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.

/pdf/the-infectious-diseases-society-of-america-guidelines-on-the-2rkj0k2p.pdf

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

http://www.clinicalmicrobiologyandinfection.com/article/S1198743X2200088X/pdf

Different performance of three point-of-care SARS-CoV-2 antigen detection devices in symptomatic patients and close asymptomatic contacts: a real-life study

Abstract Objectives Chemiluminescence immunoassay (CLIA) automated assays (fourth-generation antigen test) for SARS-CoV-2 detection are promising because of their analytical productivity, but have lower sensitivity and specificity than rt-PCR assays. The authors of this paper evaluated a recent immunoassay implemented on Siemens Atellica IM, investigating how much this could affect the actual feasibility of this diagnostic during the pandemic. Methods From the three-day routine 134 positive and 241 negative swab samples by rt-PCR test were evaluated, selected as 1/3 positive – 2/3 negative. Results Using rt-PCR as gold standard, the specificity of immunoassay was 96.7%, while sensitivity was 68.0%. Sensitivity is inversely proportional to the viral load: 100% for cycles threshold (CT) values from 14 to 29, 95% until 30 CT, then 85, 74, 72, 68%, for 31–35 CT respectively. Conclusions Our study confirms the reliability of the fourth-generation antigen assay in recognizing negative samples. Conversely, sensitivity appears to be less reliable (68.0%) than reported in the literature. This could be due to a non-randomized study group: many swab samples were taken from patients with expected low viral load (hospitalized for COVID for more than 10–12 days or asymptomatic patients for epidemiological surveillance). The strong correlation of sensitivity and viral load could prove significant to track the infectiousness of infected people, as previous studies reported that a viral load of at least 10E6 copies of RNA/mL, corresponding to 25 CT, is the threshold of transmission of the disease.

Evaluating the role of a fully automated SARS-CoV-2 antigen ECLIA immunoassay in the management of the SARS COV 2 pandemic on general population

Due to the newly emerging Omicron variant, there is a need to re-evaluate the performance of automated antigen tests. Our study aim was to evaluate the performance of the automated Liaison SARS-CoV-2 antigen assay against reverse transcriptase polymerase chain reaction (RT-PCR) in samples with Omicron variant.A prospective study was performed on 373 combined oro-nasopharyngeal samples (NPS) randomly collected from symptomatic patients. NPS were tested with Liaison SARS-CoV-2 Ag test (DiaSorin, Italy) and DS Coronex COVID-19 Multiplex RT-PCR Diagnosis Kit (DS BioTechnology, Ankara, Turkey).Of 373 samples, 124 (33.2%) were found to be RT-PCR positive and 249 (66.8%) RT-PCR negative. Taking RT-PCR as a reference, the sensitivity and specificity of the Liaison SARS-CoV-2 Ag assay were found as 84.6% (95%CI 77.3%-90%) and 100% (95%CI 98.5%-100%), respectively. For samples with a cycle threshold (Ct) value <25 (high viral load), the sensitivity increased to 100%. When antigen concentration and Ct values were compared, a strong negative correlation between antigen and Ct values was determined (P < 0.001).The Liaison antigen test met the performance criteria recommended by the WHO for samples with the Omicron variant. In addition, it showed excellent sensitivity and specificity in patients with high viral load. Therefore, Liaison antigen test can be a reliable and useful alternative in the diagnosis of SARS-CoV-2 infection, particularly in resource-constrained laboratories.

Comparison of performance of LIAISON SARS-CoV-2 antigen assay with RT-PCR during the Omicron wave.

Abstract Coronavirus disease 2019 is a serious threat to human life, and early diagnosis and screening can help control the COVID-19 pandemic. The high sensitivity of reverse transcriptase–polymerase chain reaction (RT-PCR) assay is the gold standard for the diagnosis of COVID-19, but there are still some false-negative results. Rapid antigen detection (RAD) is recommended by the World Health Organization (WHO) as a screening method for COVID-19. This review analyzed the characteristics of RDT and found that although the overall sensitivity of RAD was not as high as that of RT-PCR, but RAD was more sensitive in COVID-19 patients within 5 days of the onset of symptoms and in COVID-19 patients with Ct ≤ 25. Therefore, RAD can be used as an adjunct to RT-PCR for screening patients with early COVID-19. Finally, this review provides a combined diagnostic protocol for RAD and nucleic acid testing with the aim of providing a feasible approach for COVID-19 screening.

/pdf/combined-diagnosis-of-sars-cov-2-rapid-antigen-detection-as-2mxm7yl6.pdf

Combined Diagnosis of SARS-CoV-2: Rapid Antigen Detection as an Adjunct to Nucleic Acid Detection

SARS-CoV-2 viral antigen detection may be an interesting alternative to RT-PCR for the diagnosis of SARS-CoV-2 infection as a less laborious or expensive method but requires validation. This study aimed to compare the performance of the DiaSorin™ LiaisonXL automated quantitative antigen test (QAT) and the AAZ™ rapid antigen test (RAT) to the DiaSorin™ MDX RT-PCR assay. A total of 242 nasopharyngeal samples were tested at La Pitié-Salpêtrière University Hospital (Paris, France). Performances for the detection of variants of SARS-CoV-2 were further investigated. RATs were visually read for qualitative results and band intensity was determined. Overall sensitivity was 63.2% for QAT and 58.6% for RAT. For RT-PCR Ct value 25, sensitivity was 89.8% for both tests. Both tests showed comparable sensitivity for detection of variants. There was a strong relationship between antigen concentration and band positivity. On the same set of samples these tests share similar performances.

/pdf/comparison-of-rapid-and-automated-antigen-detection-tests-39ruv4s0.pdf

Comparison of Rapid and Automated Antigen Detection Tests for the Diagnosis of SARS-CoV-2 Infection

Comparison of two new HTLV-I/II screening methods, Abbott Alinity i rHTLV-I/II and Diasorin LIAISON® XL murex recHTLV-I/II, to Abbott architect rHTLVI/II assay.

Safietou Mansaly

Papers

Comparison of Rapid and Automated Antigen Detection Tests for the Diagnosis of SARS-CoV-2 Infection

Comparison of two new HTLV-I/II screening methods, Abbott Alinity i rHTLV-I/II and Diasorin LIAISON® XL murex recHTLV-I/II, to Abbott architect rHTLVI/II assay.