Factors affecting the sensitivity of quantitative severe acute respiratory syndrome coronavirus 2 antigen test.

INTRODUCTION: The accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test (QAT) are limited. METHODS: A total of 347 nasopharyngeal samples were collected from patients with coronavirus disease 2019 (COVID-19), and the date of onset was obtained from the electronic medical records. The SARS-CoV-2 antigen level was measured using Lumipulse Presto SARS-CoV-2 Ag (Presto), while NAAT was performed using the Ampdirect 2019-nCoV Detection Kit. RESULTS: Presto had a sensitivity rate of 95.1% (95% confidence interval: 92.8-97.4) in detecting the SARS-CoV-2 antigen in 347 samples. The number of days from symptom onset to sample collection was negatively correlated with the amount of antigen (r = -0.515) and sensitivity of Presto (r = -0.711). The patients' age was lower in the Presto-negative samples (median age, 39 years) compared with that in the Presto-positive samples (median age, 53 years; p < 0.01). A significant positive correlation was observed between age (excluding teenagers) and Presto sensitivity (r = 0.764). Meanwhile, no association was found between the mutant strain, sex, and Presto results. CONCLUSION: Presto is useful for the accurate diagnosis of COVID-19 owing to its high sensitivity when the number of days from symptom onset to sample collection is within 12 days. Furthermore, age may affect the results of Presto, and this tool has a relatively low sensitivity in younger patients.

Sars-Cov-2 antigen tests predict infectivity based on viral culture: comparison of antigen, PCR viral load, and viral culture testing on a large sample cohort.

OBJECTIVE: To define the relationship of SARS-CoV-2 antigen, viral load determined by RT-qPCR, and viral culture detection. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals and thereby inform how and where to most appropriately deploy antigen and nucleic acid amplification-based diagnostic testing modalities. METHODS: We compared the antigen testing results from three lateral flow and one microfluidics assay to viral culture detection and viral load determination performed in parallel in up to 189 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. RESULTS: Antigen tests were predictive of viral culture positivity, with the LumiraDx microfluidics method showing enhanced sensitivity (90%; 95% CI 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver operator characteristic curves of 0.94 to 0.97 and 0.92, respectively. A viral load threshold of 100 000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Adjusting for sample dilution inherent in our study design, sensitivities of antigen tests were ≥95% for detection of viral culture positive samples with viral loads >106 genome copies/mL, although specificity of antigen testing was imperfect. DISCUSSION: Antigen testing results and viral culture were correlated. For culture positive samples, the sensitivity of antigen tests was high at high viral loads that are likely associated with significant infectivity. Therefore, our data provides support for use of antigen testing in ruling out infectivity at the time of sampling.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With False-Positive Results in SARS-CoV-2 Antigen Tests: A Case Report.

A 23-year-old man presented with headache, fever, and urinary retention. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests were positive, but SARS-CoV-2 polymerase chain reaction (PCR) results were negative. MRI showed long spinal cord lesions. Due to positive serum and cerebrospinal fluid myelin oligodendrocyte glycoprotein (MOG) antibodies, we made the diagnosis of MOG-associated disease. We concluded that the antigen tests were false positives because SARS-CoV-2 IgM and IgG were not elevated. Although the mechanism behind the false-positive results is unclear, physicians should consider the possibility of a false-positive result in the SARS-CoV-2 antigen test.

COVID-19 contagious health care personnel 5-day early return-to-work program.

BACKGROUND: COVID-19 contagious health care personnel (HCP) who are self-isolating for a 10-day period increases burden to workforce shortages. Implementation of a 5-day early return-to-work (RTW) program may reduce self-isolation periods, without increasing transmission risk, during the COVID-19 pandemic. DESIGN AND METHODS: This observational cohort quality improvement study included newly diagnosed COVID-19 HCP at a multifacility health care system. The program allowed HCP to return to work 6 days after date of a positive test result if they were not immunocompromised, had mild and improving symptoms, and self-reported a SARS-CoV-2 antigen negative test on day 5. RESULTS: Between January 4 and April 3, 2022, 1,023 HCP self-enrolled and 344 (33.6%) self-reported negative test results. Among these, 161 (46.8%) self-reported negative test results on day 5 and were eligible for early RTW on day 6. A total of 714 days were saved from missed work in self-isolation. The number of tests purchased, dispensed, and reported per day of HCP time saved was 4.4. No transmission events were observed originating from HCP who participated in early RTW. CONCLUSION: Implementing a 5-day early RTW program that includes HCP self-reporting SARS-CoV-2 antigen test results can increase staffing availability, while maintaining a low risk of SARS-CoV-2 transmission.

Impact of mass rapid antigen testing for SARS-CoV-2 to mitigate Omicron outbreaks in China.

We analysed the effectiveness of various non-pharmaceutical interventions in containing the 2022 Omicron outbreak in China. The results show that the Rapid Antigen Test contributed to containing the outbreak, reducing the reproduction number by 0.788 (95% CI:-0.306, 1.880) in studied cities.

Viral load may impact the diagnostic performance of nasal swabs in nucleic acid amplification test and quantitative antigen test for SARS-CoV-2 detection.

INTRODUCTION: Compared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT). METHODS: We prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures. RESULTS: Sixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = -0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL. CONCLUSIONS: In NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.

Comparison of four commercial, automated antigen tests to detect SARS-CoV-2 variants of concern.

A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we evaluated four commercial Ag tests on automated platforms and one POCT to detect SARS-CoV-2. We evaluated PCR-positive (n = 107) and PCR-negative (n = 303) respiratory swabs from asymptomatic and symptomatic patients at the end of the second pandemic wave in Germany (February-March 2021) as well as clinical isolates EU1 (B.1.117), variant of concern (VOC) Alpha (B.1.1.7) or Beta (B.1.351), which had been expanded in a biosafety level 3 laboratory. The specificities of automated SARS-CoV-2 Ag tests ranged between 97.0 and 99.7% (Lumipulse G SARS-CoV-2 Ag (Fujirebio): 97.03%, Elecsys SARS-CoV-2 Ag (Roche Diagnostics): 97.69%; LIAISON® SARS-CoV-2 Ag (Diasorin) and SARS-CoV-2 Ag ELISA (Euroimmun): 99.67%). In this study cohort of hospitalized patients, the clinical sensitivities of tests were low, ranging from 17.76 to 52.34%, and analytical sensitivities ranged from 420,000 to 25,000,000 Geq/ml. In comparison, the detection limit of the Roche Rapid Ag Test (RAT) was 9,300,000 Geq/ml, detecting 23.58% of respiratory samples. Receiver-operating-characteristics (ROCs) and Youden's index analyses were performed to further characterize the assays' overall performance and determine optimal assay cutoffs for sensitivity and specificity. VOCs carrying up to four amino acid mutations in nucleocapsid were detected by all five assays with characteristics comparable to non-VOCs. In summary, automated, quantitative SARS-CoV-2 Ag tests show variable performance and are not necessarily superior to a standard POCT. The efficacy of any alternative testing strategies to complement nucleic acid-based assays must be carefully evaluated by independent laboratories prior to widespread implementation.

Use of Immunochromatographic SARS-CoV-2 Antigen Testing in Eight Long-Term Care Facilities for the Elderly.

The clinical validation of the NADAL COVID-19 antigen test (Nal von Minden, Moers, Germany) started in eight Slovenian long-term health care facilities in October 2020. The purpose of clinical validation is to implement the test into the everyday working process in long-term care (LTC) facilities and demonstrate how it can be used to mitigate the spread of the virus in these environments. The facilities compared the results of antigen tests to the results obtained using Cobas 6800 SARS-CoV-2 real-time reverse transcription polymerase chain reaction (RT-PCR) (Roche, USA). Sensitivity (86.96%, 95% CI: 66.41-97.23%) and specificity (88.24%, 95% CI: 80.35-93.77%) of the NADAL COVID-19 antigen test were good. Rapid antigen testing served well for early detection of infection and helped to prevent and control spread of the SARS Cov2 in six out of eight LTCs. Moreover, mini-outbreaks were quickly resolved in all six LTCs. Locally validated immunochromatographic SARS-CoV-2 antigen testing can be used to contain the spread of the virus in LTCs. Antigen tests also deliver accurate information very quickly if used early with a low threshold. The NADAL COVID-19 antigen test proved to be a good screening tool to detect SARS-COV-2 in LTCs.

[Threat of a SARS-CoV-2 endemic in a large hospital specialized in rheumatic diseases-relative all clear through consistent testing]. / Drohende Corona-Endemie in einer rheumatologischen Spezialklinik ­ relative Entwarnung durch konsequente Testung.

The severe acute respiratory coronavirus type 2 (SARS-CoV-2) pandemic is keeping most countries of the world in suspense. In Germany the prevalence of SARS-CoV­2 infections is under 2% but for weeks the numbers in Germany have also been increasing. The care in rheumatology was temporarily impaired by the first wave of the pandemic. This article reports the infection situation in the largest specialized rheumatology clinic in Germany, the Rheumatism Center Ruhrgebiet, because recently during the second wave for the first time several SARS-CoV­2 infections occurred here over one weekend, which led to considerable anxiety in many of those involved. The situation could be clarified by consistent testing of patients and personnel with the rapid antigen test and the situation could be mollified. Ultimately, only a few persons were tested positive and the courses by the patients have so far remained bland. This shows the effectiveness of the protective hygiene measures consistently implemented since April.

Evaluation of a laboratory-based high-throughput SARS-CoV-2 antigen assay for non-COVID-19 patient screening at hospital admission.

Several rapid antigen tests (RATs) for the detection of SARS-CoV-2 were evaluated recently. However, reliable performance data for laboratory-based, high-throughput antigen tests are lacking. Therefore and in response to a short-term shortage of PCR reagents, we evaluated DiaSorin's LIAISON SARS-CoV-2 antigen test in comparison to RT-qPCR, and concerning the application of screening non-COVID-19 patients on hospital admission. Applying the manufacturer-recommended cut-off of 200 arbitrary units (AU/mL) the specificity of the LIAISON Test was 100%, the overall analytical sensitivity 40.2%. Lowering the cut-off to 100 AU/mL increased the sensitivity to 49.7% and decreased the specificity to 98.3%. Confining the analysis to samples with an RT-qPCR result < 25 Ct resulted in a sensitivity of 91.2%. The quality of the LIAISON test is very similar to that of good RATs described in the literature with the advantage of high throughput and the disadvantage of relatively long analysis time. It passes the WHO quality criteria for rapid antigen tests and is characterized by particularly high specificity. The LIAISON test can therefore be used for the same applications as recommended for RATs by the WHO. Due to limited sensitivity, the LIAISON test should only be used for screening, if PCR-based assays are not available.

Evaluation of two rapid antigen tests to detect SARS-CoV-2 in a hospital setting.

Successful containment strategies for the SARS-CoV-2 pandemic will depend on reliable diagnostic assays. Point-of-care antigen tests (POCT) may provide an alternative to time-consuming PCR tests to rapidly screen for acute infections on site. Here, we evaluated two SARS-CoV-2 antigen tests: the STANDARD™ F COVID-19 Ag FIA (FIA) and the SARS-CoV-2 Rapid Antigen Test (RAT). For diagnostic assessment, we used a large set of PCR-positive and PCR-negative respiratory swabs from asymptomatic and symptomatic patients and health care workers in the setting of two University Hospitals in Munich, Germany, i.e. emergency rooms, patient care units or employee test centers. For FIA, overall clinical sensitivity and specificity were 45.4% (n = 381) and 97.8% (n = 360), respectively, and for RAT, 50.3% (n = 445) and 97.7% (n = 386), respectively. For primary diagnosis of asymptomatic and symptomatic individuals, diagnostic sensitivities were 60.9% (FIA) (n = 189) and 64.5% (RAT) (n = 256). This questions these tests' utility for the reliable detection of acute SARS-CoV-2-infected individuals, in particular in high-risk settings. We support the proposal that convincing high-quality outcome data on the impact of false-negative and false-positive antigen test results need to be obtained in a POCT setting. Moreover, the efficacy of alternative testing strategies to complement PCR assays must be evaluated by independent laboratories, prior to widespread implementation in national and international test strategies.