The Wild West of Emergency Use Authorizations for SARS-CoV-2 Testing: What Could Be the True Sensitivity?

Abstract Introduction/Objective SARS-CoV-2 is a pandemic that has required mobilization to meet urgent needs. In this mobilization, emergency use authorizations (EUA) have been issued by the FDA to expedite the deployment of these tests. This has led to a situation whereby sensitivity has not been rigorously studied for any of the assays with EUAs. Estimates can be extrapolated from the limited samples documented by the company in their instructions for use (IFU). Although the nationwide shortage of testing reagents prevent parallel testing of multiple platforms on all specimens, observations of repeat specimens at the Veteran Affairs Medical Center (VAMC) provides the first study in the literature of more complete data for SARS-CoV-2 nucleic acid (RT-PCR) assay on sensitivity on the Abbott (Abbott Park Ill) and Cepheid (Sunnyvale CA) assays. Methods A retrospective search was performed for all test results for SARS-CoV-2 by RT-PCR from 3/1/2020 to 4/14/2020 at Corporal Michael J. Crescenz Medical Center, in order to evaluate the sensitivity on Abbott m2000 and Cepheid platforms. Results across multiple reference laboratories and in-house testing platforms were collated in a table with all patients clinically requiring repeat testing recorded. Results 114/863 patients had repeat testing. The tests were performed initially by outside reference laboratories (25 patients), on the Abbott m2000 (63 patients), and Cepheid Infinity (26 patients). 15/114 (13%) had discordant results on repeat testing. This included 1 test initially done by a reference laboratory. 8 days after the initial result from the reference lab, a positive for the same patient was identified on the Abbott platform. 11 initial Abbott results were discordant on further repeat testing on two platforms - Abbott (6 patients) and Cepheid (5 patients) 1-6 days later. In addition, 3 initial Cepheid were discordant on further repeat testing by the same Cepheid platform (1-16 days later). Conclusion While the instructions for use for both platforms suggest 100% sensitivity and specificity (due to the 100% positive and negative percent agreement in limited specimens), the true sensitivity is less than 100%, particularly early in the course of the infection. In our study, the positive percent agreement (surrogate for sensitivity) was 83% for initial Abbott tests, 88% for initial Cepheid tests, and 95% by Reference laboratory platform.

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Sequencing for COVID-19 in the Pandemic Era: What Does it Mean?

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab191.300 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S140-S141

Author(s):

J M Petersen ◽

D Jhala

Keyword(s):

Public Health ◽

New York ◽

Medical Center ◽

The United States ◽

Patient Treatment ◽

Reference Laboratory ◽

Veterans Health ◽

Health Administration ◽

Rt Pcr ◽

Clinical Role

Abstract Introduction/Objective SARS-CoV-2 has been developing mutations over the course of the pandemic, leading to the rise of variants. The sequencing of these variants, however, has an unclear role for the medical center providing patient treatment. Methods/Case Report Patient specimens that were positive for the presence of SARS-CoV-2 with a cycle threshold <30 by reverse transcriptase polymerase chain reaction (RT-PCR) were sent for sequencing at the Veterans Health Administration Public Health Reference Laboratory (PHRL). Testing for SARS-CoV-2 was by RT-PCR was initially done by either the Abbott Alinity m SARS-CoV-2 assay (Chicago IL) or the Cepheid Xpert Xpress SARS-CoV- 2/Flu/RSV assay (Sunnyvale CA). All sent patient specimens had been selected by the clinical team for concern of the presence of a SARS-CoV-2 variant. Results (if a Case Study enter NA) There were a total of 8 patients (4 males and 4 females) that were sent for sequencing. The patient ages ranged from 38 to 80 years (average 58.8). The racial proportion of the 8 patients was 2 African Americans, 2 Caucasian Americans, and 4 unanswered. All were positive for SARS-CoV-2 by RT-PCR (4 Abbott assay and 4 Cepheid assay). Six of the sequenced samples showed the NextClade 20I/501Y.V1, Pango Lineage B.1.1.7, a variant first identified in the United Kingdom; four of these six patients had documentation of vaccination prior to the infection. One sequence was a NextClade 20C Pango Lineage B.1.526.1, a variant first identified in New York. The last sequence identified was a NextClade 20G, Pango Lineage B.1, a variant predominantly seen in the United States. Conclusion At the present time, sequencing of SARS-CoV-2 does not have a clear clinical role. However, from a public health and epidemiological point of view, sequencing has a role in SARS-CoV-2 variant tracing and detection. Vaccine protection against variant SARS-CoV-2 may not be complete as some infected patients had been vaccinated.

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SARS-CoV-2 patient self-testing with an antigen-detecting rapid test: a head-to-head comparison with professional testing

10.1101/2021.01.06.20249009 ◽

2021 ◽

Author(s):

Andreas K. Lindner ◽

Olga Nikolai ◽

Chiara Rohardt ◽

Franka Kausch ◽

Mia Wintel ◽

...

Keyword(s):

Extraction Procedure ◽

Rapid Test ◽

High Viral Load ◽

Ease Of Use ◽

Rt Pcr ◽

Design Procedures ◽

Percent Agreement ◽

Self Testing ◽

Accuracy Study ◽

Instructions For Use

Background Antigen-detecting rapid diagnostic tests (Ag-RDTs) have been widely recommended as a complement to RT-PCR. Considering the possibility of nasal self-sampling and the ease-of-use in performing the test, self-testing may be an option. Methods and Findings We performed a manufacturer-independent, prospective diagnostic accuracy study of nasal mid-turbinate self-sampling and self-testing when using a WHO-listed SARS-CoV-2 Ag-RDT. Symptomatic participants suspected to have COVID-19 received written and illustrated instructions. Procedures were observed without intervention. For comparison, Ag-RDTs with nasopharyngeal sampling were professionally performed. Estimates of agreement, sensitivity, and specificity relative to RT-PCR on a combined oro-/nasopharyngeal sample were calculated. Feasibility was evaluated by observer and participant questionnaires. Among 146 symptomatic adults, 40 (27.4%) were RT-PCR-positive for SARS-CoV-2. Sensitivity with self-testing was 82.5% (33/40 RT-PCR positives detected; 95% CI 68.1-91.3), and 85.0% (34/40; 95% CI 70.9-92.9) with professional testing. The positive percent agreement between self-testing and professional testing on Ag-RDT was 91.4% (95% CI 77.6-97.0), and negative percent agreement 99.1% (95% CI 95.0-100). At high viral load (>7.0 log10 SARS-CoV-2 RNA copies/ml), sensitivity was 96.6% (28/29; 95% CI 82.8-99.8) for both self- and professional testing. Deviations in sampling and testing (incomplete self-sampling or extraction procedure, or imprecise volume applied on the test device) were observed in 25 out of the 40 PCR-positives. Participants were rather young (mean age 35 years) and educated (59.6% with higher education degree). Most participants (80.9%) considered the Ag-RDT as rather easy to perform. Conclusion Ambulatory participants suspected for SARS-CoV-2 infection were able to reliably perform the Ag-RDT and test themselves. Procedural errors might be reduced by refinement of the Ag-RDTs for self-testing, such as modified instructions for use or product design/procedures. Self-testing may result in more wide-spread and more frequent testing. Paired with the appropriate information and education of the general public about the benefits and risks, self-testing may therefore have significant impact on the pandemic.

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Analisa Pengujian Repeatability Timbangan Elektronik dengan Metode Syarat Teknis Timbangan Non Otomatis dan Metode NMI Australia

Elinvo (Electronics Informatics and Vocational Education) ◽

10.21831/elinvo.v4i2.28356 ◽

2019 ◽

Vol 4 (2) ◽

pp. 176-183

Author(s):

Ponco Wali

Keyword(s):

Research Method ◽

Test Methods ◽

Test Results ◽

Repeat Testing ◽

Testing Method ◽

Technical Requirements

Testing repeat electronic scales with non-automatic scales technical requirements so far is fairly long if not using a calculator or computer. The aim of this research is to compare the repeatability testing method of electronic scales using methods according to the technical requirements of non-automatic scales and the Australian NMI method, both of which refer to OIML R76 in determining the validity or cancellation of electronic scales repeatability testing. This research method is done through repeat testing on 3 samples of electronic scales, then on each electronic scale 2 test methods are performed. The conclusion is that the electronic scales repeatability testing uses the non-automatic scales technical requirements method and the Australian NMI method has some differences although both refer to OIML R76. These differences include several points, namely the charge used, the method of adding additions, the formula for determining electronic scales, and different test results. The Australian NMI method is deemed to make it easier and more time efficient compared to the non-automatic weighing technical requirements method.

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Preanalytical Issues and Cycle Threshold Values in SARS-CoV-2 Real-Time RT-PCR Testing: Should Test Results Include These?

ACS Omega ◽

10.1021/acsomega.1c00166 ◽

2021 ◽

Author(s):

Ilka Engelmann ◽

Enagnon Kazali Alidjinou ◽

Judith Ogiez ◽

Quentin Pagneux ◽

Sana Miloudi ◽

...

Keyword(s):

Real Time ◽

Test Results ◽

Threshold Values ◽

Rt Pcr ◽

Cycle Threshold

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Is it enough for COVID-19 screening test? Limitation of swab test and general characteristics of mild symptom patients

Science Progress ◽

10.1177/00368504211026152 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110261

Author(s):

Sungwoo Choi ◽

Hyo Jeong Choi ◽

Ho Jung Kim

Keyword(s):

Screening Test ◽

Community Treatment ◽

Upper Respiratory Tract ◽

Test Results ◽

Rt Pcr ◽

Pcr Assay ◽

Positive Rate ◽

Upper Respiratory ◽

Polymerase Chain ◽

Discharge Criteria

The most common method for SARS-CoV-2 testing is throat or nasal swabbing by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. In South Korea, drive-through swab test is used for screening system and community treatment centers (CTCs), which admit and treat confirmed COVID-19 patients with mild symptoms, are being used. This retrospective study was conducted on patients admitted to a CTC on March 6, 2020. A total of 313 patients were admitted. The nasal and throat swabs were collected from the upper respiratory tract, and a sputum test was performed to obtain lower respiratory samples. The positive rate of the first set of test, sputum test was higher than that of the swab test ( p = 0.011). In the second set of test, 1 week after the first ones, the rate of positive swab tests was relatively high ( p = 0.026). In the first set of test, 66 of 152 (43.4%) patients showed 24-h consecutive negative swab test results, when the sputum test results were considered together, that number fell to 29 patients (19.1%) ( p < 0.001). Also, in the second set of test, 63 of 164 (38.4%) patients met the discharge criteria only when the swab test was considered; that number fell to 30 (18.3%) when the sputum test results were also considered ( p < 0.001). Using the swab test alone is insufficient for screening test and discharge decision. Patients who may have positive result in the sputum test can be missed.

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COVID-19 and pregnancy – where are we now? A review

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0132 ◽

2020 ◽

Vol 48 (5) ◽

pp. 428-434 ◽

Cited By ~ 7

Author(s):

Aleksandra Rajewska ◽

Wioletta Mikołajek-Bedner ◽

Joanna Lebdowicz-Knul ◽

Małgorzata Sokołowska ◽

Sebastian Kwiatkowski ◽

...

Keyword(s):

Case Fatality ◽

Fetal Distress ◽

Delivery Mode ◽

Test Results ◽

Rt Pcr ◽

Third Trimester ◽

The Third ◽

Laboratory Test Results ◽

Protective Antibodies ◽

Polymerase Chain

AbstractThe new acute respiratory disease severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious. It has caused many deaths, despite a relatively low general case fatality rate (CFR). The most common early manifestations of infection are fever, cough, fatigue and myalgia. The diagnosis is based on the exposure history, clinical manifestation, laboratory test results, chest computed tomography (CT) findings and a positive reverse transcription-polymerase chain reaction (RT-PCR) result for coronavirus disease 2019 (COVID-19). The effect of SARS-CoV-2 on pregnancy is not already clear. There is no evidence that pregnant women are more susceptible than the general population. In the third trimester, COVID-19 can cause premature rupture of membranes, premature labour and fetal distress. There are no data on complications of SARS-CoV-2 infection before the third trimester. COVID-19 infection is an indication for delivery if necessary to improve maternal oxygenation. Decision on delivery mode should be individualised. Vertical transmission of coronavirus from the pregnant woman to the fetus has not been proven. As the virus is absent in breast milk, the experts encourage breastfeeding for neonatal acquisition of protective antibodies.

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528. Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Implications of Repeat Testing on Infection Control Strategies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.722 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S331-S332

Author(s):

Catherine Foster ◽

Lucila Marquez ◽

Tjin Koy ◽

Ila Singh ◽

Judith Campbell

Keyword(s):

Infection Control ◽

Median Time ◽

Disease Transmission ◽

Retrospective Chart Review ◽

Source Control ◽

Hospitalized Children ◽

Rt Pcr ◽

Repeat Testing ◽

Children's Hospital ◽

Children’S Hospital

Abstract Background Accurate diagnosis of coronavirus disease 2019 (COVID-19) is key for source control and interrupting disease transmission. To better understand the length of viral shedding in children and potential infection control implications, we describe 51 children with COVID-19 who underwent repeat testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Texas Children’s Hospital (TCH). Methods We performed a retrospective chart review of all pediatric patients (< 21 years of age) with ≥ 2 nasopharyngeal specimens tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (rt-PCR) and at least one positive result between 3/13/2020 and 6/7/2020 through the TCH Molecular Microbiology Laboratory. Results Fifty-one patients met inclusion criteria. The median age was 8.6 years (0.02–19.2 years). Sixteen (31%) children were hospitalized. Fourteen (27%) patients underwent testing for surveillance purposes (including 3 admitted patients). Two SARS-CoV-2 tests were performed in 25 (49%) children; while 12 (24%) children had 3 tests, 4 (8%) children had 4 tests, and 10 (20%) children had ≥ 5 tests (including 1 patient with underlying malignancy who had 9 SARS-CoV-2 PCRs performed). SARS-CoV-2 testing timeline for 9 hospitalized children is shown (Fig 1). The median time between collection of tests 1 and 2 was 14 days (n=51, range 1, 53 days). For children with conversion (first detected to first not-detected sample), the median time was 15 days (n=31, range 1, 45 days). For patients with consecutive positive SARS-CoV-2 PCRs, the median time of positivity was 10 days (n=19, range 2, 31). One patient with malignancy had 5 tests over 6 weeks in the outpatient setting and each time alternated between detected and not-detected. Following diagnosis with COVID-19, one patient with sickle cell disease likely had re-infection and had a positive test after having 2 consecutive negative tests; his last SARS-CoV-2 rt-PCR was positive 68 days after initial positive. Fig 1. Timing of Repeat SARS-CoV-2 PCRs in Select Hospitalized Children with COVID-19 Conclusion We observed variation in the duration of SARS-CoV-2 rt-PCR positivity in children with COVID-19. For children with COVID-19, a single negative molecular assay for SARS-CoV-2 may not be predictive of sustained negativity. Disclosures All Authors: No reported disclosures

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The use of routine blood tests to assist the diagnosis of COVID-19 in symptomatic hospitalized patients

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563221999076 ◽

2021 ◽

pp. 000456322199907

Author(s):

IT Parsons ◽

AT Parsons ◽

E Balme ◽

G Hazell ◽

R Gifford ◽

...

Keyword(s):

Cell Count ◽

Retrospective Review ◽

Blood Test ◽

Patient Flow ◽

White Cell Count ◽

Area Under The Curve ◽

White Cell ◽

Test Results ◽

Rt Pcr ◽

Blood Tests

Introduction Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. Method A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient’s clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. Results Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of –0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. Discussion Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.

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Standardization of Diagnostic Immunohistochemistry: Literature Review and Geisinger Experience

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2014-0074-ra ◽

2014 ◽

Vol 138 (12) ◽

pp. 1564-1577 ◽

Cited By ~ 52

Author(s):

Fan Lin ◽

Zongming Chen

Keyword(s):

Quality Management ◽

Literature Review ◽

Best Practices ◽

Critical Points ◽

Medical Center ◽

Management Program ◽

Review Article ◽

Data Sources ◽

Test Results ◽

Antibody Validation

Context Immunohistochemistry has become an indispensable ancillary technique in anatomic pathology laboratories. Standardization of every step in preanalytic, analytic, and postanalytic phases is crucial to achieve reproducible and reliable immunohistochemistry test results. Objective To standardize immunohistochemistry tests from preanalytic, analytic, to postanalytic phases. Data Sources Literature review and Geisinger (Geisinger Medical Center, Danville, Pennsylvania) experience. Conclusions This review article delineates some critical points in preanalytic, analytic, and postanalytic phases; reiterates some important questions, which may or may not have a consensus at this time; and updates the newly proposed guidelines on antibody validation from the College of American Pathologists Pathology and Laboratory Quality Center. Additionally, the article intends to share Geisinger's experience with (1) testing/optimizing a new antibody and troubleshooting; (2) interpreting and reporting immunohistochemistry assay results; (3) improving and implementing a total immunohistochemistry quality management program; and (4) developing best practices in immunohistochemistry.

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Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv188 ◽

2015 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Laura G. Wesolowski ◽

Muazzam Nasrullah ◽

Robert W. Coombs ◽

Eric Rosenberg ◽

Steven F. Ethridge ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

South Carolina ◽

Massachusetts General Hospital ◽

Medical Center ◽

Fourth Generation ◽

Reference Laboratory ◽

Acute Infections ◽

Immunodeficiency Virus ◽

Antigen Antibody ◽

Hiv 1

Abstract Background. To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods. We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results. From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions. Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

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