Detection of SARS-CoV-2 in the community by nucleic acid amplification testing of saliva

AbstractEfficient wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) swabs, which requires the intervention of trained personnel. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here we describe the set-up of a laboratory, in an academic context, for the high-throughput screening of SARS-CoV-2 in the saliva from the community. A novel saliva collection device was designed to favour the safe and correct acquisition of the sample as well as the processivity of the downstream molecular analysis. To test the performance of the system,1025 paired saliva and nasopharyngeal samples were collected from individuals recruited at a public drive through testing facility and analysed in parallel. An overall moderate concordance (68%) between the two tests was found, with evidence that neither test can diagnose the infection in 100% of the cases. While the two tests performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent individuals. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study, therefore, indicates that saliva testing can be a reliable tool for wide-scale COVID-19 screening in the community.

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Face Masks Against COVID-19: An Evidence Review

10.20944/preprints202004.0203.v2 ◽

2020 ◽

Cited By ~ 18

Author(s):

Jeremy Howard ◽

Austin Huang ◽

Zhiyuan Li ◽

Zeynep Tufekci ◽

Vladimir Zdimal ◽

...

Keyword(s):

Relevant Literature ◽

Population Level ◽

Transmission Probability ◽

Analytical Framework ◽

Disease Spread ◽

Contact Tracing ◽

Source Control ◽

Individual Outcomes ◽

Route Of Transmission ◽

Asymptomatic Individuals

The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. Here,we develop an analytical framework to examine an overlooked aspect of mask usage: masks as source-control targeting egress from the wearer with benefits at the population-level, rather than as PPE used for ingress control for health-care workers with focus on individual outcomes. We consider and synthesize the relevant literature to inform multiple areas: 1) transmission characteristics of COVID-19, 2) filtering characteristics and efficacy of masks, 3) estimated population impacts of widespread community mask use, and 4) sociological considerations for policies concerning mask-wearing. A primary route of transmission of COVID-19 is likely via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control for now, in conjunction with existing hygiene, distancing, and contact tracing strategies. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

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An evidence review of face masks against COVID-19

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2014564118 ◽

2021 ◽

Vol 118 (4) ◽

pp. e2014564118 ◽

Cited By ~ 11

Author(s):

Jeremy Howard ◽

Austin Huang ◽

Zhiyuan Li ◽

Zeynep Tufekci ◽

Vladimir Zdimal ◽

...

Keyword(s):

Relevant Literature ◽

Population Level ◽

Transmission Probability ◽

Analytical Framework ◽

Disease Spread ◽

Contact Tracing ◽

Source Control ◽

Individual Outcomes ◽

Route Of Transmission ◽

Asymptomatic Individuals

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people (“source control”) with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

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Relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: a rapid scoping review

BMJ Open ◽

10.1136/bmjopen-2020-042354 ◽

2021 ◽

Vol 11 (5) ◽

pp. e042354

Author(s):

David McEvoy ◽

Conor McAloon ◽

Aine Collins ◽

Kevin Hunt ◽

Francis Butler ◽

...

Keyword(s):

Scoping Review ◽

Quantitative Measure ◽

Contact Tracing ◽

Cochrane Library ◽

International Studies ◽

Screening Process ◽

Modelling Studies ◽

Asymptomatic Individuals ◽

Definition Of ◽

The Cochrane Library

ObjectivesThe aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature.DesignRapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library.SettingInternational studies on the infectiousness of individuals infected with SARS-CoV-2.ParticipantsStudies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics.Primary outcome measuresPCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals.ResultsThere are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1.ConclusionsThere is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.

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183. chlamydia Trachomatis Seroprevalence with a pgp3 Serologic Assay and Association with Pelvic Inflammatory Disease Among Women, United States, 2013–2016

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.493 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S220-S220

Author(s):

Gloria E Anyalechi ◽

Damien Danavall ◽

Brian H Raphael ◽

Katherine E Bowden ◽

Jaeyoung Hong ◽

...

Keyword(s):

Black Women ◽

Chlamydia Trachomatis ◽

Pelvic Inflammatory Disease ◽

Inflammatory Disease ◽

White Women ◽

Transmitted Disease ◽

Population Level ◽

Reproductive Age ◽

Nucleic Acid Amplification ◽

Sexually Transmitted

Abstract Background Chlamydia trachomatis (CT) causes pelvic inflammatory disease (PID) and other sequelae; however, these associations are not fully characterized. CT serologic assays including Pgp3 ELISA may detect prior CT infection and may better elucidate these associations. We used a serologic Pgp3 multiplex bead array assay (Pgp3MBA) to measure CT seroprevalence in reproductive-age US women and assess the association with PID. Methods We performed CT Pgp3MBA on sera collected from women 18–39 years old during the 2013–2016 cycles of the National Health and Nutrition Examination Survey (NHANES) who had available urine CT nucleic acid amplification test results. Weighted Pgp3MBA CT seroprevalence and 95% confidence intervals (95% CI) were calculated. We also determined weighted prevalence ratios (PRs) and 95% CIs of self-reported lifetime PID among women with and without detectable Pgp3MBA and other characteristics to estimate these US national statistics. Results Among 2,339 women, 1,725 (73.7%) had available sera. Of these women, 1,425 (or 93.4% of those with data) were sexually experienced and had a CT seroprevalence of 35.9% (95% CI 33.4–38.4). When weighted for US women, CT seroprevalence was 30.5% (95% CI 26.6–34.4%), ranging from 16.9% (95% CI 11.0–22.8%) among non-Hispanic Asian women to 70.2% (95% CI 62.4–78.0%) among non-Hispanic black women. PID was reported by 4.2% (95% CI 3.1–5.2) of 1,413 sexually-experienced women with PID data or an estimated 3.8% (95% CI 2.6–5.0) of US women. Among US women, estimated PID varied by Pgp3MBA status; 7.3% (95% CI 4.3–10.2) of Pgp3MBA-positive women were estimated to report PID versus 2.3% (95% CI 1.3–3.4) of Pgp3MBA-negative women (PR 3.1; 95% CI 1.7–5.9). PID prevalence did not vary by age, nor self-reported recent sexually transmitted disease among US women, but was higher among non-Hispanic black women compared to non-Hispanic white women (PR 2.2; 95% CI 1.4–3.5). Conclusion Nearly one-third of US women have had CT by Pgp3MBA, with differences by race/ethnicity. Women with prior CT had three times the reported PID prevalence of women without CT. Further serologic research may refine the population-level impact of CT prevention activities, such as recommended annual CT screening, on PID incidence, particularly among non-Hispanic black women. Disclosures All Authors: No reported disclosures

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Diagnostic tests for detecting Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and pharyngeal specimens

Journal of Clinical Microbiology ◽

10.1128/jcm.00211-21 ◽

2021 ◽

Author(s):

Paul C. Adamson ◽

Jeffrey D. Klausner

Keyword(s):

Chlamydia Trachomatis ◽

Neisseria Gonorrhoeae ◽

Bacterial Infections ◽

Point Of Care ◽

High Sensitivity ◽

Population Level ◽

The United States ◽

Nucleic Acid Amplification ◽

Point Of Care Test ◽

Control And Prevention

Chlamydia trachomatis and Neisseria gonorrhoeae are two of the most often reported bacterial infections in the United States. The rectum and oropharynx are important anatomic sites of infection and can contribute to ongoing transmission. Nucleic acid amplification tests (NAATs) are the mainstays for the detection of C. trachomatis and N. gonorrhoeae infections owing to their high sensitivity and specificity. Several NAATs have been evaluated for testing in rectal and pharyngeal infections. A few assays recently received clearance by the Food and Drug Administration, including one point-of-care test. Those assays can be used for testing in symptomatic individuals, as well as for asymptomatic screening in certain patient populations. Routine screening for C. trachomatis in pharyngeal specimens is not recommended by the Centers for Disease Control and Prevention, though is often performed due to the use of multiplex assays. While expanding the types of settings for screening and using self-collected rectal and pharyngeal specimens can help to increase access and uptake of testing, additional research is needed to determine the potential benefits and costs associated with increased screening for rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections on a population level.

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A New Approach to Drug Discovery

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057111433459 ◽

2012 ◽

Vol 17 (4) ◽

pp. 542-549 ◽

Cited By ~ 57

Author(s):

Maria Cândida Monteiro ◽

Mercedes de la Cruz ◽

Juan Cantizani ◽

Catalina Moreno ◽

José R. Tormo ◽

...

Keyword(s):

Drug Discovery ◽

Antifungal Activity ◽

High Throughput Screening ◽

Low Cost ◽

Pharmacological Action ◽

Natural Extracts ◽

Microbial Extracts ◽

Set Up ◽

Microtiter Assay ◽

Selection Of

Natural products are an inexhaustible source for drug discovery. However, the validation and selection of primary screening assays are vital to guarantee a selection of extracts or molecules with relevant pharmacological action and worthy of following up. The assay must be rapid, simple, easy to implement, and produce quick results and preferably at a low cost. In this work, we developed and validated a colorimetric microtiter assay using the resazurin viability dye. The parameters of the resazurin method for high-throughput screening (HTS) using natural extracts against Aspergillus fumigatus were optimized and set up. The extracts plus RPMI-1640 modified medium containing the spores and 0.002% resazurin were added per well. The fluorescence was read after 24 to 30 h of incubation. The resazurin proved to be as suitable as Alamar Blue for determining the minimal inhibitory concentration of different antifungals against A. fumigatus and effective to analyze fungicidal and fungistatic compounds. An HTS of 12 000 microbial extracts was carried out against two A. fumigatus strains, and 2.7% of the extracts displayed antifungal activity. Our group has been the first to use this methodology for screening a collection of natural extracts to identify compounds with antifungal activity against the medically important human pathogen A. fumigatus.

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Contact Tracing Applications Against COVID-19: A Systematic Review (Preprint)

10.2196/preprints.30262 ◽

2021 ◽

Author(s):

Ahmad Nabeel ◽

Salman AlSabah ◽

Eliana Al Haddad ◽

Hutan Ashrafian

Keyword(s):

Systematic Review ◽

Critical Mass ◽

Population Level ◽

Ease Of Use ◽

Contact Tracing ◽

The Novel ◽

Scientific Databases ◽

Manual Methods ◽

Novel Coronavirus ◽

Transmission Of Disease

BACKGROUND The novel coronavirus 2019 (COVID-19) pandemic has triggered public anxiety around the world. So far, the evidence suggests that prevention on a public scale is the most effective health measure for thwarting the progress of COVID-19. Another critical aspect of preventing COVID-19 is contact tracing. OBJECTIVE We aimed to investigate the effectiveness of contact tracing applications currently available in the context of the COVID-19 pandemic. METHODS We undertook a systematic review and narrative synthesis of all literature relating to contact tracing applications in the context of COVID-19. We searched 3 major scientific databases. Only articles that were published in English and were available as full-text articles were selected for review. Data were extracted and narrative syntheses conducted. RESULTS Five studies relating to COVID-19 were included in the review. Our results suggest that digitalized contact tracing methods can be beneficial for impeding the progress of COVID-19. Three key themes were generated from this systematic review. First, the critical mass of application adoption must be attained at the population level before the sensitivity and positive predictive value of the solution can be increased. Second, usability factors such as access, ease of use and the elimination of barriers are essential in driving this uptake. Third, privacy must be ensured where possible as it is the single most significant barrier against achieving critical mass. CONCLUSIONS The COVID-19 pandemic has claimed more than 2 million lives globally, with over 100 million confirmed cases. Contact tracing can rapidly identify potentially infected individuals before the emergence of severe or critical symptoms, and it can also prevent the subsequent transmission of disease from secondary cases when implemented efficiently. Contact tracing methods have proved to be beneficial for impeding the progress of COVID-19 as compared to older, more labor intensive manual methods.

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Leveraging the Cloud for Large-Scale Software Testing – A Case Study

Software Testing in the Cloud - Advances in Computer and Electrical Engineering ◽

10.4018/978-1-4666-2536-5.ch012 ◽

2012 ◽

pp. 252-279 ◽

Cited By ~ 1

Author(s):

Anjan Pakhira ◽

Peter Andras

Keyword(s):

Large Scale ◽

Analysis Data ◽

System Level ◽

Small Scale ◽

Test Cases ◽

Software Life Cycle ◽

Technical Issues ◽

Wide Scale ◽

Set Up

Testing is a critical phase in the software life-cycle. While small-scale component-wise testing is done routinely as part of development and maintenance of large-scale software, the system level testing of the whole software is much more problematic due to low level of coverage of potential usage scenarios by test cases and high costs associated with wide-scale testing of large software. Here, the authors investigate the use of cloud computing to facilitate the testing of large-scale software. They discuss the aspects of cloud-based testing and provide an example application of this. They describe the testing of the functional importance of methods of classes in the Google Chrome software. The methods that we test are predicted to be functionally important with respect to a functionality of the software. The authors use network analysis applied to dynamic analysis data generated by the software to make these predictions. They check the validity of these predictions by mutation testing of a large number of mutated variants of the Google Chrome. The chapter provides details of how to set up the testing process on the cloud and discusses relevant technical issues.

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Leveraging the Cloud for Large-Scale Software Testing

Cloud Technology ◽

10.4018/978-1-4666-6539-2.ch055 ◽

2015 ◽

pp. 1175-1203

Author(s):

Anjan Pakhira ◽

Peter Andras

Keyword(s):

Cloud Computing ◽

Large Scale ◽

Analysis Data ◽

System Level ◽

Small Scale ◽

Test Cases ◽

Software Life Cycle ◽

Technical Issues ◽

Wide Scale ◽

Set Up

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Mass screening of asymptomatic persons for SARS-CoV-2 using saliva

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1388 ◽

2020 ◽

Cited By ~ 16

Author(s):

Isao Yokota ◽

Peter Y Shane ◽

Kazufumi Okada ◽

Yoko Unoki ◽

Yichi Yang ◽

...

Keyword(s):

Nucleic Acid ◽

Mass Screening ◽

Disease Outbreaks ◽

High Sensitivity ◽

Nucleic Acid Amplification ◽

Contact Tracing ◽

Global Pandemic ◽

Screening Study ◽

Highly Correlated ◽

Few Data

Abstract Background COVID-19 has rapidly evolved to become a global pandemic due largely to the transmission of its causative virus through asymptomatic carriers. Detection of SARS-CoV-2 in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of PCR testing. Additionally, although self-collected saliva has significant logistical advantages in mass screening, its utility as an alternative specimen in asymptomatic persons is yet to be determined. Methods We conducted a mass-screening study to compare the utility of nucleic acid amplification, such as reverse transcriptase polymerase chain reaction (RT-PCR) testing, using nasopharyngeal swabs (NPS) and saliva samples from each individual in two cohorts of asymptomatic persons: the contact tracing cohort and the airport quarantine cohort. Results In this mass-screening study including 1,924 individuals, the sensitivity of nucleic acid amplification testing with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%) and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%. The true concordance probability between the nasopharyngeal and saliva tests was estimated at 0.998 (90%CI:0.996-0.999) on the estimated airport prevalence at 0.3%. In positive individuals, viral load was highly correlated between NPS and saliva. Conclusion Both nasopharyngeal and saliva specimens had high sensitivity and specificity. Self-collected saliva is a valuable specimen to detect SARS-CoV-2 in mass screening of asymptomatic persons.

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