OVERVIEW OF TESTING FOR SARS-COV-2 (COVID-19)

Many categories of tests are used to detect SARS-CoV-2, and their performance characteristics vary.

Some tests provide results rapidly (within minutes); others require time for processing.
Some must be performed in a laboratory by trained personnel, some can be performed at the point-of-care, and others can be performed at home or anywhere.
Some tests are very sensitive (i.e., few false-negative results or few missed detections of SARS-CoV-2); others are very specific (i.e., few false-positive results or few tests incorrectly identifying SARS-CoV-2 when the virus is not present); and some are both sensitive and specific.
Some tests can be performed frequently because they are less expensive, easier to use, and supplies are readily available.

The selection and interpretation of SARS-CoV-2 tests should be based on the context in which they are being used, including the prevalence of SARS-CoV-2 in the population being tested (See Table 1) and the status (signs, symptoms, contacts) of the person being tested.

Test Types

Viral tests, including NAATs and antigen tests, are used as diagnostic tests to detect infection with SARS-CoV-2 and to inform an individual’s medical care. Viral tests can also be used as screening tests to reduce the transmission of SARS-CoV-2 by identifying infected persons who need to isolate from others. See FDA’s list of In Vitro Diagnostics Emergency Use Authorizations external icon for more information about the performance of specific authorized tests.

NAATs are high-sensitivity, high-specificity tests for diagnosing SARS-CoV-2 infection. NAATs detect one or more viral ribonucleic acid (RNA) genes and indicate a current infection or a recent infection but, due to prolonged viral RNA detection, are not always direct evidence for the presence of virus capable of replicating or being transmitted to others. Most NAATs need to be processed in a laboratory, and time to results can vary (~1–3 days), but some NAATs are point-of-care tests with results available in about 15–45 minutes. Most NAATs produce qualitative results. NAATs can be performed on upper respiratory specimens, such as nasopharyngeal, nasal mid-turbinate, anterior nasal, or saliva.
ANTIGEN TESTS are immunoassays that detect the presence of a specific viral antigen. Antigen tests generally have similar specificity, but are less sensitive than most NAATs. Most are less expensive than NAATs and can be processed at the point of care with results available in minutes and thus can be used in screening programs to quickly identify those who are likely to be contagious. Because of the performance characteristics of antigen tests, it may be necessary to confirm some antigen test results (a negative test in persons with symptoms or a positive test in persons without symptoms) with a laboratory-based NAAT. However, based on the authorization from FDA external icon, some point-of-care NAATs external icon that provide presumptive results cannot be used for confirmatory testing. Use of the Antigen Testing Algorithm external icon is recommended to determine when confirmatory testing is needed. Antigen tests can be performed on nasopharyngeal or anterior nasal specimens.

Correct interpretation of results from both antigen tests and confirmatory NAATs, when indicated, is important.

Positive test results allow for identification and isolation of infected persons, as well as a case interview to identify and notify the case’s close contact(s) of exposure and the need to quarantine.

Negative test results in persons with known SARS-CoV-2 exposure suggest no current evidence of infection. These results represent a snapshot of the time around specimen collection and could change if the same test was performed again in one or more days. Unvaccinated individuals with a negative result should continue to quarantine for 14 days or for the period established by local public health authorities. Fully vaccinated people who have a known exposure to someone with suspected or confirmed COVID-19 should get tested 3-5 days after exposure and are to wear a mask in public indoor settings for 14 days or until they receive a negative test result. For guidance on quarantine and testing of fully vaccinated people, visit Interim Public Health Recommendations for Fully Vaccinated People for more information. In healthcare facilities with an outbreak of SARS-CoV-2, recommendations for viral testing of healthcare providers, residents, and patients (regardless of vaccination status) remain unchanged.

Negative test results in persons without symptoms and no known exposure suggest no infection. All persons being tested, regardless of results, should receive counseling on the continuation of risk reduction behaviors that help prevent the transmission of SARS-CoV-2 (e.g., wearing masks, physical distancing, avoiding crowds and poorly ventilated spaces).

ANTIBODY (OR SEROLOGY) TESTS are used to detect previous infection with SARS-CoV-2 and can aid in the diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) and in adults (MIS-A). CDC does not recommend using antibody testing to diagnose current infection. Depending on the time when someone was infected and the timing of the test, the test might not detect antibodies in someone with a current infection. In addition, it is not currently known whether a positive antibody test result indicates immunity against SARS-CoV-2; therefore, at this time, antibody tests should not be used to determine if an individual is immune against reinfection. Antibody testing is being used for public health surveillance and epidemiologic purposes. Because antibody tests can have different targets on the virus, specific tests might be needed to assess for antibodies originating from past infection versus those from vaccination.

Choosing a Test

When choosing which test to use, it is important to understand the purpose of the testing (diagnostic or screening), performance of the test within the context of the level of community transmission, need for rapid results, and other considerations (See Table 1). For example, even a highly specific antigen test may have a poor positive predictive value (high number of false positives) when used in a community where prevalence of infection is low. As an additional example, use of a laboratory-based NAAT in a community with high transmission and increased test demand may result in diagnostic delays due to processing time and time to return results. Positive and negative predictive values of NAAT and antigen tests vary depending upon the pretest probability. Pretest probability considers both the prevalence of the level of community transmission as well as the clinical context of the individual being tested. Additional information on sensitivity, specificity, positive and negative predictive values for antigen tests and antibody tests, and for the relationship between pretest probability and the likelihood of positive and negative predictive values. Also see FDA’s letters to clinical laboratory staff and healthcare providers on the potential for false-positive results with antigen tests and the potential for false-negative results with molecular tests if a genetic variant of SARS-CoV-2 occurs in the part of the viral genome assessed by the test.

Table 1 summarizes some characteristics of NAATs and antigen tests to consider for a testing program. Given the risk of transmission of SARS-CoV-2 from asymptomatic and pre-symptomatic persons with SARS-CoV-2 infection, use of antigen tests in asymptomatic and pre-symptomatic persons can be considered. FDA has provided a list of FAQs for healthcare providers who are using diagnostic tests in screening asymptomatic individuals, and the Centers for Medicare & Medicaid Services will temporarily exercise enforcement discretion to enable the use of antigen tests in asymptomatic individuals for the duration of the COVID-19 public health emergency under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Laboratories that perform screening or diagnostic testing for SARS-CoV-2 must have a CLIA certificate and meet regulatory requirements. Tests that have received an EUA from FDA for point of care (POC) use can be performed with a CLIA certificate of waiver.

Table 1. NAAT and Antigen Test Differences to Consider When Planning for Diagnostic or Screening Use