information. Testing for SARS-CoV-2 Infection Last Updated: March 24, 2022 Summary Recommendations • The COVID-19 Treatment Guidelines Panel (the Panel) recommends using a nucleic acid amplification test (NAAT) with a sample collected from the upper respiratory tract (i.e., nasopharyngeal, nasal mid-turbinate, anterior nasal, or oropharyngeal) to diagnose acute infection of SARS-CoV-2; if it is not practical to use a NAAT or if NAATs are not available, an antigen test may be used (AIII). • For intubated and mechanically ventilated adults who are suspected to have COVID-19 but who do not have a confirmed diagnosis: • The Panel recommends obtaining lower respiratory tract samples to establish a diagnosis of COVID-19 if an initial upper respiratory tract sample is negative (BII). • The Panel recommends obtaining endotracheal aspirates over bronchial wash or bronchoalveolar lavage samples when collecting lower respiratory tract samples to establish a diagnosis of COVID-19 (BII). • A NAAT should not be repeated in an asymptomatic person (with the exception of health care workers) within 90 days of a previous SARS-CoV-2 infection, even if the person has had a significant exposure to SARS-CoV-2 (AIII). • SARS-CoV-2 reinfection has been reported in people after an initial diagnosis of the infection; therefore, clinicians should consider using a NAAT for those who have recovered from a previous infection and who present with symptoms that are compatible with SARS-CoV-2 infection if there is no alternative diagnosis (BIII). • The Panel recommends against the use of serologic (i.e., antibody) testing as the sole basis for diagnosis of acute SARS-CoV-2 infection (AIII). • There is insufficient evidence for the Panel to recommend either for or against the use of SARS-CoV-2 serologic testing to assess for immunity or to guide clinical decisions about using COVID-19 vaccines or anti-SARS-CoV-2 monoclonal antibodies in certain people. Rating of Recommendations: A = Strong; B = Moderate; C = Weak Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion Diagnostic Testing for SARS-CoV-2 Infection Everyone who has symptoms that are consistent with COVID-19 and people with known high-risk exposures to SARS-CoV-2 should be tested for SARS-CoV-2 infection. Such testing should employ either a nucleic acid amplification test (NAAT) or an antigen test to detect SARS-CoV-2. Testing may also be used for screening, determining the length of a patient’s isolation period, and other nondiagnostic purposes.1 A number of diagnostic tests for SARS-CoV-2 infection (e.g., NAATs, antigen tests) have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration (FDA),2 but no diagnostic test has been approved by the FDA. Diagnostic tests have been authorized for use by trained personnel in several settings, including lab facilities. They can also be used in point-of-care settings, where the test is performed by trained personnel at or near the place where the specimen was collected. Point-of-care settings include physician offices, pharmacies, long-term care facilities, and school clinics. Antigen tests can be self-administered, and most can be used in point-of-care settings, allowing results to be available within minutes. Some NAATs can also be self-administered at home or in other non-health care locations and shipped to a laboratory for testing. Although nasopharyngeal specimens remain the recommended samples for SARS-CoV-2 diagnostic testing, nasal (anterior nares or mid-turbinate) or oropharyngeal swabs are acceptable alternatives.3 Lower respiratory tract samples have a higher yield than upper respiratory tract samples, but they Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 17 are often not obtained because of concerns about aerosolization of the virus during sample collection procedures. Some of the tests that have received EUAs can also be performed on saliva specimens, but the quality of saliva specimens can be highly variable. Studies are currently evaluating the use of other sample types, including stool samples. Nucleic Acid Amplification Testing for SARS-CoV-2 Infection Reverse transcription polymerase chain reaction (RT-PCR)-based diagnostic tests (which detect viral nucleic acids) are considered the gold standard for detecting current SARS-CoV-2 infection. More recently, NAATs have included isothermal amplification platforms (e.g., nicking endonuclease amplification reaction [NEAR], loop-mediated isothermal amplification [LAMP], transcription-mediated amplification [TMA]).4 Some NAATs have also received EUAs for use in different settings, such as in laboratory facilities and point-of-care settings. Laboratory-based NAATs generally have higher sensitivity than point-of-care tests.4 Clinically, there may be a window period of up to 5 days after exposure before viral nucleic acids can be detected. Diagnostically, some NAATs may produce false negative results if a mutation occurs in the part of the virus’ genome that is assessed by that test.5 The FDA monitors the potential effects of SARS-CoV-2 genetic variations on NAAT results and issues updates