How to Start COVID-19 Testing in your Lab

Answers to Labs’ Top Questions About COVID-19 Testing

Since the beginning of the COVID-19 pandemic, many clinical laboratories rapidly adopted SARS-CoV-2 tests to help support high testing demands in the United States. With recent surges in the infection rate, test availability and turnaround time remain inadequate, with no definite vaccine or curative drug solution in sight. Testing and quarantining remain the only tried-and-true methods to limit the spread of the virus and decrease its mortality rate.

Implementing COVID-19 testing is not without its fair share of challenges, including choosing the appropriate test to adopt in the clinic or lab, regulatory demands, lack of clinical samples for validation testing, lack of testing reagents and instruments, reagent incompatibilities, and becoming established as a test provider in a fast-paced, competitive market.    

The following Q&A may assist those in setting up testing services in their clinic or laboratory:

1. What are the requirements for my lab to offer COVID-19 testing?

This depends on the type of test you plan to offer:

For a Laboratory Developed Test (LDT), we recommend you consult with your accreditation entity (CLIA, CAP, ..) since guidelines may vary significantly between states.

If you intend to offer a test authorized by the FDA under an emergency use (EUA), then the general rule is that the testing facility has to be certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a. Different tests may have specifications for intended use, so it is advised to adhere to the “Intended Use” section of the test that it’s intended to be adopted in your laboratory.

2. Should my lab offer testing as a Lab Developed Test (LDT) or a test that is FDA authorized under an emergency use (EUA)?

The main difference between these two types of tests is that an LDT is regulated at a state level, while an EUA test is regulated at the federal level. This means a specific EUA test can be adopted by any laboratory in the United States using the same testing procedure, while the same LDT test may require different criteria to be met (in terms of validation, specimen acceptance, etc..) depending on the requirements of the state in which the test is performed.

Another main difference is that EUA tests, as long as they are performed according to the "Instruction for Use" documents, can be adopted by any authorized laboratory without performing validation.  Alternatively, an LDT would require validation steps acceptable with your accreditation entity.

3. What type of test should my lab offer? Serology, Antigen, or RT-PCR ?

For COVID-19 testing there are three main types of tests: molecular tests, antigen tests, and serology tests. Each of these types of tests present its own strengths and weaknesses, and different type of tests provide different clinical information. Each type of test is summarized below:

1. Molecular testing: Tests designed to detect the presence of SARS-CoV-2 RNA in samples collected from a patient’s upper or lower respiratory tract. Generally, viral RNA is detected (post purification) by performing RT-PCR (reverse transcription-polymerase chain reaction). This type of test is the method of choice for the diagnosis of ongoing SARS-CoV-2 infections. Molecular tests have the advantage of being extremely sensitive with a limit of detection as low as 5-10 viral genome copies per reaction. Molecular tests exhibit superior accuracy (specificity) and are less prone to the generation of “false negative” results as compared to antigen tests. Disadvantages of molecular testing are 1) they are less rapid than antigen tests (RNA extraction and RT-PCR usually takes 3-4 hours) and 2) they generally require some specialized laboratory equipment should high-throughput automated sample processing be a requirement.
2. Antigen testing: These tests detect the presence of SARS-CoV-2 proteins in clinical specimens and their primary use is for the diagnosis of active, on-going SARS-CoV-2 infection. Often faster and simpler compared to molecular tests, antigen tests are easy to adopt at the point of care but are considerably less sensitive than molecular tests. Antigen tests are also prone to generating false-negative results and should only be used to test symptomatic patients, who tend to have a viral load high enough to be detected by an antigen test. Negative results obtained with SARS-CoV-2 antigen tests are considered "presumptive negative" and shall be confirmed using a separate molecular test.
3. Serology testing: Serology testing for SARS-CoV-2 measures the presence of antibodies (IgG and/or IgM) specific for SARS-CoV-2 in plasma or serum of patients suspected of having been infected with SARS-CoV-2 in the past. Since serology tests indicate signs of past or subsiding infection, they should not replace molecular and antigen testing for active SARS-CoV-2 infection. Serology testing monitors and measures community seroprevalence and identifies individuals who have developed antibodies for SARS-CoV-2 who may qualify to donate plasma to treat patients with severe COVID-19 disease. SARS-CoV-2 serology tests should not be used as a primary method to diagnose COVID-19, to screen asymptomatic subjects, to release a person from quarantine, to clear a person to return to work, or to assess if a test subject is immune to SARS-CoV-2 re-infection.

4. Which factors should I consider for choosing the right SARS-CoV-2 test?

There are several factors to consider to select the most appropriate SARS-CoV-2 test for your laboratory:

1. Instruments required to perform the test: It is relatively straightforward to adopt a test that is compatible with the equipment that already present in your laboratory. Purchasing new equipment is always an option, but this depends on how much you intend to invest as well as the availability of the instruments for purchase.
2. Test performance: Tests differ dramatically in terms of performance. You should carefully evaluate the Limit of Detection and other performance characteristics of each test before introducing them to your laboratory.
3. Price: There exists a wide variety of tests on the market they vary significantly in terms of price. In most instances, pricing is not readily available, and you should contact the seller to obtain pricing information. Pricing may change based on the number of tests you would like to order and other factors.  We recommend you discuss any flexibility in pricing and price discounts directly with the test supplier.
4. Supply: Many companies offer complete testing systems for COVID-19 (from sample collection to final result), however, only part of the testing workflow (e.g., the RT-PCR test) is actually manufactured by the company, while the remaining components are supplied by other third party entities. In this case, the company that provides the testing workflow may have limited control over the supply of all components of the test. In case of a reagent shortage, it may be impossible for the seller to provide a complete solution to your laboratory. To avoid a shortfall in testing supplies, it is important to select a complete test provider that is able to guarantee the supply of those necessary consumables to your laboratory. 
5. Simple, quick testing workflow: Automated sample extraction and easy reaction set-up for fast results and streamlined interpretation can be big advantages in SARS-CoV-2 testing. These steps minimize human error that can occur during sample processing affecting downstream results, while allowing the maximum amount of samples to be processed at your facility in a given time. It is important to determine if the test you want to provide in your facility is compatible with automation.
5. Is it as simple as choosing the test I like most and then offer it in my lab?

In principle, yes! For EUA tests, if your lab is in the United States, you can directly adopt these tests. If you do have to amend an EUA workflow (e.g. because you already have an instrument in your lab that is not included in the EUA workflow, don’t want to purchase a new one) you should contact the FDA directly or reference the “frequently asked questions” section on the FDA website to determine if you have to perform any additional validation in your laboratory.

For an LDT, these have to be validated in your laboratory, and we recommend you consult by your accreditation entity to make sure that the validation plan you intend to perform is in agreement with their guidelines.

6. How do I reach out to the right audience for SARS-CoV-2 testing?

Finding customers for COVID-19 testing during this pandemic seems like an easy job, but COVID-19 testing is a saturated space in which patients and healthcare providers may become easily confused. Labs should create their own marketing strategy to make sure that patients and healthcare providers are informed that you are offering COVID-19 testing and what are the advantages of your testing solutions. Advertising on journals and social media, directly contacting healthcare providers, local authorities, and private companies that may need testing are all good marketing steps. Also, inform your colleagues and your immediate contact network about your testing services; many laboratories receive a high volume of samples beyond their ability to process, and they may need to partner with other testing laboratories in order to analyze all of their samples.

While offering COVID-19 testing to your lab may seem like a daunting task, Zymo Research is ready to help and is able to support your lab with a complete FDA EUA SARS-CoV-2 workflow including sample collection, purification and RT-PCR kit. Zymo Research’s sample collection, RNA extraction and Quick SARS-CoV-2 RT-PCR kit are easy to use, flexible, and compatible with automation, and are widely adopted by top clinics, hospitals and labs.

The information provided in this document have been reported on the best of our knowledge. We realize that the information reported in this document is not comprehensive to all considerations that apply to a topic complex as COVID-19 testing. In addition, guidelines for COVID-19 testing change frequently. Therefore, this document is purely informative and specific information should be obtained from local and federal authorities.

Useful links

• FDA frequently asked questions
• Guidelines for reimbursement
• Association of public health laboratories
• CDC recommendations for use of serology tests