The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing (January 2023)

Abstract

Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through 1 April 2022. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel made 10 diagnostic recommendations that address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. US Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared with nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms and, in symptomatic patients, on timing of testing after symptom onset. In most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared with testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remain the testing methods of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Keywords: SARS-CoV-2; diagnostic test performance; diagnostic testing; rapid antigen tests; systematic review.

Figure 1.

Algorithm for antigen recommendations. ^aNo recommendation for or against antigen testing could be made for the specific populations of students in educational settings, employees at work, or individuals planning to attend a large social gathering (evidence gaps). ^bNo recommendation for or against home testing using NAAT could be made (evidence gap). ^cNucleic acid amplification test (NAAT) refers to rapid or laboratory-based nucleic amplification test. ^dFor NAAT, either rapid or standard laboratory-based testing is suggested (conditional recommendation). ^eFor unexposed, asymptomatic individuals undergoing procedures or planned for hospital admission, routine NAAT testing is not suggested (conditional recommendations). ^fFor NAAT in symptomatic individuals, the IDSA panel suggests collecting either nasopharyngeal (NP) swab, anterior nasal (AN) swab, oropharyngeal (OP) swab, midturbinate (MT) swab, saliva or mouth gargle specimens (conditional recommendation). ^gFor NAAT in symptomatic individuals, the IDSA panel suggests that anterior nares and midturbinate specimens can be either self-collected or collected by a healthcare provider (conditional recommendation). ^hEither point-of-care or laboratory-based antigen testing is suggested (conditional recommendation). ⁱIf the specimen is self-collected, either observed or unobserved collection is suggested (conditional recommendation). ^jThe IDSA panel suggests against using NAAT in patients with COVID-19 to guide discontinuation of isolation or prior to a procedure or surgery (conditional recommendations). ^kFor guidance on the timing of repeat testing for a specific assay, please consult the respective assay package insert or the latest FDA guidance. Abbreviations: COVID-19, coronavirus disease 2019; FDA, Food and Drug Administration; IDSA, Infectious Diseases Society of America.

Figure 2.

Approach and implications to rating the quality of evidence and strength of recommendations using the GRADE methodology (unrestricted use of the figure granted by the US GRADE Network). Abbreviation: GRADE, Grading of Recommendations Assessment, Development, and Evaluation.