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Testing for SARS-CoV-2 Infection

Last Updated: June 11, 2020

Testing for SARS-CoV-2 Infection
Summary Recommendations
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends that a molecular or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be used to diagnose acute SARS-CoV-2 infection (AIII).
  • The Panel recommends against the use of serologic testing as the sole basis for diagnosis of acute SARS-CoV-2 infection (AIII).
  • The Panel recommends against the use of serologic testing to determine whether a person is immune to SARS-CoV-2 infection (AIII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion

Virologic Testing for SARS-CoV-2 Infection

Virologic testing (i.e., using a molecular diagnostic or antigen test to detect SARS-CoV-2) should be done in all persons with a syndrome consistent with COVID-19 and in people with known high-risk exposures to SARS-CoV-2. Ideally, virologic testing should also be performed in people likely to be at repeated risk of exposure, such as health care workers and first responders. For more information, see the Centers for Disease Control and Prevention (CDC) COVID-19 website.

While initial diagnostic tests for SARS-CoV-2 infection have relied on reverse transcriptase polymerase chain reaction platforms, more recent tests have included a variety of additional platforms. A number of diagnostic tests for SARS-CoV-2 infection have received emergency use authorizations (EUAs) issued by the Food and Drug Administration (FDA).1 Formal comparisons of the sensitivity and specificity of these tests are in progress.

The CDC recommends that nasopharynx samples be used to detect SARS-CoV-2. Nasal swabs or oropharyngeal swabs are acceptable alternatives.2 Although lower respiratory tract samples have a higher yield than upper tract samples, they are often not obtained because of concerns about aerosolization of virus during sample collection procedures.

The CDC has established a priority system for diagnostic testing for SARS-CoV-2 infection based on the availability of tests;3 the CDC testing guidance is updated periodically.

The following are the current CDC priorities for COVID-19 diagnostic testing:

High Priority:

  • Hospitalized patients with symptoms
  • Health care facility workers, workers in congregate living settings, and first responders with symptoms
  • Residents in long-term care facilities or other congregate living settings, including prisons and shelters, with symptoms

Priority:

  • Persons with symptoms of potential COVID-19 infection, including fever, cough, shortness of breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or sore throat
  • Persons without symptoms who are prioritized by health departments or clinicians, for any reason, including but not limited to public health monitoring, sentinel surveillance, or screening of other asymptomatic individuals according to state and local plans

Molecular diagnostic and antigen tests can yield false-negative results. In people with a high likelihood of infection based on exposure history and/or clinical presentation, a single negative test result does not completely exclude SARS-CoV-2 infection, and repeat testing should be considered. When a person who is strongly suspected to have SARS-CoV-2 infection has a negative result on an initial antigen test, repeat testing using a molecular diagnostic test may be warranted.

Serologic (or Antibody) Testing for Diagnosis of SARS-CoV-2 Infection

Unlike molecular diagnostic and antigen tests for SARS-CoV-2 that detect the presence of the virus, serologic tests are intended to identify persons with recent or prior SARS-CoV-2 infection. Because it may take 21 days or longer after symptom onset for seroconversion or detection of immunoglobulin M and/or immunoglobulin G antibodies to SARS-CoV-2,4-9 the Panel does not recommend the use of serologic testing as the sole basis for diagnosing acute SARS-CoV-2 infection (AIII). Given that molecular diagnostic tests and antigen tests for SARS-CoV-2 occasionally yield false-negative results, in some settings, serologic tests have been used as an additional diagnostic test in patients strongly suspected to have SARS-CoV-2 infection.

No serologic tests for SARS-CoV-2 are approved by the FDA and some, but not all, commercially available serologic tests for SARS-CoV-2 have received EUAs issued by the FDA. Several professional societies and federal agencies, including the Infectious Diseases Society of America, CDC, and FDA, provide guidance for clinicians regarding serologic testing for SARS-CoV-2.

Several factors should be considered when using these tests, including:

  • Important performance characteristics, including the sensitivity and specificity (i.e., the rate of true positive and true negative results) of many of the commercially available serologic tests, have not been fully characterized. Serologic assays that have FDA EUAs are preferred for public health and clinical use. Formal comparisons of serologic tests are in progress.
  • False-positive test results may occur due to cross-reactivity from pre-existing antibodies to other coronaviruses.

Serologic Testing and Immunity to SARS-CoV-2 Infection

The Panel recommends against the use of serologic testing to determine whether a person is immune to SARS-CoV-2 infection (AIII). If serologic tests are performed and antibody is detected, results should be interpreted with caution for the following reasons:

  • It is currently unknown how long antibodies persist following infection, and
  • It is currently unknown whether the presence of antibody confers protective immunity against future infection.

In communities where the prevalence of SARS-CoV-2 infection is low, the proportion of positive tests that are false positives may be quite high. In these situations, confirmatory testing using a second independent antibody assay, ideally one that uses a different antigenic target (e.g., the nucleocapsid phosphoprotein if the first assay targeted the spike glycoprotein), can substantially improve the probability that persons with a positive test result are antibody positive.

Assuming the test is reliable, serologic tests to identify recent or prior SARS-CoV-2 infection may be used to:

  • Determine who may be eligible to donate blood to manufacture convalescent plasma.
  • Measure the immune response in SARS-CoV-2 vaccine studies.
  • Estimate the proportion of the population exposed to SARS-CoV-2.

Lastly, serologic tests should not be used to:

  • Make decisions about the grouping of persons residing in or being admitted to congregate settings (e.g., schools, dormitories, correctional facilities), or
  • Determine whether persons should return to the workplace.

References

  1. Food and Drug Administration. Coronavirus disease 2019 (COVID-19) emergency use authorizations for medical devices. 2020. Available: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd. Accessed June 5, 2020.
  2. Centers for Disease Control and Prevention. Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html. Accessed June 5, 2020.
  3. Centers for Disease Control and Prevention. Evaluating and testing persons for coronavirus disease 2019 (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html. Accessed June 5, 2020.
  4. Guo L, Ren L, Yang S, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32198501.
  5. Haveri A, Smura T, Kuivanen S, et al. Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020. Euro Surveill. 2020;25(11). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32209163.
  6. Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32350462.
  7. Okba NMA, Müller MA, Li W, et al. SARS-CoV-2 specific antibody responses in COVID-19 patients. medRxiv. 2020. Available at: https://www.medrxiv.org/content/medrxiv/early/2020/03/20/2020.03.18.20038059.full.pdf.
  8. Xiang F, Wang X, He X, et al. Antibody detection and dynamic characteristics in patients with COVID-19. Clin Infect Dis. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32306047.
  9. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32221519.