Copy number variation sequencing for the products of conception: What is the optimal testing strategy.

BACKGROUND: Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. METHODS: CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. RESULTS: Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. CONCLUSIONS: We propose an initial CNV-seq followed by QF-PCR if needed-an efficient and cost-effective strategy for the genetic analysis of POCs.

Prediction of high coronary artery calcium (CAC) scores from aortic arch calcification: An efficient tool for selection of non-optimal candidates for coronary CTA?

PURPOSE: Overutilization of healthcare resources is causing a high socioeconomic burden. Patients with high coronary artery calcium (CAC) scores > 1000AU are not optimal candidates for coronary CTA and better suited for other diagnostic strategies. Therefore, our objective was to evaluate whether a 4-scale aortic arch calcification severity (AoArCa) score from CT and X-Ray predicts high-CAC scores. METHODS: Patients referred to coronary/aortic CT-Angiography were enrolled. The severity of aortic arch calcification (AoArCa) was scored as grade: 0 = absent, 1 = minimal (<25 % of circumference), 2 = mild (25-50 %), 3 = moderate (50-75 %) and 4 = severe (75-100 %) on both thoracic CT and X-ray. RESULTS: In 130 patients, the absence of AoArCa by CT was highly accurate to rule out CAC > 1000AU (sens. 100 %). No or minimal AoArCa had a high NPV of 95.6 % to rule out CAC > 1000 and grade 0,1 + 2 a NPV of 86.96 %. The AUC of AoArCa by CT for predicting high CAC > 1000 was c = 0.84 (p < 0.001; 95 %CI: 0.771--0.91). For moderate-to-severe AoArCa, accuracy was c = 0.792 (p < 0.001). The intermodality agreement between CT and X-Ray based AoArCa Scores was good (r = 0.824, p < 0.001); ICC = 0.902. For X-ray, AUC was c = 0.715 to predict CAC > 1000 (p < 0.001). In regression models, only moderate-or-severe AoArCa, but not the other CVRF predicted CAC > 1000 (p < 0.001), and there was an association of the number of CVRF. CONCLUSIONS: Patients with moderate-to-severe aortic arch calcification have a high probability of CAC > 1000AU, but not those with no, minimal and mild. The absence of AoArCa rules out CAC > 1000AU. AoArCa severity may serve as valuable tool for selecting the diagnostic strategy.

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Responses from a survey of National Control Laboratories and National Regulatory Authorities.

The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is reviewing World Health Organization (WHO) manuals, guidelines and recommendations for vaccines and biotherapeutics to identify the extent to which animal-based testing methods are described. The aim is to recommend where updates to these documents can lead to an increased and more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction and Refinement of animal tests) in the quality control and batch release testing requirements for vaccines and biotherapeutics. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing. Developing recommendations that are widely applicable by both the manufacturers and national regulatory authorities for vaccines and biological therapeutics globally requires a detailed understanding of how different organisations view the opportunities and barriers to better integration of the 3Rs. To facilitate this, we developed and distributed a survey aimed at individuals who work for national regulatory authorities (NRAs) and/or national control laboratories (NCLs). In this paper, we present the key findings from this survey and how these will help inform the recommendations for wider integration of 3Rs approaches by WHO in their guidance documents applicable to the quality control and batch release testing of vaccines and biotherapeutics.

Risk assessment of parabens in a transcriptomics-based in vitro test.

Parabens have been used for decades as preservatives in food, drugs and cosmetics. The majority however, were banned in 2009 and 2014 leaving only methyl-, ethyl-, propyl-, and butyl-derivates available for subsequent use. Methyl- and propylparaben have been extensively tested in vivo, with no resulting evidence for developmental and reproductive toxicity (DART). In contrast, ethylparaben has not yet been tested for DART in animal experiments, and it is currently debated if additional animal studies are warranted. In order to perform a comparison of the four currently approved parabens, we used a previously established in vitro test based on human induced pluripotent stem cells (iPSC) that are exposed to test substances during their differentiation to neuroectodermal cells. EC50 values for cytotoxicity were 906 µM, 698 µM, 216 µM and 63 µM for methyl-, ethyl-, propyl- and butylparaben, respectively, demonstrating that cytotoxicity increases with increasing alkyl chain length. Genome-wide analysis demonstrated that FDR-adjusted significant gene expression changes occurred only at cytotoxic or close to cytotoxic concentrations, for example 1720 differentially expressed genes (DEG) at 1000 µM ethylparaben, 1 DEG at 316 µM, and no DEG at 100 µM or lower concentrations. The highest concentration of ethylparaben that did not induce any cytotoxicity nor DEG was 1670-fold above the highest concentration reported in biomonitoring studies (60 nM ethylparaben in cord blood). In conclusion, cytotoxicity and gene expression alterations of ethylparaben occurred at concentrations of approximately three orders of magnitude above human blood concentrations; moreover, the substance fitted well into a scenario where toxicity increases with the alkyl chain length, and gene expression changes only occur at cytotoxic or close to cytotoxic concentrations. Therefore, no evidence was obtained suggesting that in vivo DART with ethylparaben would lead to different results as the methyl- or propyl derivates.

Performance of different rapid antigen testing strategies for SARS-CoV-2: A living rapid review.

BACKGROUND: Rapid antigen detection tests (RADTs) for SARS-CoV-2 testing offer several advantages over molecular tests, but there is little evidence supporting an ideal testing algorithm. We aimed to examine the diagnostic test accuracy (DTA) and the effectiveness of different RADT SARS-CoV-2 testing strategies. METHODS: Following PRISMA DTA guidance, we carried out a living rapid review and meta-analysis. Searches were conducted in Ovid MEDLINE® ALL, Embase and Cochrane CENTRAL electronic databases until February 2022. Results were visualized using forest plots and included in random-effects univariate meta-analyses, where eligible. RESULTS: After screening 8010 records, 18 studies were included. Only one study provided data on incidence outcomes. Seventeen studies were DTA reports with direct comparisons of RADT strategies, using RT-PCR as the reference standard. Testing settings varied, corresponding to original SARS-CoV-2 or early variants. Strategies included differences in serial testing, the individual collecting swabs and swab sample locations. Overall, specificity remained high (>98%) across strategies. Although results were heterogeneous, the sensitivity for healthcare worker-collected samples was greater than for self-collected samples. Nasal samples had comparable sensitivity when compared to paired RADTs with nasopharyngeal samples, but sensitivity was much lower for saliva samples. The limited evidence for serial testing suggested higher sensitivity if RADTs were administered every 3 days compared to less frequent testing. CONCLUSIONS: Additional high-quality research is needed to confirm our findings; all studies were judged to be at risk of bias, with significant heterogeneity in sensitivity estimates. Evaluations of testing algorithms in real-world settings are recommended, especially for transmission and incidence outcomes.

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods.

SARS-CoV-2 viral-load measurements from a single-specimen type are used to establish diagnostic strategies, interpret clinical-trial results for vaccines and therapeutics, model viral transmission, and understand virus-host interactions. However, measurements from a single-specimen type are implicitly assumed to be representative of other specimen types. We quantified viral-load timecourses from individuals who began daily self-sampling of saliva, anterior-nares (nasal), and oropharyngeal (throat) swabs before or at the incidence of infection with the Omicron variant. Viral loads in different specimen types from the same person at the same timepoint exhibited extreme differences, up to 109 copies/mL. These differences were not due to variation in sample self-collection, which was consistent. For most individuals, longitudinal viral-load timecourses in different specimen types did not correlate. Throat-swab and saliva viral loads began to rise as many as 7 days earlier than nasal-swab viral loads in most individuals, leading to very low clinical sensitivity of nasal swabs during the first days of infection. Individuals frequently exhibited presumably infectious viral loads in one specimen type while viral loads were low or undetectable in other specimen types. Therefore, defining an individual as infectious based on assessment of a single-specimen type underestimates the infectious period, and overestimates the ability of that specimen type to detect infectious individuals. For diagnostic COVID-19 testing, these three single-specimen types have low clinical sensitivity, whereas a combined throat-nasal swab, and assays with high analytical sensitivity, was inferred to have significantly better clinical sensitivity to detect presumed pre-infectious and infectious individuals.

Perceived COVID-19 risk and testing experiences in the San Ysidro U.S./Mexico border region.

Racial and ethnic disparities in COVID-19 incidence are pronounced in underserved U.S./Mexico border communities. Working and living environments in these communities can lead to increased risk of COVID-19 infection and transmission, and this increased risk is exacerbated by lack of access to testing. As part of designing a community and culturally tailored COVID-19 testing program, we surveyed community members in the San Ysidro border region. The purpose of our study was to characterize knowledge, attitudes, and beliefs of prenatal patients, prenatal caregivers, and pediatric caregivers at a Federally Qualified Health Center (FHQC) in the San Ysidro region regarding perceived risk of COVID-19 infection and access to testing. A cross-sectional survey was used to collect information on experiences accessing COVID-19 testing and perceived risk of COVID-19 infection within San Ysidro between December 29, 2020 and April 2, 2021. A total of 179 surveys were analyzed. Most participants identified as female (85%) and as Mexican/Mexican American (75%). Over half (56%) were between the age of 25 and 34 years old. Perceived Risk: 37% reported moderate to high risk of COVID-19 infection, whereas 50% reported their risk low to none. Testing Experience: Approximately 68% reported previously being tested for COVID-19. Among those tested, 97% reported having very easy or easy access to testing. Reasons for not testing included limited appointment availability, cost, not feeling sick, and concern about risk of infection while at a testing facility. This study is an important first step to understand the COVID-19 risk perceptions and testing access among patients and community members living near the U.S./Mexico border in San Ysidro, California.

COVID-19 testing strategies that fail to incorporate culturally competent methods to reach traditionally underserved communities can lead to persistent transmission and increased infection rates. During the early stages of the COVID-19 pandemic, we surveyed 179 people living in a community with high burden of COVID-19 infection about their perception of infection risk and their experiences accessing testing. Capturing and understanding these community perceptions on COVID-19 risk are vital when developing a testing program that is accessible and appropriate for the target population. In our study, we found half of survey respondents thought their risk of COVID-19 infection as low to none and over half of respondents stated they had already been tested for COVID-19. These findings provide insight to the beliefs of individuals who live and seek health care in communities with high rates of COVID-19 infection and will help guide the design and implementation of culturally tailored testing strategies.

Quantitative Analysis of the Effectiveness of Antigen- and Polymerase Chain Reaction-Based Combination Strategies for Containing COVID-19 Transmission in a Simulated Community.

The number of coronavirus disease 2019 (COVID-19) cases continues to surge, overwhelming healthcare systems and causing excess mortality in many countries. Testing of infectious populations remains a key strategy to contain the COVID-19 outbreak, delay the exponential spread of the disease, and flatten the epidemic curve. Using the Omicron variant outbreak as a background, this study aimed to evaluate the effectiveness of testing strategies with different test combinations and frequencies, analyze the factors associated with testing effectiveness, and optimize testing strategies based on these influencing factors. We developed a stochastic, agent-based, discrete-time susceptible-latent-infectious-recovered model simulating a community to estimate the association between three levels of testing strategies and COVID-19 transmission. Antigen testing and its combination strategies were more efficient than polymerase chain reaction (PCR)-related strategies. Antigen testing also showed better performance in reducing the demand for hospital beds and intensive care unit beds. The delay in the turnaround time of test results had a more significant impact on the efficiency of the testing strategy compared to the detection limit of viral load and detection-related contacts. The main advantage of antigen testing strategies is the short turnaround time, which is also a critical factor to be optimized to improve PCR strategies. After modifying the turnaround time, the strategies with less frequent testing were comparable to daily testing. The choice of testing strategy requires consideration of containment goals, test efficacy, community prevalence, and economic factors. This study provides evidence for the selection and optimization of testing strategies in the post-pandemic era and provides guidance for optimizing healthcare resources.

HIV Infection Indicator Disease-Based Active Case Finding in a University Hospital: Results from the SHOT Project.

In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as "the three 95": 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4+ cells/µL and 60% with less than 350 CD4+ cells/µL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count <100/mm3, one (9.1%) <200/mm3, and one (9.1%) <300/mm3. Regarding risk factors, 81.8% declared having had unprotected sexual intercourse and 54.5% were heterosexual. All patients promptly started a combination antiretroviral regimen and 10 (90.9%) obtained an undetectable HIV-RNA status. Eight of the eleven (72.7%) patients are currently on follow-up in our outpatient clinic. A proactive indicator disease-guided screening can help avoid missed opportunities to diagnose HIV infection in a hospital setting. Implementing this kind of intervention could favor early diagnosis and access to treatment.

High Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiation.

Human-relevant tests to predict developmental toxicity are urgently needed. A currently intensively studied approach makes use of differentiating human stem cells to measure chemically-induced deviations of the normal developmental program, as in a recent study based on cardiac differentiation (UKK2). Here, we (i) tested the performance of an assay modeling neuroepithelial differentiation (UKN1), and (ii) explored the benefit of combining assays (UKN1 and UKK2) that model different germ layers. Substance-induced cytotoxicity and genome-wide expression profiles of 23 teratogens and 16 non-teratogens at human-relevant concentrations were generated and used for statistical classification, resulting in accuracies of the UKN1 assay of 87-90%. A comparison to the UKK2 assay (accuracies of 90-92%) showed, in general, a high congruence in compound classification that may be explained by the fact that there was a high overlap of signaling pathways. Finally, the combination of both assays improved the prediction compared to each test alone, and reached accuracies of 92-95%. Although some compounds were misclassified by the individual tests, we conclude that UKN1 and UKK2 can be used for a reliable detection of teratogens in vitro, and that a combined analysis of tests that differentiate hiPSCs into different germ layers and cell types can even further improve the prediction of developmental toxicants.

Assessing COVID-19 testing strategies in K-12 schools in underserved populations: study protocol for a cluster-randomized trial.

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021.

An Integrated Testing Strategy for Ecotoxicity (ITS-ECO) Assessment in the Marine Environmental Compartment using Mytilus spp.: A Case Study using Pristine and Coated CuO and TiO2 Nanomaterials.

An integrated testing strategy for ecotoxicity assessment (ITS-ECO) was developed to aid in the hazard and fate assessment of engineered nanomaterials (ENMs) deposited in marine environments using the bivalve Mytilus spp. as a test species. The ENMs copper(II) oxide (CuO) and titanium dioxide (TiO2 ), either in pristine form (core) or with functionalized coatings (polyethylene glycol [PEG], carboxyl [COOH], and ammonia [NH3 ]) were selected as case study materials based on their production levels and use. High-throughput in vitro testing in Tier 1 of the ITS-ECO revealed CuO ENMs to elicit cytotoxic effects on lysosomes of hemocytes of mussels, with the hazard potential CuO PEG > CuO COOH > CuO NH3 > CuO core, whereas TiO2 ENMs were not cytotoxic. Genotoxicity in hemocytes as well as gill cells of mussels following in vivo exposure (48 h) to CuO ENMs was also seen. Longer in vivo exposures in Tier 2 (48 h-21 days) revealed subacute and chronic oxidative effects for both CuO and TiO2 ENMs, in some cases leading to lipid peroxidation (core TiO2 ENMs). In Tier 3 bioaccumulation studies, distinct patterns of uptake for Cu (predominantly in gills) and Ti (predominantly in digestive glands) and between the different core and coated ENMs were found. Clear NM-specific and coating-dependent effects on hazard and fate were seen. Overall, using a tiered testing approach, the ITS-ECO was able to differentiate the hazard (acute, subacute, and chronic effects) posed by ENMs of different compositions and coatings and to provide information on fate for environmental risk assessment of these ENMs. Environ Toxicol Chem 2022;41:1390-1406. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Molecular accuracy vs antigenic speed: SARS-CoV-2 testing strategies.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has hit every corner of the world faster than any infectious disease ever known. In this context, rapid and accurate testing of positive cases are essential to follow the test-trace-isolate strategy (TETRIS), which has proven to be a key approach to constrain viral spread. Here, we discuss how to interpret and combine molecular or/and antigen-based detection methods for SARS-CoV-2 as well as when they should be used. Their application can be cleverly designed as an algorithm to prevent viral dissemination according to distinct epidemiological contexts within surveillance programs.

Optimization of blood testing strategies for voluntary blood donors in military blood centers / 中国输血杂志

【Objective】 To explore the optimization of blood testing strategies for voluntary blood donors in military blood centers. 【Methods】 From January 2017 to December 2020, the testing results of five serological indicators of voluntary blood donors from our center were collected via the blood transfusion management system . The positive NAT results of HBV, HCV and HIV, as well as the unqualified serological indicators, including the unqualified rate over the years, unqualified rate of military/civilian blood donor, reactive rate of dual-ELISA-reagent or one-ELISA-reagent etc., were retrospectively analyzed. 【Results】 The ratio of military blood donors to civilian blood donors in our center was 1: 4 during 2017~2020. The total unqualified rate of blood testing indicators of military blood donors was ALT>anti-HCV>HBsAg>HIV antigen/anti-HIV>anti-TP>NAT, and that of civilian blood donors was HBsAg > anti-TP > ALT > anti-HCV > HIV antigen/anti-HIV > NAT. The total unqualified rate of HBsAg, anti-HCV and anti-TP in our center decreased year by year, the HIV antigen/anti-HIV fluctuated, and the ALT increased year by year (P<0.01). The ALT deferral rate among military blood donors was the highest, accounting for 65.85%(594/902) of the donation deferral. The reactive rate of dual-ELISA-reagent to HBsAg, anti-HCV, HIV antigen/anti-HIV and anti-TP in civilian blood donors were 72.87%, 33.02%, 16.56% and 67.67%, respectively (P<0.05). Among the 123 668 ELISA negative samples during 2017~2020, 56 cases of HBV DNA(+ ) were detected by NAT, including 3 cases of military blood donors. 【Conclusion】 The current blood screening strategy of military blood centers can basically guarantee the safety of blood use in clinical. For military blood donors, ALT deferral, caused by ALT results that are higher than the ALT threshold, was the main reason for blood scrapping. Strengthening the promotion and implementation of NAT, as well as adjusting the critical value of ALT is of positive significance for reducing the risk of blood transfusion-transmitted diseases and the waste of blood sources, thereby improving the safety and security level of the clinical blood supply for the troops, promoting the treatment capabilities of officers and soldiers, and even improving the combat effectiveness of the troops.

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals.

Animal testing has long been integral to the development of biologicals, including vaccines. The use of animals can provide important information on potential toxicity, insights into their mechanism of action, pharmacokinetics and dynamics, physiologic distribution, and potency. However, the use of these same methods is often adopted into the post-licensure phase of the product life cycle for the monitoring of product qualities, such as potency or safety, as part of their routine batch release. The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) and the World Health Organization (WHO) are collaborating on a project to review animal-based testing methods described in WHO manuals, guidelines and recommendations for biologicals to identify where updates can lead to a more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction, and Refinement of animal tests) in batch release testing requirements. An international working group consisting of more than 30 representatives from pharmaceutical and biotechnology companies, national control laboratories and regulatory bodies is performing this review. This project aims to address concerns about inconsistencies in the guidance for the scientifically justified use of animal methods required for the post-licensure quality control and batch release testing of biologicals, and the near absence of recommendations for the application of 3Rs principles within the relevant guidelines. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing and help support faster access to products by the global communities who need them most urgently.

Optimal control-based vaccination and testing strategies for COVID-19.

BACKGROUND AND OBJECTIVE: Assuming the availability of a limited amount of effective COVID-19 rapid tests, the effects of various vaccination strategies on SARS-CoV-2 virus transmission are compared for different vaccination scenarios characterized by distinct limitations associated with vaccine supply and administration. METHODS: The vaccination strategies are defined by solving optimal control problems of a compartmental epidemic model in which the daily vaccination rate and the daily testing rate for the identification and isolation of asymptomatic subjects are the control variables. Different kinds of algebraic constraints are considered, representing different vaccination scenarios in which the total amount of vaccines available during the time period under consideration is limited or the number of daily available vaccines is limited. These optimal control problems are numerically solved by means of a direct transcription technique, which allows both equality and inequality constraints to be straightforwardly included in the formulation of the optimal control problems. RESULTS: Several numerical experiments are conducted, in which the objective functional to be minimized is a combination of the number of symptomatic and asymptomatic infectious subjects with the cost of vaccination of susceptible subjects and testing of asymptomatic infectious subjects. The results confirm the hypothesis that the implementation of early control measures significantly reduces the number of symptomatic infected subjects, which is a key aspect for the resilience of the healthcare system. The sensitivity analysis of the solutions to the weighting parameters of the objective functional reveals that it is possible to obtain a vaccination strategy that allows vaccination supplies to be saved while keeping the same number of symptomatic infected subjects. Furthermore, it indicates that if the vaccination plan is not supported by a sufficient rate of testing, the number of symptomatic infected subjects could increase. Finally, the sensitivity analysis shows that a significant reduction in the efficacy of the vaccines could also lead to a relevant increase in the number of symptomatic infected subjects. CONCLUSIONS: The numerical experiments show that the proposed approach, which is based on optimal control of compartmental epidemic models, provides healthcare systems with a suitable method for scheduling vaccination plans and testing policies to control the spread of the SARS-CoV-2 virus.

High Performance of SARS-Cov-2N Protein Antigen Chemiluminescence Immunoassay as Frontline Testing for Acute Phase COVID-19 Diagnosis: A Retrospective Cohort Study.

Objectives: COVID-19 emerged and rapidly spread throughout the world. Testing strategies focussing on patients with COVID-19 require assays that are high-throughput, low-risk of infection, and with small sample volumes. Antigen surveillance can be used to identify exposure to pathogens and measure acute infections. Methods: A total of 914 serum samples, collected from 309 currently infected COVID-19 patients, 48 recovered ones, and 410 non-COVID-19 patients, were used to measure N protein antigen levels by a chemilumineseent immunoassay. Diagnostic performances were analyzed in different periods after onset. Results: There was a high level of N protein antigen in COVID-19 patients (0.56 COI), comparing to the recovered patients (0.12 COI) and controls (0.19 COI). In receiver-operating characteristic curve analysis, the area under the curve of serum N protein antigen was 0.911 in the first week after onset. In this period, Sensitivity and specificity of serologic N protein antigen testing was 76.27 and 98.78%. Diagnosis performance of specific antibodies became better from the third week after onset. Subgroup analysis suggested that severe patients had higher levels of antigens than mild patients. Conclusions: High level of serum antigen suggested early infection and serious illness. Serum N protein antigen testing by chemiluminescence immunoassay is considered as a viable assay used to improve diagnostic sensitivity for current patients.

On testing for infections during epidemics, with application to Covid-19 in Ontario, Canada.

During an epidemic, accurate estimation of the numbers of viral infections in different regions and groups is important for understanding transmission and guiding public health actions. This depends on effective testing strategies that identify a high proportion of infections (that is, provide high ascertainment rates). For the novel coronavirus SARS-CoV-2, ascertainment rates do not appear to be high in most jurisdictions, but quantitative analysis of testing has been limited. We provide statistical models for studying testing and ascertainment rates, and illustrate them on public data on testing and case counts in Ontario, Canada.

Modeling of network based digital contact tracing and testing strategies, including the pre-exposure notification system, for the COVID-19 pandemic.

With more than 1.7 million COVID-19 deaths, identifying effective measures to prevent COVID-19 is a top priority. We developed a mathematical model to simulate the COVID-19 pandemic with digital contact tracing and testing strategies. The model uses a real-world social network generated from a high-resolution contact data set of 180 students. This model incorporates infectivity variations, test sensitivities, incubation period, and asymptomatic cases. We present a method to extend the weighted temporal social network and present simulations on a network of 5000 students. The purpose of this work is to investigate optimal quarantine rules and testing strategies with digital contact tracing. The results show that the traditional strategy of quarantining direct contacts reduces infections by less than 20% without sufficient testing. Periodic testing every 2 weeks without contact tracing reduces infections by less than 3%. A variety of strategies are discussed including testing second and third degree contacts and the pre-exposure notification system, which acts as a social radar warning users how far they are from COVID-19. The most effective strategy discussed in this work was combining the pre-exposure notification system with testing second and third degree contacts. This strategy reduces infections by 18.3% when 30% of the population uses the app, 45.2% when 50% of the population uses the app, 72.1% when 70% of the population uses the app, and 86.8% when 95% of the population uses the app. When simulating the model on an extended network of 5000 students, the results are similar with the contact tracing app reducing infections by up to 79%.