A Guide to Setting up a Coronavirus (COVID-19) Clinical Diagnostic Testing Laboratory

There is an urgent need to set up new COVID-19 diagnostic testing labs and put procedures in place for existing labs to handle the new COVID-19 testing processes. The Centers for Disease Control and Prevention (CDC) provides specific guidelines on how best to collect, handle and ship COVID-19 specimens. The CDC provides current guidelines related to laboratory biosafety and COVID-19. All laboratory personnel should receive adequate training and even complete assessments to ensure everyone understands these guidelines because no lab ever wants to have hazardous outcomes that will impact patients, laboratory staff, and outcomes of COVID-19 testing.

Collecting, Handling, and Testing Clinical Specimens

In order to overcome challenges with collecting, handling and testing clinical specimens, laboratory staff must be trained on one set of standardized guidelines related to carrying out the steps for validating diagnostic testing. Prior to testing any patient, the laboratory must understand that COVID-19 clinical diagnostic testing should be conducted in consultation with the patient’s healthcare provider. Most patients in need of testing are referred by a healthcare provider and then sent to the nearest testing site. When conducting the initial COVID-19 testing, the CDC recommends collecting and testing an upper respiratory specimen.¹ Nasopharyngeal specimen is the preferred choice for swab-based SARS-CoV-2 testing.¹ When collection of a nasopharyngeal swab is not possible, the following are acceptable alternatives¹:

An oropharyngeal (OP) specimen collected by a healthcare professional, or
A nasal mid-turbinate (NMT) swab collected by a healthcare professional or by onsite self-collection (using a flocked tapered swab), or
An anterior nares (nasal swab; NS) specimen collected by a healthcare professional or by onsite self-collection (using a flocked or spun polyester swab).

If both NP and OP swabs both are collected, it is important to combine in a single tube to maximize test sensitivity and limit testing resources. In addition, CDC also recommends testing lower respiratory tract specimens, when available.¹ For patients, who develop a productive cough, sputum should be collected and tested for SARS-CoV-2. The induction of sputum is not recommended. When collecting sputum, the lab should have the patient rinse his or her mouth with water and then have the patient give a deep cough. 2-3mL of sputum should go directly into a sterile, leak-proof, screw-cap sputum collection cup of sterile dry container.¹

When it is clinically indicated (e.g., those receiving invasive mechanical ventilation), a lower respiratory tract aspirate or bronchoalveolar lavage sample should be collected and tested as a lower respiratory tract specimen.¹Each specimen collected should have the 1) unique patient ID number, 2) laboratory requisition number, 3) type of specimen collected. The collected specimens should be stored at 2-8°C for up to 72 hours after collection. If a delay in testing or shipping should occur, the specimens should be stored at -70°C or below.

RT-PCR testing

COVID-19 testing laboratories check for COVID-19 by conducting a reverse transcriptase polymerase chain reaction (RT-PCR) that is used to detect the virus’s RNA in collected upper and lower respiratory tract specimens. Positive results do not rule out bacterial infection or co-infection with other viruses.²The agent detected may not be the definite cause of disease. All positive results must be reported to the appropriate public health authorities.²It is important for negative results to be combined with clinical observations, patient history, and epidemiological information.²

Antibody testing

Antibodies consist of proteins that the body’s white blood cells produce to fight an infection. Antibodies can remain in the blood long after an infection clears. Antibody tests can be used to test to see if someone has been exposed to COVID-19. Due to the demand, one major challenge is developing testing sites geared towards COVID-19 antibody testing. Due to the number of people globally, in the near future, there will be a demand for COVID-19 testing laboratories to develop at-home COVID-19 antibody testing, have more testing sites within the community, and provide these tests to the sites of healthcare providers. By completing and producing these recommendations, this will increase the overall testing capacity.

Clinical Laboratory Improvement Amendments (CLIA)

The Centers for Medicare and Medicaid Services (CMS) has amended the CLIA guidelines to meet the needs of the current COVID-19 pandemic. During this pandemic, a separate certificate for laboratories that are located at a temporary testing site, provided that the designated primary site or home base has such a certificate (using the address of the primary site) and the work being performed in the temporary testing site falls within the parameters of the primary site’s certificate.³ Laboratories need a CLIA certificate to perform COVID-19 testing. Under CLIA, laboratories are prohibited from testing human specimens for the purpose of diagnosis, prevention, treatment, or health assessment without a valid CLIA certificate.³ To become CLIA-certified, laboratories must comply with the accuracy, quality, and reliability requirements as dictated by the statute.³ The purpose of these requirements is to ensure that the information that patients or their health care providers receive from a clinical laboratory is accurate and reliable test results.³ Laboratories that wish to become CLIA certified must apply for a CLIA Certificate by completing a CLIA application.

ISO 15189:2012

ISO 15189:2012 is an international regulatory standard that specifies the quality and competence requirements for clinical laboratories. This standard is primarily divided into two sections, management requirements and technical requirements. Some of the management requirements are document control, recording corrective and preventive actions taken for non-conforming activities, evaluation and audits. The technical requirements include the requirements for laboratory personnel, laboratory information management, reporting and release of test results.⁸ The standard focuses on quality management and implementation of continuous quality improvement programs, enabling laboratories to ensure the accuracy and reliability of test results. ISO 15189 standard encourages laboratories to identify opportunities for improvement and involve staff in solving problems and implementing solutions. Accreditation to the ISO 15189 standard enables laboratories to minimize pre- and post-analytical errors, and improve the quality of results. Several countries have made ISO 15189 accreditation mandatory for clinical laboratories. However, in the United States, accreditation of clinical laboratories to the ISO 15189 standard is not mandatory, rather it is voluntary.⁹

HIPAA

The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule permits a covered entity to disclose the protected health information (PHI) of an individual who has been infected with, or exposed to, COVID-19, with law enforcement, paramedics, other first responders, and public health authorities without the individual’s HIPAA authorization in certain circumstances.⁷ However, when storing specimens within the clinical diagnostic laboratory, all specimens should receive the LIMS barcoded, de-identifier. The LIMS barcoded, de-identifier will be beneficial in generating a unique patient identifier. Clinical diagnostic laboratories and the clinical practice should maintain copies of all signed informed consent forms because this protects their entity along with any approved collaborators.

COVID-19 packaging under United Nations 3373 (UN3373)

COVID-19 specimens are assigned to the category UN3373 Biological Substance Category B. COVID-19 specimens, assigned to UN 3373, are human materials that are being transported for the purpose of diagnosis or investigation. Such materials include excreta, blood and its components, as well as other tissues and fluids. Packaging should consist of three components: 1) leak-proof primary receptacle(s); 2) leak-proof secondary packaging; and 3) outer packaging of adequate strength for its capacity, mass and intended use, and with at least one surface having minimum dimensions of 100 mm × 100 mm.^4,11

Shipment of COVID-19 Specimens

COVID-19 specimens are considered dangerous goods. Therefore, these specimens must be packed and shipped per the current International Air Transport Association (IATA) Dangerous Goods Regulations. IATA works with local governments to ensure dangerous goods are transported in an effective, efficient, safe manner to prevent contamination. Laboratory personnel must complete and pass the IATA competency-based training and assessment principles for transporting dangerous goods.^5,11

Laboratory Staff

When recruiting laboratory personnel, the laboratory management needs to consider recruiting individuals with an educational background in biological sciences, biomedical sciences, chemistry, clinical laboratory science or biotechnology. This educational background provides new laboratory staff with knowledge in the areas in organic chemistry, histology, genetics, immunology, molecular pathology and biology. This will aid in newly hired laboratory staff in understanding the dynamics surrounding clinical specimens and working within a laboratory.

In addition, laboratory staff must have good verbal communication skills. Laboratory staff will meet with patients and sometimes even the patient’s family to explain the procurement protocol and obtain signatures for informed consent forms (ICF) to obtain specimen(s) for laboratory testing. Based upon the number of specimens collected and the number of assigned COVID-19 protocol, it is important for clinical diagnostic laboratories, who work 8-hour shifts to have 1 laboratory manager, 1 lead laboratory coordinator, who will also assist with administrative duties, 2 lab technicians, who will procure, store and ship COVID-19 specimens, and 1 individual overseeing finances. The laboratory manager and lead laboratory coordinator will work together to conduct laboratory training, order adequate supplies, maintain scheduling, communicate with healthcare providers, and ensure compliance in all areas of the diagnostic laboratory. Many diagnostic laboratories will bring in undergraduate or graduate student interns to assist with clerical duties and shipping specimens.

Laboratory Information Management System (LIMS)

All laboratory staff should be trained on using a LIMS. A LIMS is a secure, desktop or web application, which is needed for accurate, automated data transfer of all demographic and clinical data associated with each collected specimen. Since there is an urgent need for clinical diagnostic testing of COVID-19 specimens, a coronavirus lab software solution will aid in preventing errors between the clinical site and clinical diagnostic laboratory. For example, a COVID-19 LIMS will be an efficient tool to utilize in recording the referring healthcare provider, type of specimen collected, location of each specimen, confirmed diagnosis of each collected specimen, etc. Laboratory technicians should be responsible for entering data into LIMS for each collected specimen. A LIMS is useful in generating accurate data needed for reporting purposes. A cloud LIMS software can even be accessed using a tablet or mobile device, which is useful for remote testing sites and for managing operations¹¹.

Minimizing risks per CDC Lab Biosafety Guidelines

Personal protective equipment (PPE) should be procured for those collecting COVID-19 specimens. COVID-19 diagnostic testing laboratories must provide staff with face shield or goggles, N95 or higher respirator, isolation gowns, gloves, centrifuge safety cups, and sealed centrifuge rotors.⁶ These labs should have equipment to process samples, virus isolation, routine diagnostic testing, and environmental specimen testing. It is mandatory to decontaminate work surfaces and equipment with appropriate EPA-registered disinfectants and laboratory waste management must be in place.⁶Adequate supplies for packing and shipping is mandatory per IATA Dangerous Goods Regulations.⁶ The laboratory must ensure adequate supplies of sanitizer, disinfectant wipes, cleaners, and PPE are never depleted.

Conclusion

The major challenges clinical diagnostic laboratories face are 1) preventing contamination within the clinical diagnostic laboratory, 2) keeping up with the demand for clinical lab testing and 3) maintaining an efficient laboratory geared towards preventing errors. Adequate staffing, supplies, and proper training are needed to prevent hazardous situations and are needed for accurate reporting of diagnostic testing. This article outlines the key, critical steps to help managers and directors expedite the set up of a COVID-19 diagnostic testing laboratory. Laboratory managers and directors can use this paper as a tool to select and hire staff, regulatory training needed in shipping COVID-19 specimens, standardized protocol for collecting and validating COVID-19 testing, importance of utilizing LIMS, etc. It is important to have a model that will aid in overcoming the challenges associated with the current, urgent need for diagnostic testing of COVID-19 specimens.

References

Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html
Accelerated emergency use authorization (EUA) summary COVID-19 RT-PCR Test (Laboratory Corporation of America). https://www.fda.gov/media/136151/download
Clinical laboratory improvement amendments (CLIA) laboratory guidance during COVID-19 public health emergency. https://www.cms.gov/files/document/qso-20-21-clia.pdf-0
UN3373 medical packaging. https://www.un3373.com/category-biological-substances/category-b/
IATA: Appendix H-dangerous goods training guidelines-competency-based training and assessment approach. https://www.iata.org/contentassets/90f8038b0eea42069554b2f4530f49ea/dgr-61-en-appendix-h.pdf
CDC COVID-19 lab biosafety guidelines. https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-biosafety-guidelines.html
COVID-19 and HIPAA: Disclosures to law enforcement, paramedics, other first responders and public health authorities. https://www.hhs.gov/sites/default/files/covid-19-hipaa-and-first-responders-508.pdf
ISO 15189:2012(en) Medical laboratories — Requirements for quality and competence. https://www.iso.org/standard/56115.html
Schneider F, Maurer C, Friedberg RC. International Organization for Standardization (ISO) 15189. Ann Lab Med. 2017;37(5):365–370. doi:10.3343/alm.2017.37.5.365. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500734/
COVID-19 Clinical Data Management using LIMS https://cloudlims.com/blog/covid-19-clinical-data-management-using-lims.html
Biobanking Best Practices for COVID-19 Specimens https://cloudlims.com/blog/biobanking-best-practices-for-covid-19-specimens.html