scholarly journals Antigen Testing for COVID-19 Asymptomatic Screening: Why it Should be Preferred Over PCR Insights From Navy Region Japan’s Experience With a Comprehensive Antigen Testing Strategy

2021 ◽  
Author(s):  
Ross A Mullinax
Keyword(s):  
Public Health ◽  
Infectious Virus ◽  
Infectious Period ◽  
Test Results ◽  
Testing Strategy ◽  
Viral Loads ◽  
Viral Culture ◽  
Polymerase Chain ◽  
Antigen Testing

ABSTRACT Polymerase chain reaction (PCR) is commonly used in asymptomatic screening testing, but is suboptimal for this purpose as it will identify many old persistent positives that are no longer infectious. This can result in placement of individuals that are not infectious to others into isolation. This results in substantial adverse impact to military manning and operations, without any benefit to public health. Antigen testing does not have this same drawback. Antigen testing, while less sensitive than PCR, will identify the vast majority of infectious positives, especially those with higher viral loads that are more likely to transmit to others. Importantly, use of antigen testing will also greatly increase the certainty of benefit from isolation, reducing the risk of isolating those individuals who are beyond their infectious period and pose no threat to public health. The literature on this topic is reviewed, with particular focus on studies that perform viral culture in addition to PCR and antigen testing. This allows for determination of sensitivity for infectious virus. Also, Navy Region Japan’s experience with a comprehensive antigen testing strategy is described. The challenges presented by persistent positive PCR test results are examined, as well as the real-world benefits from implementing widespread use of antigen testing.

scholarly journals Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study

BMJ ◽  
2021 ◽  
pp. n1637 ◽  
Author(s):  
Marta García-Fiñana ◽  
David M Hughes ◽  
Christopher P Cheyne ◽  
Girvan Burnside ◽  
Mark Stockbridge ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Viral Load ◽  
Predictive Value ◽  
High Viral Load ◽  
Test Results ◽  
Chain Reaction ◽  
Viral Loads ◽  
Flow Test ◽  
Polymerase Chain ◽  
Lateral Flow Test

Abstract Objective To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. Design Observational cohort study. Setting Community LFT pilot at covid-19 testing sites in Liverpool, UK. Participants 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. Interventions Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. Main outcome measures Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. Results Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >10 6 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>10 4 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<10 4 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. Conclusions The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

scholarly journals Duration of Infectious Virus Shedding in Patients With Severe Coronavirus Disease 2019 Who Required Mechanical Ventilation

2021 ◽  
Author(s):  
Toshihito Nomura ◽  
Hiroki Kitagawa ◽  
Keitaro Omori ◽  
Norifumi Shigemoto ◽  
Masaki Kakimoto ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Quantitative Polymerase Chain Reaction ◽  
University Hospital ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Virus Shedding ◽  
Viral Culture ◽  
Respiratory Management

Abstract Approximately 5% of patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 develop severe COVID-19. Severe COVID-19 requires respiratory management with mechanical ventilation and an extended period of treatment. Prolonged infectious virus shedding is a concern in severe COVID-19 cases, but few reports have examined the duration of infectious virus shedding. Therefore, we investigated the duration of infectious virus shedding in patients transferred to Hiroshima University Hospital with severe COVID-19 requiring mechanical ventilation. Nasopharyngeal swab specimens were collected and analyzed using both viral culture and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) tests between December 2020 and February 2021. Of the 23 patients tested, the proportions of those with positive test results at first specimen collection on RT-qPCR and viral culture tests were 95·7% and 30·4%, respectively. All six patients with positive viral culture test results who were followed-up tested negative 24 days after symptom onset but remained positive on RT-qPCR. The longest negative conversion time was observed in a dialysis patient on immunosuppressive drugs. This study indicated that patients with severe COVID-19 remain culture positive for ≥ 10 days after symptom onset. Additionally, immunosuppressed patients with severe COVID-19 could consider isolation for ≥ 20 days.

scholarly journals Diurnal variation in SARS-CoV-2 PCR test results: Test accuracy may vary by time of day

2021 ◽  
Author(s):  
Candace D. McNaughton ◽  
Nicholas M. Adams ◽  
Carl Hirschie Johnson ◽  
Michael J. Ward ◽  
Thomas A. Lasko
Keyword(s):  
Public Health ◽  
Diurnal Variation ◽  
False Negative ◽  
Time Of Day ◽  
Test Accuracy ◽  
Test Results ◽  
Clinical Tests ◽  
Viral Shedding ◽  
Asymptomatic Patients ◽  
Polymerase Chain

AbstractFalse negative tests for SARS-CoV-2 are common and have important public health and medical implications. We tested the hypothesis that the proportion of positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests varied by time of day, suggesting variation in viral shedding by time of day. Among 30,000 clinical tests performed among symptomatic and asymptomatic patients in the Vanderbilt Affiliated Healthcare Network from March-June 2020, we found evidence for diurnal variation in the proportion of positive SARS-CoV-2 tests, with a peak around 2pm in the afternoon and 2-fold variation over the day. Variation was most pronounced in outpatient and inpatient testing locations. These findings have important implications for public health testing and vaccination strategies.

scholarly journals Antigen-based testing but not real-time PCR correlates with SARS-CoV-2 virus culture

2020 ◽  
Author(s):  
Andrew Pekosz ◽  
Charles K. Cooper ◽  
Valentin Parvu ◽  
Maggie Li ◽  
Jeffrey C. Andrews ◽  
...  
Keyword(s):  
Real Time ◽  
Infectious Virus ◽  
Virus Isolation ◽  
Low Cost ◽  
Test Results ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Effective Implementation ◽  
Virus Culture ◽  
Polymerase Chain

SUMMARYIndividuals can test positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) after no longer being infectious.1-8 Positive SARS-CoV-2 antigen-based testing exhibits a temporal pattern that corresponds with active, replicating virus and could therefore be a more accurate predictor of an individual’s potential to transmit SARS-CoV-2.2,3,9 Using the BD Veritor System for Rapid Detection of SARS-CoV-2 later flow antigen detection test, we demonstrate a higher concordance of antigen-positive test results with the presence of cultured, infectious virus when compared to RT-PCR. When compared to infectious virus isolation, the sensitivity of antigen-based testing is similar to RT-PCR. The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. Coupled with a rapid time-to-result, low cost, and scalability, antigen-based testing should facilitate effective implementation of testing and public health interventions that will better contain COVID-19.

scholarly journals Diurnal Variation in SARS-CoV-2 PCR Test Results: Test Accuracy May Vary by Time of Day

2021 ◽  
pp. 074873042110518
Author(s):  
Candace D. McNaughton ◽  
Nicholas M. Adams ◽  
Carl Hirschie Johnson ◽  
Michael J. Ward ◽  
Jonathan E. Schmitz ◽  
...  
Keyword(s):  
Public Health ◽  
Diurnal Variation ◽  
False Negative ◽  
Time Of Day ◽  
Test Accuracy ◽  
Test Results ◽  
Viral Shedding ◽  
Regional Health Care ◽  
Asymptomatic Patients ◽  
Polymerase Chain

False negative tests for SARS-CoV-2 are common and have important public health and medical implications. We tested the hypothesis of diurnal variation in viral shedding by assessing the proportion of positive versus negative SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests and cycle time (Ct) values among positive samples by the time of day. Among 86,342 clinical tests performed among symptomatic and asymptomatic patients in a regional health care network in the southeastern United States from March to August 2020, we found evidence for diurnal variation in the proportion of positive SARS-CoV-2 tests, with a peak around 1400 h and 1.7-fold variation over the day after adjustment for age, sex, race, testing location, month, and day of week and lower Ct values during the day for positive samples. These findings have important implications for public health testing and vaccination strategies.

scholarly journals Viral Shedding among Re-Positive Severe Acute Respiratory Syndrome Coronavirus-2 Positive Individuals in Republic of Korea

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2089
Author(s):  
Jeong-Min Kim ◽  
Boyeong Ryu ◽  
Young June Choe ◽  
Hye-Jun Jo ◽  
Hyeokjin Lee ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Index Patient ◽  
Test Results ◽  
Serological Tests ◽  
Past Infection ◽  
Viral Shedding ◽  
Viral Culture ◽  
Polymerase Chain ◽  
Pcr Test

This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close contacts. We attempted virus isolation in individuals with re-positive SARS-CoV-2 PCR test results using cell culture and confirmed the presence of neutralizing antibodies using serological tests. Viral culture was negative in all 108 individuals with re-positive SARS-CoV-2 PCR test results in whom viral culture was performed. Three new cases of SARS-CoV-2 infection were identified among household contacts using PCR. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Thus, there was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with re-positive SARS-CoV-2 PCR test results.

scholarly journals Application of a Serial Antigen Based Testing Strategy for SARS-CoV-2 and Student Adherence in a University Setting, Wisconsin — October–November 2020

2021 ◽  
Author(s):  
John Paul Bigouette ◽  
Laura Ford ◽  
Ian Pray ◽  
Kimberly Langolf ◽  
Juliana Kahrs ◽  
...  
Keyword(s):  
Male Students ◽  
Test Results ◽  
Antigen Test ◽  
Testing Strategy ◽  
Rt Pcr ◽  
Testing Strategies ◽  
Serial Testing ◽  
Polymerase Chain ◽  
Antigen Tests ◽  
University Setting

Abstract Background Serial SARS-CoV-2 testing has been implemented at institutions of higher education (IHEs) and other settings. Testing strategies can include algorithms specifying confirmatory reverse transcription polymerase chain reaction (RT-PCR) testing after an antigen test. It is unknown how testing strategies perform detecting SARS-CoV-2, including individual adherence to serial testing requirements. Methods Student serial testing adherence was defined as completing ≥80% of weekly tests from October 5–November 14, 2020 and evaluated using logistic regression. Medical records were reviewed for all positive antigen test encounters and 10% of daily negative antigen test encounters during October 19–November 30, 2020. Results were used to estimate the proportion of individuals requiring only antigen tests, requiring and completing RT-PCR testing, and associated costs of tests. Results Two-thirds (66.5%; 1,166/1,754) of eligible on-campus students adhered to weekly testing; female students were more adherent (adjusted odds ratio [aOR]:2.07, 95% CI:1.66–2.59) than male students. Of all antigen test encounters, 11.5% (1,409/12,305) reported &gt;1 COVID-19 symptoms. Of non-COVID-19 exposed antigen test encounters, 88% (10,386/11,769) did not require confirmatory RT-PCR testing. Only 28% (390/1,387) of testing encounters had an associated recommended confirmatory RT-PCR test performed. We estimated the testing strategy captured 61% (235/389) of predicted RT-PCR positive specimens. Conclusions At this IHE, most students voluntarily adhered to serial testing. The majority of antigen test results did not require confirmatory RT-PCR testing, but when required, most students did not obtain it. Including strategies to increase the proportion of individuals obtaining indicated confirmatory testing might improve the testing program’s performance.

scholarly journals Factors that Influence the Reported Sensitivity of Rapid Antigen Testing for SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentin Parvu ◽  
Devin S. Gary ◽  
Joseph Mann ◽  
Yu-Chih Lin ◽  
Dorsey Mills ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Upper Respiratory Tract ◽  
Antigen Test ◽  
Test Sensitivity ◽  
Viral Culture ◽  
Polymerase Chain ◽  
Asymptomatic Individuals ◽  
Design Factors ◽  
Antigen Testing

Tests that detect the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen in clinical specimens from the upper respiratory tract can provide a rapid means of coronavirus disease 2019 (COVID-19) diagnosis and help identify individuals who may be infectious and should isolate to prevent SARS-CoV-2 transmission. This systematic review assesses the diagnostic accuracy of SARS-CoV-2 antigen detection in COVID-19 symptomatic and asymptomatic individuals compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) and summarizes antigen test sensitivity using meta-regression. In total, 83 studies were included that compared SARS-CoV-2 rapid antigen-based lateral flow testing (RALFT) to RT-qPCR for SARS-CoV-2. Generally, the quality of the evaluated studies was inconsistent; nevertheless, the overall sensitivity for RALFT was determined to be 75.0% (95% confidence interval: 71.0–78.0). Additionally, RALFT sensitivity was found to be higher for symptomatic vs. asymptomatic individuals and was higher for a symptomatic population within 7 days from symptom onset compared to a population with extended days of symptoms. Viral load was found to be the most important factor for determining SARS-CoV-2 antigen test sensitivity. Other design factors, such as specimen storage and anatomical collection type, also affect the performance of RALFT. RALFT and RT-qPCR testing both achieve high sensitivity when compared to SARS-CoV-2 viral culture.

scholarly journals SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing

2021 ◽  
Author(s):  
Gage K. Moreno ◽  
Katarina M. Braun ◽  
Ian W. Pray ◽  
Hannah E. Segaloff ◽  
Ailam Lim ◽  
...  
Keyword(s):  
Intercollegiate Athletics ◽  
High Frequency ◽  
Index Patient ◽  
Mitigation Strategies ◽  
Athletic Programs ◽  
Test Results ◽  
Antigen Test ◽  
Rt Pcr ◽  
Polymerase Chain ◽  
Antigen Testing

AbstractBackgroundHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing.MethodsDuring the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks.ResultsIn Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition.ConclusionsThese findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings.SummaryHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.

scholarly journals A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prediction Model From Standard Laboratory Tests

2020 ◽  
Author(s):  
Vafa Bayat ◽  
Steven Phelps ◽  
Russell Ryono ◽  
Chong Lee ◽  
Hemal Parekh ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Laboratory Tests ◽  
Independent Set ◽  
Molecular Testing ◽  
Test Results ◽  
Clinical Sensitivity ◽  
Complementary Method ◽  
Machine Learning Model ◽  
Polymerase Chain ◽  
Antigen Testing

Abstract Background With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Methods We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. Results In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). Conclusions Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.

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