Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Securing your relationship: Quality of intimate relationships during the COVID-19 pandemic can be predicted by attachment style -
  The COVID-19 pandemic along with the restrictions that were introduced within Europe starting spring 2020 allows for the identification of predictors for relationship quality during unstable and stressful times. The present study began as strict measures were enforced in response to the rising spread of the COVID-19 within Austria, Poland, Spain and Czech Republic. Here, we investigated quality of romantic relationships among 313 participants as movement restrictions were implemented and subsequently phased out cross-nationally. Participants completed self-report questionnaires over a period of seven weeks, where we predicted relationship quality and change in relationship quality using machine learning models that include a variety of potential predictors related to psychological, demographic and environmental variables. On average, our machine learning tools predicted 29% (linear models) and 22% (non-linear models) of the variance with regard to relationship quality. Here, the most important predictors consisted of attachment style (anxious attachment being more influential than avoidance), age, and number of conflicts within the relationship. Interestingly, environmental factors such as the local severity of the pandemic did not exert a measurable influence with respect to predicting relationship quality. As opposed to overall relationship quality, the change in relationship quality during lockdown restrictions could not be predicted accurately by our machine learning models when utilizing our selected features. In conclusion, we demonstrate cross-culturally that attachment security is a major predictor of relationship quality during COVID-19 lockdown restrictions, whereas sexual behavior, fear, pathogenic threat and the severity of governmental regulations did not significantly influence the accuracy of prediction.
  🖺 Full Text HTML: Securing your relationship: Quality of intimate relationships during the COVID-19 pandemic can be predicted by attachment style
• Containing the Spread of Infectious Disease on College Campuses -

  College campuses are highly vulnerable to infectious disease outbreaks, and there is a pressing need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world reopen to in-person instruction in the midst of the COVID-19 pandemic. Towards addressing this need, we applied a stochastic compartmental model to quantify the impact of university-level responses to past mumps outbreaks in college campuses and used it to determine which control interventions are most effective. Mumps is a very relevant disease in such settings, given its airborne mode of transmission, high infectivity, and recurrence of outbreaks despite availability of a vaccine. Our model aims to simultaneously overcome three crucial issues: stochastic variation in small populations, missing or unobserved case data, and changes in disease transmission rates post-intervention. We tested the model and assessed various interventions using data from the 2014 and 2016 mumps outbreaks at Ohio State University and Harvard University, respectively. Our results suggest that in order to decrease infectious disease incidence on their campuses, universities should apply diagnostic protocols that address false negatives from molecular tests, stricter quarantine policies, and effective awareness campaigns among their students and staff. Our model can be applied to data from other outbreaks in college campuses and similar small-population settings.

  🖺 Full Text HTML: Containing the Spread of Infectious Disease on College Campuses
• Covid-19 Pfizer Vaccine: The Worst-Case Scenario -
  The BioNTech/Pfizer BNT162b2 vaccine against Covid-19 is composed of an RNA having 4284 nucleotides, divided into 6 sections, which bring the information to create a factory of S Spike proteins, the ones used by Sars-CoV-2 (Covid-19) to infect the subject. After that, these proteins are directed outside the cell, triggering the immune reaction and antibody production. The problem is the heavy alteration of the mRNA: the Uracyl is replaced to fool the immune system, the letters of all codon triplets are replaced by a C or a G, to extremely increase the speed of protein production, replacement of some amino acids with Proline, the addition of a not clear sequence (3'-UTR), combined with alternative splicing, which is the possibility of errors in translation of the sequence and synthesis of proteins; they are not produced equal, but slightly different. All this can be the cause of many hereditary diseases and various types of tumors, from appearance to their growth, up to the metastasis formation. In essence, what will be created is anything but well defined as protein S Spike: just a transcription error, wrong production of amino acids, then proteins, to cause serious long-term damage to human health, despite the DNA is not modified, being instead in the cell nucleus and not in the cytoplasm, where the modified mRNA arrives. However, in this case, the correlation between speed of synthesis and protein expression with synthesis errors, as well as the mechanism that could affect the translation of the sequence remain obscure, as many trials are owned by BioNTech/Pfizer.
  🖺 Full Text HTML: Covid-19 Pfizer Vaccine: The Worst-Case Scenario
• Predictions of COVID-19 dynamics in the UK: short-term forecasting and analysis of potential exit strategies -

  Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a stay at home order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. The model captures a range of age-dependent heterogeneities, reduced transmission from asymptomatic infections and produces a good fit to the key epidemic features over time. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020 on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. We find that significant relaxation of social distancing measures from 7th May onwards can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Our work confirms the effectiveness of stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. It also provides strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.

  🖺 Full Text HTML: Predictions of COVID-19 dynamics in the UK: short-term forecasting and analysis of potential exit strategies
• Characterization of cell-cell communication in COVID-19 patients -
  COVID-19 patients display a wide range of disease severity, ranging from asymptomatic to critical symptoms with high mortality risk. Our ability to understand the interaction of SARS-CoV-2 infected cells within the lung, and of protective or dysfunctional immune responses to the virus, is critical to effectively treat these patients. Currently, our understanding of cell-cell interactions across different disease states, and how such interactions may drive pathogenic outcomes, is incomplete. Here, we developed a generalizable workflow for identifying cells that are differentially interacting across COVID-19 patients with distinct disease outcomes and use it to examine five public single-cell RNA-seq datasets with a total of 85 individual samples. By characterizing the cell-cell interaction patterns across epithelial and immune cells in lung tissues for patients with varying disease severity, we illustrate diverse communication patterns across individuals, and discover heterogeneous communication patterns among moderate and severe patients. We further illustrate patterns derived from cell-cell interactions are potential signatures for discriminating between moderate and severe patients.
  🖺 Full Text HTML: Characterization of cell-cell communication in COVID-19 patients
• Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2 -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic has resulted in over 80 million cases and 1.7 million deaths to date while the number of cases continues to rise. With limited therapeutic options, the identification of safe and effective therapeutics is urgently needed. The repurposing of known clinical compounds holds the potential for rapid identification of drugs effective against SARS-CoV-2. Here we utilized a library of FDA-approved and well-studied preclinical and clinical compounds to screen for antivirals against SARS-CoV-2 in human pulmonary epithelial cells. We identified 13 compounds that exhibit potent antiviral activity across multiple orthogonal assays. Hits include known antivirals, compounds with anti-inflammatory activity, and compounds targeting host pathways such as kinases and proteases critical for SARS-CoV-2 replication. We identified seven compounds not previously reported to have activity against SARS-CoV-2, including B02, a human RAD51 inhibitor. We further demonstrated that B02 exhibits synergy with remdesivir, the only antiviral approved by the FDA to treat COVID-19, highlighting the potential for combination therapy. Taken together, our comparative compound screening strategy highlights the potential of drug repurposing screens to identify novel starting points for development of effective antiviral mono- or combination therapies to treat COVID-19.
  🖺 Full Text HTML: Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2
• Direct measurement of B lymphocyte gene expression biomarkers in peripheral blood enables early prediction of seroconversion after vaccination -
  Vaccination is a common and efficient means to reduce the mortality and morbidity of emerging infectious diseases. Among responders, injected antigen induces acquired immunity pathways and leads to the final production of antigen-specific antibodies. The whole process may take weeks to months, depending on the antigen. Typically, seroconversion to influenza vaccine is expected after one month with a responder rate of ~50%. An early biomarker to predict response is desirable. Peripheral blood gene expression (or transcript abundance, TA) datasets in the public domain were analyzed for early biomarkers among responders. As peripheral blood samples (such as peripheral blood mononuclear cells, PBMC) are cell mixture samples containing various blood cell-types (leukocyte subpopulations, LS). We first develop a model that enables the determination of TA in B lymphocytes of certain genes directly in PBMC samples without the need of prior cell isolation. These genes are called B cell informative genes. Then a ratio of two B cell informative genes (a target gene and a stably expressed reference gene) measured in PBMC was used as a new biomarker to gauge the target gene expression in B lymphocytes. This method having an obvious advantage over conventional methods by eliminating the tedious procedure of cell sorting and enables directly determining TA of a leukocyte subpopulation in cell mixture samples is called Direct LS-TA method. By using a B lymphocyte-specific gene such as TNFRSF17 or TXNDC5 as target genes with either TNFRSF13C or FCRLA as reference genes, the B cell biomarkers were determined directly in PBMC which was highly correlated with TA of target genes in purified B lymphocytes. These Direct LS-TA biomarkers in PBMC increased significantly early after vaccination in both the discovery dataset and a meta-analysis of 7 datasets. Responders had almost a 2-fold higher Direct LS-TA biomarker level of TNFRSF17 (SMD=0.84, 95% CI=0.47-1.21 after log2). And Direct LS-TA biomarkers of TNFRSF17 and TXNDC5 measured at day 7 predict responder with sensitivity values of higher than 0.7. The Area-under curves (AUC) in receiver operation curve (ROC) analysis were over 0.8. Here, we report a straightforward approach to directly analyses B lymphocyte gene expression in PBMC, which could be used in a routine clinical setting as it avoids the labor-intensive procedures of B lymphocyte isolation. And the method allows the practice of precision medicine in the prediction of vaccination response. Furthermore, response to vaccination could be predicted as early as on day 7. As vaccination response is based on the similar acquired immunology pathway in the upcoming worldwide vaccination campaign against COVID-19, these biomarkers could also be useful to predict seroconversion for individuals.
  🖺 Full Text HTML: Direct measurement of B lymphocyte gene expression biomarkers in peripheral blood enables early prediction of seroconversion after vaccination
• Engineering, production and characterization of Spike and Nucleocapsid structural proteins of SARS-CoV-2 in Nicotiana benthamiana as vaccine candidates against COVID-19 -
  The COVID-19 pandemic, which is caused by SARS-CoV-2 has rapidly spread to more than 216 countries and has put global public health at high risk. The world urgently needs a cost-effective and safe SARS-CoV-2 coronavirus vaccine, antiviral and therapeutic drugs to control the COVID-19 pandemic. In this study, we engineered the Nucleocapsid (N) and Spike protein (S) variants (Receptor binding domain, RBD and S1 domain) of SARS-CoV-2 genes and produced in Nicotiana benthamiana plant. The purification yields were at least 20 mg of pure protein/kg of plant biomass for each target protein. The S protein variants of SARS-CoV-2 showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. The purified plant produced N and S variants were recognized by N and S protein specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant produced N and S protein variants. In addition, IgG responses of plant produced N and S antigens elicited significantly high titers of antibody in mice. This is the first report demonstrating production of functional active S1 domain and Nucleocapsid protein of SARC-CoV-2 in plants. In addition, in this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies compared to RBD or N proteins. Thus, obtained data support that plant produced N and S antigens, developed in this study, are promising vaccine candidates against COVID-19.
  🖺 Full Text HTML: Engineering, production and characterization of Spike and Nucleocapsid structural proteins of SARS-CoV-2 in Nicotiana benthamiana as vaccine candidates against COVID-19
• Corruption in the Times of Pandemia -
  The public health and economic crisis caused by the COVID-19 pandemic has pushed governments to substantially and swiftly increase spending. Consequently, public procurement rules have been relaxed in many places to expedite transactions. However, this may also create opportunities for inefficiency and corruption. Using contract-level information on public spending from Colombia’s e-procurement platform, and a difference-in-differences identification strategy, we find that municipalities classified by a machine learning algorithm as more prone to corruption react to the spending surge by using a larger proportion of discretionary non-competitive contracts and increasing their average value, especially to procure crisis-related items. Additionally, in places that rank higher on our corruption scale, contracts signed during the emergency are more likely to have cost overruns, be awarded to campaign donors, and exhibit implementation inefficiencies. Our evidence suggests that these negative shocks may increase waste and corruption, and thus governments should bolster instances of monitoring and oversight.
  🖺 Full Text HTML: Corruption in the Times of Pandemia
• Pharmacophore-based peptide biologics neutralize SARS-CoV-2 S1 and deter S1-ACE2 interaction in vitro -
  Effective therapeutics and stable vaccine are the urgent need of the day to combat COVID-19 pandemic. SARS-CoV-2 spike protein has a pivotal role in cell-entry and host immune response, thus regarded as potential drug- and vaccine-target. As the virus utilizes the S1 domain of spike to initiate cell-attachment and S2 domain for membrane fusion, several attempts have been made to design viral-receptor and viral-fusion blockers. Here, by deploying interactive structure-based design and pharmacophore-based approaches, we designed short and stable peptide-biologics i.e. CoV-spike-neutralizing peptides (CSNPs) including CSNP1, CSNP2, CSNP3, CSNP4. We could demonstrate in cell culture experiments that CSNP2 binds to S1 at submicromolar concentration and abrogates the S1-hACE2 interaction. CSNP3, a modified and downsized form of CSNP2, could neither interfere with the S1-hACE2 interaction nor bind to S1. CSNP4 exhibited dose-dependent binding to both S1 and hACE2 and abolished the S1-hACE2 interaction in vitro. CSNP4 possibly enhance the mAb-based S1 neutralization by limiting the spontaneous movement of spike receptor-binding domain (RBD), whereas CSNP2 allowed RBD-mAb binding without any steric hindrance. Taken together, we suggest that CSNP2 and CSNP4 are potent and stable candidate peptides that can neutralize the SARS-CoV-2 spike and possibly pose the virus to host immune surveillance.
  🖺 Full Text HTML: Pharmacophore-based peptide biologics neutralize SARS-CoV-2 S1 and deter S1-ACE2 interaction in vitro
• In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 -
  Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
  🖺 Full Text HTML: In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19
• Meta-analysis of virus-induced host gene expression reveals unique signatures of immune dysregulation induced by SARS-CoV-2 -
  The clinical outcome of COVID-19 has an extreme age, genetic and comorbidity bias that is thought to be driven by an impaired immune response to SARS-CoV-2, the causative agent of the disease. The unprecedented impact of COVID-19 on global health has resulted in multiple studies generating a variety of large gene expression datasets in a relatively short period of time. In order to better understand the immune dysregulation induced by SARS-CoV-2, we carried out a meta-analysis of these transcriptomics data available in the published literature. Datasets included both those available from SARS-CoV-2 infected cell lines in vitro and those from patient samples. We focused our analysis on the identification of viral perturbed host functions as captured by co-expressed gene module analysis. Transcriptomics data from lung biopsies and nasopharyngeal samples, as opposed to those available from other clinical samples and infected cell lines, provided key signatures on the role of the host's immune response on COVID-19 pathogenesis. For example, severity of infection and patients' age are linked to the absence of stimulation of the RIG-I-like receptor signaling pathway, a known critical immediate line of defense against RNA viral infections that triggers type-I interferon responses. In addition, co-expression analysis of age-stratified transcriptional data provided evidence that signatures of key immune response pathways are perturbed in older COVID-19 patients. In particular, dysregulation of antigen-presenting components, down-regulation of cell cycle mechanisms and signatures of hyper-enriched monocytes were strongly correlated with the age of older individuals infected with SARS-CoV-2. Collectively, our meta-analysis highlights the ability of transcriptomics and gene-module analysis of aggregated datasets to aid our improved understanding of the host-specific disease mechanisms underpinning COVID-19.
  🖺 Full Text HTML: Meta-analysis of virus-induced host gene expression reveals unique signatures of immune dysregulation induced by SARS-CoV-2
• H3N2 outbreak from New York (2014-2015) shows sequence fragments matching to Escherichia phage Lambda have integrated into influenza genomes -
  Letter Influenza (commonly known as ”the flu”) has 4 types - out of which 3 (A/B/C) infect humans [1]. Influenza A and B genomes each have 8 negative-sense, single-stranded viral RNA segments (C has a 7-segment genome) [2]. Two of these segments - glycoproteins hemagglutinin (HA) and neuraminidase on the surface of the virus - are used to subtype the virus [3]. The ability of these segments to mix and match (HxNx, currently there are 129 subtypes) creates a constantly mutating virus - making it difficult to devise an effective virus [4, 5]. Also, the hemagglutinin gene causes aberrant coagulation leading to a hyper-inflammatory response [6]. Lab-edited influenza viruses in circulation This is compounded by the escape of viruses being modified in laboratories that are trying to enhance the speed of development of therapeutics. For example, Covid19 patients from Wuhan and Hong Kong were infected with Influenza A appended with DNA-expression vector sequences facilitating protein transcrip- tion (18s) [7]. In another example, canine 28s was found to be integrated with Influenza A genomes in patients from Hong Kong [8]. Madin Darby canine kidney cell-lines are used to make Influenza vaccines, suggesting that some of these viruses might have escaped into circulation. ”Flucelvax Quadrivalent is the only cell-based inactivated flu vaccine that has been licensed by the FDA for use in the United States.” (https://www.cdc.gov/flu/prevent/cell-based.htm) H3N2 genomic reads have sequence fragments that match to Escherichia phage Lambda (among others) Here, Influenza samples isolated from human respiratory tract 2014-2015 from New York (Accid:PRJNA431639 [9], n=122) shows the integration of some sequence fragments matching to the Escherichia phage Lambda ev017 (Accid:NC 049948.1) in all of the eight fragments. In order to exclude the possibility of sequencing artifacts, only the occurrence of exact reads in different samples were recorded (Table 1). SPADES assembler generates full length segments along with the Escherichia phage Lambda The SPADES assembler [10] makes full length segments from these sequences (SI:spades.contigs.fa) showing the same integration. Fig 1 shows these exogenous sequences flanking a full length polymerase PA (segment 3) - note how the ends have complimentary runs of TTT (UUU) and AAA, which helps the RNA fold onto itself, probably helping better packing.
  🖺 Full Text HTML: H3N2 outbreak from New York (2014-2015) shows sequence fragments matching to Escherichia phage Lambda have integrated into influenza genomes
• Resuming professional football during the Covid-19 pandemic in a country with high infection rates A prospective cohort study -

  Objectives: The risk of viral transmission associated with contact sports such as Football during the COVID-19 pandemic is unknown. The aim of this study was to describe the development of infective and immune status of professional football players, team staff and league officials over a truncated football season resumed at the height of the Covid-19 pandemic in a country with high infection rates and to investigate the clinical symptoms related to Covid-19 infection in professional football players. Methods: Prospective cohort study of 1337 football players, staff and officials during a truncated football season (9 weeks) with a tailored infection control program based on preventive measures and regular SarS-CoV-2 PCR swab testing (every 3-5 days) combined with serology testing for immunity (every 4 weeks). Clinical symptoms in positive participants were recorded using a 26-item, Likert-scale-based scoring system. Results: During the study period, 85 subjects returned positive (cycle threshold (cT)<30) or reactive (30<cT<40) PCR tests, of which 36 were players. The infection rate was in line with that of the general population at the time. More than half of the infected were asymptomatic, the remaining had only mild symptoms, no one required hospitalization. Symptom severity was associated to lower cT values. Social contacts and family were the most common sources of infection, no infection could be traced to training or matches. Conclusion: Sports played outdoors involving close contact between athletes represent a limited risk for SARS-CoV-2 infection and severe illness when preventive measures are in place.

  🖺 Full Text HTML: Resuming professional football during the Covid-19 pandemic in a country with high infection rates A prospective cohort study
• SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe -

  People with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.

  🖺 Full Text HTML: SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe

From Clinical Trials

• Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients - Condition:   Covid19
  Intervention:   Drug: Methylprednisolone, Placebo
  Sponsor:   Azienda Unità Sanitaria Locale Reggio Emilia
  Not yet recruiting

• Dendritic Cell Vaccine to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Biological: AV-COVID-19
  Sponsors:   Indonesia-MoH;   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   RSUP Dr. Kariadi Semarang, indonesia;   Faculty of Medicine University of Diponegoro, Indonesia
  Recruiting

• Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Dalcetrapib;   Other: Placebo
  Sponsors:   DalCor Pharmaceuticals;   The Montreal Health Innovations Coordinating Center (MHICC);   Covance
  Not yet recruiting

• suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19 - Condition:   Covid19
  Interventions:   Drug: Anakinra;   Drug: Placebo
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Recruiting

• Evaluating the Impact of EnteraGam In People With COVID-19 - Condition:   Covid19
  Interventions:   Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate;   Other: Standard of care
  Sponsors:   Entera Health, Inc;   Lemus Buhils, SL;   Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)
  Not yet recruiting

• Efficacy and Safety of Remdesivir and Tociluzumab for the Management of Severe COVID-19: A Randomized Controlled Trial - Conditions:   Covid19;   Covid-19 ARDS
  Interventions:   Drug: Remdesivir;   Drug: Tocilizumab
  Sponsors:   M Abdur Rahim Medical College and Hospital;   First affiliated Hospital of Xi'an Jiaoting University
  Recruiting

• Inhaled Ivermectin and COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Ivermectin Powder
  Sponsor:   Mansoura University
  Not yet recruiting

• Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home - Condition:   Covid19
  Intervention:   Drug: tenofovir disoproxil and emtricitabine
  Sponsor:   University Hospital, Caen
  Recruiting

• Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID 19 Vaccine ERUCOV-VAC - Condition:   COVID-19 Vaccine
  Interventions:   Biological: ERUCOV-VAC;   Other: Placebo Vaccine
  Sponsors:   Health Institutes of Turkey;   TC Erciyes University
  Recruiting

• AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   AstraZeneca;   R-Pharm
  Not yet recruiting

• Anti-COVID19 AKS-452 - ACT Study - Condition:   Covid19
  Intervention:   Biological: AKS-452
  Sponsors:   University Medical Center Groningen;   Akston Biosciences Corporation
  Not yet recruiting

• Study in Adults to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, Given in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19. - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  Not yet recruiting

• Surgical Face Mask Effects in Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: Sit-To-Stand test
  Sponsor:   Cliniques universitaires Saint-Luc- Université Catholique de Louvain
  Not yet recruiting

• Evaluation of Prognostic Modification in COVID-19 Patients in Early Intervention Treatment - Condition:   Covid19
  Interventions:   Drug: Azithromycin / Ivermectin / Ribaroxaban / Paracetamol;   Drug: Azithromycin / Ribaroxaban / Paracetamol
  Sponsors:   Gilberto Cruz Arteaga;   Coordinación de Investigación en Salud, Mexico
  Recruiting

• Dendritic Cell Vaccine, AV-COVID-19, to Prevent COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: AV-COVID-19;   Other: GM-CSF
  Sponsors:   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   Indonesia Ministry of Health;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Recruiting

From PubMed

• Therapeutic approaches against coronaviruses acute respiratory syndrome - Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA-approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in-depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against...

• The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus that infects humans and a number of animal species causing coronavirus disease-19 (COVID-19), a respiratory distress syndrome which has provoked a global pandemic and a serious health crisis in most countries across our planet. COVID-19 inflammation is mediated by IL-1, a disease that can cause symptoms such as fever, cough, lung inflammation, thrombosis, stroke, renal failure and headache, to name a few....

• Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons - Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed...

• Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections - CONCLUSIONS: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

• The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19 - The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitro studies and the clinic that apilimod blocks antiviral immune responses. We therefore warn that the immunosuppression observed in many COVID-19 patients might be aggravated by...

• Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology - The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05...

• Fucoidan and Lung Function: Value in Viral Infection - Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to...

• Conus venom fractions inhibit the adhesion of Plasmodium falciparum erythrocyte membrane protein 1 domains to the host vascular receptors - Using high-throughput BioPlex assays, we determined that six fractions from the venom of Conus nux inhibit the adhesion of various recombinant PfEMP-1 protein domains (PF08_0106 CIDR1α3.1, PF11_0521 DBL2β3, and PFL0030c DBL3X and DBL5e) to their corresponding receptors (CD36, ICAM-1, and CSA, respectively). The protein domain-receptor interactions permit P. falciparum-infected erythrocytes (IE) to evade elimination in the spleen by adhering to the microvasculature in various organs including the...

• Uncovering Flexible Active Site Conformations of SARS-CoV-2 3CL Proteases through Protease Pharmacophore Clusters and COVID-19 Drug Repurposing - The infectious SARS-CoV-2 causes COVID-19, which is now a global pandemic. Aiming for effective treatments, we focused on the key drug target, the viral 3C-like (3CL) protease. We modeled a big dataset with 42 SARS-CoV-2 3CL protease-ligand complex structures from ∼98.7% similar SARS-CoV 3CL protease with abundant complex structures. The diverse flexible active site conformations identified in the dataset were clustered into six protease pharmacophore clusters (PPCs). For the PPCs with distinct...

• In silico analysis of phytochemicals as potential inhibitors of proteases involved in SARS-CoV-2 infection - In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CL^(pro)/M(pro)), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV M^(pro)), SARS-CoV main proteinase (SARS CoV 3CL^(pro)), and one human cellular transmembrane serine proteinase...

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread worldwide and has affected more than 10 million individuals. A typical feature of COVID-19 is the suppression of type I and III interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains elusive. Here, we reported that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III...

• The potential mechanism of N-acetylcysteine in treating COVID-19 - N-Acetylcysteine (NAC) has been proposed and used to treat coronavirus disease 2019 (COVID-19). By reviewing the existing pathological studies of COVID-19, it was found that abundant mucus secretion, formation of a hyaline membrane (supportive of acute respiratory distress syndrome), and interstitial fibrous exudation may be important characteristics of COVID-19 and may be pathological targets of drug therapy. In addition, multiple extrapulmonary organ injuries in COVID-19 may be associated with...

• The fight against human viruses: how NMR can help - CONCLUSION: Considering the NMR-based work conducted on different viruses, we believe that in the close future much more NMR efforts will be devoted to discover novel anti SARS-CoV-2 agents.

• A Review of Treatment of Coronavirus Disease 2019 (COVID-19): Therapeutic Repurposing and Unmet Clinical Needs - For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of...

• Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions - Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. This study reports that remdesivir at nanomolar concentrations inhibits carboxylesterase-2 (CES2) through covalent modifications. CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.

From Patent Search

• Covid 19 - Chewing Gum - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - link

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - link

• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - link

• SARS-CoV-2 RBD共轭纳米颗粒疫苗 - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - link

• Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - link