal amplification techniques. Multiple pipetting steps and repeated freezing and thawing of reagents can still lead to cross-contamination, as does opening the reaction chamber after reaction is completed. However, the advent of microfluidics and lateral flow technologies in isothermal amplification processes has seen the development of "fully enclosed microstructured devices into which performing the isothermal amplification reduces the risk of sample contamination and allows integration and portable device realization." Even more cutting-edge techniques to reduce contamination such as the CUT-LAMP technique of Bao et al. or the dUTP/UDG system for COVID-19 RT-LAMP reactions of Kellner et al. hold further promise in making isothermal amplification processes in the laboratory easier to manage. That said, labs running isothermal amplification processes such as LAMP requiring analysis with agarose gel electrophoresis or a method requiring the opening of reaction vessels will preferably have a secondary area set up for analysis steps so as to minimize the chances of contamination.
3.2.2 Instruments and assays
High- and moderate-complexity CLIA testing
Thermal cyclers are the standard instruments for PCR testing. Today, real-time or quantitative (qPCR) systems largely fill this niche. However, digital and droplet digital PCR systems are emerging, and they have the benefit of producing even more rapid, precise, sensitive, accurate, and reproducible results, and they are capable of direct quantification and multiplexing. Other instruments and accessories for PCR workflows include proper power supplies, analytical balances, electrophoresis chambers, water and/or dry baths, and mini/micro centrifuges. However, if you're considering the addition of PCR workflow to your laboratory, the thermal cycler is typically where the largest up-front cost will be. As such, it's important to ask yourself critical questions to help guide your acquisition decisions.
As part of their June 2018 survey on PCR equipment, Lab Manager poses five questions potential buyers should ask before making PCR purchases:
- Do your current and long-term needs require basic PCR systems, qPCR systems, or digital PCR systems?
- What sample formats do you anticipate using?
- What throughput requirements do you have now and anticipate in the near future?
- What are you willing to sacrifice in regards to temperature ramp up and cool down times and accuracies?
- Do you anticipate needing to run more than one independent PCR at the same time (multiblock PCR)?
Given the considerable investment that goes into these and other life science instruments, you may want to seek vendors who have a strong track record of supporting and supplying parts for instruments they manufacture and distribute years after the instruments are introduced.
As for PCR-based assays, the U.S. FDA has issued EUAs for more than 100 of them. The most up-to-date listing is of course found at the FDA website. However, sorting through the extra details can be tedious. The Center for Systems Biology at Harvard has been maintaining a contextual PDF chart of the various COVID-19 diagnostic tests, which includes information such as run time, manufacturer-supplied data, and published clinical data (when available). This may prove useful in deciding on one or more particular tests. As with many aspects of this pandemic, other factors that may influence your choice of test kit include overall availability, cost, reagents included with the assay, and reagents separately required and their availability.
Isothermal amplification techniques have the advantage of not requiring an expensive thermal cycler. Instrument-appropriate reaction vessels, baths, heating units, turbidimeters, thermocyclers, etc. may be required, depending on what type of amplification you're doing. Companies like Meridian Bioscience offer LAMP-based molecular platforms, though they may not offer a specific COVID-19 assay to run on the platform. As can be seen in Table 1, two isothermal amplification assays that run on their own proprietary instrument have received EUAs and are CLIA-waved, with a third potentially on the way. Using these systems and their COVID-19 assays at the point of care provides a somewhat more attractive option for laboratories wanting to add COVID-19 or even multiplex viral assays to their offerings.
If you're running a POL, or attempting to provide COVID-19 testing at the point of care, you'll be looking at the following assay and instrument options shown in Table 1:
High- and moderate-complexity CLIA testing
Reagent shortages since April have hampered efforts to expand testing in parts of the world, including the United States. As such, your reagent choices will likely be closely tied to both the assays you choose to implement and how reliably the supplier can get them to you. This in turn is likely driven by whether you're using a lab-developed test or a test kit. In some cases, e.g., the Xiamen Zeesan Biotech SARS-CoV-2 Test Kit (Real-time PCR), all but the Virus RNA Extraction Kit is included. On the other hand, Biomeme's SARS-CoV-2 Real-Time RT-PCR Test requires the separate acquisition of PCR buffer and external controls other than the exogenous RNA Process Control that comes with the kit. Yale's SalivaDirect is a more flexible test, validated for use with multiple instruments and reagents that are not proprietary to Yale. Pay close attention to what comes with the assay, typically by reviewing the instructions for use (IFU; found on the FDA's EUA page).
For PCR, the five basic reagents are template DNA, PCR primers, nucleotides, PCR buffer, and thermostable DNA polymerase. Some of these components can be acquired pre-mixed as a "master mix." For example, Thermo Fisher's PCR Master Mix contains a thermostable DNA polymerase called Taq, nucleotides called deoxynucleotide triphosphates (dNTPs), and a buffer, which "saves time and reduces contamination due to a reduced number of pipetting steps."
The FDA EUA devices (Table 1) all come with the necessary reagents, with the exception of any controls or references you may require. Refer to the IFU for the waived test kit to determine what additional consumables you'll require.
High- and moderate-complexity CLIA testing
Non-reagent consumables for high- and moderate-complexity CLIA testing include PCR tubes and plates; pipettes and tips; films, foils, and sealing mats; swabs; and viral transport media, among others. Some like Kellner et al. have experimented with methods to make isothermal amplifications methods more approachable in resource-poor environments by, for example, developing a pipette-free version of LAMP.
The FDA EUA devices (Table 1) may require a few extra consumables. For example, the Accula SARS-CoV-2 test kit comes with swabs and the Xpert Xpress SARS-CoV-2 kit comes with disposable transfer pipettes. Refer to the IFU for the waived test kit to determine what additional consumables you'll require.
3.2.5 Software and services
A June 2020 report by Weemaes et al. in the Journal of the American Medical Informatics Association describes the bottlenecks they encountered in their test workflows at the Belgian National Reference Center, and how they updated their laboratory information system (LIS) with functionality to resolve those bottlenecks. In addition to adding a COVID-19–specific order set into the computerized physician order entry (CPOE) module integrated with both their LIS and electronic health record (EHR), they included an up-to-date triage criteria component, a tool for optimizing sampling and packaging, a COVID-19 status button, and improved reporting modules for automating reference testing and epidemiological reporting. They also added extra database and data mining functionality to facilitate research and insights into epidemiologies and treatments. Their conclusion: "Rapidly developed, agile extendable LIS functionality and its meaningful use alleviates the administrative burden on laboratory personnel and improves turnaround time of SARS-CoV-2 testing." The Association of Public Health Laboratories comes to a similar conclusion in regard to laboratory informatics solutions and public health laboratories' COVID-19 testing.
As such, adding COVID-19 and other respiratory illness testing to your workflow may necessitate an information management system, or an upgrade of your existing software systems. You may experience many of the same bottlenecks the Belgian National Reference Center experienced, especially if you're still working primarily with paper-based test ordering. Those researchers found that paper-based COVID-19 test requests often:
- omitted critical clinical status and contact information;
- slowed down epidemiological and research studies;
- hindered proper preanalytical biosafety procedures; and
- impeded rapid response to evolving test criteria and clinical insights through test ordering protocols.
How interoperable your laboratory software solution is with other systems such as EHRs is also worth consideration. The next chapter addresses system interoperability in greater detail, but it's worth mentioning it here in the context of adding software to improve testing workflows for SARS-CoV-2 and other respiratory viruses. Broadly speaking, improving interoperability among clinical informatics systems—whether at the point of care or within a specific laboratory—is recognized as an important step towards improving health outcomes. However, while developers of EHRs and other clinical informatics systems have intended to improve their software's interoperability, the COVID-19 pandemic has unfortunately shown the inadequacies still inherent in that software's overall design. As such, any research into acquiring a laboratory information management system (LIMS), LIS, or other clinical information management solution should take into account how well that solution is able to integrate with your other clinical systems, as well as any other third-party systems like physician or hospital EHRs. And it's not just the software solutions you'll want to consider. Will the new instruments you add to get you rolling with clinical respiratory illness testing integrate with your software?
Finally, although rare, you may find you don't have the in-house expertise to fully implement a COVID-19 testing line to your laboratory. In such a case, you may need to turn to a laboratory services consultancy with experience in SARS-CoV-2 test method validation, instrument procurement and implementation, and legal matters. (See the next section for a representative example of consultants advertising COVID-19 testing knowledge and services for labs.)
3.2.6 Major vendors and consultants
Table 2 lists the major vendors developing and selling PCR, isothermal amplification, and NGS supplies, instruments, and software for both clinical diagnostics and life science research. "Research use only" equipment like Siemens Healthcare's Fast Track Cycler was ignored for completing the table. The vendor list was largely compiled from vendors identified in a handful of online market reports on PCR, with an added sprinkling of a few additional reagent vendors (e.g., Jena Bioscience, LGC, and New England BioLabs) who address isothermal amplification supplies in addition to PCR. Note that this is not an endorsement for any particular vendor.
Table 2's "Software" column represents whether or not the vendor offers laboratory informatics software such as a LIMS or LIS. Those vendors' solutions may or may not be tailored to handle the specific requirements of a clinical diagnostic or virology lab handling COVID-19 and other viruses. (See the next chapter for more in-depth information about working an informatics solution into COVID-19 and other viral testing workflow.) A non-endorsed, representative example of vendors who do include:
- AgileBio - COVID-19 LC
- BioSoft Integrators, LLC - LabOptimize LIMS for COVID-19
- CloudLIMS.com, LLC - CloudLIMS for COVID-19
- Common Cents Systems, Inc. - Apollo LIMS for COVID-19
- Comp Pro Med, Inc. - COVID-19 Rapid Deployment LIS
- Illumina, Inc. - BaseSpace Clarity LIMS for COVID-19
- LabLynx, Inc. - COVIDLiMS
- LabVantage Solutions, Inc. - LabVantage COVID-19 LIMS
- Physion, LLC - Ovation LIMS for COVID-19
- Sunquest Information Systems, Inc. - Mitogen LIMS for COVID-19 (PDF)
Additionally, when in-house knowledge is lacking, a consultant may be required. These consultants are meant to be representative examples of those laboratory consulting firms indicating they have the knowledge to help a laboratory with COVID-19-related testing and other issues. This list is not an endorsement for any particular consultant:
- ARUP Laboratories (Utah)
- Colaborate (Florida)
- Elite Diagnostics (North Carolina)
- Freed Associates (California)
- Lighthouse Lab Services (North Carolina)
- Optimum Healthcare IT (Florida)
- Triumverate Environmental (Massachusetts)
3.3 What other considerations should be made?
3.3.1 U.S. regulatory compliance
In the previous chapter, the regulatory hurdles of the Health Insurance Portability and Accountability Act (HIPAA) and the Clinical Laboratory Improvement Amendments (CLIA) were addressed. For those laboratories that are already operating in the clinical laboratory sphere, it should be relatively simple to address the additional considerations and pandemic-specific changes to those two regulations as described previously. In addition to that information, you can always periodically check the U.S. Department of Health & Human Services' (HHS') Office for Civil Rights and their COVID-19 announcements and guidance, as well as the Centers for Medicare & Medicaid Services (CMS) emergencies page.
If for some reason you're not a clinical lab—or want to start a new lab—and want to take on COVID-19 and other clinical testing, you're going to need to get fast tracked into the CLIA program, for starters. Fortunately, CMS has already displayed a willingness to help labs wanting to perform COVID-19 testing receive their CLIA certificate rapidly. Form CMS-116 will need to be completed and submitted to your state survey agency contact. Of course, while you're waiting, you'll also want to become familiar with the trappings of CLIA by tapping into resources like the CMS page for CLIA, CDC page for CLIA, and resources available from professional organizations like the American Academy of Family Physicians. If all goes as plan, and directions are followed, you should have your CLIA certificate in no time. CMS adds:
We want to ensure that laboratories located in the United States applying for a CLIA certificate are able to begin testing for COVID-19 as quickly as possible. Once the laboratory has identified a qualified laboratory director and has provided all required information on the CMS-116 application, a CLIA number will be assigned. Once the CLIA number has been assigned, the laboratory can begin testing as long as applicable CLIA requirements have been met (e.g., establishing performance specifications).
On the HIPAA side of things, you'll want to tap into resources such as the HHS' HIPAA training materials and resources, as well as their previously mentioned COVID-19 announcements and guidance.
- taking the time to get accredited to ISO 15189:2012 Medical laboratories — Requirements for quality and competence, "used by medical laboratories in developing their quality management systems and assessing their own competence";
- understanding and training on packaging (e.g., UN3373 Biological Substance, Category B) and shipping COVID-19 specimens (e.g., International Air Transport Association (IATA) Dangerous Goods Regulations), if you will be conducting such activities;
- understanding the significance of and validating workflow procedures to at least Biosafety Level 2 (note there is no single U.S. government entity which has total responsibility for enforcing biosafety levels); and
- understanding and training on Occupational Safety and Health Administration (OSHA) requirements for laboratory workers and employers for COVID-19.
The topic of reporting COVID-19 results to local and regional health departments—as well as any internal medical reporting—is covered in detail in the next chapter. You'll want to be sure you and your team understand your state's health department reporting requirements, as well as what code sets (LOINC, SNOMED, ICD, and CPT) to use. The success of epidemiologists' response to outbreaks and pandemics depends on quality data reporting, and using the correct code sets helps labs meet reporting requirements, as well as ensure proper payment. The U.S. Centers for Disease Control and Prevention provides guidance on how to report COVID-19 laboratory data, which also makes for necessary reading.
3.3.3 Billing, Medicare, and Medicaid
The COVID-19 pandemic has unquestionably put the U.S. health care system in a tough spot. That health care system, with all its warts, has arguably not done well to handle so many unanticipated health issues from a broad portion of the population. From a provider side, proper reimbursement for COVID-19 testing is among the many issues that must be addressed. One key aspect of ensuring proper reimbursement in a reasonable time frame is first making sure a clear preregistration process that captures critical patient and facility information is conducted. (This can be facilitated and made easier as a first-step process in a clinical informatics solution, for example.) Critical patient and facility information includes (but is not limited to):
- name, date of birth, and gender
- race and ethnicity
- demographic information such as full address and phone number
- ordering physician or attending health care provider for test (if applicable)
- facility's National Provider Identifier (NPI)
- patient insurance company name, policy ID, group ID, insured's name, and insured relationship to patient (if insured)
- whether or not it's the patient's first test (federal reporting requirement)
- whether or not the patient is a resident of a congregate care setting (federal reporting requirement; also, e.g., additional Medicaid reimbursement may be available in some states)
- whether or not the patient is a healthcare worker (federal reporting requirement; also, e.g., may affect the patient's worker's compensation claim)
- whether or not the patient is pregnant (federal reporting requirement; also, e.g., Medicare will only accept a COVID-19 code as secondary if the primary diagnosis code is viral disease complicating pregnancy, childbirth, or puerperium)
Secondarily, it's also important to have a plan in place for testing the uninsured. While the Families First and Coronavirus Relief Act (FFCRA) and the National Disaster Management System (NDMS) provide legal mechanisms for reimbursement for what should otherwise be free patient testing for SARS-CoV-2 and the associated visit, ambiguities of these mechanisms and how they are enforced are still creating problems. For example, while providers can turn to the NDMS (until funds run out) to pay uninsured claims at 110% of Medicare rates—with states' opting to cover those costs through their Medicaid program—providers are not obligated by the law to seek reimbursement from those entities and can optionally bill the uninsured patient directly, which is against the spirit of the FFCRA. As such, it's important to know what your lab's policy will be on managing uninsured patient claims. How will you get reimbursed if you're accepting uninsured patients? Resources that may help with these decisions include the NDMS Definitive Care Reimbursement Program portal and the Health Resources & Services Administration's information page and associated FAQ.
For Medicare, Medicaid, and otherwise insured patients, the lab will likely have (or presumably acquire) someone on hand with billing experience. The preregistration information previously mentioned will still be important to implement. For further guidance on billing issues, you may wish to consult with CMS' extensive document titled COVID-19 Frequently Asked Questions (FAQs) on Medicare Fee-for-Service (FFS) Billing. Also, the next chapter addresses code sets for reporting and billing, which may prove useful.
- Kenneth Research (23 June 2020). "Polymerase Chain Reaction Market Sector Analysis Report, Regional Outlook & Competitive Share & Forecast - 2023". MarketWatch. https://www.marketwatch.com/press-release/polymerase-chain-reaction-market-sector-analysis-report-regional-outlook-competitive-share-forecast---2023-2020-06-23. Retrieved 06 August 2020.
- Dove, A. (2018). "PCR: Thirty-five years and counting". Science 360 (6389): 670–672. doi:10.1126/science.360.6389.673-c.
- Wong, G.; Wong, I. Chan, K. et al. (2015). "A Rapid and Low-Cost PCR Thermal Cycler for Low Resource Settings". PLoS One 10 (7): e0131701. doi:10.1371/journal.pone.0131701.
- Kuznetsov, S.; Doonan, C.; Wilson, N. et al. (2015). "DIYbio Things: Open Source Biology Tools as Platforms for Hybrid Knowledge Production and Scientific Participation". Proceedings of the 33rd Annual ACM Conference on Human Factors in Computing Systems: 4065–68. doi:10.1145/2702123.2702235.
- Norton, D. (11 May 2016). "Phila. med tech startup working on multimillion dollar government contract". Philadelphia Business Journal. https://www.bizjournals.com/philadelphia/news/2016/05/11/government-contract-biomeme-hiring-med-tech.html. Retrieved 06 August 2020.
- An, J.; Jiang, Y.; Shi, B. et al. (2020). "Low-Cost Battery-Powered and User-Friendly Real-Time Quantitative PCR System for the Detection of Multigene". Micromachines 11: 435. doi:10.3390/mi11040435.
- Herper, M.; Branswell, H. (10 March 2020). "Shortage of crucial chemicals creates new obstacle to U.S. coronavirus testing". STAT. https://www.statnews.com/2020/03/10/shortage-crucial-chemicals-us-coronavirus-testing/. Retrieved 10 April 2020.
- Hale, C. (18 March 2020). "Qiagen aims to more than quadruple its COVID-19 reagent production in 6 weeks". Fierce Biotech. https://www.fiercebiotech.com/medtech/qiagen-aims-to-more-than-quadruple-its-covid-19-reagent-production-6-weeks. Retrieved 10 April 2020.
- Mehta, A. (03 April 2020). "Mystery surrounds UK claim of Covid-19 test reagent ‘shortage’". Chemistry World. https://www.chemistryworld.com/mystery-surrounds-uk-claim-of-covid-19-test-reagent-shortage/4011457.article. Retrieved 10 April 2020.
- Roche, B. (08 April 2020). "Irish scientists develop reagent in effort to ease Covid-19 testing delays". The Irish Times. https://www.irishtimes.com/news/science/irish-scientists-develop-reagent-in-effort-to-ease-covid-19-testing-delays-1.4223897. Retrieved 10 April 2020.
- Padma, T.V. (13 May 2020). "Efforts to combat Covid-19 in India hit by imported reagent shortages". Chemistry World. https://www.chemistryworld.com/news/efforts-to-combat-covid-19-in-india-hit-by-imported-reagent-shortages/4011718.article#/. Retrieved 19 May 2020.
- David, E.; Farber, S.E. (20 June 2020). "Survey shows resources for COVID-19 diagnostic testing still limited months later". ABC News. https://abcnews.go.com/Health/survey-shows-resources-covid-19-diagnostic-testing-limited/story?id=71341885. Retrieved 08 July 2020.
- Johnson, K. (02 July 2020). "NC Labs Facing Shortages In COVID-19 Testing Chemicals". Patch. https://patch.com/north-carolina/charlotte/nc-labs-facing-shortages-covid-19-testing-chemicals. Retrieved 08 July 2020.
- Mervosh, S.; Fernandez, M. (04 August 2020). "‘It’s Like Having No Testing’: Coronavirus Test Results Are Still Delayed". The New York Times. https://www.nytimes.com/2020/08/04/us/virus-testing-delays.html. Retrieved 05 August 2020.
- Courage, K.H. (31 July 2020). "Should we be testing fewer people to stop the spread of Covid-19?". Vox. https://www.vox.com/2020/7/31/21336212/covid-19-test-results-delays. Retrieved 05 August 2020.
- Alcoba-Florez, J.; González-Montelongo, R.; Íñigo-Campos, A.; García-Martínezde Artola, D.; Gil-Campesino, H.;
The Microbiology Technical Support Team; Ciuffreda, L.; Valenzuela-Fernández, A.; Flores, C. (2020). "Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples". International Journal of Infectious Diseases 97: 66–68. doi:10.1016/j.ijid.2020.05.099.
- Shapiro, M. (29 July 2020). "Streamlined diagnostic approach to COVID-19 can avoid potential testing logjam". Research News @ Vanderbilt. https://news.vanderbilt.edu/2020/07/29/streamlined-diagnostic-approach-to-covid-19-can-avoid-potential-testing-logjam/. Retrieved 06 August 2020.
- Adams, N.M.; Leelawong, M.; Benton, A. et al. (2020). "COVID‐19 diagnostics for resource‐limited settings: Evaluation of “unextracted” qRT‐PCR". Journal of Medical Virology. doi:10.1002/jmv.26328.
- Mehar, P. (27 July 2020). "Improving the speed of gold-standard COVID-19 diagnostic test". Tech Explorist. https://www.techexplorist.com/improving-speed-gold-standard-covid-19-diagnostic-test/34069/. Retrieved 06 August 2020.
- Wee, S.K.; Sivalingam, S.P.; Yap, E.P.H. (2020). "Rapid Direct Nucleic Acid Amplification Test without RNA Extraction for SARS-CoV-2 Using a Portable PCR Thermocycler". Genes 11 (6): 664. doi:10.3390/genes11060664.
- Council for Scientific and Industrial Research (30 July 2020). "Faster, local COVID-19 test kits could be ready by year-end". Engineering News. Creamer Media. https://www.engineeringnews.co.za/article/faster-local-covid-19-test-kits-could-be-ready-by-year-end-2020-07-30/. Retrieved 07 August 2020.
- Ranoa, D.R.E.; Holland, R.L.; Alnaji, F.G. et al. (2020). "Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction". bioRxiv. doi:10.1101/2020.06.18.159434.
- Thomas, L. (06 August 2020). "Fast, cheap and easy COVID-19 test from Yale". News Medical - Life Sciences. https://www.news-medical.net/news/20200806/Fast-cheap-and-easy-COVID-19-test-from-Yale.aspx. Retrieved 16 August 2020.
- Xu, R.; Cui, B.; Duan, X. et al. (2020). "Saliva: Potential diagnostic value and transmission of 2019-nCoV". International Journal of Oral Science 12: 11. doi:10.1038/s41368-020-0080-z.
- Greenwood, M. (24 April 2020). "Saliva samples preferable to deep nasal swabs for testing COVID-19". YaleNews. https://news.yale.edu/2020/04/24/saliva-samples-preferable-deep-nasal-swabs-testing-covid-19. Retrieved 01 May 2020.
- "First saliva collection device FDA EUA authorized for COVID-19 testing". Spectrum Solutions. 2020. https://spectrumsolution.com/fda-authorized-covid-19-updates/. Retrieved 16 August 2020.
- Vault Health (14 April 2020). "Vault Health Launches First-of-its-Kind Saliva-based FDA EUA Approved Test for COVID-19". PR Newswire. https://www.prnewswire.com/news-releases/vault-health-launches-first-of-its-kind-saliva-based-fda-eua-approved-test-for-covid-19-301039633.html. Retrieved 01 May 2020.
- Gallagher, G.M. (15 August 2020). "FDA Grants Emergency COVID-19 Authorization to Yale's Open Source Method of Saliva Testing". ContagionLive. https://www.contagionlive.com/news/fda-grants-emergency-covid19-authorization-yale-open-source-method-saliva-testing. Retrieved 16 August 2020.
- Zillgitt, J. (15 August 2020). "FDA approves COVID-19 saliva test developed at Yale in partnership with the NBA, NBPA". USA Today. https://www.usatoday.com/story/sports/nba/2020/08/15/fda-approves-covid-19-saliva-test-developed-yale-nba-nbpa-aid/5590452002/. Retrieved 16 August 2020.
- Weissleder, R.; Lee, H.; Ko, J. et al. (15 August 2020). "COVID-19 Diagnostics in Context". Harvard Center for Systems Biology. https://csb.mgh.harvard.edu/covid. Retrieved 16 August 2020.
- Rohde, R. (20 July 2020). "COVID-19 Pool Testing: Is It Time to Jump In?". American Society for Microbiology. https://asm.org/Articles/2020/July/COVID-19-Pool-Testing-Is-It-Time-to-Jump-In. Retrieved 06 August 2020.
- Masha, M.; Chau, S. (04 August 2020). "Pooled virus tests help stretched health services". Asia Times. https://asiatimes.com/2020/08/pooled-virus-tests-help-stretched-health-services/. Retrieved 06 August 2020.
- Citroner, G. (03 August 2020). "How Pooled Testing Can Help Us Fight Spread of COVID-19". Healthline. https://www.healthline.com/health-news/how-pooled-testing-can-help-us-fight-spread-of-covid-19. Retrieved 06 August 2020.
- Service, R.F. (2020). "Radical shift in COVID-19 testing needed to reopen schools and businesses, researchers say". Science. doi:10.1126/science.abe1546.
- 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.
- "In Vitro Diagnostics EUAs". U.S. Food and Drug Administration. 11 August 2020. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas. Retrieved 12 August 2020.
- Clark, C. (06 August 2020). "COVID Antigen Tests: Coming to Case Counts Near You?". MedPage Today. https://www.medpagetoday.com/infectiousdisease/covid19/87930. Retrieved 07 August 2020.
- 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.
- 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. https://www.biorxiv.org/content/10.1101/2020.04.06.025635v2.article-info.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7188121.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7144851.
- 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.
- Thi, V.L.D.; Herbst, K.; Boerner, K. et al. (2020). "A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples". Science Translational Medicine: eabc7075. doi:10.1126/scitranslmed.abc7075. PMID 32719001.
- Esbin, M.N.; Whitney, O.N.; Chong, S. et al. (2020). "Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection". RNA 26 (7): 771–83. doi:10.1261/rna.076232.120. PMC PMC7297120. PMID 32358057. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7297120.
- Hale, C. (09 July 2020). "Oxford researchers develop portable COVID-19 test costing less than $25". Fierce Biotech. https://www.fiercebiotech.com/medtech/oxford-researchers-develop-portable-covid-19-test-costing-less-than-25. Retrieved 07 August 2020.
- Sheridan, K. (06 August 2020). "This California company has a better version of a simpler, faster Covid-19 test". STAT. https://www.statnews.com/2020/08/06/better-simpler-faster-covid-19-test/. Retrieved 08 August 2020.
- Heidt, A. (09 July 2020). "Saliva Tests: How They Work and What They Bring to COVID-19". The Scientist. https://www.the-scientist.com/news-opinion/saliva-tests-how-they-work-and-what-they-bring-to-covid-19-67720. Retrieved 08 August 2020.
- Broughton, J.P.; Deng, X.; Yu, G. et al. (2020). "CRISPR–Cas12-based detection of SARS-CoV-2". Nature Biotechnology 38: 870–74. doi:10.1038/s41587-020-0513-4. PMID 32300245.
- GlobalData Healthcare (14 July 2020). "CRISPR biotechnology set to disrupt Covid-19 testing market". Verdict Medical Devices. https://www.medicaldevice-network.com/comment/crispr-biotechnology-disrupt-covid-19-testing-market/.
- World Health Organization (05 August 2020). "COVID-19 Target product profiles for priority diagnostics to support response to the COVID-19 pandemic v.0.1". World Health Organization. https://www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1. Retrieved 12 August 2020.
- Peplow, M. (10 August 2020). "Rapid COVID-19 testing breaks free from the lab". Chemical & Engineering News. https://cen.acs.org/analytical-chemistry/diagnostics/Rapid-COVID-19-testing-breaks/98/web/2020/08. Retrieved 12 August 2020.
- Krieger, L.M. (10 August 2020). "Coronavirus: How to test everyone, all the time". The Mercury News. https://www.mercurynews.com/2020/08/10/coronavirus-how-to-test-everyone-all-the-time/. Retrieved 12 August 2020.
- Brown, D. (10 August 2020). "Point-of-care testing could be ‘biggest advance’ in COVID-19 fight". McKnight's. https://www.mcknights.com/news/point-of-care-testing-could-be-biggest-advance-in-covid-19-fight/. Retrieved 12 August 2020.
- Wisson, J. (28 July 2020). "COVID-19 and effective cohorting: Rapid point of care triage testing". Health Europa. https://www.healtheuropa.eu/covid-19-and-effective-cohorting-rapid-point-of-care-triage-testing/101696/. Retrieved 12 August 2020.
- Tromberg, B.J.; Schwetz, T.A.; Pérez-Stable, E.J. et al. (2020). "Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States — The NIH RADx Initiative". New England Journal of Medicine. doi:10.1056/NEJMsr2022263.
- 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. https://www.nih.gov/news-events/news-releases/nih-delivering-new-covid-19-testing-technologies-meet-us-demand. Retrieved 12 August 2020.
- Leichman, A.K. (27 July 2020). "10 ways Israeli scientists are improving corona testing". Isael21c. https://www.israel21c.org/how-israeli-scientists-are-improving-corona-testing/. Retrieved 11 August 2020.
- Mifflin, T.E. (2003). "Chapter 1: Setting Up a PCR Laboratory". In Dieffenbach, C.; Dveksler, G. (PDF). PCR Primer (2nd ed.). Cold Spring Harbor Laboratory Press. pp. 5–14. ISBN 9780879696542. http://www.biosupplynet.com/pdf/01_pcr_primer_p.5_14.pdf. Retrieved 13 August 2020.
- Degen, H.-J.; Deufel, A.; Eisel, D. et al., ed. (2006). "Chapter 2: General Guidelines" (PDF). PCR Applications Manual (3rd ed.). Roche Diagnostics GmbH. pp. 19–38. https://www.gene-quantification.de/ras-pcr-application-manual-3rd-ed.pdf. Retrieved 13 August 2020.
- Ahmed, S. (2014). "Chapter 12: Setting-up a PCR Lab" (PDF). Manual of PCR. Genetics Resource Centre. http://grcpk.com/wp-content/uploads/2014/10/12.-Setting-up-PCR-Lab.pdf. Retrieved 13 August 2020.
- Redig, J. (01 August 2014). "The Devil is in the Details: How to Setup a PCR Laboratory". BiteSizeBio. https://bitesizebio.com/19880/the-devil-is-in-the-details-how-to-setup-a-pcr-laboratory/. Retrieved 13 August 2020.
- "The basics of PCR: Detecting viruses and bacteria red-handed" (PDF). BioChek BV. May 2018. https://www.biochek.com/wp-content/uploads/2018/05/BioChek-E-book-The-basics-of-PCR.pdf. Retrieved 13 August 2020.
- Das, P.K.; Ganguly, S.B.; Mandal, B. (2018). "Mitigating PCR /Amplicon Contamination in a High Risk High Burden Mycobacterial Reference Laboratory in a Resource Limited Setting". Mycobacterial Diseases 8 (2): 261. doi:10.4172/2161-1068.1000261.
- World Health Organization (31 January 2018). "Dos and Don'ts for molecular testing". World Health Organization. https://www.who.int/malaria/areas/diagnosis/molecular-testing-dos-donts/en/. Retrieved 14 August 2020.
- Diego, J. G.-B.; Fernández-Soto, P.; Crego-Vicente, B. et al. (2019). "Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: Towards a ready-to-use test". Scientific Reports 9: 14744. doi:10.1038/s41598-019-51342-2. PMC PMC6791938. PMID 31611563. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6791938.
- Martzy, R.; Kolm, C.; Krska, R. et al. (2019). "Challenges and perspectives in the application of isothermal DNA amplification methods for food and water analysis". Analytical and Bioanalytical Chemistry 411: 1695–1702. doi:10.1007/s00216-018-1553-1. PMC PMC6453865. PMID 30617408. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6453865.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC4263587.
- Roskos, K.; Hickerson, A.I.; Lu, H.-W. et al. (2013). "Simple System for Isothermal DNA Amplification Coupled to Lateral Flow Detection". PLoS One 8 (7): e69355. doi:10.1371/journal.pone.0069355. PMC PMC3724848. PMID 23922706. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC3724848.
- Bao, Y.; Jiang, Y.; Xiong, E. et al. (2020). "CUT-LAMP: Contamination-Free Loop-Mediated Isothermal Amplification Based on the CRISPR/Cas9 Cleavage". ACS Sensors 5 (4): 1082–91. doi:10.1021/acssensors.0c00034. PMID 32242409.
- "Loop-mediated Isothermal Amplification (LAMP)". New England BioLabs. 17 June 2014. https://www.neb.com/protocols/2014/06/17/loop-mediated-isothermal-amplification-lamp. Retrieved 14 August 2020.
- Fernández-Soto, P.; Mvoulouga, P.O.; Akue, J.P. et al. (2014). "Development of a Highly Sensitive Loop-Mediated Isothermal Amplification (LAMP) Method for the Detection of Loa loa". PLoS One 9 (4): e94664. doi:10.1371/journal.pone.0094664. PMC PMC3983228. PMID 24722638. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC3983228.
- Kerkhof, J. (13 June 2018). "PCR Equipment Survey Results". Lab Manager. https://www.labmanager.com/surveys/what-to-look-for-in-a-pcr-system-2154. Retrieved 14 August 2020.
- Lab Manager (07 April 2020). "Results from the Lab Manager Life Science Technology Survey". Lab Manager. https://www.labmanager.com/surveys/results-from-the-lab-manager-life-science-technology-survey-22257. Retrieved 14 August 2020.
- "Alethia". Meridian Bioscience. https://www.meridianbioscience.com/platform/molecular/alethia/. Retrieved 14 August 2020.
- Moran, A.; Beavis, K.G.; Matushek, S.M. et al. (2020). "Detection of SARS-CoV-2 by Use of the Cepheid Xpert Xpress SARS-CoV-2 and Roche cobas SARS-CoV-2 Assays". Journal of Clinical Microbiology 58 (8): e00772-20. doi:10.1128/JCM.01072-20. PMC PMC7383516. PMID 32303565. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7383516.
- Loeffelholz, M.J.; Alland, D.; Butler-Wu, S.M. et al. (2020). "Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test". Journal of Clinical Microbiology 58 (8): e00926-20. doi:10.1128/JCM.00926-20. PMC PMC7383535. PMID 32366669. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7383535.
- Goldenberger, D.; Leusinger, K.; Sogaard, K.K. et al. (2020). "Brief validation of the novel GeneXpert Xpress SARS-CoV-2 PCR assay". Journal of Virological Methods 284: 113925. doi:10.1016/j.jviromet.2020.113925. PMC PMC7351036. PMID 32659240. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7351036.
- Cepheid (09 June 2020). "Cepheid Announces Development of Four-in-One Combination Test for SARS-CoV-2, Flu A, Flu B and RSV". PR Newswire. https://www.prnewswire.com/news-releases/cepheid-announces-development-of-four-in-one-combination-test-for-sars-cov-2-flu-a-flu-b-and-rsv-301072489.html. Retrieved 13 August 2020.
- Hogan, C.A.; Garamani, N.; Lee, A.S. et al. (2020). "Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens". Journal of Clinical Microbiology 58 (8): e01072-20. doi:10.1128/JCM.01072-20. PMC PMC7383558. PMID 32461285. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7383558.
- "MAUDE - Manufacturer and User Facility Device Experience". U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/TextSearch.cfm. Retrieved 13 August 2020.
- Ravi, N.; Cortade, D.L.; Ng, E. et al. (2020). "Diagnostics for SARS-CoV-2 detection: A comprehensive review of the FDA-EUA COVID-19 testing landscape". Biosensors and Bioelectronics 165: 112454. doi:10.1016/j.bios.2020.112454. PMC PMC7368663. PMID 32729549. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7368663.
- Devine, C. (03 July 2020). "Coronavirus test used by White House has questionable accuracy". CNN Politics. https://www.cnn.com/2020/07/03/politics/coronavirus-white-house-test-abbott/index.html. Retrieved 08 July 2020.
- Perrone, M. (14 May 2020). "FDA probes accuracy issue with Abbott’s rapid virus test". Associated Press. https://apnews.com/c8ab010e8e02dfe7beb34a5e5df11279. Retrieved 19 May 2020.
- Basu, A.; Zinger, T.; Inglima, K. et al. (2020). "Performance of Abbott ID Now COVID-19 Rapid Nucleic Acid Amplification Test Using Nasopharyngeal Swabs Transported in Viral Transport Media and Dry Nasal Swabs in a New York City Academic Institution". Journal of Clinical Microbiology 58 (8): e01136-20. doi:10.1128/JCM.01136-20. PMC PMC7383552. PMID 32471894. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7383552.
- Mitchell, S.L.; St. George, K. (2020). "Evaluation of the COVID19 ID NOW EUA assay". Journal of Clinical Virology 128: 104429. doi:10.1016/j.jcv.2020.104429. PMC PMC7227587. PMID 32425657. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7227587.
- "Cue COVID-19 Test Instructions for Use" (PDF). Cue Health, Inc. June 2020. https://www.cuehealth.com/s/IN9100003-1_10_IFU-Cue-COVID-19-Test-Cartridge-Pack-Professional.pdf. Retrieved 13 August 2020.
- "The Talis Advantage". Talis Biomedical. https://talis.bio/technology/. Retrieved 13 August 2020.
- "SARS-CoV-2 Test Kit (Real-time PCR) Instructions for Use" (PDF). Xiamen Zeesan Biotech. July 2020. https://www.fda.gov/media/140717/download. Retrieved 14 August 2020.
- "Biomeme SARS-CoV-2 Real-Time RT-PCR Test Instructions for Use" (PDF). Biomeme, Inc. 2020. https://www.fda.gov/media/141052/download. Retrieved 14 August 2020.
- "PCR Master Mix (2X)". Thermo Fisher Scientific. https://www.thermofisher.com/order/catalog/product/K0171#/K0171. Retrieved 16 August 2020.
- "Isothermal Reaction Guide". OptiGene Limited. http://www.optigene.co.uk/isothermal-reaction-guide/. Retrieved 16 August 2020.
- Kashir, J.; Yaqinuddin, A. (2020). "Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19". Medical Hypotheses 141: 109786. doi:10.1016/j.mehy.2020.109786. PMC PMC7182526. PMID 32361529. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7182526. "Reagent-wise, the costs would be similar to that of real time RT-PCR ..."
- "Accula Test" (PDF). Mesa Biotech, Inc. April 2020. https://www.fda.gov/media/136355/download. Retrieved 16 August 2020.
- Weemaes, M.; Martens, S.; Cuypers, L. et al. (2020). "Laboratory information system requirements to manage the COVID-19 pandemic: A report from the Belgian national reference testing center". JAMIA: ocaa081. doi:10.1093/jamia/ocaa081. PMC PMC7197526. PMID 32348469. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7197526.
- Association of Public Health Laboratories (2020). "LIMS (Laboratory Information Management System)" (PDF). Association of Public Health Laboratories. https://www.aphl.org/aboutAPHL/publications/Documents/INFO-2020-LIMS.pdf. Retrieved 18 August 2020.
- Kun, L.; Coatrieux, G.; Quantin, C. et al. (2008). "Improving outcomes with interoperable EHRs and secure global health information infrastructure". Studies in Health Technology and Informatics 137: 68–79. PMID 18560070.
- Global Center for Health Innovation (n.d.). "Improving Patient Care through Interoperability" (PDF). Global Center for Health Innovation. http://s3.amazonaws.com/rdcms-himss/files/production/public/Improving-Patient-Carethrough-Interoperability.pdf. Retrieved 16 August 2020.
- Glaser, J. (12 June 2020). "It’s Time for a New Kind of Electronic Health Record". Harvard Business Review. https://hbr.org/2020/06/its-time-for-a-new-kind-of-electronic-health-record. Retrieved 18 August 2020.
- Limoli, C.; Papathomas, G. (07 July 2020). "Physicians deserve better software: Covid-19 has shown why medical records need to adapt". MedCity News. https://medcitynews.com/2020/07/physicians-deserve-better-software-covid-19-has-shown-why-medical-records-need-to-adapt/. Retrieved 18 August 2020.
- Jason, C. (23 July 2020). "EHR Optimization, Health IT Projects Needed After COVID-19 Surge". EHR Intelligence. https://ehrintelligence.com/news/ehr-optimization-health-it-projects-needed-after-covid-19-surge. Retrieved 18 August 2020.
- Centers for Medicare and Medicaid Services. "Frequently Asked Questions (FAQs), CLIA Guidance During the COVID-19 Emergency" (PDF). https://www.cms.gov/files/document/clia-laboratory-covid-19-emergency-frequently-asked-questions.pdf. Retrieved 20 August 2020.
- Paul, S. (29 May 2020). "A Guide to Setting up a Coronavirus (COVID-19) Clinical Diagnostic Testing Laboratory". Clinical Lab Manager. https://www.clinicallabmanager.com/insight/a-guide-to-setting-up-a-coronavirus-covid-19-clinical-diagnostic-testing-laboratory-22850. Retrieved 20 August 2020.
- Buchan, B.W.; Mahlen, S.D.; Relich, R.F. (January 2019). "Interim Clinical Laboratory Guideline for Biological Safety" (PDF). The American Society for Microbiology. https://asm.org/ASM/media/Policy-and-Advocacy/Biosafety-white-paper-2019.pdf. Retrieved 20 August 2020.
- Centers for Disease Control and Prevention (15 August 2020). "Frequently Asked Questions about Coronavirus (COVID-19) for Laboratories". Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/lab/faqs.html. Retrieved 20 August 2020.
- "COVID-19 - Control and Prevention /Laboratory Workers and Employers". Occupational Safety and Health Administration. https://www.osha.gov/SLTC/covid-19/laboratory.html. Retrieved 20 August 2020.
- "ISO 15189:2012 Medical laboratories — Requirements for quality and competence". International Organization for Standardization. August 2014. https://www.iso.org/standard/56115.html. Retrieved 20 August 2020.
- National Academy of Sciences and National Research Council (2012). "Appendix E - Country and Region Overviews". Biosecurity Challenges of the Global Expansion of High-Containment Biological Laboratories: Summary of a Workshop. National Academies Press. pp. 193–204. doi:10.17226/13315. ISBN 9780309225786. https://www.ncbi.nlm.nih.gov/books/NBK196149/.
- Preskitt, J.T. (2008). "Health care reimbursement: Clemens to Clinton". Baylor University Medical Center Proceedings 21 (1): 40–4. doi:10.1080/08998280.2008.11928358. PMC PMC2190551. PMID 18209755. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC2190551.
- Fifer, R. (July 2016). "Health Care Economics: The Real Source of Reimbursement Problems". American Speech-Language-Hearing Association. https://www.asha.org/Articles/Health-Care-Economics-The-Real-Source-of-Reimbursement-Problems/. Retrieved 21 August 2020.
- Huckman, R.S. (07 April 2020). "What Will U.S. Health Care Look Like After the Pandemic?". Harvard Business Review. https://hbr.org/2020/04/what-will-u-s-health-care-look-like-after-the-pandemic. Retrieved 21 August 2020.
- Dorsett, M. (2020). "Point of no return: COVID-19 and the U.S. healthcare system: An emergency physician’s perspective". Science Advances 6 (26): eabc5354. doi:10.1126/sciadv.abc5354. PMC PMC7319747. PMID 32637627. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7319747.
- Slotkin, J.R.; Murphy, K.; Ryu, J. (11 June 2020). "How One Health System Is Transforming in Response to Covid-19". Harvard Business Review. https://hbr.org/2020/06/how-one-health-system-is-transforming-in-response-to-covid-19. Retrieved 21 August 2020.
- Mendelson, D. (30 June 2020). "The Impact Of COVID-19 On Providers: Risk, Recession And Reimbursement". Forbes. https://www.forbes.com/sites/danielmendelson/2020/06/30/the-impact-of-covid-19-on-providers-risk-recession-and-reimbursement/. Retrieved 21 August 2020.
- Flinn, B. (12 June 2020). "States Leverage Medicaid to Provide Nursing Homes a Lifeline through COVID-19". LeadingAge. https://www.leadingage.org/regulation/states-leverage-medicaid-provide-nursing-homes-lifeline-through-covid-19. Retrieved 21 August 2020.
- Division of Federal Employees' Compensation (2020). "Claims under the Federal Employees' Compensation Act due to the 2019 Novel Coronavirus (COVID-19)". U.S. Department of Labor. https://www.dol.gov/owcp/dfec/InfoFECACoverageCoronavirus.htm. Retrieved 21 August 2020.
- Department of Attorney General (2020). "Worker's Compensation for First Responders". State of Michigan. https://www.michigan.gov/ag/0,4534,7-359-98784_98791-523085--,00.html. Retrieved 21 August 2020.
- "COVID-19 Claims Reimbursement to Health Care Providers and Facilities for Testing and Treatment of the Uninsured". Health Resources & Services Administration. May 2020. https://www.hrsa.gov/CovidUninsuredClaim. Retrieved 21 August 2020.
- "Coding Guidance for COVID-19". American College of Emergency Physicians. 2020. https://www.acep.org/administration/reimbursement/covid-19/. Retrieved 21 August 2020.
- Adler, L.; Young, C.L. (13 July 2020). "The laws governing COVID-19 test payment and how to improve them". USC-Brookings Schaeffer Initiative for Health Policy. Brookings Institution. https://www.brookings.edu/blog/usc-brookings-schaeffer-on-health-policy/2020/07/13/the-laws-governing-covid-19-test-payment-and-how-to-improve-them/. Retrieved 21 August 2020.
- Dawson, L. (22 April 2020). "The National Disaster Medical System (NDMS) and the COVID-19 Pandemic". KFF. https://www.kff.org/coronavirus-covid-19/issue-brief/the-national-disaster-medical-system-ndms-and-the-covid-19-pandemic/. Retrieved 21 August 2020.
- Congressional Research Service (17 April 2020). "Health Care Provisions in the Families First Coronavirus Response Act, P.L. 116-127". https://crsreports.congress.gov/product/pdf/R/R46316. Retrieved 21 August 2020.
Citation information for this chapter
Chapter: 3. Adding COVID-19 and other virus testing to your laboratory
Edition: Edition 2.0
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: August 2020