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

Abstract

Background 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. Objective The 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 non-medical settings. Methods 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 April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. Conclusions U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to 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 contrast, Ag tests have high specificity, and, 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 to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method 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.

Dual antiviral therapy in haematological patients with protracted SARS‐CoV‐2 infection

“…SARS-CoV-2 antigen nasal swab, confirmed with rt-PCR test, was used to confirm infection at treatment baseline and to assess viral clearance. 11 Antigen test was preferred to PCR at screening since it has been described to better correlate with viral culture. 12 One patient was asymptomatic for SARS-CoV-2 infection, with a persistent antigen positivity at nasal swab in the last 9 months, confirmed by both RT-PCR and viral culture tests, but with urgent need of immuno-chemotherapy due to pulmonary involvement of diffuse large B-cell lymphoma.…”

Diagnostic stewardship and the coronavirus disease 2019 (COVID-19) pandemic: Lessons learned for prevention of emerging infectious diseases in acute-care settings

“…However, during periods of low COVID-19 prevalence, the positive predictive value decreases, and falsely positive test results may lead to unnecessary isolation among hospitalized patients or unnecessary delays in surgery. 5,6,34,35 Also of concern are false-negative results, which can occur especially with antigen tests in asymptomatic persons. A systematic review reported a pooled sensitivity of 81% (95% CI, 78%-84%) for antigen test detection of SARS-CoV-2 compared to standard nucleic acid amplification testing.…”

Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

“…[1][2][3][4][5][6] Indeed, Ag-RDTs are a powerful tool given the low cost (compared with molecular tests), speed, and portability-all of which improve accessibility in remote or lower-resourced settings and at-home use. 5,7,89 However, Ag-RDTs and some rapid molecular tests have lower analytical sensitivity than most gold-standard reverse-transcription quantitative PCR (RT-qPCR) tests and therefore require high viral loads (typically greater than 10 5 copies/mL) to reliably yield positive results. 7,8,[10][11][12][13][14][15][16][17][18] Further, Ag-RDTs are frequently used in unintended ways.…”

“…5,7,89 However, Ag-RDTs and some rapid molecular tests have lower analytical sensitivity than most gold-standard reverse-transcription quantitative PCR (RT-qPCR) tests and therefore require high viral loads (typically greater than 10 5 copies/mL) to reliably yield positive results. 7,8,[10][11][12][13][14][15][16][17][18] Further, Ag-RDTs are frequently used in unintended ways. 15,19 For example, although many Ag-RDTs are not authorized for asymptomatic use and/or have poor clinical sensitivity in asymptomatic populations [20][21][22][23] they are widely used for test-to-enter and serial-screening purposes.…”

“…Viralload timecourses from individuals in these studies show that for some individuals, several days can pass between when viral loads reach potentially infectious levels and when viral loads rise to the limits of detection (LODs) of Ag-RDTs (approximately 10 5 to 10 7 copies/mL). 7,8,[10][11][12][13][14][15][16][17]51,52 . During this window, previously conceptualized as a period of cryptic transmission, 59 false-negative Ag-RDT results may embolden social contact and increase transmission.…”