The emergence of the SARS-CoV-2 Variant of Concern (VOC) Omicron has been characterized by an explosive number of cases in almost every part of the world. The dissemination of different sub-lineages and recombinant genomes also led to several posterior waves in many countries. The circulation of this VOC and its major sub-lineages (BA.1 to BA.5) was monitored in community cases and in international travelers returning to Venezuela, by a rapid partial sequencing method. The specific sub-lineage assignment was performed by complete genome sequencing. Epidemic waves of SARS-CoV-2 cases were observed among international travelers during 2022, a situation not seen before December 2021. The succession of the Omicron VOC sub-lineages BA.1 to BA.5 occurred sequentially, except for BA.3, which was almost not detected. However, the sub-lineages generally circulated two months earlier in international travelers than in community cases. The diversity of Omicron sub-lineages found in international travelers was related to the one found in the USA, consistent with the most frequent destination of international travel from Venezuela this year. These differences are compatible with the delay observed in Latin American countries in the circulation of the different lineages of the Omicron VOC.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

Crataegus Oxyacantha is used in the treatment of cardiovascular diseases. In related to your biosafety, only in vitro and in vivo genotoxicity of the fruit and the leaf is described, however, the teratogenic potential is unknown. The aim this study was evaluating the transplacental genotoxicity effect of aqueous and hydroalcoholic extract of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in liver. Three different doses of the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), sampling in rats were every 24 h during the last 6 days of gestation and only one sample was taken in neonates at birth. A sample of the mother's and neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the aqueous and hydroalcoholic extract generated cytotoxic and genotoxic damage in the short term. On the other hand, only the aqueous extract showed a teratogenic effect. Based on these results, the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf should not be administered during pregnancy.

This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection, and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus disease 2019 (COVID-19) for assay of the SARS-CoV-2 anti-N IgG at two time points (Phase 1 & 2) between November 2020 and February 2021. Out of 390 HCWs with COVID-19 diagnosis, 267 (68.5%) had detectable SARS-CoV-2 anti-N IgG antibodies at the end of phase I. These antibodies persisted for 4-5 and 6-7 months in 76.4% and 16.1%, respectively. In the multivariate logistic regression model analysis, black participants were more likely to sustain SARS-CoV-2 anti-N IgG for 4-5 months. However, participants who were HIV positive were less likely to sustain SARS-CoV-2 anti-N IgG antibodies for 4-5 months. In addition, individuals who were <45 years of age were more likely to sustain SARS-CoV-2 anti-N IgG for 6-7 months. Of the 202 HCWs selected for phase 2, 116 participants (57.4%) had persistent SARS-CoV-2 anti-N IgG for an extended mean period of 223 days (7.5 months). Findings support the longevity of vaccine responses against SARS CoV-2 in black Africans.

Due to species barriers and poor adaptability to new host environments, few pathogens cause global pandemics. But, SARS-CoV-2 is one exception with its high transmissivity and delayed onset of symptoms. Fortunately, the world was able to tap on the technologies especially the maturing RT-qPCR designed to combat SARS to launch an initial offensive on SARS-CoV-2. These initial efforts may have bought time for scientists to develop more refined diagnostic tests that specifically target SARS-CoV-2. This article describes the effort put forth by the biotech industry and academia in Singapore to develop diagnostic tests that aid the early detection of positive cases, and thereby help contain the virus. Direct tests such as RT-qPCR and antigen rapid test profile the virus nucleic acid and surface proteins, respectively. But, of equal importance in case detection and treatment is serological tests that measure the relative abundance of IgM and IgG which is indicative of infection phase and quality of immune response in positive cases. Other tests such as isothermal amplification, CRISPR-based diagnostics and breath tests are also in development or at initial field deployment, and would undoubtedly provide valuable use experience useful for the development of molecular assays to detect and combat the next pathogen of global concern.

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The Random Forest algorithm correctly identified 83% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as shown by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 demonstrates some trends of vegetation cover evolution in response to climate change in the considered area. The potential applications in terms of permafrost modeling (hiperborea.omp.eu) are finally discussed.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization and their expressional profile in different tissues was studied. These in-silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p<0.010 for hand washing). The risk perception of COVID-19 infection had a slight direct relationship with preventive behaviors (B=0.28, p=0.021 for total behavior; B=0.13, p=0.015 for hand washing), with the exception of the preventive behavior of using additional protection at work (p=0.339). We found that fear and risk perception are associated with increased practice of hand washing and use of additional protection at work. Further studies are required on the influence of working conditions, job performance and the occurrence of mental health problems in frontline personnel with regard to COVID-19.

The disease COVID-19 is brought on by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) First appeared in China in December 2019 and quickly spread around the world after being declared a worldwide pandemic by the World Health Organization in March 2020. COVID-19, Medical Laboratory Professionals, SARS-COV-2, Diagnostic, Importance and difficulties for testing were the selected terms to search the databases of PubMed and Google Scholar for previously published material. Many diagnostic tests are applied in corona virus detection like Droplet Digital PCR (ddPCR), Multiplex PCR, Loop-mediated Isothermal Amplification (LAMP) and more. There is a lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies. Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been in the past associated with adverse effects on human health among which belong also respiratory diseases. Our study is focused on the evaluation of PAH exposure by measuring the concentrations of their monohydroxylated metabolites (OH-PAHs) in urine and comparing their concentrations with the incidence of respiratory diseases in 2-year-old children from two locations of the Czech Republic – a control locality Ceske Budejovice and a previously highly contaminated mining district Most. Methods: The total number of 248 participants were sampled for urine samples that were analysed for the presence of 11 OH-PAHs using liquid-liquid extraction with ethyl acetate and clean-up employing dispersive solid phase extraction with a sorbent Z-Sep. Separation, identification and quantification of the target compounds was achieved by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The incidence of respiratory diseases was evaluated according to the questionnaires provided by the paediatricians. Results and discussion: The concentrations of measured OH-PAHs were higher in the urine samples collected from 2-year-old children living in Most compared to 2-year-old children from Ceske Budejovice. The same trend was observed also when the urine samples were analysed when these children were studied as newborns in our previous study. From all of the monitored respiratory diseases, only influenza due to unidentified influenza virus showed a difference between tested locations where the 2-year-old children living in Most were more frequently diagnosed with this disease. Conclusion: Even though the air pollution and lifestyle in both cities is very similar, we have observed higher incidence of respiratory diseases as well as higher concentration of OH-PAHs in urine of the 2-year-old children from Most. Therefore, we hypothesize that the population living in this previously highly contaminated location (in 1970s and 1980s) can carry some long-term health burden.

Background: The duration of the vaccine's protective efficacy against SARS-CoV-2 is unknown. Evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of three immunoassays for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (Euroimmun Anti-SARS-CoV-2 ELISA IgG and Abbott SARS-CoV-2 CLIA IgG) and one lateral flow immunoassay (LFIA Test Livzon IgG) were tested. 300 samples distributed in 3 groups were analyzed: 100 subjects over 18 years old and under 45 years old, 100 subjects between 45-65 years old and another 100 over 65 years old. collected before vaccination, at 21 days, 1, 2, 3 and 6 months post-vaccination. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and agreement (I. Kappa) were calculated for each serological test. Results: Maximum sensitivity for IgG was 98.7%, 98.1%, and 97.8% for the ELISA Euroimmun, CLIA Abbott, and Livzon LFIA assays and maximum specificity for IgG was 99.4%, 99.9%. % and 98.4% ELISA, CLIA and LFIA respectively at 3 months after vaccination with a decrease in antibody levels from the sixth month. The best agreement was observed between ELISA and CLIA 100%; (k = 1.00). The agreement between ELIA, CLIA and LIFIA was 99% (k = 0964) at the second and third month after vaccination. Seroconversion was faster and longer lasting in the younger age groups. Conclusion: Our study showed an equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and that the LIFIA assay is the most cost-effective, reliable and accurate for routine use in population studies of seroconversion and seroprevalence.

Currently SARS-CoV-2 is spreading around the world as an Omicron strain. Recently, the Omicron variants (BQ.1 and BQ.1.1) were identified as novel Variants of Concern. UpToDate, there is little information about the Omicron Variants BQ.1 and BQ.1.1. The widely altered Omicron variants are spread globally, providing a high risk of infection surges with devastating consequences in some areas. The Omicron type of SARS-CoV-2 has a harm risk of reinfection, according to early reported findings. COVID-19 Variants particularly, BQ.1 and BQ.1.1 have gained global attention and caused a worldwide sensation since their discovery. Therefore, this communication discusses the present status of COVID-19 Variants BQ.1 and BQ.1.1, and their consequences.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. A majority of the currently available tools either require computational expertise to deploy or limit user input to pre-selected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: 1) visualization of spatiotemporal dynamics of SARS-CoV-2 lineages, and 2) structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in the pediatric, adult, and elderly population (n > 1.7 million genomes). While the spatiotemporal dynamics of variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate large-scale surveillance of circulating pathogens. The ViralVar webserver is freely available at http://viralvar.org/.

A human case of dengue virus 2 was detected from a febrile patient living in the Sare yoba, Kolda region (Southern Senegal). Phylogenetic analysis based on the partial sequence of the NS5 gene reveals that the virus belongs to the DENV2 Sylvatic genotype and is closely related to a strain (JF260983/ 98.98% identity) detected in Spain from a tourist who travelled to Guinee Bissau (bordering Kolda region) in 2009. This highlights a potential recent underreported circulation of sylvatic Dengue in the southern part of Senegal and calls for re-enforced integrated surveillance among humans, non-human primates and arboreal mosquitoes throughout a one-health approach.

The detection of waste plastics in the marine and terrestrial environment using satellite Earth Observation data offers the possibility of large-scale mapping, and reducing on-the-ground manual investigation. In addition, costs are kept to a minimum by utilizing free-to-access Copernicus data. A Machine Learning based classifier was developed to run on Sentinel-1 and -2 data. In support of the training and validation, a dataset was created with terrestrial and aquatic cases by manually digitizing varying landcover classes alongside plastics under the sub-categories of greenhouses, plastic, tyres and waste sites. The trained classifier, including an Artificial Neural Network and post-processing decision tree, was verified using five locations encompassing these different forms of plastic. Although exact matchups are challenging to digitize, the performance has generated high accuracy statistics, and the resulting land cover classifications have been used to map the occurrence of plastic waste in aquatic and terrestrial environments.

Minigastrin (MG) analogs for therapy of CCK2R-expressing malignancies are limited by low stability in vivo or excessive accumulation in non-target organs. By modifying the C-terminal receptor-binding sequence, metabolization could be prevented and tumor targeting significantly improved. In this work, N-terminal changes of the peptide length were evaluated. Based on the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂), two new MG analogs were synthesized, by either introduction of a penta-DGlu moiety or depletion of the four N-terminal amino acids and introduction of a non-charged hydrophilic linker. Two CCK2R-expressing cell lines were used to demonstrate receptor interaction. Stability of the ¹⁷⁷Lu-labeled peptide analogs was evaluated in human serum up to 24 h after incubation and in BALB/c mice up to 30 min after injection. The biodistribution profile and tumor targeting potential was evaluated in xenografted BALB/c nude mice. For both new MG analogs, the combination of strong receptor-specific cell interaction, high stability and enhanced tumor targeting could be demonstrated. Shortening of the peptide sequence lowered the absorption in the dose-limiting organs, whereas elongation increased uptake in renal tissue.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Primary systemic treatment (PST) downsizes the tumor and improves pathological response. The aim of this study is to analyze the feasibility and tolerance of primary concurrent radio-chemotherapy (PCRT) in breast cancer patients. Patients with localized TN/HER2+ tumors were enrolled in this prospective study. Radiation is delivered concomitantly during the first 3 weeks of chemotherapy, and it is based on a 15 fractions scheme (40.5Gy/2.7Gy per fraction to whole breast and nodal levels I-IV. Chemotherapy is based on Pertuzumab-Trastuzumab-Paclitaxel followed by anthracyclines in HER2+ and CBDCA-Paclitaxel followed by anthracyclines in TN breast cancers patients. 58 patients were enrolled, 25 patients (43%) were TN and 33 patients HER2+ (57%). With a median follow-up of 24.2 months, 56 patients completed PCRT and surgery. A total of 35 patients (87.5%) achieved &gt;90% loss of invasive carcinoma cell in the surgical specimen. The 70.8% and the 53.1% of patients with TN and HER-2+ subtype respectively achieved complete pathological response (pCR). This is the first study of concurrent neoadjuvant treatment in breast cancer in which three strategies are applied simultaneously: fractionation of RT in 15 sessions, adjustment of CT to tumor phenotype and local planning by PET. The pCR rates are encouraging.

G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs) involved in the regulation of 60% of human gene activity remains poorly explored. Similar to what we have previously done with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 hours post-infection, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h while at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. By RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17 and FURIN), in renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.

Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of monoclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerful therapeutic potential. Methods: Layers were immunized twice with 14-day interval using purified RBD of SARS-CoV-2. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgY to RBD was measured by indirect ELISA. Neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry strain using fluorescence and cell viability assay. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bind RBD of S protein of SARS-CoV-2 in situ, neutralize the virus in vitro, and lower viral RNA amplification without significant alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicated that chicken polyclonal IgYs can be attractive targets for pre-clinical and clinical development for rapid management of outbreaks of emerging and re-emerging viruses.

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at the respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two MMPs closely related: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and genes expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus, and functions in calcium regulation, contractile dysfunction, genes expression and ribosomal RNA transcription. Our particular interest lies in the role MMP-2 and MT1-MMP serve within the nucleus, as it may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies in cancer and other diseases.

Some of the lineages of SARS-CoV-2, the new coronavirus responsible for COVID-19, exhibit higher transmissibility or partial resistance to antibody mediated neutralization and were des-ignated by WHO as Variants of Interests (VOIs) or Concern (VOCs). The aim of this study was to monitor the dissemination of VOIs and VOCs in Venezuela during a year. A 614 nt genomic fragment was sequenced for the detection of some relevant mutations of these variants. Their presence was confirmed by complete genome sequencing, with a correlation higher than 99% between both methodologies. After the previously reported introduction of the Gamma VOC since the beginning of the year 2021, the variants Alpha VOC and Lambda VOI were detected as early as March 2021, at a very low frequency. In contrast, the Mu VOI, detected in May 2021, was able to circulate throughout the country. After the detection of Delta VOC in June 2021, it be-came the predominant circulating variant. With the arrival of the Omicron VOC in December, this variant was able to displace the Delta one in less than one month. This succession of variants was accompanied by a reduction in the Cycle threshold (Ct) values, in agreement with the in-crease in transmissibility described for these variants.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.

Background: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. Methods: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio – Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). Results: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Conclusion: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.

The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.

Crop-type mapping is an important intermediate step for cost-effective crop management at the field level, as an overview of all fields with a particular crop type can be used for monitoring or yield forecasting, for instance. Our study used a data set with 2400 fields and corresponding satellite observations from the federal state of Bavaria, Germany. The study classified corn, winter wheat, winter barley, sugar beet, potato, and winter rapeseed as the main crops grown in Upper Bavaria. We additionally experimented with a rejection class "Other", which summarised further crop types. Corresponding Sentinel-2 data included the normalised difference vegetation index (NDVI) and raw bands from 2016 to 2018 for each selected field. The influence of raw bands compared to NDVI was analysed and the classification algorithms, i.e. support vector machine (SVM) and random forest (RF), were compared. The study showed that the use of an index should be critically questioned and that raw bands provided a wider spectral bandwidth, which significantly improved the mapping of crop types. The results underline the use of RF with raw bands and achieved overall accuracies (OA) of up to 92%. We also predicted crop types in an unknown year with significantly different weather conditions and several months before the end of the growing season. Thus, the influence of climate anomalies and the accuracy depending on the time of prediction were assessed. The crop types of a test site and year without labels could be determined with an OA of up to 86%. The results demonstrate the usefulness of the proof-of-concept and its readiness for use in real applications.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Diabetes and chronic kidney disease (CKD) are a major public health burden in low-and-middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on estimated Glomerular Filtration Rate using the ‘Modification of Diet in Renal Disease’ equations and presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model Factors associated with CKD were: aged 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34); being female (2.2, 1.2-3.8), hypertensive (1.9, 1.1-3.5) and household income between 128.2-256.4 US$ (2.9, 1.0-8.2) compared with income ≤128.2$. However, after adjustment of other covariates, only duration of hypertension and household income (128.2-256.4 US$) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.

Abstract: Commercialization of extra virgin olive oil (EVOO) requires a best before date recom-mended at up to 24 months after bottling, stored under specific conditions. Thus, it is expected that the product retains its chemical properties and preserves its ‘extra virgin’ category. However, in-adequate storage conditions could alter the properties of EVOO. In this study, Arbequina EVOO was exposed to five storage conditions for up to one year to study the effects on the quality of the oil and the compounds responsible for flavor. Every 15 or 30 days, samples from each storage condition were analyzed determining physicochemical parameters, the profiles of phenols, volatile compounds, α-tocopherol and antioxidant capacity. Principal component analysis was utilized to better elucidate the relationships between composition of EVOOs and the storage conditions. EVOOs stored at -23 and 23 °C in darkness and 23 °C with light, differed from the oils stored at 30 and 40 °C in darkness. The former were associated with higher quantity of non-oxidized phenolic compounds and the latter with higher elenolic acid, oxidized oleuropein and ligstroside derivatives, which also increased with storage time. E-2-Nonenal (detected at trace levels in fresh oil) was selected as a marker of the degradation of Arbequina EVOO quality over time, with significant linear regressions identified for the storage conditions at 30 and 40 °C. Therefore, early oxidation in EVOO could be monitored by measuring E2-Nonenal levels.

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

The furin cleavage site, with an arginine doublet (RR), is one of the clues of the SARS-CoV-2 origin. This furin-RR is encoded by the CGG-CGG sequence. Because arginine can be encoded by six codons, in a previous work we found that in SARS-CoV-2, CGG was the minority arginine codon (3%). Also, analyzing the RR doublet from a large sample of furin cleavage sites of several kinds of viruses, we found that none of them were encoded by CGG-CGG. Here, we come back to the core of the matter, but from the perspective that in the human genome, in contrast, CGG is the majoroty arginine codon (21%). Here, we highlighted that the 6 arginine codons provide genetic markers to a traceability on the RR origin in the furin site, as well as, to weigh the probability of the theories about the origin of the virus.

Novel Coronavirus (2019-nCOV) causes inflammatory response with worsening symptoms. Classification of potential anti-viral and anti-inflammatory drugs in managing the symptoms of the COVID-19 and reducing morbidity is important. The objective of this study is to identify a group of drugs, best suited for COVID-19 treatment based on recent developments in clinical trials, FDA drug evaluation, directions and developments and from drug therapies globally. Online literature search was done on Medline, PubMed and google scholar databases for studies on various treatments and drug therapies for COVID-19 and relevant studies were identified and the identified drugs are described in detail as per their Pharmacological, pharmaceutical properties of the drugs, mechanism of action, current COVID-19 drug therapy, contraindications and drug-drug interactions Certain drugs can inhibit action against viral infection and protect lungs from severe inflammatory response. This article summarizes several drugs like Hydroxychloroquine, Chloroquine, Remdesivir, Favipiravir, Lopinavir, Ritonavir, Dexamethasone, Ivermectin, Baricitinib, Casirivimab / imdevimab, Bamlanivimab along with auxiliary treatment like convalescent plasma transfusion. Remdesivir is first drug approved by FDA. Hydroxychloroquine, dexamethasone and remdesivir are showing results against COVID-19 but it is important to test the efficacy and safety of such drugs though some drugs have shown remarkable results.

Abstract: An efficient and environmentally Pumice as a new catalyst for designing of 3,4- dihydropyrimidin-2(1H) ones / thiones via one-pot multi component condensation of aromatic aldehydes, urea/ thiourea and ethyl acetoacetate or acetyl acetone in excellent yields (96-99 %). The advantages using of this new catalyst is very cheap, available, non-toxic, stable under thermal conditions, easy work-up, improved yields, the product of reaction is very pure without using chromatographic methods and solvent free conditions.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

Hadhramout Initiative Against Corona (HIAC ) formed a working group of clinicians relevant to the management of COVID-19 to formulate clinical practice guidelines (CPG) for clinicians caring for the patients infected with COVID-19 in Yemen. The regional guidelines on the management of COVID-19 were thoroughly reviewed and its applicability was assessed for Yemen. HIAC’s recommendations covered (2) sections: the first one is the diagnosis, including case definition, risk stratification of the affected cases, investigations (prioritization of reverse transcription-polymerase chain reaction (RT-PCR) testing, D-dimer, chest x-ray, and chest computed tomography, while the second part covers the treatments (mainly Favipiravir, Remdesivir, Hydroxychloroquine, and Glucocorticoid, Anticoagulants, and Supportive measures). In conclusion, the adoption of cost-effective and evidence-based guidelines in Yemen will standardize the management of the patients infected with COVID-19 and protect both the patients and the health care workers from malpractice.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19 , is considered a pathogen with animal origin, mainly transmitted human to human. It has been experimentally and naturally demonstrated that several animals can be infected by SARS-CoV-2. There are strong evidences that minks are highly susceptible to SARS-CoV-2 infection, since several cases of human to mink infection have been reported, and it has been suggested mink to human infection exists, which so far it is the most reliable example of a zoonotic event of COVID-19 . However, all these cases reported are form mink farms, with the exception of one case in the USA in which the virus was detected in a mink located in the wild, but it was demonstrated that the animal was infected on a fur farm. In the present work, we have detected SARS-CoV-2 RNA in two wild American minks (Neovison vison) in Valencian Community (Eastern Spain) during invasive species trapping campaigns. The animals were trapped from areas known for harbouring self-sustained populations, far away from the nearest fur farm. SARS-CoV-2 RNA was detected in mesenteric lymph nodes samples by RT-PCR. A partial region of the Spike protein gene was amplified and sequence obtaining a 397 nt size sequence. Phylogenetic analysis shown that both sequences were identical to the consensus variant SARS CoV-2 sequence (from Wuhan). This research describes the first infection report of a true wild American mink not related to infected fur farms or direct contact with humans, which is believed to be the first example of wild animals in which SARS-CoV-2 has been detected.

The emergence of COVID-19 has prompted an unprecedented scientic publication with the aim of better understanding this new disease. This study assessed the scientic impact and disciplinary priorities of the published papers on the pandemic by comparing epidemiological (EP) and social sciences (SS) research interests. Papers were identified via keywords searching using Google Scholar and Scopus databases. From an initial 1720 papers, we identified 597 relevant articles, of which 347 were for EP researches and 250 for SS studies. We extracted information, such as authors' countries, and research thematic related to EP and SS. The results revealed that most papers were authored by Asian (37.5%), European (30.5%) and American (19.6%) scientists. Only 10.1% and 2.3% of authors were aliated with African and Oceanian institutions, respectively, indicating that the regions most affected by the pandemic mainly contributed to the scientic publications. In total, 26 research themes were recorded from both EP and SS studies. There was a high signicant dierence among themes in both research fields (Chi-square = 1204.3, df = 1, p-value < 0.001). EP papers mostly dealt with clinical trials (54.5%) and diagnosis (53.3%). These papers assessed the incidence and epidemiological characteristics of the disease (incubation period, symptomatic period, recovering or death), testing tests developed, drugs and vaccines used. SS papers were mainly concerned with the sociocultural analyses (78%) and economic impact (55.6%) of the pandemic. They mainly focused on behavioral changes induced by the pandemic and strategies developed to mitigate its impacts. This study highlights the difference between regions and gaps between scientific disciplines concerning the proposed responses to control the pandemic. It is important to promote collaborative and interdisciplinary studies for health emergencies.

In December 2019, an unusual cluster of pneumonia cases were reported in Wuhan and promptly confirmed to be caused by a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of which the disease it caused would be known as COVID-19. In March 2020, in the absence of any vaccines, and in response to the global spread of SARS-CoV-2 the UK implemented non-pharmaceutical intervention (NPI) measures in the form of a national lockdown to decelerate the spread. Compliance with NPIs can have significant impact on reducing disease transmission however there are currently no studies measuring compliance within the horse ownership world which naturally brings groups of people together during everyday caregiving activities. This article describes the reported horse owner compliance during the COVID-19 pandemic from March 2020 to December 2020 as deduced from 1036 respondents which completed an anonymous online survey between December 30th, 2020 and January 11th, 2021. Where rules/guidance did exist, there was good compliance with 92.76% of respondents indicating that they were following them. The most common rule/guidance implemented was social distancing, which was also the most common rule/guidance to be breached. Riding with others whilst at the yard (hacking or in an arena) and meeting up with non-household members (family and friends) when off the yard were also common rules/guidelines breached. Respondents who kept their horses at either DIY livery, or on a private yard were most likely to breach rules/regulations whereas respondents who kept their horses at full livery were least likely to breach rules/regulations. The results indicate that compliance of horse owners with COVID-19 rules/guidance is high when rules/guidance exists. However, just under half of respondents indicated that there were no rules/guidelines on their yards indicating that there is room for an increased contribution from the horse owning community by encouraging more yards to impose control measures where they currently do not exist.

Wheat is one of the global strategic crops and ranks third in terms of cereals production. Wheat crop is exposed to many fungal infections during the cultivation stages, some of which have the ability to secrete numbers of toxic secondary metabolites that threaten the quality of grains, consumer health, producer economics and global trade exchange. Fifty-four random samples were collected from wheat which originated from different countries. The samples included 14 of soft wheat to study the extent of their contamination with Deoxynivalenol (DON) and T-2 toxin by auto-ELISA technology and r-biopharm Microtiter plate. All samples were contaminated with DON toxin except one sample, and the contamination average ranged between 40.7 and 1018.8 µg kg-1. The highest contamination rates were in Lithuanian and the lowest in Indian wheat. Meanwhile the highest average level of T-2 toxin contamination was in Lithuanian wheat grains with a rate of 377.4µg kg-1 and the lowest in Polish wheat with an average of 115.3µg kg-1. GC-MS/MS and multiple reaction monitoring mode (MRM), was used to detect 15 triazole derivatives in collected samples, which may be used to combat fungal diseases on wheat during the growing season. Only 9 derivatives were found; Simeconazole, Penconazole, Hexaconazole, Cyproconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole. These derivatives varied according to the origin of wheat samples as well as their its concentration whereas, another 6 derivatives were not detected in all samples. A direct inverse relationship was found between the DON concentration in the samples and the residues of Simeconazole, Penconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole and the T-2 toxin showed the same relationship except for Tebuconazole. The safe and rational use of some triazole derivatives may be a new approach and a promising strategy not only to reduce plant diseases and their problems, but also to get rid of some mycotoxins as contaminates.

It is known for decades that viruses from the Coronoviridae family can adapt to human-to-human transmission. In 2020, SARS-CoV-2 caused a global pandemic of unprecedented scale imposing the loss of millions of human lives and being at the heart of a global economic crisis. Thus, we overviewed key research advances generated from the identification of the etiological agent to a better understanding of its origin, evolution and factors underlying global spread. Furthermore, we analyze the scientific productivity using the PubMed database. We found that the total number of publications increased more than 8% in 2020 when compared with 2019 or the average publications per year in the previous quinquennial. Remarkably, 86,638 publications related with COVID-19 and SARS-CoV-2 were published in 2020. Furthermore, there was also an increase in 2020 of publications in other major infectious diseases, such as AIDS, tuberculosis, or malaria. This success is likely the result from the vigorous, international, collaborative, and multidisciplinary response by the research community. During 2020 it was demonstrated, that with adequate support, it is possible to boost the rate of scientific progress in infectious diseases. Sustained investment in science will be key to address existing and future pandemics as the human population increases.

Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

The COVID-19 pandemic caused by SARS-CoV-2 has been showing a speedy growth in the number of infected patients with a remarkable mortality rate, thus it has become a worldwide public health concern. From March 8, 2020, the disease was confirmed to start spreading in Bangladesh. Since then, people got infected so exponentially that the country positions at the list of top infected countries in the world. Therefore, the objective of this comprehensive review was representing overall scenario of COVID-19 in different sectors of Bangladesh, particularly prioritizing the health sector. Up to 14 September 2020, 339,332 confirmed cases and 4,759 deaths were reported. An alarming fact is that while the global mutation rate of coronavirus is 7.23 % in average, the rate is 12.6 % in Bangladesh. Although the government ruled preventive strategies such as nationwide lockdown, social distancing, contact monitoring, quarantine and isolation, it was difficult to implement those due to lack of public awareness, inappropriate attitudes and so on. Moreover, the overburdened healthcare system had a weak response at initial stage because of insufficient healthcare facilities. Consequently, this pandemic affected severely almost all the important sectors of the country, specifically the economy, agriculture and health sectors. Hence, focusing on healthcare system as well as maintaining social distance and other essential precautions can limit the spread of infection and help to alleviate the severity of the pandemic.

Globally, the COVID-19 pandemic has brought the world to a standstill with the infected cases surpassing millions. The causative agent of COVID-19, the SARS-CoV-2 is a novel coronavirus that emerged from the wet animal market in Wuhan, China in early December 2019. Soon after, human-to-human transmission increased the rate of infection making the disease widespread with new hotspots emerging around the world.The epidemiological reports based on clinical characteristics including age, gender, symptoms (both severe and non-severe), and the conditions requiring intensive medical care, along with case fatality revealed that people with co-existing health conditions like diabetes, hypertension, cigarette smoking, and others with cardiovascular and kidney diseases were more susceptible to COVID-19 infection with poor prognosis in cases related to the severity of symptoms and requiring ICU, medical ventilators with a high fatality rate. Even people with immunosuppressed conditions like HIV and cancer, alongwith old age and pregnant women are vulnerable to COVID-19 infection and can cause severe health complications.It is extremely important to have a comprehensive idea of the underlying pathophysiology related to these health conditions which makes them more susceptible to contract SARS-CoV-2 infection in correlation with the development of severe symptoms. This review will provide an extensive viewpoint related to COVID-19 patients having coexisting health conditions together with the association between the prognosis of the disease and the pathogenesis of the SARS-CoV-2 infection, based on the current information available.

The developments of confirmed daily Sars-CoV-2 infections can be modeled a posteriori in a comparatively simple and satisfactory way by means of a special exponential function: its exponential coefficient varies exponentially with time itself. This property enables the function to directly simulate the „daily case“ curve fragments observed for the first waves of the current epidemics in a number of counties and countries. Linear combinations of two or more of the functions allow for the modeling of the complete curves observed in the vast majority of all regions for which case number developments have been tabulated.

Although RNA modifications were discovered decades ago, the identification of enzymes that write, read, and erase RNA modifications enabled their functional study and spawned the field of epitranscriptomics. Coupling that knowledge to new methods has enabled the precise pinpointing of epitranscriptomic modifications across the transcriptome plus the elucidation of their functional consequences. PCIF1 (Phosphorylated CTD Interacting Factor 1) was shown to add N6, 2’-O-dimethyladenosine (m⁶Am) marks at the first nucleotide after the 5’ N7-methylguanosine (m⁷G) cap. In this review, we discuss the epitranscriptomic regulation of mRNA in general, and focus on m⁷G cap-adjacent m⁶Am in particular. m⁶Am positions can now be distinguished from N6-methyladenosine (m⁶A) using new techniques leveraging PCIF1-knockout cells. Although m⁶Am modification sites can be detected precisely, conflicting data have been published regarding how cap-adjacent m⁶Am marks affect their host mRNA. Discrepancies in the data mean that the effects of cap-adjacent m⁶Am on mRNA stability, decapping, and translation continue to be debated. Finally, while PCIF1 is predominantly nuclear, a subset of results suggest a possible cytoplasmic role as well. Taken together, these contradictory results which employed different methodologies and cell lines means that further experiments are required to determine the ultimate biological function(s) of m⁷G cap-adjacent m⁶Am.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

(1) Background: A global pandemic due to COVID-19 emerged in November 2019 and hit France in early March 2020. It not only resulted in a loss of lives but also in very strict confinement measures. The objective of this study was to understand what the determinants of the change in participants’ behavior and mental state were during the confinement. (2) Methods: An online survey was launched on April 23rd, 2020, and closed on May 7th, 2020. The final sample included 1454 participants from 24 to 65 years old. Descriptive and multivariate analyses were then performed. (3) Results: 28.7% reported having a more balanced diet, against 17.1% with a less balanced diet. 22.7% of respondents reported an increased alcohol consumption, as opposed to only 12.2% declaring a decrease and 11.2% of respondents increased their tobacco consumption, while 6.3% decreased it. 50.6% of the participants reported being more depressed, stressed, or irritable since the beginning of the lockdown. Confinement had a negative effect on every behavior studied in this survey, except for nutrition. We also found that negative mental state changes were strongly associated with nutrition, sleep, physical activity, and alcohol consumption changes.

RaTG13 (a bat derived SARS-like CoV) is the closest relative sequence of SARS-CoV-2 reported till date. The sample from which RaTG13 was sequenced was a bat fecal swab collected in 2013 from Tongguan, Mojiang, Yunnan province, China. The Illumina based sequence of RaTG13, MN996532.1, was deposited on 27^th Jan 2020 and the raw data (Illumina), https://www.ncbi.nlm.nih.gov/sra/SRX7724752[accn]. There are discrepancies in dates about when the metagenome sequencing of RaTG13 sample was done (2018 or 2020), both stated by the same corresponding author. Comparison of the RNA Seq data of RaTG13 fecal swab to the corresponding data from the bat fecal swabs deposited by the same working group using the same methods indicated that the RaTG13 raw data seemed to be different in various aspects. The fecal swab sample showed abnormally less read of bacterial reads in the swab was exceptionally low, i.e. 0.7%, compared to the 20-90% abundance in other fecal swabs from bats processed by similar methods. Also, another raw data in the form of amplicon sequences was deposited in May 2020; however, the dates mentioned on the files of the sequenced amplicons were older (2017, 2018). The genome assembly of RaTG13 could not be done de-novo and the average coverage of the genome ~8%. Also, literature indicates that RaTG13 RBD cannot bind to Rhinolophus ACE-2 receptors. Collectively, the anomalies in the raw data of RaTG13 and other issues pose an important question about the overall authenticity of the RaTG13 genome sequence.

For more than ten years, Central Chile faces drought conditions, which impact crop production and quality, increasing food security risk. Under this scenario, implementing management practices that allow increasing water use efficiency is urgent. The study was carried out in kiwifruit trees, located in the O’Higgins region, Chile; for season 2018-2019 and 2019-2020. We evaluate nine vegetation indices in the VNIR and SWIR regions derived from Sentinel-2 (A/B) satellites to know how much variability in the canopy water status could explain. Over the study's site were installed sensors that continuously measure the leaf's turgor pressure (Yara Water-Sensor). A strong correlation between turgor pressure and vegetation indices was obtained with the Spearman's rho coefficient ($\rho$). However, the NIR range's indices were influenced by the vegetative development of the crop rather than its water status. Red-edge showed better performance as the vegetative growth did not affect it. It is necessary to expand the study to consider higher variability in kiwifruit's water conditions and incorporate the sensitivity of different wavelengths.

Background: A new coronavirus (SARS-CoV-2) that emerged from Wuhan, Hubei Province, China, has spread throughout the world and is declared a pandemic by the World Health Organization (WHO). A lot remains to be understood of SARS-CoV-2 and the disease (COVID-19). SARS-CoV-2 has until recently been identified as responsible for both asymptomatic and serious life-threatening infections. The unavailability of specific therapeutic agents is a major hurdle in the treatment and management of COVID-19 patients. The present review attempts to evaluate the immunobiochemical aspects of the pathogenesis, diagnosis, and management of SARS-CoV-2 infection. Main Body: This review is a comprehensive evaluation of the data collected through various sources, including Google Scholar, PubMed, and Scopus. The articles were searched and selected using key words such as “Coronavirus disease (COVID-19)”, “Diagnosis of COVID-19”, Pathogenesis of Covid-19”, “management of COVID-19”, “Immunology of COVID-19”, and “Complications of COVID-19”. The study noted that the novel Coronavirus infection could result in an exaggerated immune response, causing a cytokine storm and damaging several organs of the body. The infected patients develop several complications, including immunological, hematological, and biochemical alterations. Consequently, COVID-19 patients may develop cardiovascular, liver, renal, and neurological complications, among others. Conclusion: An increased understanding of the immunobiochemical aspects of the disease may contribute to better management of SARS-CoV-2-infected persons, as evidenced from the available literature. A holistic approach to the management of COVID-19 patients taking into consideration the effect of COVID-19 infection on various organs of the body assumes increased significance in patient management.

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (&lt;5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.

Coronavirus is now a significant human pathogen with the emergence of SARS-CoV-2. Until now there has been no data to support a threat to agricultural industries. Using a comparative genomic protein analysis, this study examined the angiotensin-converting enzyme II (ACEII) gene of 17 animal species with an emphasis on agriculture. To determine viral vulnerability the 20 known SARS-CoV-2 receptor-binding domain (RBD)/ACEII receptor interaction sites were compared to determine their potential susceptibility to the SARS-CoV-2 virus. With the known bat host’s (XP_032963186) number of binding sites as a threshold, we note that ALL animal species examined in this study contained significant numbers (≥10) of SARS-CoV-2 binding sites and could be at risk for SARS-CoV-2 infection. The data from this study suggest SARS-CoV-2 imposes a grave threat to the safety and security of the agricultural industry. Urgent studies are needed to determine if infected animals can transmit SARS-CoV-2 before and/or after processing.

COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection with the virus retaining viability for over 5 days at temperatures between 22–25^oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38^oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50^◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.

This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) affects human respiratory function causing COVID-19 disease. Safe natural products with potential antiviral phytochemicals with benefits to control high-altitude sickness could be adopted as adjunct therapy for COVID-19. The red petals of Rhododendron arboreum, commonly available and consumed in the Himalayan region may have phytochemicals with potential antiviral properties against COVID-19 targets.Purpose: This study was aimed to profile the secondary metabolites of R. arboreum petals, to assess their absorption, distribution, metabolism and elimination (ADME) properties and evaluate their antiviral potential by docking against COVID-19 targets such as SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin Converting Enzyme 2 (ACE2) receptor (PDB ID: 1R4L) that mediates the viral replication and entry into the host respectively.Methods: The phytochemicals of R. arboreum petals were mainly profiled using Gas Chromatography-Mass Spectroscopy (GC-MS) and ¹H-NMR. In addition, the phytochemicals reported from the literature were tabulated. The ADME properties of the phytochemicals were predicted using SwissADME tool. Molecular docking simulation of the phytochemicals against SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin converting enzyme 2 (ACE2) receptor (PDB ID: 1R4L) were carried out using PyRx.Results: R. arboreum petals were found to be rich in appreciable proportions of secondary metabolites such as Quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, 5-O-Feruloylquinic acid, 2,4-Quinolinediamine, Coumaric acid, Caffeic acid, Epicatechin, Catechin, 3-Hydroxybenzoic acid, Shikimic acid, Protocatechuic acid, Epicatechin gallate, Quercetin, Quercetin-O-pentoside, Quercetin-O-rhamnoside, Kaempferol-O-pentoside and Kaempferol. Several of these phytochemicals were reported to exhibit inhibitory activities against a range of viruses. From the molecular docking studies, 5-O-Feruloylquinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed strong binding affinity with SARS-CoV-2 M^pro and human ACE2 receptor.Conclusion: This report showed that R. arboreum petals are rich in several antiviral phytochemicals that also docked against SARS-CoV-2 M^Pro and Human ACE2 receptor. This is the first report highlighting R. arboreum petals as a reservoir of antiviral phytochemicals with potential for synergetic activities. The outcomes merit further in vitro, in vivo and clinical studies on R. arboreum phytochemicals to develop natural formulations against COVID-19 disease for therapeutic benefits.

Coronavirus disease is the current cause of global concern. The massive outbreak of COVID-19 has led the World Health Organization (WHO) to declare this as a pandemic situation. The Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) is responsible for COVID-19 leading to acute respiratory distress and substantial mortality in humans. However, the first laboratory confirmation of SARS-CoV-2 in a pet dog in Hong Kong has shown the possibility of human-to-animal transmission (zooanthroponotic) of the virus. Thereafter, many animals including cat, tiger, lion and mink have also been reported to acquire the virus in several countries. In this situation the role of veterinarian assumes important in treating the animals, helping in food security, disease diagnosis, surveillance and boosting the economy of livestock stakeholders at the grassroot level. In the absence of any selective vaccine or drug against SARS-CoV-2, the world is anticipated to triumph over this pandemic with collaborative, multisectoral, and transdisciplinary approach linking human, animal and environmental health. This article gives an insight into the confirmed SARS-CoV-2 outbreaks in animals, including the factors behind the shuffling of the virus among variety of species and also emphasizes on the role of veterinarian in managing and safeguarding public health so as to pave the way for adopting one health approach in order to conserve biodiversity.

The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel pentapeptide from bovine milk β-lactoglobulin which lowers cholesterol levels. However, the molecular mechanisms underlying the suppression of intestinal cholesterol absorption by IIAEK are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in Caco-2 cells in a human intestinal model. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1) protein. Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered IIAEK common binding amino acid sequence, GFYLFVEGGR. Transfection of IAP siRNA counteracted the decrease in ABCA1 mRNA levels in Caco-2 cells. IIAEK significantly increased IAP mRNA and protein levels, and significantly decreased ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway with a specific activation of IAP and down-regulation of intestinal ABCA1.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

This paper presents the super-twisting algorithm (STA) direct power control (DPC) scheme for the control of active and reactive powers of grid-connected DFIG. Simulations of 5 KW DFIG has been presented to validate the effectiveness and robustness of the proposed approach in the presence of uncertainties with respect to vector control (VC). The proposed controller schemes with fixed gains are effective in reducing the ripple of active and reactive powers, effectively suppress sliding-mode chattering and the effects of parametric uncertainties not affecting system performance.

Nigeria is the most populous country in the African continent. The aim of this study was to analyze risk factors for COVID-19 prevalence and deaths in all 6 geopolitical regions and 37 states in Nigeria. We analyzed the data retrieved from various sources, including Nigeria CDC, Nigeria National Bureau of Statistics, Unicef-Nigeria multiple indicator cluster survey and the Institute of Health Metrics and Evaluation, University of Washington. We examined 4 clinical risk factors (prevalence of TB, HIV, smoking and BCG vaccination coverage) and 5 sociodemographic factors (age ≥65, population density, literacy rate, unemployment and GDP per capita). Multivariate modeling was conducted using generalized linear model. Our analysis showed that the incidence of confirmed COVID-19 cases differed widely across the 37 states, from 0.09 per 100,000 in Kogi to 83.7 in Lagos. However, more than 70% of confirmed cases were concentrated in just 7 states: Lagos, Abuja, Oyo, Kano, Edo, Rivers and Delta. Case mortality rate (CMR) per million population also varied considerably, with Lagos, Abuja and Edo having CMR above 9. On bivariate analysis, higher CMR correlated positively with GDP and to a lesser extent with TB and population density. On multivariate analysis, which is more definitive, states with higher HIV prevalence and BCG coverage had lower CMR, while high GDP states had a greater CMR. This study indicates that COVID-19 has disproportionately affected certain states in Nigeria. Population susceptibility factors include higher economic development but not literacy or unemployment. Death rates were mildly lower in states with higher HIV prevalence and BCG vaccination coverage.

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.

Water-soluble and cytocompatible polymers were investigated to enhance a transporting efficiency of biomolecules into cells in vitro. The polymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) unit, a hydrophobic monomer unit, and a cationic monomer unit bearing an amino group were synthesized for complexation with model biomolecules, siRNA. The cationic MPC polymer was shown to interact with both siRNA and the cell membrane and was successively transported siRNA into cells. When introducing 20 − 50 mol% hydrophobic units into the cationic MPC polymer, transport of siRNA into cells. The MPC units (10 − 20 mol%) in the cationic MPC polymer were able to impart cytocompatibility, while maintaining interaction with siRNA and the cell membrane. The level of gene suppression of the siRNA/MPC polymer complex was evaluated in vitro and it was as the same level as that of a conventional siRNA transfection reagent, whereas its cytotoxicity was significantly lower. We concluded that these cytocompatible MPC polymers may be promising complexation reagent for introducing biomolecules into cells, with the potential to contribute to future fields of biotechnology, such as in vitro evaluation of gene functionality, and the production of engineered cells with biological functions.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O₃SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18^rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O₃SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O₃SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O₃SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O₃SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O₃SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.

In Wuhan city of China, an episode of novel coronavirus (COVID-19) happened. during late December and it has quickly spread to all places in the world. Until May 29, 2020, cases were high in the USA with 1.7 Million, Russia with approximately 387 thousand, the UK with 271 thousand confirmed cases. Everybody on the planet is anxious to know when the coronavirus pandemic will end. In this scourge, most nations force extreme medication measures to contain the spread of COVID-19. Modeling has been utilized broadly by every national government and the World Health Organization in choosing the best procedures to seek after in relieving the impacts of COVID-19. Many epidemiological models are studied to understand the spread of the illness and its prediction to find maximum capacity for human-to-human transmission so that control techniques can be adopted. Also, arrangements for the medical facilities required such as hospital beds and medical supplies can be made in advance. Many models are used to anticipate the results keeping in view the present scenario. There is an urgent need to study the various models and their impacts. In this study, we present a systematic literature review on epidemiological models for the outbreak of novel coronavirus in India. The epidemiological dynamics of COVID-19 is also studied. Here, In addition, an attempt to take out the results from the exploration and comparing it with the real data. The study helps to choose the models that are progressive and dependable to predict and give legitimate methods for various strategies.

Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.

Coronavirus disease 2019 (COVID-19) fatal outcomes have been associated with multiple cardiovascular risk factors. In new epidemic areas, such as Latin America, there is a lack of studies about this. Here, we evaluated those factors in a retrospective cohort of patients in a national reference hospital of Lima, Peru. Design. A retrospective cohort observational study was done. For this study, information was obtained from clinical records of the hospital for the cases that were laboratory-diagnosed and related, during March 6^th and April 30^th, 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs at the National Institute of Health. Calculation of the odds ratio (OR) with the respective 95% confidence interval (95% CI) was done, also logistic regression for adjusted OR (multivariate) was done. Values of p < 0.05 were considered significant for all analyses. Results. One hundred six hospitalized patients were evaluated. The mean age of patients was 61.58 years (SD 16.81). Cardiovascular risk factors among them were hypertension (46.2%), diabetes (28.3%), and obesity (28.3%), among others. Fifty-six patients died (52.8%). Mortality associated factors at the multivariate analysis were arterial hypertension (OR=1.343, 95% 1.089-1.667), myocardial injury (OR=1.303, 95% 1.031-1.642), and mechanical ventilation (OR 1.262, 95% 1.034-1.665), as associated factors. Conclusion. As observed in other regions of the world, cardiovascular risk factors represent a significant and independent threat to be considered in patients with COVID-19. Further studies and interventions in Peru and Latin America are expected.

Summary CoV-GLUE is an online web application for the interpretation and analysis of SARS-CoV-2 virus genome sequences, with a focus on amino acid sequence variation. It is based on the GLUE data-centric bioinformatics environment and provides a browsable database of amino acid replacements and coding region indels that have been observed in sequences from the pandemic. Users may also analyse their own SARS-CoV-2 sequences by submitting them to the web application to receive an interactive report containing visualisations of phylogenetic classification and highlighting genomic variation of potentially high impact, for example linked to primer mismatches.Availability and implementation Available at http://cov-glue.cvr.gla.ac.uk. Implemented using GLUE, an open source framework for the development of virus sequence data resources. Contact josh.singer@glasgow.ac.uk

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as “Whether there are differences based on gender in risk and severity of infection or mortality rate?” and “What are the biological explanation and mechanisms underlying these differences?” Emerging evidence has proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. From an immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.

Our first modern global pandemic is caused by a nanosized lipid vesicle, called SARS-CoV-2. Its molecular structure and biogenesis have remarkable similarities with Extracellular Vesicles (EVs, most notably exosomes) that are constantly shed by all cells during their life. Their resemblance may not be a coincidence. Growing body of evidence has shown that EVs have significant roles in various biological processes, including viral infection, transmission and anti-viral response. Drawing comparison with the virus might shed light on how we could fight the COVID-19 disease. This may include novel EV research and diagnostics technologies as well as novel EV-based treatments.

The ongoing COVID-19 pandemic is one of the biggest health and societal challenges of the recent decades. Among the causes of mortality triggered by SARS-CoV-2 infection, the presence of an inflammatory "cytokine storm" (CS) at later stages of the disease has been found to play a determinant role. Here, we used available transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients suffering from a CS to obtain gene-signatures associated to this pathological process. Using these signatures, we interrogated the Connectivity MAP (CMap) dataset that contains the effects of over 5,000 small molecules on the transcriptome of human cancer cell lines, and looked for molecules which effects on transcription mimic or oppose those associated to the CS. Consistent with their medical use, this analysis found a significant enrichment of glucocorticoids or inhibitors of the Janus Kinases (JAK) as drugs that could revert the CS. On the other hand, molecules that potentiate the immune response such as PKC activators are predicted to worsen the CS. Besides these expected findings, our analysis also reveals a potential effect of the antibiotic doxycycline or MAPK/RAF/MEK inhibitors in reverting the CS, or of topoisomerase inhibitors and the anti-alcohol abuse drug disulfiram in potentiating its effects. Finally, our analyses support that the gender-related differences in the severity of COVID-19 are related to the anti-inflammatory properties of female hormones. While acknowledging that this is an analysis based on limited available data, we decided to share it as a resource that might help others in the selection of drugs that could be tested in the context of experimental models of CS triggered by viral infections.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

COVID-19 pandemic that started in China has spread within 3 months to the entire globe. We tested the hypothesis that the vaccination against tuberculosis by BCG correlates with a better outcome for COVID-19 patients. Our analysis covers 55 countries complying with predetermined thresholds on the population size and number of deaths per million (DPM). We found a strong negative correlation between the years of BCG administration and the DPM along with the progress of the pandemic, corroborated by permutation tests. The results from multivariable regression tests with 23 economic, demographic, health-related, and pandemic restriction quantitative properties, substantiate the dominant contribution of BCG years to the COVID-19 outcomes. The analysis of countries according to an age-group partition reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (0-24 years). Furthermore, a strong correlation and statistical significance are associated with the degree of BCG coverage for the most recent 15 years, but no association was observed in these years for other broadly used vaccination protocols for measles and rubella. We propose that BCG immunization coverage, especially among the most recently vaccinated contributes to attenuation of the spread and severity of the COVID-19 pandemic.

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of betacoronaviruses in the aftermath of the 2002-03 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-20 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind, allowing the follow up of disease spread and transmission dynamics in near real time. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2.

As the first initiative of its kind in Algeria, here is presented a solar-powered mobile “Ultraviolet Germicidal Irradiation” disinfection unit (UVGI) based on a special germicidal ultraviolet-C (UVC) radiator. The system was designed to disinfect several objects such as: medical tools, reusable masks, face-shields, gloves, phones, laptops, keys, money and many other portable devices that need to be disinfected/sterilized. It offers the advantage of complete autonomy through the built-in photovoltaic (PV) system that includes a solar panel, a gel battery, a charge controller and a power inverter. The system provides an extra 220V-50Hz outlet with 375VA maximum power to be used when energy is needed. The system is easily scalable to generate higher ultraviolet dosages by adding more UVC lamps. The chemical-free germicidal UVC sanitizing method employed by this device effectively disactivates a very wide range of microorganisms (microbes, bacteria and fungi and viruses including the actual SARS-CoV-2 that causes COVID-19 respiratory disease) and it has several advantages in comparison to chemical-based sanitizing methods. The total cost to make this open source device is below 1000 € and is easily customizable and scalable. This device is an open source, secure and fast equipment for objects and surface disinfection. The device will be fully automated by adding PIR sensors or remote control after further funding will be received.

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with M protein of SARS-CoV; whereas, the similarity was only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of the M protein having a sugar transport-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the semiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

The human angiotensin-converting enzyme 2 (ACE2) has a crucial role on blood pressure control; however, ACE2 is also the primary SARS-CoV-2 (S domain) virus receptor. Inhibiting or even reducing the expression of the native ACE2 might diminish the viral entry into the cells, but may cause a failure of ACE2 biological activity, primarily in patients with comorbidities, including diabetes mellitus or hypertension. Since the ACE2 catalytic site and the SARS-Cov-2 receptor are distinct, we designed a Crispr-Cas9 model system, predicting the respective sequences for a guide RNA (gRNA) and a single-stranded oligo dideoxy nucleotide (ssODN), to introduce point mutations into the exon 1 of the human ACE2 gene, which encodes the alpha-helix, implicated on the binding of the SARS-CoV-2 envelope S protein. Protein modeling predicted that the specific substitutions of residues Phe28, Lys31, and Tyr41 for Ala at the ACE2 alpha-helix do not significantly alter ACE2 native conformation. The analysis of the impact of these mutations on ACE2 receptor function predicted a weakening of the binding of the SARS-CoV-2 protein S. An experimental genome editing of cells based on these Crispr-Cas9 elements might reduce the SARS-CoV-2 ability to enter the epithelial cell, preserving the biological activity of ACE2 enzyme.