Impact of Sampling Type, Frequency, and Scale of the Collection System on SARS-CoV-2 Quantification Fidelity
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ABSTRACT:
SUBMITTER: George A
PROVIDER: S-EPMC8791033 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The impact of repeated sample collection on COVID-19 test performance is unknown. The FDA and CDC currently recommend the primary collection of diagnostic samples to minimize the perceived risk of false-negative findings. We therefore evaluated the association between repeated sample collection and test performance among 325 symptomatic patients undergoing COVID-19 testing in Atlanta, GA. High concordance was found between consecutively collected mid-turbinate samples with both molecular (n = 74, 100% concordance) and antigen-based (n = 147, 97% concordance, kappa = 0.95, CI = 0.88-1.00) diagnostic assays. Repeated sample collection does not decrease COVID-19 test performance, demonstrating that multiple samples can be collected for assay validation and clinical diagnosis.
| S-EPMC8295385 | biostudies-literature
Project description:PurposeTo evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure.MethodsHospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire.ResultsThe test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals.ConclusionOropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.
| S-EPMC8107404 | biostudies-literature
Project description:Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity.
| S-EPMC8282446 | biostudies-literature
Project description: Not available
| S-BSST379 | biostudies-other
Project description:A suitable tool for monitoring the spread of SARS-CoV-2 is to identify potential sampling points in the wastewater collection system that can be used to monitor the distribution of COVID-19 disease affected clusters within a city. The applicability of the developed methodology is presented through the description of the 72,837 population equivalent wastewater collection system of the city of Nagykanizsa, Hungary and the results of the analytical and epidemiological measurements of the wastewater samples. The wastewater sampling was conducted during the 3rd wave of the COVID-19 epidemic. It was found that the overlap between the road system and the wastewater network is high, it is 82 %. It was showed that the proposed methodological approach, using the tools of network science, determines confidently the zones of the wastewater collection system and provides the ideal monitoring points in order to provide the best sampling resolution in urban areas. The strength of the presented approach is that it estimates the network based on publicly available information. It was concluded that the number of zones or sampling points can be chosen based on relevant epidemiological intervention and mitigation strategies. The algorithm allows for continuous effective monitoring of the population infected by SARS-CoV-2 in small-sized cities.
| S-EPMC8554011 | biostudies-literature
Project description:IntroductionMost SARS-CoV-2 antigen-detecting rapid diagnostic tests require nasopharyngeal sampling, which is frequently perceived as uncomfortable and requires healthcare professionals, thus limiting scale-up. Nasal sampling could enable self-sampling and increase acceptability. The term nasal sampling is often not used uniformly and sampling protocols differ.MethodsThis manufacturer-independent, prospective diagnostic accuracy study, compared professional anterior nasal and nasal mid-turbinate sampling for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test. The second group of participants collected a nasal mid-turbinate sample themselves and underwent a professional nasopharyngeal swab for comparison. The reference standard was real-time polymerase chain reaction (RT-PCR) using combined oro-/nasopharyngeal sampling. Individuals with high suspicion of SARS-CoV-2 infection were tested. Sensitivity, specificity, and percent agreement were calculated. Self-sampling was observed without intervention. Feasibility was evaluated by observer and participant questionnaires.ResultsAmong 132 symptomatic adults, both professional anterior nasal and nasal mid-turbinate sampling yielded a sensitivity of 86.1% (31/36 RT-PCR positives detected; 95%CI: 71.3-93.9) and a specificity of 100.0% (95%CI: 95.7-100). The positive percent agreement was 100% (95%CI: 89.0-100). Among 96 additional adults, self nasal mid-turbinate and professional nasopharyngeal sampling yielded an identical sensitivity of 91.2% (31/34; 95%CI 77.0-97.0). Specificity was 98.4% (95%CI: 91.4-99.9) with nasal mid-turbinate and 100.0% (95%CI: 94.2-100) with nasopharyngeal sampling. The positive percent agreement was 96.8% (95%CI: 83.8-99.8). Most participants (85.3%) considered self-sampling as easy to perform.ConclusionProfessional anterior nasal and nasal mid-turbinate sampling are of equivalent accuracy for an antigen-detecting rapid diagnostic test in ambulatory symptomatic adults. Participants were able to reliably perform nasal mid-turbinate sampling themselves, following written and illustrated instructions. Nasal self-sampling will facilitate scaling of SARS-CoV-2 antigen testing.
| S-EPMC8425459 | biostudies-literature
Project description:In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present the development and characterization of a collection of over 40 new monoclonal antibodies directed against different SARS-CoV-2 proteins. Recombinant SARS-CoV-2 proteins were expressed, purified, and used as immunogens. Upon development of specific hybridomas, the obtained monoclonal antibody (mAb) clones were tested for binding to recombinant proteins and infected cells. We generated mAbs against structural proteins, the Spike and Nucleocapsid protein, several non-structural proteins (nsp1, nsp7, nsp8, nsp9, nsp10, nsp16) and accessory factors (ORF3a, ORF9b) applicable in flow cytometry, immunofluorescence, or Western blot. Our collection of mAbs provides a set of novel, highly specific tools that will allow a comprehensive analysis of the viral proteome, which will allow further understanding of SARS-CoV-2 pathogenesis and the design of therapeutic strategies.
| S-EPMC8875891 | biostudies-literature
Project description:ObjectiveTo assess the frequency, fidelity, and impact of replication studies in the clinical decision support system (CDSS) literature.Materials and methodsA PRISMA-compliant review identified CDSS replications across 28 health and biomedical informatics journals. Included articles were assessed for fidelity to the original study using 5 categories: Identical, Substitutable, In-class, Augmented, and Out-of-class; and 7 IMPISCO domains: Investigators (I), Method (M), Population (P), Intervention (I), Setting (S), Comparator (C), and Outcome (O). A fidelity score and heat map were generated using the ratings.ResultsFrom 4063 publications matching search criteria for CDSS research, only 12/4063 (0.3%) were ultimately identified as replications. Six articles replicated but could not reproduce the results of the Han et al (2005) CPOE study showing mortality increase and, over time, changed from truth testing to generalizing this result. Other replications successfully tested variants of CDSS technology (2/12) or validated measurement instruments (4/12).DiscussionA replication rate of 3 in a thousand studies is low even by the low rates in other disciplines. Several new reporting methods were developed for this study, including the IMPISCO framework, fidelity scores, and fidelity heat maps. A reporting structure for clearly identifying replication research is also proposed.ConclusionThere is an urgent need to better characterize which core CDSS principles require replication, identify past replication data, and conduct missing replication studies. Attention to replication should improve the efficiency and effectiveness of CDSS research and avoiding potentially harmful trial and error technology deployment.
| S-EPMC8363796 | biostudies-literature
Project description:The shedding of pathogens by infected humans enables the use of sewage monitoring to conduct wastewater-based epidemiology (WBE). Although most WBE studies use data from large sewage treatment plants, timely data from smaller catchments are needed for targeted public health action. Traditional sampling methods, like autosamplers or grab sampling, are not conducive to quick ad hoc deployments and high-resolution monitoring at these smaller scales. This study develops and validates a cheap and easily deployable passive sampler unit, made from readily available consumables, with relevance to the COVID-19 pandemic but with broader use for WBE. We provide the first evidence that passive samplers can be used to detect SARS-CoV-2 in wastewater from populations with low prevalence of active COVID-19 infections (0.034 to 0.34 per 10,000), demonstrating their ability for early detection of infections at three different scales (lot, suburb, and city). A side by side evaluation of passive samplers (n = 245) and traditionally collected wastewater samples (n = 183) verified that the passive samplers were sensitive at detecting SARS-CoV-2 in wastewater. On all 33 days where we directly compared traditional and passive sampling techniques, at least one passive sampler was positive when the average SARS-CoV-2 concentration in the wastewater equaled or exceeded the quantification limit of 1.8 gene copies per mL (n = 7). Moreover, on 13 occasions where wastewater SARS-CoV-2 concentrations were less than 1.8 gene copies per mL, one or more passive samplers were positive. Finally, there was a statistically significant (p < 0.001) positive relationship between the concentrations of SARS-CoV-2 in wastewater and the levels found on the passive samplers, indicating that with further evaluation, these devices could yield semi-quantitative results in the future. Passive samplers have the potential for wide use in WBE with attractive feasibility attributes of cost, ease of deployment at small-scale locations, and continuous sampling of the wastewater. Further research will focus on the optimization of laboratory methods including elution and extraction and continued parallel deployment and evaluations in a variety of settings to inform optimal use in wastewater surveillance.
| S-EPMC8291133 | biostudies-literature
Project description:The SARS-CoV-2 coronavirus has caused a global pandemic. Despite the initial success of vaccines at preventing infection, genomic variation has led to the proliferation of variants capable of higher infectivity. Mutations in the SARS-CoV-2 genome are the consequence of replication errors, highlighting the importance of understanding the determinants of SARS-CoV-2 replication fidelity. The RNA-dependent RNA polymerase (RdRp) is the central catalytic subunit for SARS-CoV-2 RNA replication and genome transcription. Here, we report the fidelity of ribonucleotide incorporation by SARS-CoV-2 RdRp (nsp12), along with its co-factors nsp7/nsp8, using steady-state kinetic analysis. Our analysis suggests that in the absence of the proofreading subunit (nsp14), the nsp12/7/8 complex has a surprisingly low base substitution fidelity (10-1-10-3). This is orders of magnitude lower than the fidelity reported for other coronaviruses (10-6-10-7), highlighting the importance of proofreading for faithful SARS-CoV-2 replication. We performed a mutational analysis of all reported SARS-CoV-2 genomes and identified mutations in both nsp12 and nsp14 that appear likely to lower viral replication fidelity through mechanisms that include impairing the nsp14 exonuclease activity or its association with the RdRp. Our observations provide novel insight into the mechanistic basis of replication fidelity in SARS-CoV-2 and the potential effect of nsp12 and nsp14 mutations on replication fidelity, informing the development of future antiviral agents and SARS-CoV-2 vaccines.
| S-EPMC9854147 | biostudies-literature