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Background: Over the course of the pandemic, many countries have repeatedly closed schools and shifted students to remote learning. However, evidence for negative mental and physiological health consequences of such measures for students is increasing, highlighting the need for evidence-based recommendations on how to safely reopen schools. This study presents experiences when implementing opt-in, at-home SARS-CoV-2 screening using rapid diagnostic tests (RDTs) to facilitate safe face-to-face-teaching during a pandemic. Methods: We present data form a prospective study implementing an RDT-based screening program at a primary school in southwest Germany. We conducted qualitative in-depth interviews with participating children, parents, and school stakeholders to elicit implementation experiences and screening perception. Results: The screening intervention was highly accepted and appreciated among participants; no positive RDT was reported over the duration of the study. Self-testing at home before coming to school was feasible, but more positive consequences of screening participation (e.g., easing of mask mandates) besides a personal feeling of safety would be appreciated. Participants preferred home-based RDTs over some other measures, particularly mask mandates. Despite the RDTs being licensed as self-tests in Germany, additional training can help avoid mistakes, and ensuring intervention ownership and improving pre-implementation communication can facilitate buy-in. Conclusions: Ag-RDT-based SARS-CoV-2 screening programs relying on self-testing at home proved feasible and accepted among primary school students, parents, and school staff who participated in this study.
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Déficience intellectuelleRésumé
Background Currently, more than 500 different AgPOCTs for SARS-CoV-2 diagnostics are on sale (July 2021), for many of which no data about sensitivity other than self-acclaimed values by the manufacturers are available. In many cases these do not reflect real-life diagnostic sensitivities. Therefore, manufacturer-independent quality checks of available AgPOCTs are needed, given the potential implications of false-negative results. Objective The objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) in order to rapidly identify poor performing products. Methods We present a methodology for quick assessment of the sensitivity of SARS-CoV-2 lateral flow test stripes suitable for quality evaluation of many different products. We established reference samples with high, medium and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison. Results Among 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads (∼7.0 * 10 8 to ∼1.7 * 10 5 SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample (∼1.4 * 10 6 copies/ ml), while only five tests detected the Ct28 test sample (∼1.7 * 10 5 copies/ ml). In the low range of analytical sensitivity we found three saliva spit tests only delivering positive results for the Ct21 sample (∼2.2 * 10 7 copies/ ml). Comparison with published data support our AgPOCT ranking. Importantly, we identified an AgPOCT offered in many local drugstores and supermarkets, which did not reliably recognize the sample with highest viral load (Ct16 test sample with ∼7.0 * 10 8 copies/ ml) leading to serious doubts in its usefulness in SARS-CoV-2 diagnostics. Conclusion The rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.
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Objectives: To assess the performance of antigen-based rapid diagnostic tests (Ag-RDTs) for SARS CoV-2 when implemented for large-scale universal screening of asymptomatic individuals. Methods: This study presents data from a pragmatic implementation study for universal Ag-RDT-based screening at a tertiary care hospital in Germany where all incoming patients without symptoms suggestive of SARS-CoV-2 were screened with an Ag-RDT prior to admission since October 2020. Results: In total, 49,542 RDTs were performed in 27,199 asymptomatic individuals over a duration of five months. Out of 222 positive results, 196 underwent in-house confirmatory testing with PCR, out of which 170 were confirmed positive, indicating a positive predictive value (PPV) of 86.7%. Negative Ag-RDTs were not routinely tested with PCR, but a total of 94 cases of false negative Ag-RDTs were detected due to PCR tests being performed within the following five days with a median CT-value of 33. Conclusions: This study provides evidence that Ag-RDTs can have a high diagnostic yield for transmission relevant infections with limited false-positives when utilized at the point of care on asymptomatic patients and thus can be a suitable public-health test for universal screening.
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ABSTRACT Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and Results We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until April 30 th , 2021. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS 2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy data sets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 71.2% (95% confidence interval [CI] 68.2 to 74.0) and increased to 76.3% (CI 73.1 to 79.2) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. The LumiraDx showed the highest sensitivity with 88.2% (CI 59.0 to 97.5). Of instrument-free Ag-RDTs, Standard Q nasal performed best with 80.2% sensitivity (CI 70.3 to 87.4). Across all Ag-RDTs sensitivity was markedly better on samples with lower Ct-values, i.e., <20 (96.5%, CI 92.6 to 98.4) and <25 (95.8%, CI 92.3 to 97.8), in comparison to those with Ct ≥25 (50.7%, CI 35.6 to 65.8) and ≥30 (20.9%, CI 12.5 to 32.8). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, CI 76.3 to 89.2) compared to testing after one week (61.5%, CI 52.2 to 70.0). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, CI 70.4 to 79.9) in comparison to other sample types (e.g., nasopharyngeal 71.6%, CI 68.1 to 74.9) although CIs were overlapping. Concerns of bias were raised across all data sets, and financial support from the manufacturer was reported in 24.1% of data sets. Our analysis was limited by the included studies’ heterogeneity in design and reporting, making it difficult to draw conclusions from. Conclusion In this study we found that Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data. AUTHOR SUMMARY Why was this study done? – Antigen rapid diagnostic tests (Ag-RDTs) are considered an important diagnostic tool to fight the spread of SARS-CoV-2 – An increasing number of Ag-RDTs is offered on the market, and a constantly growing body of literature evaluating their performance is available – To inform decision makers about the best test to choose, an up to date summary of their performance is needed What did the researchers do and find? – On a weekly basis, we search multiple data bases for evaluations of Ag-RDTs detecting SARS-CoV-2 and post the results on www.diagnosticsglobalhealth.org – Based on the search results up until April 30 th , 2021, we conducted a systematic review and meta-analysis, including a total of 133 clinical and analytical accuracy studies – Across all meta-analyzed studies, when Ag-RDTs were performed according to manufacturers’ recommendations, they showed a sensitivity of 76.3% (CI 73.1 to 79.2), with the LumiraDx (sensitivity 88.2%, CI 59.0 to 97.5) and of the instrument-free Ag-RDT Standard Q (74.9% sensitivity, CI 69.3 to 79.7) performing best. – Across all Ag-RDTs, sensitivity increased to 95.8% (CI 92.3 to 97.8) when restricting the analysis to samples with high viral loads (i.e., a Ct-value <25) and to 83.8% (CI 76.3 to 89.2) when tests were performed on patients within the first week after symptom onset What do these findings mean? – Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease – Out of all assessed tests, the Lumira Dx showed the highest accuracy. The Standard Q wasthe best performing test when only considering those that don’t require an instrument – A standardization of reporting methods for clinical accuracy studies would enhance future test-comparisons
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BackgroundNasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients. MethodsWe performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated. ResultsAmong the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling. ConclusionThis study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.
Sujets)
COVID-19Résumé
BackgroundThe SARS-Cov-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings. MethodsThe effectiveness of peracetic acid (PAA) dry fogging in decontaminating common healthcare setting surfaces was evaluated after experimentally contaminating nine surfaces (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button and smartphone touch screen) with more than 106 TCID50 of SARS-CoV-2. ResultsWhen fumigated with PAA dry fog for an hour, no infectious SARS-CoV-2 virus was recovered from experimentally inoculated coupons of representing nine different surface types. In contrast, high titer recovery of infectious virus was demonstrated for corresponding untreated drying controls of the same materials. ConclusionStandard surface decontaminating processes, including sprays and wipes, are laborious and often cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost and overall effectiveness of a PAA dry fogging suggest it should be considered for decontaminating settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.
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BackgroundNasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. MethodsWe systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval October 1st, 2020) for comparative studies of alternative specimen types [saliva, oropharyngeal (OP), and nasal (NS) swabs] versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in sub-groups. The QUADAS 2 tool was used to assess bias. ResultsFrom 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives [NS (0.82, 95% CI: 0.73-0.90), OP (0.84, 95% CI: 0.57-1.0), saliva (0.88, 95% CI: 0.81 - 0.93)] than NP swabs, while combined OP/NS matched NP performance (0.97, 95% CI: 0.90-1.0). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield. ConclusionsNP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric vs. adult, late vs. early in disease course) and head-to head studies of sampling strategies are urgently needed.
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Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application "Molecular Mimicry Map (3M) of SARS-CoV-2" (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
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COVID-19 , Maladies auto-immunes , Syndrome respiratoire aigu sévèreRésumé
Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods: We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta- analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.