ABSTRACT Background The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at pace, there is an unmet clinical need to develop tests that are prognostic, to triage the high volumes of patients arriving in hospital settings. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. 1 In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. We demonstrate here for the first time that saliva metabolomics can reveal COVID-19 severity. Methods 88 saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing. COVID severity was classified using clinical descriptors first proposed by SR Knight et al. Metabolites were extracted from saliva samples and analysed using liquid chromatography mass spectrometry. Results In this work, positive percent agreement of 1.00 between a PLS-DA metabolomics model and the clinical diagnosis of COVID severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, for overall percent agreement of 1.00. Conclusions This research demonstrates that liquid chromatography-mass spectrometry can identify salivary biomarkers capable of separating high severity COVID-19 patients from low severity COVID-19 patients in a small cohort study.
In tropical Africa, SARS-CoV-2 epidemiology is poorly described because of lack of access to testing and weak surveillance systems. Since April 2020, we followed SARS-CoV-2 seroprevalence in plasma samples across the Kenya National Blood Transfusion Service. We developed an IgG ELISA against full length spike protein. Validated in locally-observed, PCR-positive COVID-19 cases and in pre-pandemic sera, sensitivity was 92.7% and sensitivity was 99.0%. Using sera from 9,922 donors, we estimated national seroprevalence of SARS-CoV-2 antibodies at 4.3% in April-June 2020 and 9.1% in August-September 2020. The second COVID-19 wave peaked in November 2020. Here we estimate national seroprevalence in early 2021. Between January 3 and March 15, 2021, we collected 3,062 samples from donors aged 16-64 years. Among 3,018 samples that met our study criteria 1,333 were seropositive (crude seroprevalence 44.2%, 95% CI 42.4-46.0%). After Bayesian test-performance adjustment and population weighting to represent the national population distribution, the national estimate of seroprevalence was 48.5% (95% CI 45.2-52.1%). Seroprevalence varied little by age or sex but was higher in Nairobi, the capital city, and lower in two rural regions. Almost half of Kenyan adult donors had evidence of past SARS-CoV-2 infection by March 2021. Although high, the estimate is corroborated by other population-specific estimates in country. Between March and June, 2% of the population were vaccinated against COVID-19 and the country experienced a third epidemic wave. Natural infection is outpacing vaccine delivery substantially in Africa, and this reality needs to be considered as objectives of the vaccine programme are set.
Objectives: Although high altitude training has been increasingly popular in endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. More generally, we aimed to evaluate the utility of blood RNA sequencing as a modern and sensitive method of athlete9s health monitoring. Methods: Seven elite female speed skaters were profiled before and after 1h intense exercise, on the 18th day of Live High, Train High (LHTH) training programme. Whole blood RNA sequencing (RNA-seq) with globin depletion was used to measure gene expression changes associated with high intensity exercise at high altitude. Eight public microarray datasets were used to identify genes uniquely regulated at high altitude. Gene markers derived from single cell RNA-seq data were used to evaluate the changes of individual cell types in the whole blood. Results: Using individual cell type signatures, we were able to deconvolute the changes of finely defined cell populations from the whole blood RNA-seq. We have detected the increase in neutrophils, platelets, erythrocytes, and CD14 monocytes, and the decrease in natural killers, CD8 T cells, memory CD4 T cells, B cells, and plasmacytoid dendritic cells. The levels of naive CD4 T cells, CD16 monocytes, and myeloid dendritic cells were unchanged. Leveraging the previously published transcriptomic data allowed us to define the expression signature unique to high-altitude adaptation. Among the identified genes we highlight PHOSPHO1, which has a known role in erythropoiesis, and MARC1 with a proposed role in endogenic NO metabolism. Finally, we find that platelets and, to a lesser extent, erythrocytes are the two major cell types that uniquely respond to altitude exercise, while neutrophils represent a more generic marker of intense exercise. Conclusions: Using publicly available data from both single-cell RNA-seq atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for dynamic evaluation of physiological changes in an athlete9s body. In addition to the measurement of individual gene expression changes, our approach allowed us to estimate changes of blood cell type counts from a small peripheral blood sample, without sorting or other expensive and unfeasible equipment. We also discuss a surprising parallel of hypoxia and increased thrombosis, and hypothesize about the role exercise can play in COVID-19 outcomes.
To prevent the catastrophic health and economic consequences from COVID-19 epidemics, some nations have aimed for no community transmission outside of quarantine. To achieve this, governments have had to respond rapidly to outbreaks with public health interventions. But the exact characteristics of an outbreak that trigger these measures differ and are poorly defined. We used existing data from epidemics in Australia to establish a practical model to assist stakeholders in making decisions about the optimal timing and extent of interventions. We found that the number of reported cases on the day that interventions commenced strongly predicted the size of the outbreaks. We quantified how effective interventions were at containing outbreaks in relation to the number of cases at the time the interventions commenced. We also found that containing epidemics from novel variants that had higher transmissibility would require more stringent interventions that commenced earlier. In contrast, increasing vaccination coverage would enable more relaxed interventions. Our model highlights the importance of early and decisive action in the early phase of an outbreak if governments aimed for zero community transmission, although new variants and vaccination coverage may change this.
The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (principally alpha, beta and gamma variants), and then by the delta variant. We demonstrate that these emerging VOCs were associated with an increase in virulence, as measured by risk of hospitalization, intensive care unit admission, and death. Compared to non-VOC SARS-CoV-2 strains, and adjusting for comorbidity, age and sex of cases, and temporal trends, the elevation in risk associated with N501Y-positive variants was 74% (62-86%) for hospitalization; 138% (105-176%) for ICU admission; and 83% (57-114%) for death. Increases with delta variant were even larger: 105% (80-133%) for hospitalization; 241% (163-344%) for ICU admission; and 121% (57-211%) for death. The progressive increase in transmissibility and virulence of SARS-CoV-2 variants will result in a significantly larger, and more deadly, pandemic.
Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.
While many transmission models have been developed for community spread of respiratory pathogens, less attention has been given to modeling the interdependence of disease introduction and spread seen in congregate settings, such as prisons or nursing homes. As demonstrated by the explosive outbreaks of COVID-19 seen in congregate settings, the need for effective outbreak prevention and mitigation strategies for these settings is critical. Here we consider how interventions that decrease the size of the susceptible populations, such as vaccination or depopulation, impact the expected number of infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a branching process, while spread between residents is modeled via a compartmental model. Control is modeled as a proportional decrease in both the number of susceptible residents and the reproduction number. We find that vaccination or depopulation can have a greater than linear effect on anticipated infections. For example, assuming a reproduction number of 3.0 for density-dependent COVID-19 transmission, we find that reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. We highlight the California state prison system as an example for how these findings provide a quantitative framework for implementing infection control in congregate settings. Additional applications of our modeling framework include optimizing the distribution of residents into independent residential units, and comparison of preemptive versus reactive vaccination strategies.
To control future epidemics, discovery platforms are urgently needed, for the rapid development of diagnostic assays. Molecular diagnostic tests for COVID-19 emerged shortly after the isolation of SARS-CoV-2, however, serological tests based on antiviral antibody detection, revealing previous exposure to the virus, required longer developmental phases, due to the need for correctly folded and glycosylated antigens. The delay between the identification of a new virus and the development of reliable serodiagnostic tools limits our readiness for the control of a future epidemic. In this context, we propose the protozoan Leishmania tarentolae as an easy-to-handle micro-factory for the rapid production of viral antigens, to be used at the forefront of emerging epidemics. As a study model, we engineered L. tarentolae to express the SARS-CoV-2 Receptor Binding Domain (RBD) and report the ability of the purified RBD antigen to detect SARS-CoV-2 infection, with a sensitivity and reproducibility comparable to that of a reference antigen produced in human cells. This is the first application of an antigen produced in L. tarentolae for the serodiagnosis of a Coronaviridae infection. Based on our results, we propose L. tarentolae as an effective system for viral antigen production, even in countries that lack high-tech cell factories.
Abstract Introduction COVID-19 large scale immunization in the US has been associated with infrequent breakthrough positive molecular testing. Whether a positive test is associated with a high viral RNA load, specific viral variant, recovery of infectious virus, or symptomatic infection is largely not known. Methods In this study, we identified 133 SARS-CoV-2 positive patients who had received two doses of either Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines, the 2nd of which was received between January and April of 2021. The positive samples were collected between January and May of 2021 with a time that extended from 2 to 100 days after the second dose. Samples were sequenced to characterize the whole genome and Spike protein changes and cycle thresholds that reflect viral loads were determined using a single molecular assay. Local SARS-CoV-2 IgG antibodies were examined using ELISA and specimens were grown on cell culture to assess the recovery of infectious virus as compared to a control unvaccinated cohort from a matched time frame. Results Of 133 specimens, 24 failed sequencing and yielded a negative or very low viral load on the repeat PCR. Of 109 specimens that were used for further genome analysis, 68 (62.4%) were from symptomatic infections, 11 (10.1%) were admitted for COVID-19, and 2 (1.8%) required ICU admission with no associated mortality. The predominant virus variant was the alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted when genomes were compared to a large control cohort from a matched time frame. A significant reduction of the recovery of infectious virus on cell culture as well as delayed time to the first appearance of cytopathic effect was accompanied by an increase in local IgG levels in respiratory samples of vaccinated individuals but upper respiratory tract IgG levels were not different between symptomatic or asymptomatic infections. Conclusions Vaccination reduces the recovery of infectious virus in breakthrough infections accompanied by an increase in upper respiratory tract local immune responses.
Abstract Importance: Maintenance hemodialysis (MHD) patients have a high mortality risk after COVID-19 and an altered humoral response to vaccines, but vaccine clinical efficacy remains unknown in this population. Objective: To estimate the association between vaccination and COVID-19 hospitalization rate in MHD patients Design: Using Bayesian multivariable spatiotemporal models, we estimated the expected number of SARS-CoV-2 severe infections (infections with hospital admission) in MHD patients from simultaneous cases in the general population. Setting: French population-based retrospective analysis in MHD and non-dialysis patients. Participants: Models were fitted from 3620 hospitalizations of MHD patients and 457,160 hospitalizations in the general population. Exposure: Severe SARS-CoV-2 infections in the general population and vaccine exposure. Main Outcome and Measure: Weekly incidence of severe infections in MHD patients. Results: During the first epidemic wave, incidence of severe infections in MHD patients was approximately proportional to incidence in the general population. However, our model overestimated incidence during the second wave, suggesting an effect of prevention measures during the 2nd wave. A second model (based on data up to the end of the 2nd wave) estimated that the risk in MHD patients decreased between waves 1 and 2, with incidence rate ratio (IRR) = 0.70 (95% CI: 0.64, 0.76). Moreover, while this model correctly estimated the reported MHD cases up to the end of the 2nd wave, predictions overestimated the expected number of cases from the beginning of the vaccination campaign. Using vaccination coverages as additional predictors permitted to correctly fit the weekly reported number of cases, with IRR in MHD patients of 0.41 (95% CI: 0.28, 0.58) for vaccine exposure in MHD patients and 0.50 (95% CI: 0.40, 0.61) per 10% increase in vaccination coverage in the same-age general population. Conclusions and Relevance: Our findings suggest that both individual and herd immunity due to vaccination may yield a protective effect against severe forms of COVID-19 in MHD patients.
Simultaneously tracking the global COVID-19 impact across multiple populations is challenging due to regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide reliable and standardized data streams to support monitoring and decision-making world-wide, in real time, and with limited local resources. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS), in partnership with Facebook, invites daily cross-sectional samples from the social media platform9s active users to participate in the survey since launch April 23, 2020. COVID-19 indicators through December 20, 2020, from N=31,142,582 responses representing N=114 countries, weighted for nonresponse and adjusted to basic demographics, were benchmarked with government data. COVID-19-related signals showed similar concordance with reported benchmark case and test positivity. Bonferroni significance and minimal Spearman correlation strength thresholds were met in the majority. Light Gradient Boost machine learning trained on national and pooled global data verified known symptom indicators, and predicted COVID-19 trends similar to other signals. Risk mitigation behavior trends are correlated with, but sometimes lag, risk perception trends. In regions with strained health infrastructure, but active social media users, we show it is possible to define suitable COVID-19 impact trajectories. This syndromic surveillance public health tool is the largest global health survey to date, and, with brief participant engagement, can provide meaningful, timely insights into the COVID-19 pandemic and response in regions under-represented in epidemiological analyses.
Anticipating the medium- and long-term trajectory of pathogen emergence has acquired new urgency given the ongoing COVID-19 pandemic. For many human pathogens the burden of disease depends on age and prior exposure. Understanding the intersection between human population demography and transmission dynamics is therefore critical. Here, we develop a realistic age-structured (RAS) mathematical model that integrates demography, social mixing and immunity to establish the suite of possible scenarios of future age-incidence and burden of mortality. With respect to COVID-19, we identify a plausible transition in the age-structure of risks once the disease reaches seasonal endemism, whether assuming long-lasting or brief protective immunity, and across a range of assumptions of relative severity of primary versus subsequent reinfections. We train the model using diverse real-world demographies and age-structured social mixing patterns to bound expectations for changing age-incidence and disease burden. The mathematical framework is flexible and can help tailoring mitigation strategies countries worldwide with varying demographies and social mixing patterns.
Purpose: The present study aimed to compare and analyze the sex-specific epidemiological, clinical characteristics, comorbidities, and other information of confirmed COVID-19 patients from the southeast region in Bangladesh for the first time. Methods: 385 lab-confirmed cases were studied out of a total of 2471 tested samples between June 5 and September 10, 2020. RT-PCR was used for COVID-19 identification and SPSS (version 25) for statistical data analysis. Results: We found that male patients were roughly affected compared to females patients (male 74.30% vs. female 25.7%) with an average age of 34.86 +/- 15.442 years, and B (+ve) blood group has been identified as a high-risk factor for COVID-19 infection. Workplace, local market, and bank were signified as sex-specific risk zone (p < 0.001). Pre-existing medical conditions such as diabetes, hypertension, cardiovascular and respiratory diseases were identified among the patients. Less than half of the confirmed COVID-19 cases in the southeast region were asymptomatic (37.73%) and more prevalent among females than males (male vs. female: 36.84% vs. 40.51%, p = 0.001). Conclusions: The findings may help health authorities and the government to take necessary steps for identification and isolation, treatment, prevention, and control of this global pandemic. Keywords: COVID-19, Coronavirus disease, Epidemiological, Clinical features, Asymptomatic, Comorbidities
Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition: COVID 19
Interventions: Diagnostic Test: Cognitive assessment; Diagnostic Test: Imaging; Diagnostic Test: Routine care; Other: Psychiatric evaluation
Sponsors: Central Hospital, Nancy, France; Centre Hospitalier Universitaire de Besancon; University Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-Thionville; Centre hospitalier Epinal; Hopitaux Civils de Colmar
Not yet recruiting
Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition: Covid19
Interventions: Drug: NTR-441; Drug: Placebo
Sponsor: Neutrolis
Recruiting
COVID-19 Vaccinations With a Sweepstakes - Condition: Covid19
Intervention: Behavioral: Philly Vax Sweepstakes
Sponsors: University of Pennsylvania; Philadelphia Department of Public Health
Active, not recruiting
Covid-19 Virtual Recovery Study - Condition: Covid19
Interventions: Behavioral: Strength RMT; Behavioral: Strength RMT and nasal breathing; Behavioral: Endurance RMT; Behavioral: Endurance RMT and nasal breathing; Behavioral: Low dose RMT
Sponsor: Mayo Clinic
Not yet recruiting
A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition: Covid19 Vaccine
Interventions: Biological: MVC-COV1901(S protein with adjuvant); Biological: MVC-COV1901(Saline)
Sponsor: Medigen Vaccine Biologics Corp.
Not yet recruiting
Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 - Condition: Covid19
Interventions: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium
Sponsors: UPECLIN HC FM Botucatu Unesp; Chiesi Farmaceutici S.p.A.
Not yet recruiting
Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition: COVID-19
Interventions: Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine; Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
Sponsors: Jiangsu Province Centers for Disease Control and Prevention; CanSino Biologics Inc.
Not yet recruiting
Efficacy of Amantadine Treatment in COVID-19 Patients - Condition: Patients With Moderate or Severe COVID-19
Intervention: Drug: Amantadine
Sponsors: Noblewell; Medical Research Agency (ABM); Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
Recruiting
Covid-19 Patients Management During Home Isolation - Condition: Covid19
Interventions: Procedure: Oxygen therapy and physical therapy; Device: Oxygen therapy
Sponsor: Cairo University
Not yet recruiting
Ivermectin Versus Standard Treatment in Mild COVID-19 - Condition: Covid19
Intervention: Drug: Ivermectin Tablets
Sponsor: Assiut University
Not yet recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
Chinese Herbal Formula for COVID-19 - Condition: Covid19
Interventions: Drug: mQFPD; Drug: organic brown rice
Sponsor: University of California, San Diego
Not yet recruiting
Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: Assiut University
Not yet recruiting
Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition: Covid19
Intervention: Drug: cholecalciferol 6 lakh IU
Sponsor: Postgraduate Institute of Medical Education and Research
Not yet recruiting
Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay - The COVID-19 pandemic caused by SARS-CoV-2 is an unprecedentedly significant health threat, prompting the need for rapidly developing antiviral drugs for the treatment. Drug repurposing is currently one of the most tangible options for rapidly developing drugs for emerging and reemerging viruses. In general, drug repurposing starts with virtual screening of approved drugs employing various computational methods. However, the actual hit rate of virtual screening is very low, and most of the…
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of COVID-19 adenoviral vector vaccines^(1-3). VITT resembles heparin-induced thrombocytopenia (HIT) as it is associated with platelet-activating antibodies against platelet factor 4 (PF4)⁴; however, patients with VITT develop thrombocytopenia and thrombosis without heparin exposure. The objective of this study was to determine the binding site on PF4 of antibodies from patients with VITT. Using alanine scanning…
SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction - The multidomain non-structural protein 3 (Nsp3) is the largest protein encoded by coronavirus (CoV) genomes and several regions of this protein are essential for viral replication. Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication. We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions…
Inhibitory activities of bipyrazoles: a patent review - INTRODUCTION: Bipyrazole is constituted from two pyrazole units either in their fully aromatic or partially hydrogenated forms. Pyrazoles are widely available in pharmaceutical and agrochemical products. Some pyrazoles are essential parts of commercial drugs in the market. This inspired us to collect the pharmacological activities of bipyrazoles that have potential therapeutic behaviours in several biological aspects but none of them were included in commercial drugs.
Indeterminate QuantiFERON Gold Plus results reveal deficient IFN-gamma responses in severely ill COVID-19 patients - Background: SARS-CoV-2 is a novel positive-sense single stranded RNA virus that has caused a recent pandemic. Most patients have a mild disease course, while approximately 20 percent have moderate-to-severe disease, often requiring hospitalization and, in some cases, care in the intensive care unit. Results: By investigating a perceived increased rate of indeterminate QuantiFERON®-TB Gold Plus results in hospitalized COVID patients, we demonstrate that severely ill COVID-19 patients have at…
Porcine epidemic diarrhea virus inhibits HDAC1 expression to facilitate its replication via binding of its nucleocapsid protein to host transcription factor Sp1 - Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing acute intestinal infection in pigs, with high mortality often seen in neonatal pigs. The newborns rely on innate immune responses against invading pathogens because of lacking adaptive immunity. However, how PEDV disables the innate immunity of newborns towards severe infection remains unknown. We found that PEDV infection led to reduced expression of histone deacetylases (HDACs), especially HDAC1 in porcine IPEC-J2 cells….
Qualification of ELISA and neutralization methodologies to measure SARS-CoV-2 humoral immunity using human clinical samples - In response to the SARS-CoV-2 pandemic many vaccines have been developed and evaluated in human clinical trials. The humoral immune response magnitude, composition and efficacy of neutralizing SARS-CoV-2 are essential endpoints for these trials. Robust assays that are reproducibly precise, linear, and specific for SARS-CoV-2 antigens would be beneficial for the vaccine pipeline. In this work we describe the methodologies and clinical qualification of three SARS-CoV-2 endpoint assays. We…
Novel 1,2,3-Triazole Derivatives as Potential Inhibitors against Covid-19 Main Protease: Synthesis, Characterization, Molecular Docking and DFT Studies - The highly contagious nature of Covid-19 attracted us to this challenging area of research, mainly because the disease is spreading very fast and until now, no effective method of a safe treatment or a vaccine is developed. A library of novel 1,2,3-triazoles based 1,2,4-triazole, 1,3,4-oxadiazole and/or 1,3,4-thiadiazole scaffolds were designed and successfully synthesized. Different spectroscopic tools efficiently characterized all the newly synthesized hybrid molecules. An interesting finding…
In silico analysis of echinocandins binding to the main proteases of coronaviruses PEDV (3CL(pro)) and SARS-CoV-2 (M(pro)) - The porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two highly pathogenic viruses causing tremendous damages to the swine and human populations, respectively. Vaccines are available to prevent contamination and to limit dissemination of these two coronaviruses, but efficient and widely affordable treatments are needed. Recently, four natural products targeting the 3C-like protease (3CL^(pro)) of PEDV and inhibiting replication of the…
A SARS-CoV-2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD-Independent Mechanism - The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin-converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2. Nevertheless, infection studies revealed potent and…
Synthesis of antimicrobial azoloazines and molecular docking for inhibiting COVID-19 - Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition…
Kynurenic acid may underlie sex-specific immune responses to COVID-19 - Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA-to-kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that…
Pacemaker-related Candida parapsilosis fungaemia in an immunosuppressed renal transplant recipient - Renal transplant recipients are at risk for opportunistic infections due to their immunosuppressed state. We describe the case of a 59-year-old renal transplant recipient who presented with sepsis and bilateral pulmonary emboli due to Candida parapsilosis She was treated with intravenous caspofungin and had a transoesophageal echocardiogram, which revealed vegetations on her pacemaker leads. She then underwent surgery to replace her pacemaker; however, her blood cultures remained positive for C….
Re-Du-Ning injection ameliorates LPS-induced lung injury through inhibiting neutrophil extracellular traps formation - CONCLUSION: These findings demonstrate that RDN ameliorates LPS-induced ALI through suppressing MAPK pathway to inhibit the formation of NETs.
SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse…
Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link
SARS-CoV-2 anti-viral therapeutic - - link
A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link
新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link
检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link
一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR，并结合Sanger测序，能够快速、准确地获取SARS‑CoV‑2基因信息，从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株，且具备良好的准确性、灵敏度、特异性以及重复性。 - link
一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域，公开了一种新冠病毒肺炎重症化预测系统及方法，包括以下步骤：步骤一，采集患者血常规信息和用户信息；步骤二，将患者血常规信息按照用户信息进行等级分类；步骤三，将已经等级分类的患者血常规信息与对应等级的标准信息进行比较；步骤四，当患者血常规信息在标准信息范围内则判定患者为轻症患者，当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link
MEDIDOR DE SATURACION - - link
폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link
백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link