scholarly journals Analysis and Applications of Adaptive Group Testing Methods for COVID-19

2020 ◽  
Author(s):  
Cassidy Mentus ◽  
Martin Romeo ◽  
Christian DiPaola
Keyword(s):  
Nursing Homes ◽  
Group Testing ◽  
Entire Group ◽  
Lower Prevalence ◽  
Rt Pcr ◽  
Testing Methods ◽  
Clinical Screening ◽  
Cruise Ships ◽  
Testing Strategies ◽  
Binary Splitting

AbstractTesting strategies for Covid-19 to maximize number of people tested are urgently needed. Recently, it has been demonstrated that RT-PCR has the sensitivity to detect one positive case in a mixed sample of 32 cases [12], In this paper we propose adaptive group testing strategies based on generalized binary splitting (CBS) [5], where we restrict the group test to the largest group that can be used. The method starts by choosing a group from the population to be tested, performing a test on the combined sample from the entire group, and progressively splitting the group further into subgroups. Compared to individual testing at 4% prevalence, we save 74%; at 1% we save 91%; and at .1% we save 98% of tests. We analyze the number of times each sample is used and show that the method is still efficient if we resort to testing a case individually if the sample is running low.In addition we recommend clinical screening to filter out individuals with symptoms and show this leaves us with a population with lower prevalence. Our approach is particularly applicable to vulnerable confined populations such as nursing homes, prisons, military ships and cruise ships.

scholarly journals Modeling Effectiveness of Testing Strategies to Prevent Coronavirus Disease 2019 (COVID-19) in Nursing Homes—United States, 2020

2021 ◽  
Author(s):  
Isaac See ◽  
Prabasaj Paul ◽  
Rachel B Slayton ◽  
Molly K Steele ◽  
Matthew J Stuckey ◽  
...  
Keyword(s):  
Nursing Homes ◽  
Infection Control ◽  
Relative Sensitivity ◽  
Turnaround Time ◽  
Potential Effect ◽  
Infection Control Practice ◽  
Healthcare Personnel ◽  
Test Frequency ◽  
Testing Strategies ◽  
Serial Testing

Abstract Background Identifying asymptomatic individuals early through serial testing is recommended to control coronavirus disease 2019 (COVID-19) in nursing homes, both in response to an outbreak (“outbreak testing” of residents and healthcare personnel) and in facilities without outbreaks (“nonoutbreak testing” of healthcare personnel). The effectiveness of outbreak testing and isolation with or without nonoutbreak testing was evaluated. Methods Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every 3 days, or daily) and isolation of asymptomatic persons compared with symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (ie, “effectiveness”) through either outbreak testing alone or outbreak plus nonoutbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. Results Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding nonoutbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of nonoutbreak testing were mostly negated if accompanied by decreases in infection control practice. Conclusions When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.

scholarly journals Early detection of superspreaders by mass group pool testing can mitigate COVID-19 pandemic

2020 ◽  
Author(s):  
Maxim B Gongalsky
Keyword(s):  
New York ◽  
Early Detection ◽  
Group Testing ◽  
Scale Model ◽  
Rt Pcr ◽  
Infected People ◽  
Group Matrix ◽  
New Strategy ◽  
Mass Group ◽  
Log Normal

Background Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow. Though applied to COVID-19 pandemic the results are universal and can be used for other infectious heterogenous epidemics. Funding No funding

scholarly journals False Negative Mitigation in Group Testing for COVID-19 Screening

2021 ◽  
Vol 8 ◽  
Author(s):  
Amir Reza Alizad Rahvar ◽  
Safar Vafadar ◽  
Mehdi Totonchi ◽  
Mehdi Sadeghi
Keyword(s):  
Viral Load ◽  
False Negative ◽  
Group Testing ◽  
False Negative Rate ◽  
Screening Strategy ◽  
Web Interface ◽  
Rt Pcr ◽  
Promising Candidate ◽  
Testing Method ◽  
High False Negative Rate

After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.

scholarly journals Rapid Point-Of-Care Serology and Clinical History Assessment Increase Protection Provided by RT-PCR Screening: A Pilot Study Involving Three Nursing Homes in Brescia, a Hotspot of Lombardy

2021 ◽  
Vol 9 ◽  
Author(s):  
Antonella Savio ◽  
Stefano Calza ◽  
Gianbattista Guerrini ◽  
Valentina Romano ◽  
Eleonora Marchina
Keyword(s):  
Nursing Homes ◽  
Close Contact ◽  
Fisher Exact Test ◽  
Rt Pcr ◽  
Positive Serology ◽  
Serological Screening ◽  
Pcr Screening ◽  
Exact Test ◽  
Viral Spread

Background: COVID-19 outbursts have been registered worldwide within care homes with asymptomatic transmission combined with shortage/inaccuracy of diagnostic tests undermining the efforts at containment of the disease. Nursing facilities in Lombardy (Italy) were left with no, or limited, access to testing for 8 weeks after the outbreak of COVID-19.Methods: This study includes 246 residents and 286 workers of three different nursing homes in Brescia-Lombardy. Clinical questionnaires and rapid serology tests were devised to integrate the data of the first available RT-PCR screening. Follow-up serology after 60-days was performed on 67 of 86 workers with positive serology or clinically suspicious.Findings: Thirty-seven residents and 18 workers had previous positive RT-PCR. Thorough screening disclosed two additional RT-PCR-positive workers. Serology screening revealed antibodies in 59 residents and 48 workers, including 32/37 residents and all workers previously positive at RT-PCR. Follow up serology disclosed antibodies in two additional workers with recent symptoms at the time of screening. The professionals in close contact with residents had more infections (47/226–20.79% vs. 1/60–1.66%; p = 0.00013 Fisher exact-test). A suspicious clinical score was present in 44/64 residents and in 41/50 workers who tested positive with either method with totally asymptomatic disease more frequent among residents 28.1 vs. 10.0% (p = 0.019 Fisher exact-test).Interpretation: Based on the available RT-PCR ± results at the time of symptoms/contacts, our integrated clinical and serological screening demonstrated sensitivity 89% and specificity 87%. This multimodal assessment proved extremely useful in understanding the viral spread in nursing homes, in defining its stage and in implementing protective measures. Rapid serology tests demonstrated efficient and particularly suited for older people less able to move/cooperate.

RESTRICTED RANDOM TESTING: ADAPTIVE RANDOM TESTING BY EXCLUSION

2006 ◽  
Vol 16 (04) ◽  
pp. 553-584 ◽  
Author(s):  
KWOK PING CHAN ◽  
TSONG YUEH CHEN ◽  
DAVE TOWEY
Keyword(s):  
Simple Technique ◽  
Test Case ◽  
Test Cases ◽  
Random Testing ◽  
Testing Methods ◽  
Failure Patterns ◽  
Subsequent Test ◽  
Testing Strategies ◽  
Adaptive Random Testing ◽  
Input Domain

Restricted Random Testing (RRT) is a new method of testing software that improves upon traditional Random Testing (RT) techniques. Research has indicated that failure patterns (portions of an input domain which, when executed, cause the program to fail or reveal an error) can influence the effectiveness of testing strategies. For certain types of failure patterns, it has been found that a widespread and even distribution of test cases in the input domain can be significantly more effective at detecting failure compared with ordinary RT. Testing methods based on RT, but which aim to achieve even and widespread distributions, have been called Adaptive Random Testing (ART) strategies. One implementation of ART is RRT. RRT uses exclusion zones around executed, but non-failure-causing, test cases to restrict the regions of the input domain from which subsequent test cases may be drawn. In this paper, we introduce the motivation behind RRT, explain the algorithm and detail some empirical analyses carried out to examine the effectiveness of the method. Two versions of RRT are presented: Ordinary RRT (ORRT) and Normalized RRT (NRRT). The two versions share the same fundamental algorithm, but differ in their treatment of non-homogeneous input domains. Investigations into the use of alternative exclusion shapes are outlined, and a simple technique for reducing the computational overheads of RRT, prompted by the alternative exclusion shape investigations, is also explained. The performance of RRT is compared with RT and another ART method based on maximized minimum test case separation (DART), showing excellent improvement over RT and a very favorable comparison with DART.

scholarly journals Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources

2020 ◽  
Vol 153 (6) ◽  
pp. 715-718 ◽  
Author(s):  
Baha Abdalhamid ◽  
Christopher R Bilder ◽  
Emily L McCutchen ◽  
Steven H Hinrichs ◽  
Scott A Koepsell ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Group Testing ◽  
Viral Rna ◽  
Optimal Parameters ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Web Based ◽  
Negative Patient ◽  
Cycle Threshold ◽  
Unselected Group

Abstract Objectives To establish the optimal parameters for group testing of pooled specimens for the detection of SARS-CoV-2. Methods The most efficient pool size was determined to be five specimens using a web-based application. From this analysis, 25 experimental pools were created using 50 µL from one SARS-CoV-2 positive nasopharyngeal specimen mixed with 4 negative patient specimens (50 µL each) for a total volume of 250 µL. Viral RNA was subsequently extracted from each pool and tested using the CDC SARS-CoV-2 RT-PCR assay. Positive pools were consequently split into individual specimens and tested by extraction and PCR. This method was also tested on an unselected group of 60 nasopharyngeal specimens grouped into 12 pools. Results All 25 pools were positive with cycle threshold (Ct) values within 0 and 5.03 Ct of the original individual specimens. The analysis of 60 specimens determined that 2 pools were positive followed by identification of 2 individual specimens among the 60 tested. This testing was accomplished while using 22 extractions/PCR tests, a savings of 38 reactions. Conclusions When the incidence rate of SARS-CoV-2 infection is 10% or less, group testing will result in the saving of reagents and personnel time with an overall increase in testing capability of at least 69%.

Molecular Response of CML Patients to INFα Based Treatment or to STI Based Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4872-4872
Author(s):  
Debora Luzi ◽  
Rosanna Capozzi ◽  
Annamaria Rauco ◽  
Roberta Pace ◽  
Emilio Donti ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Response Duration ◽  
Cytogenetic Response ◽  
The Other ◽  
Entire Group ◽  
Molecular Response ◽  
Rt Pcr ◽  
Molecular Remission ◽  
First Time

Abstract Introduction: Continous improving results have been obtained during last two decades in the control of Ph’positive chronic myeloid leukemia(CML). However the final goal of molecular remission remains difficult to obtain even in the STI age. Aims : Evaluation of the rate of molecular response to IFNα,IFNα based treatment,to STI or to STI-INFα combination was analized in 100 consecutive Ph+ CML patients observed in a single Institution over a period of 20 years. Patients, Methods and Results All patients were treated at the time of diagnosis (87) or late (13) during the course of their disease. Distribution according to treatment was: INFα,63pts (late or early:13,50);INFα-ARA-C combination,20pts;STI,14 pts;STI-INFα association, 3 pts. Two pts, both initially assigned to INFα-ARA-C combination, were crossed-over to STI, one because relapsing off-therapy after a long lasting continous (25 mths) molecular remission and the other in cytogenetic response because intolerant to the initial treatment. In addition, other 3 pts patients, with persistent complete cytogenetic, but not molecular remission to INFα or INFα-ARA-C combination were subsequentially trated with the STI-IFNα association. At present,99/100 pts are evaluable. The median times of follow-up for the entire group and form the different treatment subgroups are: late IFNα 154 months(42–263); early IFNα, 71 months(1–197); IFNα-ARA-C, 61 months(5–203); STI- IFNα,78 mths(11–47), STI,31 mths(3–41). A complete kariotypic remission(CKR) was observed in 15/63 IFNα treated pts, in 10/20 IFNα-ARA-C pts group, in 10/13 cases of STI group and in 3 /3 pts who received STI-IFNα. A molecular response(RT-nested PCR, JQ Guo, Leukemia: 2002,15,2447–53) was observed in 4/15,2/10,5/10 and in 2/3 CKR pts initially trated with the different modalities listed above. Response was confirmed from 2 to 7 consecutive or not consecutive times in the 2/4 cases responsive to INFα, in the 2 cases responsive to INFα-ARA-C combination,4/5cases responsive to STI and in 2/3 cases responsive to STI-IFNα association. The 2nd and the 3rd molecular remission to STI were obtained in the patient molecularly and cytogenetically relapsed off-therapy and, for the first time from the diagnosis, in the other patient in CKR to IFNα-ARA-C combination and crossed to STI treatment. Furthermore, all 3 cases, in CKR, but not molecular response to other treatments at the time of cross-over to STI-IFNα combination, achieved a persistent (in 2 to 3 tests over a period ranging from 6+ to 12+ mths) molecular remission. The first interval between the start of the treatment and the first molecular response varied from 12 to 52, from 3 to 22, from 11 to 24, from 5 to 11 mths in the groups initially treated with IFNα, IFNα-ARA-C, STI or STI-IFNα respectively. The 2 pts, crossed-over to STI alone, both, obtained a response after 29 mths of therapy. In addition in the 3 pts crossed-over to STI-IFNα therapy, the molecular response was obtained after 14,23 and 25 mths from the start of last treatment. Conclusion It is not possible to achieve any conclusion regarding the treatment effect on molecular response duration because of the different length of follow-up of various groups of patients. However in responsive patients to IFN alone or combined to ARA-C or STI, consecutive negative RT-PCR tests were observed more frequently than in patients receving STI alone.

scholarly journals Sequential battery of COVID-19 testing to maximize negative predictive value before surgeries

2020 ◽  
Vol 47 ◽  
Author(s):  
NEERAJ SINHA ◽  
GALIT BALAYLA
Keyword(s):  
Immune Response ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Chest Ct ◽  
Viral Dynamics ◽  
Rt Pcr ◽  
Testing Methods ◽  
Course Of Illness ◽  
Epidemiologic Survey ◽  
Novel Virus

ABSTRACT SARS-CoV-2 is a novel virus which has proven to be highly contagious. Specific viral dynamics and immune response to the virus are yet to be fully defined and determining the sensitivity and specificity of the available testing methods is still a work in progress. This study examines the published information on the testing methods, and finds that yield of COVID-19 tests changes with specimen types and with time through course of illness. We propose a sequential battery of testing consisting of an epidemiologic survey, RT-PCR tests, serologic tests and chest CT on surgical candidates which may increase the negative predictive value, and facilitate surgical procedures.

scholarly journals Assessment of Successful qRT-PCR of SARS-CoV-2 Assay in Pool Screening Using Isopropyl Alcohol Purification Step in RNA Extraction

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Mayank Gangwar ◽  
Alka Shukla ◽  
Virendra Kumar Patel ◽  
Pradyot Prakash ◽  
Gopal Nath
Keyword(s):  
Isopropyl Alcohol ◽  
Rna Extraction ◽  
Group Testing ◽  
Research Work ◽  
Rt Pcr ◽  
Purification Step ◽  
E Gene ◽  
Qrt Pcr ◽  
Pcr Targeting ◽  
Pooled Samples

The study is aimed at establishing the optimal parameters for RNA purification of pooled specimens, in SARS-CoV-2 assay. This research work evaluates the difference of extracted RNA purity of pooled samples with and without treatment with isopropyl alcohol and its effect on real-time RT-PCR. As per the protocol of the Indian Council of Medical Research (ICMR), 5 sample pools were analysed using qRT-PCR. A total of 100 pooled samples were selected for the study by mixing 50 μL of one COVID-19 positive nasopharyngeal/oropharyngeal (NP/OP) specimen and 50 μL each of 4 known negative specimens. Pool RNA was extracted using the column-based method, and 1 set of pooled extracted RNA was tested as such, while RNA of the second set was treated additionally with chilled isopropyl alcohol (modified protocol). Further, the purity of extracted RNA in both the groups was checked using Microvolume Spectrophotometers (Nanodrop) followed by RT-PCR targeting E-gene and RNaseP target. The results showed that the purity index of extracted RNA of untreated pooled specimens was inferior to isopropyl alcohol-treated templates, which was observed to be 85% sensitivity and 100% specificity. The average Cq (E gene) in the unpurified and purified pool RNA group was 34.66 and 31.48, respectively. The nanodrop data suggested that purified RNA concentration was significantly increased with an average value of 24.73 ± 1.49   ng / uL , which might be the reason for high sensitivity and specificity. Thus, this group testing of SARS-CoV-2 cases using pools of 5 individual samples would be the best alternative for saving molecular reagents, personnel time, and can increase the overall testing capacity. However, purity of RNA is one of the important determinants to procure unfailing results, thus, this additional purification step must be included in the protocol after RNA has been extracted using commercially available kit before performing qRT-PCR.

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