The SARS-CoV-2 testing landscape is continually changing as additional tests receive an emergency use authorization (EUA) from the FDA. Technology to conduct molecular, antigen, and serology tests is now available and additional technologies are anticipated. The availability of evidence regarding the performance of these different tests as well as guidelines for their best use in different populations is still limited.
Testing resource constraints continue, especially related to swabs, reagents, and media. In addition, many commercial laboratories are experiencing high volumes and test results are delayed. For these reasons, it is important to continue to use an evidence-based approach when making COVID-19 testing priorities. LAC DPH priorities for COVID-19 diagnostic testing plus rationale are outlined below.
Laboratories Providing COVID-19 PCR Molecular Testing (9-16-20) Reference Guide LA County Department of Health Services (LAC DHS) has created this guide to help organizations identify a laboratory provider that best fits their needs. This document provides an overview of some of the laboratories offering testing to LA County providers and residents.
California Testing Task Force Lab List The Testing Task Force is maintaining a list of labs that have met certain criteria for readiness and can receive samples for RT-PCR COVID testing.
All laboratories (regardless of their location) that test Los Angeles County residents must register with the California Department of Public health (CDPH).
Only tests with emergency use authorizations (EUA) from the FDA should be used for patient care. A wide variety of molecular tests, antigen tests, and SARS-CoV-2 serologic tests now have EUA.
Clinicians should remember that test accuracy is dependent on many factors including the test technology, specimen collection and handling, pretest clinical probability of disease, community prevalence of disease, and the specific characteristics of the assay.
It is particularly important for clinicians to review the EUA for any SARS-CoV-2 test(s) they are using to understand the specific performance characteristics and the instructions for use. All SARS-CoV-2 EUAs are listed on the FDA COVID-19 Emergency Authorization website.
Molecular Tests are currently the most accurate tests for diagnosing COVID-19. Viral RNA can be detected by reverse transcription polymerase chain reaction (RT-PCR) in a laboratory or by other nucleic acid amplification techniques as a point-of-care (POC) test. RT-PCR is highly sensitive and specific for detecting SARS-CoV-2 virus and is the recommended “gold standard” method for diagnosing current infection.
Molecular tests are typically performed on nasopharyngeal swabs but can also be performed on other respiratory tract specimens (e.g., oropharyngeal swabs, nasal swabs, saliva, lower respiratory tract samples). A positive molecular test for SARS-CoV-2 generally confirms the diagnosis of COVID-19; however, tests may remain positive long after a patient is no longer infectious due to prolonged detection of RNA. False-negative tests have been well documented (see Variation in False-Negative Rate of RT-PCR–Based SARS-CoV-2 Tests by Time Since Exposure). Molecular test diagnostic accuracy is dependent on the timing of testing (more sensitive earlier in infection), sampling technique and type, clinical probability of disease, and the specific test characteristics.
Laboratory turn-around time for PCR test results should be less than 48 hours, however results are often delayed due to high demand for testing.
See FDA list of EUAs for Molecular Tests for more information on the performance and intended use of specific authorized tests.
Antigen Tests detect the presence of viral proteins that are part of the SARS-CoV-2 virus. The four currently available SARS-CoV-2 antigen tests with EUAs are authorized for use in laboratories and as POC tests for settings with a Clinical Laboratory Improvement Amendments (CLIA) waiver and can provide results within 30 minutes.
The Association of Public Health Laboratories updated the Considerations for Implementation of SARS-CoV-2 Rapid Antigen Testing (9-2-20) which provides an overview of the currently available antigen tests including these key points:
APHL suggests utility of antigen tests in symptomatic patients with a high pre-test probability of infection and provides example scenarios for when SARS-CoV-2 antigen tests may reasonably be used. APHL does not recommend using SARS-CoV-2 antigen tests for screening asymptomatic persons due to the high risk of both false positive and false negative results.
The CDC published Interim Guidance for Rapid Antigen Testing for SARS-CoV-2 (8-16-20) which provide general guidance for the use and interpretation of currently available antigen tests based on the pretest probability of infection in the recipient of the test and the prevalence of COVID-19 in the community.
See FDA’s list of EUAs for Antigen Tests for more information about the performance and intended use of specific authorized tests.
Serology Tests detect waning or past SARS-CoV-2 virus infection indirectly, by measuring the antibody response to the virus. Serology assays should not replace direct viral detection methods for diagnosing an active SARS-CoV-2 infection. At this point in time, until the presence, durability, and duration of immunity is established, serology tests they should not be used to determine immune status. Healthcare providers and systems considering using serologic tests for patient care should adopt strategies to minimize false positive results as outlined in the recently released CDC antibody testing guidance and summarized briefly below.
A list of EUA authorized serology tests plus performance information can be found here.
Minimizing False Positive Serology Results
The CDC emphasizes the importance of minimizing false positive test results, particularly when the results will be returned to individuals. The CDC expects that in most parts of the U.S. at this point in time, including areas that have been heavily impacted, the prevalence of SARS-CoV-2 antibody is expected to be low, ranging from <5% to 25%, so that testing will result in relatively more false positive results. As recent local community-wide seroprevalence studies indicate that the prevalence of SARS CoV-2 antibodies in the LA County adult population is <5%, false positive results could be very common unless testing is done strategically.
Suggested strategies to improve the positive predictive value include using a serological assay with high specificity (99.5%) and by testing populations and individuals with an elevated likelihood of previous exposure to SARS-CoV-2 (such as persons with a history of COVID-19-like illness or in outbreak settings). An additional approach when a high positive predictive value (e.g., 95%) cannot be assured with a single serology test, is to use an orthogonal testing algorithm where a first positive serology is tested with a second test with a different design. See CDC Table 1 for examples of using one or two tests in populations with various prevalences of SARS-CoV-2 antibodies. The FDA is providing a calculator that will allow users to see the estimated performance of a single test or two independent tests based on their performance characteristics and the estimated prevalence of SARS-CoV-2 antibodies in the target population. For more information, see the CDC guidelines section on Testing Strategies.Use of Serologic Tests
CDC Recommendations for Use of Serologic Tests include:Diagnostic uses:
When SARS-CoV-2 serology tests should not be used:
See CDC COVID-19 Antibody Testing in Clinical and Public Health Settings Guidelines, CDPH Serology Indications Guidance, and Infectious Diseases Society of America (IDSA) Guidelines on the Diagnosis of COVID-19: Serologic Testing for more information.
Healthcare providers and systems are encouraged to expand SARS CoV-2 diagnostic testing to more patients with symptoms of COVID-19. Testing asymptomatic persons may be recommended if they are part of an outbreak or case investigation, or if they are staff or residents in a high-risk congregate living setting, or if they are a close contact to a confirmed case.
Healthcare providers and systems should be able to provide their patients with timely access to SARS-CoV-2 diagnostic testing when indicated. A Reference Guide to Laboratories Providing COVID-19 PCR Molecular Testing is now available to help healthcare organizations and other entities identify a laboratory provider that best fits their needs.
Rationale includes, ensuring optimal care options for all hospitalized patients, lessening the risk of nosocomial infections, and detecting and controlling outbreaks in acute- and subacute-care health facilities and high-risk congregate living settings.Testing is Strongly Encouraged
Rationale includes, ensuring that those who are at highest risk of complications are rapidly identified.Recommend Testing assuming sufficient resources
Rationale is to detect new cases to decrease community spread.
Routine testing of asymptomatic persons in the general population is not recommended in the absence of a known exposure.
If such testing is undertaken it is important to emphasize that if they test negative that it only means that the test did not detect the virus at the time the test was taken. A negative result can also happen if the test was taken too early and/or the test missed the infection. A negative test does NOT mean the person can safely ignore physical distancing and mask requirements. Refer the patient to Information about Testing.
Note: if facilities elect to conduct pre-admission or pre-procedure screening of patients for COVID-19, it is important to continue to practice COVID-19 infection prevention precautions on patients testing negative due to the risk of false negatives.