Point-of-Care Testing in Primary Care

Point-of-care testing (POCT) in pediatric primary care is essential for clinicians to make a timely and accurate diagnosis. The COVID-19 pandemic has highlighted the importance of timely and accurate testing strategies to correctly identify the etiology of upper and lower respiratory infections. Additionally, pediatric POCT continues to be important in rural and underserved communities where access to hospital laboratories may be less available. This chapter will focus on seven rapid tests: Group A streptococcus (GAS), influenza A & B, SARS-CoV-2 (COVID-19), human immunodeficiency virus (HIV), C-reactive protein (CRP), human chorionic gonadotropin (hCG), and hemoglobin A1c (HbA1c). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Characteristics of SARS-CoV-2, COVID-19, and laboratory diagnosis / Características del SARS-CoV-2, COVID-19 y su diagnóstico en el laboratorio

La enfermedad COVID­19 es causada por el virus SARS-CoV-2, descrito por primera vez en diciembre del 2019 en Wuhan, China, y declarada en marzo del 2020 como una pandemia mundial. Actualmente existen diversos métodos diagnósticos para COVID-19, siendo el estándar de oro la detección del material genético mediante la reacción en cadena de la polimerasa (PCR), en su variante, la RT-PCR, que detecta el material genético de tipo ARN presente en el virus. Sin embargo, es necesario disponer de pruebas rápidas con alta sensibilidad y precisión para realizarlas a gran escala y brindar un diagnóstico oportuno. Adicionalmente, se debe disponer de otras herramientas que, si bien no van a establecer un diagnóstico, le van a permitir al profesional brindar un mejor manejo clínico y epidemiológico que ayuden a predecir el agravamiento del paciente y su posible ingreso a UCI, destacando entre estas los niveles de dímero D, linfocitos, ferritina, urea y creatinina, entre otras. En esta revisión se evalúa la utilidad y limitaciones de los diferentes métodos diagnósticos para COVID-19, al igual que las características, fisiopatología y respuesta inmune al SARS-CoV-2, así como algunos aspectos preanalíticos de importancia que ayudan a minimizar errores en el diagnóstico como consecuencia de procedimientos incorrectos en la toma, transporte y conservación de la muestra, y que permiten al profesional emitir resultados veraces y confiables. Lo anterior se realizó basado en artículos originales, revisiones y guías clínicas

COVID­19 is caused by the SARS-CoV-2 virus, first described in December 2019 in Wuhan, China, and declared a global pandemic in March 2020. Currently there are various diagnostic methods for COVID-19, the gold standard is the detection of genetic material through polymerase chain reaction (PCR) in its variant, RT-PCR, which detects RNA-type genetic material present in the virus. However, it is necessary to have rapid tests with high sensitivity and precision to be performed on a large scale and provide timely diagnosis. Furthermore, other tools must be available, and although they will not establish the diagnosis, will allow the professional to provide better clinical and epidemiological management that will help predict the worsening of the patient and possible admission to the ICU. Among these, levels of D-dimer, lymphocytes, ferritin, urea and creatinine. In this review, the usefulness and limitations of the different diagnostic methods for COVID-19 are evaluated, as well as the characteristics, pathophysiology and immune response to SARS-CoV-2, and some important preanalytical aspects that allow minimizing diagnostic errors as a consequence of incorrect procedures in the collection, transport and conservation of the sample, that allow the professional to yield accurate and reliable results. This article was completed based on original articles, reviews and clinical guidelines

Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation.

Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that upon phagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turn mediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF. Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrin-mediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present study describes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells. These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which may contribute to tissue damage and severe disease.

Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study.

BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.

Unbinding of hACE2 and inhibitors from the receptor binding domain of SARS-CoV-2 spike protein.

The first direful biomolecular event leading to COVID-19 disease is the SARS-CoV-2 virus surface spike (S) protein-mediated interaction with the human transmembrane protein, angiotensin-converting enzyme 2 (hACE2). Prevention of this interaction presents an attractive alternative to thwart SARS-CoV-2 replications. The development of monoclonal antibodies (mAbs) in the convalescent plasma treatment, nanobody, and designer peptides, which recognizes epitopes that overlap with hACE2 binding sites in the receptor-binding domain (RBD) of S protein (S/RBD) and thereby blocking the infection has been the center stage of therapeutic research. Here we report atomistic and reliable in silico structure-energetic features of the S/RBD interactions with hACE2 and its two inhibitors (convalescent mAb, B38, and an alpaca nanobody, Ty1). The discovered potential of mean forces exhibits free energy basin and barriers along the interaction pathways, providing sufficient molecular insights to design a B38 mutant and a Ty1-based peptide with higher binding capacity. While the mutated B38 forms a 60-fold deeper free energy minimum, the designer peptide (Ty1-based) constitutes 38 amino acids and is found to form a 100-fold deeper free energy minimum in the first binding basin than their wild-type variants in complex with S/RBD. Our strategy may help to design more efficacious biologics towards therapeutic intervention against the current raging pandemic.Communicated by Ramaswamy H. Sarma.

Viral Vaccines

Since antiquity, humans have strived to find ways to prevent the suffering and mortality caused by infectious pathogens. No interventions in medical history have had a bigger impact on human health than the development of preventative vaccines against infectious diseases. Viruses represent important pathogens responsible for epidemics and, in the case of influenza and SARS-CoV-2, global pandemics responsible for substantial - and sometimes staggering - morbidity and mortality. This article reviews the viral vaccines used today in clinical practice, summarizes the differences in vaccine design and manufacturing, and identifies priorities for future research and development of new viral vaccines. © 2022 Elsevier Inc. All rights reserved.

Epidemiological surveillance and environmental hygiene, SARS-CoV-2 infection in the community, urban wastewater control in Cyprus, and water reuse

Background: Nowadays public health faces many challenges. Epidemiological surveillance and environmental hygiene and infection in community from SARS-CoV-2 along with its control in municipal wastewaters and reuse of water are amongst them. Epidemiology and environmental microbiology considers wastewater release of great importance. The purpose of this study is the detection and classification of COVID-19 infection in community wastewater and their removal by efficient functional processes. Methods and materials: A descriptive review of the published literature over the last 15-years in Greek and English was carried out via Medline, Scopus, and Google Scholar databases with the perspective of creating a research protocol. The study material consists of recent articles on the subject using keywords. Thus, the most effective techniques, wastewater-based epidemiology, and quantitative microbial risk assessment, for virus surveillance in wastewater are further analyzed. Results and contexts: The process and management of wastewater at a global level, is a high risk and a great challenge due to the huge amount of biomedical waste and wastewater that ends up in wastewater treatment plants. It may be an obstacle to human health, especially in the ongoing pandemic situation that must be evaluated in the operations of the plant in the environment along with the presence of other dangerous pathogenic microbes. Conclusions: It is vital the relationship between humanity and environment be reconsidered and more sustainable behavioural choices be encouraged. Scientific evidence pinpoints that the onset of new viral pathogens with a high epidemic-pandemic potential is often the result, complex, interactions among animals, individuals, and environment.

Estimating Exposure Risk to Guide Behaviour During the SARS-COV2 Pandemic.

The end of 2020 and the beginning of 2021 was a challenging time for many countries in Europe, as the combination of colder weather, holiday celebrations, and the emergence of more transmissible virus variants conspired to create a perfect storm for virus transmission across the continent. At the same time lockdowns appeared to be less effective than they were earlier in the pandemic. In this paper we argue that one contributing factor is that existing ways of communicating risk-case numbers, test positivity rates, hospitalisations etc.-are difficult for individuals to translate into a level of personal risk, thereby limiting the ability of individuals to properly calibrate their own behaviour. We propose an new more direct measure of personal risk, exposure risk, to estimate the likelihood that an individual will come into contact with an infected person, and we argue that it can play an important role, alongside more conventional statistics, to help translate complex epidemiological data into a simple measure to guide pandemic behaviour. We describe how exposure risk can be calculated using existing data and infection prediction models, and use it to evaluate and compare the exposure risk associated with 39 European countries.

Long COVID: Is there a kidney link?

Metabolic causes such as altered bioenergetics and amino acid metabolism may play a major role in Long COVID. Renal-metabolic regulation is an integral part of these pathways but has not been systematically or routinely investigated in Long COVID. Here we discuss the biochemistry of renal tubular injury as it may contribute to Long COVID symptoms. We propose three potential mechanisms that could be involved in Long COVID namely creatine phosphate metabolism, un-reclaimed glomerular filtrate and COVID specific proximal tubule cells (PTC) injury-a tryptophan paradigm. This approach is intended to allow for improved diagnostics and therapy for the long-haul sufferers.

[Potential of Interferon Lambda as an Inhibitor of SARS-CoV-2]

This study provides an overview of scientific results on the feasibility of using type III interferons against SARS-CoV-2. We have analyzed data obtained from the PubMed electronic database for the period 2020-2022. The results of our own studies of pharmacological substances based on recombinant IFN-lambda1 and its pegylated form are also presented. Completed and ongoing investigations allow us to position IFN-lambda as an effective therapeutic agent against SARS-CoV-2.

MEDICINAL PLANTS AND VACCINATIONS USED AGAINST COVID-19: A COMPREHENSIVE REVIEW

The newly emerged severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), the causative agent of corona virus disease 2019 (COVID-19), has deteriorated the global order economically, socially and politically. As an emergency of global concern, the disease continuously spread havoc with its dreadful health manifestations with no regard for any race, religion and region. The mortality rates in different countries are surprisingly variable and there is debate about population-wise differential response to virus. Different countries have imposed lock-down to reduce the spread of virus;however, the positive outcomes of lock-down in terms of reducing mortality rate and transmission of virus are still questioned. Further, public accusations and debate of world powers regarding the origin of virus has created regional hate sentiments and political chaos which could result is serious repercussions following miscalculation of actual facts. Scientific communities are struggling to cope with the disease by developing potential vaccines against the S protein of SARS-CoV-2 and were testing the already marketed drugs against this coronavirus. Therefore, several medicinal plants and various vaccinations have been used against Covid-19. This review highlights the origin, virulence, vaccination but most importantly the plants extracts used against the causative agent of COVID-19.

[The experience of community pharmacy in SARS-CoV-2 antigen detection tests programs.]

SARS-CoV-2 infection was an unprecedented pandemic with unprecedented global health and socio-economic impact. More than 13 million cases had been confirmed in Spain by August 2022, and diagnostic testing to detect cases of infection in the country has helped to partially mitigate the spread of the virus. In 2021, the first self-testing antigen tests were marketed for dispensing in community pharmacies, and over-the-counter dispensing was allowed from July of that year. The network of community pharmacies played a key role, not only in the informed dispensing of these tests, but also in actively participating in the performance, supervision and reporting of results to the health authorities, and even in the issuing of digital certificates. A compilation has been made of all the available data on the subject, with a deadline of 13 February 2022, which is considered to be the end of the sixth wave of the epidemic in Spain. The results of the action taken by community pharmacies in twelve Autonomous Communities, which somehow participated in these initiatives by carrying out or supervising a total of 1,043,800 tests, from which 109,570 positive cases (10.5% of the total) were detected and reported to the National Health System, are presented in this article. Although the results are provisional, because many of the programmes are still ongoing, they are a clear demonstration of the potential that community pharmacies can play in Public Health work.

Impact of COVID-19 on vacation recreational walking: Evidence from an urban coastal destination

This study examined the impact of COVID-19 on recreational walking while on vacation, a relevant activity among tourists especially in urban destinations. We surveyed visitors to Costa Daurada, an urban coastal destination in Catalonia in August 2020. Only 5% of participants reported lower recreational walking levels compared to normal circumstances;75% reported similar levels;and 20% reported higher levels. Higher recreational walking levels were associated with visiting local amenities or strolling and with a higher level of perceived safety from COVID-19 when walking. Higher perceived overcrowding was associated with less recreational walking. The pandemic may have altered recreational behavior while on vacation in urban settings especially by increasing outdoor activities such as recreational walking. If persistent, such behavioral changes could have relevant implications for both the tourism and recreation sectors and for local policymakers who aim to promote walkability while managing tourist pedestrian flows.

SARS-CoV-2 Transmission among Students after the Full Reopening of Schools

Objective Closing of schools within the scope of the pandemic measures and switching to online education have negatively affected the mental and physical health of children as well as their education. The effect of complete reopening of schools on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully known. In the 2021–2022 academic year, the Ministry of National Education of Türkiye has decided to continue face-to-face education at all levels and in all private and public schools, by following a series of measures. There are no studies on school transmission reported from Türkiye since then. This study aimed to assess the dynamics of coronavirus diseases 2019 (COVID-19) transmission in schools by evaluating the data of the school contact screening outpatient clinic of a tertiary children's hospital. Methods According to the Ministry of National Education guidelines in Türkiye, all students in a class with two polymerase chain reaction (PCR)–confirmed COVID-19 cases are sent to their homes and have a SARS-CoV-2 PCR test on the fifth day. While the students with negative test results return to school, students who test positive continue to stay at home until the 10th day. The current study retrospectively analyzed the screening results of primary, middle, and high school students who presented at the school contact screening polyclinic during the first semester of the 2021–2022 academic season. Discussion There were a total of 11,608 presentations to the school contact screening polyclinic, and 1,107 children tested positive with SARS-CoV-2 PCR (9.5%). The median weekly positivity rate was 9.7% in primary school, 9.4% in middle school, and 5.6% in high school. The weekly positivity rate increased from the 16th week at all school levels;the positivity rates ran in parallel before this time but significantly increased from the 16th week to the half-term break. Conclusion The curve of the positivity rates in schools was similar to Türkiye's pandemic curve. In this respect, the low SARS-CoV-2 transmission in schools correlated with the low number of cases in the community. [ FROM AUTHOR] Copyright of Journal of Pediatric Infectious Diseases is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

An Effective Platform for SARS-CoV-2 Prevention by Combining Neutralization and RNAi Technology

At present, the coronavirus disease 2019 (COVID-19) pandemic is a global health crisis. Scientists all over the globe are urgently looking forward to an effective solution to prevent the spread of the epidemic and avoid more casualties at an early date. In this study, we establish an effective platform for the prevention of SARS-CoV-2 by combining the neutralization strategy and RNAi technology. To protect normal cells from infection, the customized cells are constructed to stably express viral antigenic receptor ACE2 on the cell membrane. These modified cells are used as bait for inducing the viral entry. The transcription and replication activities of viral genome are intercepted subsequently by the intracellular shRNAs, which are complementary to the viral gene fragments. A pseudotyped virus reconstructed from the HIV lentivirus is utilized as a virus model, by which we validate the feasibility and effectiveness of our strategy in vitro. Our work establishes an initial model and lays the foundation for future prevention and treatment of various RNA viruses. [ABSTRACT FROM AUTHOR] Copyright of Chinese Journal of Polymer Science (Springer Science & Business Media B.V.) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Screening for Potential Traditional Herbal Inhibitors Against 3-Chymo-trypsin-like Main Protease (3CLpro) from Four Different Coronaviruses: An in silico Approach

Background: The recent outbreak of the COVID-19 pandemic has raised a global health concern due to the unavailability of any vaccines or drugs. The repurposing of traditional herbs with broad-spectrum anti-viral activity can be explored to control or prevent a pandemic. Objective(s): The 3-chymotrypsin-like main protease (3CLpro), also referred to as the "Achilles' heel" of the coronaviruses (CoVs), is highly conserved among CoVs and is a potential drug target. 3CLpro is essential for the virus' life cycle. The objective of the study was to screen and identify broad--spectrum natural phytoconstituents against the conserved active site and substrate-binding site of 3CLpro of HCoVs. Method(s): Herein, we applied the computational strategy based on molecular docking to identify potential phytoconstituents for the non-covalent inhibition of the main protease 3CLpro from four different CoVs, namely, SARS-CoV-2, SARS-CoV, HCoV-HKU1, and HCoV-229E. Result(s): Our study shows that natural phytoconstituents in Triphala (a blend of Emblica officinalis fruit, Terminalia bellerica fruit, and Terminalia chebula fruit), namely chebulagic acid, chebulinic acid, and elagic acid, exhibited the highest binding affinity and lowest dissociation constants (Ki), against the conserved 3CLpro main protease of SARSCoV-2, SARS-CoV, HCoV-HKU1, and HCoV-229E. Besides, phytoconstituents of other herbs like Withania somnifera, Glycyrrhiza glabra, Hyssopus officinalis, Camellia sinensis, Prunella vulgaris, and Ocimum sanctum also showed good binding affinity and lower Ki against the active site of 3CLpro. The top-ranking phyto-constituents' binding interactions clearly showed strong and stable interactions with amino acid residues in the catalytic dyad (CYS-HIS) and substrate-binding pocket of the 3CLpro main proteases. Conclusion(s): This study provides a valuable scaffold for repurposing traditional herbs with anti--CoV activity to combat SARS-CoV-2 and other HCoVs until the discovery of new therapies.Copyright © 2021 Bentham Science Publishers.

Automatic detection of novel corona virus (SARS-CoV-2) infection in computed tomography scan based on local adaptive thresholding and kernel-support vectors

The recent studies have indicated the requisite of computed tomography scan analysis by radiologists extensively to find out the suspected patients of SARS-CoV-2 (COVID-19). The existing deep learning methods distribute one or more of the subsequent bottlenecks. Therefore, a straight forward method for detecting COVID-19 infection using real-world computed tomography scans is presented. The detection process consists of image processing techniques such as segmentation of lung parenchyma and extraction of effective texture features. The kernel-based support vector machine is employed over feature vectors for classification. The performance parameters of the proposed method are calculated and compared with the existing methodology on the same dataset. The classification results are found outperforming and the method is less probabilistic which can be further exploited for developing more realistic detection system.

Applications of alignment-free sequence descriptors in the characterization of sequences in the age of big data: a case study with Zika virus, SARS, MERS, and COVID-19

This chapter gives a detailed presentation of the theoretical background and computational approaches to the utility of alignment-free sequence descriptors and multidimensional variable reduction methods in the characterization and visualization of biological sequence data. The utility of such novel methods developed by the authors of this chapter is shown using data on case studies of severe acute respiratory syndrome, Middle East respiratory syndrome, Coronavirus disease-2019, and Zika viruses. © 2023 Elsevier Inc. All rights reserved.

The Impact of Energy Prices on Precious Metals: A Comparison of the SARS-COV2 Period and Prior Period

Commodities are defined as goods that are traded. Thousands of different items are sold on international markets, but strategically important commodities such as gold, silver, and oil are used far more frequently in the real estate industry and financial markets. Oil and these metals are employed in numerous industrial applications throughout the economy, but they also draw substantial investment. The purpose of this study is to investigate the causal connections between the prices of gold and silver, two precious metals, and oil and natural gas, the two most often used energy sources. This was accomplished by comparing the weekly prices of Brent Petroleum (BRENT), Crude Oil (WTI), Natural Gas (NG), and the weekly data of Gold and Silver during and before the SARS-CoV2 epidemic. The study employed the Distributed Delayed Autoregressive Bound Test (ARDL) approach to examine the relationship between the prices of energy (natural gas, Brent oil, and crude oil) and precious metals (silver and gold). The ARDL test showed that the prices of WTI, Brent, and NG had a big effect on the prices of silver and gold during and before the SARS-COV2 pandemic.