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Open accessJournal ArticleDOI: 10.1371/JOURNAL.PCBI.1008726

Group testing as a strategy for COVID-19 epidemiological monitoring and community surveillance.

04 Mar 2021-PLOS Computational Biology (Public Library of Science (PLoS))-Vol. 17, Iss: 3
Abstract: We propose an analysis and applications of sample pooling to the epidemiologic monitoring of COVID-19. We first introduce a model of the RT-qPCR process used to test for the presence of virus in a sample and construct a statistical model for the viral load in a typical infected individual inspired by large-scale clinical datasets. We present an application of group testing for the prevention of epidemic outbreak in closed connected communities. We then propose a method for the measure of the prevalence in a population taking into account the increased number of false negatives associated with the group testing method.

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Topics: Population (53%), Epidemiological Monitoring (53%)
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18 results found


Open accessJournal ArticleDOI: 10.1186/S12879-020-05750-9
Ya-Peng Cui1, Shunjiang Ni1, Shifei Shen1Institutions (1)
Abstract: Testing is one of the most effective means to manage the COVID-19 pandemic. However, there is an upper bound on daily testing volume because of limited healthcare staff and working hours, as well as different testing methods, such as random testing and contact-tracking testing. In this study, a network-based epidemic transmission model combined with a testing mechanism was proposed to study the role of testing in epidemic control. The aim of this study was to determine how testing affects the spread of epidemics and the daily testing volume needed to control infectious diseases. We simulated the epidemic spread process on complex networks and introduced testing preferences to describe different testing strategies. Different networks were generated to represent social contact between individuals. An extended susceptible-exposed-infected-recovered (SEIR) epidemic model was adopted to simulate the spread of epidemics in these networks. The model establishes a testing preference of between 0 and 1; the larger the testing preference, the higher the testing priority for people in close contact with confirmed cases. The numerical simulations revealed that the higher the priority for testing individuals in close contact with confirmed cases, the smaller the infection scale. In addition, the infection peak decreased with an increase in daily testing volume and increased as the testing start time was delayed. We also discovered that when testing and other measures were adopted, the daily testing volume required to keep the infection scale below 5% was reduced by more than 40% even if other measures only reduced individuals’ infection probability by 10%. The proposed model was validated using COVID-19 testing data. Although testing could effectively inhibit the spread of infectious diseases and epidemics, our results indicated that it requires a huge daily testing volume. Thus, it is highly recommended that testing be adopted in combination with measures such as wearing masks and social distancing to better manage infectious diseases. Our research contributes to understanding the role of testing in epidemic control and provides useful suggestions for the government and individuals in responding to epidemics.

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Topics: Random testing (53%), Epidemic model (52%)

5 Citations


Open accessJournal ArticleDOI: 10.1016/J.EPIDEM.2020.100413
Dor Ben-Amotz1Institutions (1)
27 Oct 2020-Epidemics
Abstract: It has long been known that pooling samples may be used to reduce the total number of tests required in order to identify each infected individual in a population. Pooling is most advantageous in populations with low infection (positivity) rates, but is expected to remain better than non-pooled testing in populations with infection rates up to 30%. For populations with infection rates lower than 10%, additional testing efficiency may be realized by performing a second round of pooling to test all the samples in the positive first-round pools. The present predictions are validated by recent COVID-19 (SARS-CoV-2) pooled testing and detection sensitivity measurements performed using non-optimal pool sizes, and quantify the additional improvement in testing efficiency that could have been obtained using optimal pooling. Although large pools are most advantageous for testing populations with very low infection rates, they are predicted to become highly non-optimal with increasing infection rate, while pool sizes smaller than 10 remain near-optimal over a broader range of infection rates.

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Topics: Pooling (53%), Population (51%)

2 Citations


Open accessJournal ArticleDOI: 10.1177/20499361211032039
14 Jul 2021-
Abstract: Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.

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Topics: Population (52%)

2 Citations


Open accessJournal ArticleDOI: 10.3390/DIAGNOSTICS11071166
Immacolata Polvere1, Elena Silvestri1, Lina Sabatino1, Antonia Giacco1  +12 moreInstitutions (1)
26 Jun 2021-
Abstract: Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, it has been clear that testing large groups of the population was the key to stem infection and prevent the effects of the coronavirus disease of 2019, mostly among sensitive patients. On the other hand, time and cost-sustainability of virus detection by molecular analysis such as reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) may be a major issue if testing is extended to large communities, mainly asymptomatic large communities. In this context, sample-pooling and test grouping could offer an effective solution. Here we report the screening on 1195 oral-nasopharyngeal swabs collected from students and staff of the Universita degli Studi del Sannio (University of Sannio, Benevento, Campania, Italy) and analyzed by an in-house developed multiplex RT-qPCR for SARS-CoV-2 detection through a simple monodimensional sample pooling strategy. Overall, 400 distinct pools were generated and, within 24 h after swab collection, five positive samples were identified. Out of them, four were confirmed by using a commercially available kit suitable for in vitro diagnostic use (IVD). High accuracy, sensitivity and specificity were also determined by comparing our results with a reference IVD assay for all deconvoluted samples. Overall, we conducted 463 analyses instead of 1195, reducing testing resources by more than 60% without lengthening diagnosis time and without significant losses in sensitivity, suggesting that our strategy was successful in recognizing positive cases in a community of asymptomatic individuals with minor requirements of reagents and time when compared to normal testing procedures.

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Topics: Population (51%)

1 Citations


Open accessJournal ArticleDOI: 10.4155/BIO-2021-0054
06 Aug 2021-Bioanalysis
Abstract: Robust surveillance testing is a key strategic plan to prevent COVID-19 outbreaks and slow the spread of the SARS-CoV-2 pandemic; however, limited resources, facilities and time often impair the implementation of a widespread surveillance effort. To mitigate these resource limitations, we employed a strategy of pooling samples, reducing reagent cost and processing time. Through utilizing academic faculty and labs, successful pooled surveillance testing was conducted throughout Fall 2020 semester to detect positive SARS-CoV-2 infections in a population of 4400 students. During the semester, over 25,000 individual COVID status evaluations were made by pooling eight individual samples into one quantitative reverse transcription polymerase chain reaction. This pooled surveillance strategy was highly effective at detecting infection and significantly reduced financial burden and cost by $3.6 million.

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Topics: Population (52%)

1 Citations


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77 results found


Open accessJournal Article
01 Jan 2014-MSOR connections
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.

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Topics: R Programming Language (78%)

229,202 Citations


Open accessJournal ArticleDOI: 10.2807/1560-7917.ES.2020.25.3.2000045
Victor M. Corman1, Olfert Landt, Marco Kaiser, Richard Molenkamp2  +20 moreInstitutions (5)
23 Jan 2020-Eurosurveillance
Abstract: Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

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Topics: European union (57%)

4,402 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2196-X
Roman Wölfel1, Victor M. Corman2, Wolfgang Guggemos, M Seilmaier  +15 moreInstitutions (4)
01 Apr 2020-Nature
Abstract: Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

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Topics: Virus receptor (62%), Coronavirus (60%), Viral shedding (59%) ... read more

4,325 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.2565
Yan Bai, Lingsheng Yao, Tao Wei, Fei Tian1  +3 moreInstitutions (2)
14 Apr 2020-JAMA
Abstract: This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.

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Topics: Asymptomatic carrier (57%)

3,104 Citations


Open accessJournal ArticleDOI: 10.1016/S1473-3099(20)30196-1
Abstract: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.

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2,287 Citations


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20208