Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review.

The endothelium is a complex organ with a multitude of properties essential for control of vascular functions. Dysfunction of the vascular endothelium is regarded as an important factor in the pathogenesis of diabetic micro- and macro-angiopathy. Endothelial dysfunction in Type I and II diabetes complicated by micro- or macro-albuminuria is generalized in that it affects many aspects of endothelial function and occurs not only in the kidney. The close linkage between microalbuminuria and endothelial dysfunction in diabetes is an attractive explanation for the fact that microalbuminuria is a risk marker for atherothrombosis. In Type I diabetes, endothelial dysfunction precedes and may cause diabetic microangiopathy, but it is not clear whether endothelial dysfunction is a feature of the diabetic state itself. In Type II diabetes, endothelial function is impaired from the onset of the disease and is strongly related to adverse outcomes. It is not clear whether impaired endothelial function is caused by hyperglycaemia or by other factors. Impaired endothelial function is closely associated with and may contribute to insulin resistance regardless of the presence of diabetes. Endothelial dysfunction in diabetes originates from three main sources. Hyperglycaemia and its immediate biochemical sequelae directly alter endothelial function or influence endothelial cell functioning indirectly by the synthesis of growth factors, cytokines and vasoactive agents in other cells. Finally, the components of the metabolic syndrome can impair endothelial function.

[Vascular complications in diabetes mellitus: role of endothelial dysfunction].

miRNet is an easy-to-use, web-based platform designed to help elucidate microRNA (miRNA) functions by integrating users' data with existing knowledge via network-based visual analytics. Since its first release in 2016, miRNet has been accessed by >20 000 researchers worldwide, with ∼100 users on a daily basis. While version 1.0 was focused primarily on miRNA-target gene interactions, it has become clear that in order to obtain a global view of miRNA functions, it is necessary to bring other important players into the context during analysis. Driven by this concept, in miRNet version 2.0, we have (i) added support for transcription factors (TFs) and single nucleotide polymorphisms (SNPs) that affect miRNAs, miRNA-binding sites or target genes, whilst also greatly increased (>5-fold) the underlying knowledgebases of miRNAs, ncRNAs and disease associations; (ii) implemented new functions to allow creation and visual exploration of multipartite networks, with enhanced support for in situ functional analysis and (iii) revamped the web interface, optimized the workflow, and introduced microservices and web application programming interface (API) to sustain high-performance, real-time data analysis. The underlying R package is also released in tandem with version 2.0 to allow more flexible data analysis for R programmers. The miRNet 2.0 website is freely available at https://www.mirnet.ca.

miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology.

The role of JAK/STAT signaling pathway and its inhibitors in diseases.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.

Antibody tests in detecting SARS-CoV-2 infection: A meta-analysis

The latest advances in high-throughput techniques during the past decade allowed the systems biology field to expand significantly. Today, the focus of biologists has shifted from the study of individual biological components to the study of complex biological systems and their dynamics at a larger scale. Through the discovery of novel bioentity relationships, researchers reveal new information about biological functions and processes. Graphs are widely used to represent bioentities such as proteins, genes, small molecules, ligands, and others such as nodes and their connections as edges within a network. In this review, special focus is given to the usability of bipartite graphs and their impact on the field of network biology and medicine. Furthermore, their topological properties and how these can be applied to certain biological case studies are discussed. Finally, available methodologies and software are presented, and useful insights on how bipartite graphs can shape the path toward the solution of challenging biological problems are provided.

Bipartite graphs in systems biology and medicine: a survey of methods and applications.

Summary Background With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. Methods We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. Findings In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. Interpretation ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies. Funding None

/pdf/antibody-tests-in-detecting-sars-cov-2-infection-a-meta-1jof5vaujj.pdf

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

https://escholarship.org/content/qt7mp855jw/qt7mp855jw.pdf?t=p2nbop

Network analysis of genes and their association with diseases.

BACKGROUND Pneumatic tube system (PTS) is a widely used method of transporting blood samples in hospitals. The aim of this study was to evaluate the effects of the PTS transport in certain routine laboratory parameters as it has been implicated with hemolysis. METHODS A systematic review and a meta-analysis were conducted. PubMed and Scopus databases were searched (up until November 2016) to identify prospective studies evaluating the impact of PTS transport in hematological, biochemical and coagulation measurements. The random-effects model was used in the meta-analysis utilizing the mean difference (MD). Heterogeneity was quantitatively assessed using the Cohran's Q and the I2 index. Subgroup analysis, meta-regression analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed for all outcomes. RESULTS From a total of 282 studies identified by the searching procedure, 24 were finally included in the meta-analysis. The meta-analysis yielded statistically significant results for potassium (K) [MD=0.04 mmol/L; 95% confidence interval (CI)=0.015-0.065; p=0.002], lactate dehydrogenase (LDH) (MD=10.343 U/L; 95% CI=6.132-14.554; p<10-4) and aspartate aminotransferase (AST) (MD=1.023 IU/L; 95% CI=0.344-1.702; p=0.003). Subgroup analysis and random-effects meta-regression analysis according to the speed and distance of the samples traveled via the PTS revealed that there is relation between the rate and the distance of PTS with the measurements of K, LDH, white blood cells and red blood cells. CONCLUSIONS This meta-analysis suggests that PTS may be associated with alterations in K, LDH and AST measurements. Although these findings may not have any significant clinical effect on laboratory results, it is wise that each hospital validates their PTS.

Panagiota I. Kontou

Papers

Antibody tests in detecting SARS-CoV-2 infection: A meta-analysis

Bipartite graphs in systems biology and medicine: a survey of methods and applications.

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

Network analysis of genes and their association with diseases.

The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis.