SARS-CoV-2: The Self-Nonself Issue and Diagnostic Tests.

Objective At present, false negatives/positives have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Searching for the molecular basis of such tests' unreliability, this study aimed at defining how specific are the sequences used in serological and polymerase chain reaction (PCR) tests to detect SARS-CoV-2. Materials and Methods Analyses were performed on the leading SARS-CoV-2 biomarker spike glycoprotein (gp). Sharing of peptide sequences between the spike antigen and the human host was analyzed using the Peptide Search program from Uniprot database. Sharing of oligonucleotide sequences was investigated using the nucleotide Basic Local Alignment Search Tool (BLASTn) from National Center for Biotechnology Information (NCBI). Results Two main points stand out: (1) a massive pentapeptide sharing exists between the spike gp and the human proteome, and only a limited number of pentapeptides (namely 107) identify SARS-CoV-2 spike gp as nonself when compared with the human proteome, and (2) the small phenetic difference practically disappears at the genetic level. Indeed, almost all of the 107 pentadecameric nucleotide sequences coding for the pentapeptides unique to SARS-CoV-2 spike gp are present in human nucleic acids too. Conclusion The data are of immunological significance for defining the issue of the viral versus human specificity and likely explain the fact that false positives can occur in serological and PCR tests for SARS-CoV-2 detection.

Diagnosing COVID-19: diagnostic importance of detecting E gene of the SARS-CoV-2 genome

Aim: To evaluate the significance of E gene analysis in addition to N and RdRp genes of SARS-CoV-2, and to compare the specificity and sensitivity of targets. Material(s) and Method(s): We used two reverse transcription-PCR assays: one targeting N, E and RdRp and the other targeting N and RdRp genes and analyzed variation in threshold cycle (Ct) values. Result(s): Of the 155 samples, 70.32% tested positive: all three genes were detected in 45.87%, N and RdRp in 19.27% and only N in 34.86%. Patients negative for the E gene were tested after symptoms disappeared and Ct values were significantly higher. Conclusion(s): Samples negative for the E gene were potentially false positive and clinical conditions should be assessed while interpreting results.Copyright © 2023 Future Medicine Ltd.

Building insights on true positives vs. False positives: Bayes' rule

COVID-19 pandemic policies requiring disease testing provide a rich context to build insights on true positives versus false positives. Our main contribution to the pedagogy of data analytics and statistics is to propose a method for teaching updating of probabilities using Bayes' rule reasoning to build understanding that true positives and false positives depend on the prior probability. Our instructional approach has three parts. First, we show how to construct and interpret raw frequency data tables, instead of using probabilities. Second, we use dynamic visual displays to develop insights and help overcome calculation avoidance or errors. Third, we look at graphs of positive predictive values and negative predictive values for different priors. The learning activities we use include lectures, in-class discussions and exercises, breakout group problem solving sessions, and homework. Our research offers teaching methods to help students understand that the veracity of test results depends on the prior probability as well as helps students develop fundamental skills in understanding probabilistic uncertainty alongside higher-level analytical and evaluative skills. Beyond learning to update the probability of having the disease given a positive test result, our material covers naive estimates of the positive predictive value, the common mistake of ignoring the disease's base rate, debating the relative harm from a false positive versus a false negative, and creating a new disease test. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Investigating the Validity of Botometer-Based Social Bot Studies

The idea that social media platforms like Twitter are inhabited by vast numbers of social bots has become widely accepted in recent years. Social bots are assumed to be automated social media accounts operated by malicious actors with the goal of manipulating public opinion. They are credited with the ability to produce content autonomously and to interact with human users. Social bot activity has been reported in many different political contexts, including the U.S. presidential elections, discussions about migration, climate change, and COVID-19. However, the relevant publications either use crude and questionable heuristics to discriminate between supposed social bots and humans or-in the vast majority of the cases-fully rely on the output of automatic bot detection tools, most commonly Botometer. In this paper, we point out a fundamental theoretical flaw in the widely-used study design for estimating the prevalence of social bots. Furthermore, we empirically investigate the validity of peer-reviewed Botometer-based studies by closely and systematically inspecting hundreds of accounts that had been counted as social bots. We were unable to find a single social bot. Instead, we found mostly accounts undoubtedly operated by human users, the vast majority of them using Twitter in an inconspicuous and unremarkable fashion without the slightest traces of automation. We conclude that studies claiming to investigate the prevalence, properties, or influence of social bots based on Botometer have, in reality, just investigated false positives and artifacts of this approach.

Emergency department care of ABSSSI with dalbavancin infusion, direct discharge, and outpatient telemedicine follow up: a study protocol.

Novel therapeutic strategies such as the long-acting lipoglycopeptide antibiotics allow for the treatment and discharge of selected emergency department (ED) patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI), who require intravenous antibiotics and would otherwise be hospitalized. The COVID-19 pandemic highlighted the need to develop strategies that may reduce hospitalization. The telehealth approach has shown success in remote management of cellulitis patients and could aid in the remote follow up of overall ABSSSI patients. This article describes a study protocol for the telemedicine follow up of patients diagnosed with ABSSSI in the ED, requiring intravenous treatment, receiving a single dalbavancin dose, and directly discharged. A telehealth system for remote follow up is evaluated as well as the possible inclusion of point-of-care ultrasound for the appropriate diagnosis of ABSSSI. The study will be conducted in compliance with regulatory requirements; and all collected data will be kept strictly confidential and in accordance with all relevant legislation on the control and protection of personal information. Dissemination of the study protocol may help increasing knowledge and awareness on this topic, with the aim of optimizing patient management, reducing hospitalization and lower the impact on healthcare associated costs.

Consequences and Lessons from 2020 Pandemic Disaster: Game-Theoretic Recalibration of COVID-19 to Mobilize and Vaccinate by Rectifying False Negatives and False Positives

The main purpose of this applied research paper is to optimize the probabilities of the false negative (FN) error, β, and the false positive (FP) error, α in a pandemic healthcare setting. The overall objective is to estimate the number of those patients falsely declared uninfected, and those falsely declared infected, aiming to recalibrate the overall count of cases aligned with the world’s mobilization and vaccination efforts. Incomplete FN results can have devastating impacts on current efforts to contain the SARS-CoV-2 (COVID-19) outbreak as infected patients are mistakenly given the go-ahead to return to normal life, likely infecting others. The whole world experienced in 2020 that the number of deaths were undercounted due to existence of false negatives or asymptomatic carriers. But there did not exist universally unbiased scientific methods other than controversial comparisons with the past seasonal death records. This game-theoretic research effort fills a void to replace guesswork and judgment-calls by employing data-scientific health informatics. This article reasons by citing real-data examples why von Neumann’s mixed-strategy game-theoretic feasible solutions to predict the FN cases are noteworthy to prevent more fatalities by facilitating timely pandemic mobilization. FP counts are however not so critical other than causing panic and waste of resources. In the wake of vaccination relief efforts, this research topic is still valid and invaluable for the future unprecedented pandemics such as a hypothetical COVID-35. A fringe benefit of the article is to transform hypothesis testing from subjective to objective for scientific, medical and engineering decisions. Evolutionary game theory may be incorporated for evolving and mutating pandemic variants e.g. OMICRON and DELTA for further research tips. Copyright © 2022 by the authors.

Building insights on true positives vs. false positives: Bayes’ rule

COVID-19 pandemic policies requiring disease testing provide a rich context to build insights on true positives versus false positives. Our main contribution to the pedagogy of data analytics and statistics is to propose a method for teaching updating of probabilities using Bayes’ rule reasoning to build understanding that true positives and false positives depend on the prior probability. Our instructional approach has three parts. First, we show how to construct and interpret raw frequency data tables, instead of using probabilities. Second, we use dynamic visual displays to develop insights and help overcome calculation avoidance or errors. Third, we look at graphs of positive predictive values and negative predictive values for different priors. The learning activities we use include lectures, in-class discussions and exercises, breakout group problem solving sessions, and homework. Our research offers teaching methods to help students understand that the veracity of test results depends on the prior probability as well as helps students develop fundamental skills in understanding probabilistic uncertainty alongside higher-level analytical and evaluative skills. Beyond learning to update the probability of having the disease given a positive test result, our material covers naïve estimates of the positive predictive value, the common mistake of ignoring the disease's base rate, debating the relative harm from a false positive versus a false negative, and creating a new disease test. © 2022 Decision Sciences Institute.

Current RT-qPCR to detect SARS-CoV-2 may give positive results for related coronaviruses.

Some weeks after the first CoVID-19 outbreak, the World Health Organization published some real-time PCR (qPCR) protocols developed by different health reference centers. These qPCR designs are being used worldwide to detect SARS-CoV-2 in the population, to monitor the prevalence of the virus during the pandemic. Moreover, some of these protocols to detect SARS-CoV-2 have widely been applied to environmental samples for epidemiological surveillance purposes. In the present work, the specificity of these currently used RT-qPCR designs was validated in vitro using SARS-CoV-2 and highly related coronaviral genomic sequences and compared to performance of the commercially available GPS™ CoVID-19 dtec-RT-qPCR Test. Assays performed with SARS-CoV-2-related genomes showed positive amplification when using some of these qPCR methods, indicating they may give SARS-CoV-2 false positives. This finding may be particularly relevant for SARS-CoV-2 monitoring of environmental samples, where an unknown pool of phylogenetically close-related viruses may exist.

Nucleotide Sequence Sharing between the Human Genome and Primers for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Detection.

This study shows that oligonucleotide sequences are shared between the human genome and primers that have been proposed/used for SARS-CoV-2 detection by polymerase chain reaction (PCR). The high level of sharing (namely, up to 19mer with a maximum number of gaps equal to 2) might bear implications for the diagnostic validity of SARS-CoV-2 detection by PCR.

Conundrum of re-positive COVID-19 cases: A systematic review of case reports and case series.

BACKGROUND: The systematic review was conducted to summarize and synthesize evidence from all available case series and case reports published on re-positive COVID-19 cases. METHODS: The systematic review was registered with Prospero (CRD42020210446). PRISMA guidelines were followed for conducting the systematic review. Inclusion criteria for studies included case reports and case series which have documented cases of positive reverse transcriptase polymerase chain reaction (RT-PCR) after a period of clinical improvement or a negative RT-PCR report. Reviews, opinions, and animal studies were excluded. Methodological quality was assessed using the modified Murad scale. RESULTS: A total of 30 case reports/case series were included in the study, wherein a total of 219 cases were included. In re-positive cases, the age range varied from 10 months to 91 years. The pooled proportion of positive cases after follow-up using random-effects was 12% (95% confidence interval [CI]: 09%-15%). Among the re-positives, a total of 57 cases (26%) had comorbidities. A total of 51 (23.3%) and 17 (7.8%) re-positive cases had been treated with antivirals and corticosteroids, respectively. Only a few studies have confirmed the presence of antibodies after the first episode. Studies that included contact tracing of re-positives did not find any positive cases among close contacts of re-positive cases. CONCLUSION: The systemic review found that reinfection is a possibility within 123 days of a negative RT-PCR test in a small number of cases of COVID-19. This has wider ramifications in framing clinical, preventive, and public health policy guidelines.

Positive outcomes associated with the COVID-19 pandemic in Australia.

ISSUE ADDRESSED: To investigate whether Australians have experienced any positive effects during the COVID-19 pandemic. METHODS: National online longitudinal survey. As part of a June 2020 survey, participants (n = 1370) were asked 'In your life, have you experienced any positive effects from the COVID-19 pandemic' (yes/no) and also completed the World Health Organisation-Five well-being index. Differences were explored by demographic variables. Free-text responses were thematically coded. RESULTS: Nine hundred sixty participants (70%) reported experiencing at least one positive effect during the COVID-19 pandemic. Living with others (P = .045) and employment situation (P < .001) at baseline (April) were associated with experiencing positive effects. Individuals working for pay from home were more likely to experience positive effects compared to those who were not working for pay (aOR = 0.45, 95% CI: 0.32, 0.63, P < .001) or who were working for pay outside the home (aOR = 0.40, 95% CI: 0.28, 0.58, P < .001). 54.2% of participants reported a sufficient level of well-being, 23.2% low well-being and a further 22.6% very low well-being. Of those experiencing positive effects, 945/960 (98%) provided an explanation. The three most common themes were 'Family time' (33%), 'Work flexibility' (29%) and 'Calmer life' (19%). CONCLUSIONS: A large proportion of participants reported positive effects resulting from changes to daily life due to the COVID-19 pandemic in Australia. SO WHAT: The needs of people living alone, and of those having to work outside the home or who are unemployed, should be considered by health policymakers and employers in future pandemic preparedness efforts.

The Effect of the COVID-19 Pandemic on Riding Lesson Barns and Summer Camps in Ontario.

The COVID-19 pandemic has direct effects on the operations of riding lesson facilities and summer camps, with little government guidance on how to implement these. An online survey link was distributed to riding lesson facilities in Ontario. Descriptive statistics of respondents (n = 72) reported a decrease in both the number of riding lessons offered and the number of riding students per lesson. Scheduling riding times and limiting access to specific places on the farm ensured controlled access to the farms. Strict hygiene procedures were implemented including disinfecting high contact areas and shared tack. Summer camps followed the same procedures, although some farms chose not to offer camps at all. The use of facemasks was not prevalent in either riding lessons (43.3%) or camps (25%), likely because the activities took place outside. However, recent evidence shows that facemasks are perhaps even more important when outdoors, and it is recommended that riding lesson facilities re-evaluate their requirements for students and staff to wear facemasks while in the barn. In spite of the hardships, many positive aspects were noted including time to attend to repair and maintenance needs, scrutinizing business practices, more respect for barn rules, and more time to bond with the horses.

A Comprehensive Approach Is Vital for Diagnosing COVID-19: A Case of False Negative.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace throughout the world, and the World Health Organization (WHO) declared it as pandemic on March 11, 2020. We present a case of COVID-19 patient whose reverse transcription-polymerase chain reaction (RT-PCR) initially was false negative and later turned positive, which will stress the importance of a comprehensive approach while evaluating a patient with a differential of COVID-19. The clinicians should be aware of the sensitivity and specificities of these tests which can have grave implications on the patient and community if the diagnosis is missed just based on the laboratory tests due to the highly contagious nature of the disease.