Covid-19 Sentry

Contents

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

From Preprints

• Does face mask use elicit risk-compensation? Quasi-experimental evidence from Denmark during the SARS-CoV-2 pandemic -
  Background: Public use of face masks has been widely adopted to halter the SARS-CoV-2 pandemic but a key concern has been whether the effectiveness of face mask use is limited due to the elicitation of false feelings of security that decrease the observance of other protective behaviors, so-called risk-compensation. Methods: We exploit quasi- experimental variation, prompted by three major changes in policy, to assess whether public use of face masks elicit risk-compensation by increasing the number of close contacts or decreasing attention to distancing and hygiene measured in daily nationally representative surveys (N = 106,880). Results: Number of close contacts: Face mask use prompted by the policy changes decrease the number of contacts in two of the three interventions. In the remaining intervention, it has no effect. Attention to hygiene: Across the changes face masks use does not affect people’s attention to hygiene. Attention to distancing: In two of three interventions, face mask use increase attention to distancing. In the remaining intervention, we see a decrease in attention. Conclusions: Overall, face mask may occasionally elicit a narrow form of risk-compensation; specifically, reducing engagement in physical distancing. However, such narrow forms of risk-compensation are limited: The results do not reveal any effects on the actual number of physical contacts, only on the psychological attention to distancing advice. Moreover, the negative effect only appears for one of three interventions. The other two interventions suggest that face mask use increases attention to physical distancing.

• Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis -

  Objective: The COVID-19 pandemic generated a massive amount of clinical data, which potentially holds yet undiscovered answers related to COVID-19 morbidity, mortality, long term effects, and therapeutic solutions. The objective of this study was to generate insights on COVID-19 mortality-associated factors and identify potential new therapeutic options for COVID-19 patients by employing artificial intelligence analytics on real-world data. Materials and Methods: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within Interrogative Biology® platform was used for network learning, inference causality and hypothesis generation to analyze 16,277 PCR positive patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated causal networks that enabled unbiased identification of significant predictors of mortality for specific COVID-19 patient populations. These findings were validated by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. Results: We found that in the SARS-CoV-2 PCR positive patient cohort, early use of the antiemetic agent ondansetron was associated with increased survival in mechanically ventilated patients. Conclusions: The results demonstrate how real world COVID-19 focused data analysis using artificial intelligence can generate valid insights that could possibly support clinical decision-making and minimize the future loss of lives and resources.

  🖺 Full Text HTML: Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis
• The military as a neglected pathogen transmitter and its implications for COVID-19: A systematic review -

  Background: The risk of outbreaks escalating into pandemics has soared with globalization. Therefore, understanding transmission mechanisms of infectious diseases has become critical to formulating global public health policy. This systematic review assessed the evidence for the military as a disease vector, an historically relevant one, yet overlooked in times of COVID-19. Methods: We searched 3 electronic databases without temporal restrictions. We identified 2010 of 6477 studies spanning over two centuries (1810 – 2020) that met our inclusion criteria and provided evidence for the military as a pathogen transmitter, within itself or between it and civilians. Two researchers independently extracted study data using a standardized form. Through team discussions, studies were grouped according to their type of transmission mechanism and direct quotes were extracted to generate themes and sub–themes. A content analysis was later performed and frequency distributions for each theme were generated. Results: Biological mechanisms driving transmission included person–to–person transmission, contaminated food and water, vector–borne, and airborne routes. Social mechanisms facilitating transmission included crowded living spaces, unhygienic conditions, strenuous working, training conditions, absent or inadequate vaccination programs, pressure from military leadership, poor compliance with public health advice, contractor mismanagement, high–risk behaviours, and occupation–specific freedom of movement. Contaminated food and/or water was the most common biological transmission route. Living conditions were the most common social transmission mechanism, with young, low ranking military personnel repeatedly reported as the most affected group. Certain social mechanisms, such as employment–related freedom of movement, were unique to the military as a social institution. While few studies explicitly studied civilian populations, considerably more contained information that implied that civilians were likely impacted by outbreaks described in the military. Conclusions: Features of the military identified in this study pose a significant public health threat, especially to countries with substantial military presence or underdeveloped health systems. Many social transmission mechanisms, unlike biological ones, were unique to the military, facilitating large–spreader events and affecting civilian health. As an increasingly interconnected world faces the challenges of COVID–19 and future infectious diseases, the identified features of the military may exacerbate current and similar challenges and impair attempts to implement successful and equitable pandemic policies.

  🖺 Full Text HTML: The military as a neglected pathogen transmitter and its implications for COVID-19: A systematic review
• Just-in-time, but still planned: Lessons learned from speeding up the development and implementation of an intervention to promote COVID-19 vaccination in university students -
  We describe the just-in-time, planned development of an online intervention promoting COVID-19-vaccination among University students, just before they were eligible for being vaccinated. We applied the six steps of Intervention Mapping within a time frame much shorter than usual, without losing scientific rigor. In step 1, we created a logic model of the problem. In step 2, we defined the behavioral outcome: taking the vaccination. We selected relevant determinants in an online survey and formulated change objectives. In step 3, we linked the objectives to theory- and evidence-based change methods and translated those into practical applications, taking into account the parameters for effectiveness. Students indicated preferring science-based information from experts; therefore, the final webpage, step 4, included four video-interviews, with a student asking questions to experts; the first two about worries & trust, and the second two on attitudes and perceived norms. In step 5, the intervention was fully implemented by the leadership of the University. Ideally in step 6, first-time interventions are systematically evaluated; however, not in times of COVID-19. This project was executed under unavoidable time pressure. Nevertheless, Intervention Mapping helped us developing an intervention that hopefully will positively affect students’ vaccination behavior in times of need.

• A Mixed Method Analysis of Burnout and Turnover Intentions Among Higher Education Professionals During COVID-19 -
  The COVID-19 pandemic rapidly and dramatically altered higher education including changes to the workplace. Many staff and faculty positions were eliminated while other employees experienced furloughs or reduced work hours. Our study examines the experiences of 1,080 higher education professionals serving in various functional roles during the COVID-19 pandemic from 830 institutions of higher education in the United States. We utilized an explanatory sequential mixed methods research design to examine quantitative and qualitative survey data from October 2020 to understand how jobs in higher education changed during the pandemic and how these changes were associated with an individual’s burnout and intention to leave higher education. Using multiple regression and thematic analysis and the job-demands and resources framework, we find that higher education professionals who experienced significant disruption in their work had increased odds of experiencing burnout. We also find that eliminating staff positions and significant levels of burnout were associated with increased intentions to leave their current profession in higher education. In open ended responses, higher education professionals described how increased job demands through decreased staff and increased workloads were not accompanied with increased resources, leading to burnout. These working conditions negatively affected participants’ personal lives, including their physical and mental health. We conclude with recommendations for research on working conditions in higher education in the pandemic-era and emphasize that institutional leaders should seek systemic changes to support employees.
  🖺 Full Text HTML: A Mixed Method Analysis of Burnout and Turnover Intentions Among Higher Education Professionals During COVID-19
• Immunity to SARS-CoV-2 up to 15 months after infection -
  Background: Information concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset. Methods: The levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison. Findings: Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months. Conclusion: The data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies. Funding: EU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.
  🖺 Full Text HTML: Immunity to SARS-CoV-2 up to 15 months after infection
• Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space -
  Computational tools for integrative analyses of diverse single-cell experiments are facing formidable new challenges including dramatic increases in data scale, sample heterogeneity, and the need to informatively cross- reference new data with foundational datasets. Here, we present SCALEX, a deep-learning method that integrates single- cell data by projecting cells into a batch-invariant, common cell-embedding space in a truly online manner (i.e., without retraining the model). SCALEX substantially outperforms online iNMF and other state-of-the-art non-online integration methods on benchmark single-cell datasets of diverse modalities, (e.g., scRNA-seq, scATAC-seq), especially for datasets with partial overlaps, accurately aligning similar cell populations while retaining true biological differences. We showcase SCALEX’s advantages by constructing continuously expandable single-cell atlases for human, mouse, and COVID-19 patients, each assembled from diverse data sources and growing with every new data. The online data integration capacity and superior performance makes SCALEX particularly appropriate for large-scale single-cell applications to build-upon previously hard-won scientific insights.
  🖺 Full Text HTML: Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space
• **ToxPi*GIS Toolkit: Creating, viewing, and sharing integrative visualizations for geospatial data using ArcGIS** -

  Background: Presenting a comprehensive picture of geographic data comprising multiple factors is an inherently integrative undertaking. Visualizing such data in an interactive form is essential for public sharing and geographic information systems (GIS) analysis. The Toxicological Prioritization Index (ToxPi) framework has been used as an integrative model layered atop geospatial data, and its deployment within the dynamic ArcGIS universe would open up powerful new avenues for sophisticated, interactive GIS analysis. Objective: We propose an actively developed suite of software, the ToxPiGIS Toolkit, for creating, viewing, sharing, and analyzing interactive ToxPi figures in ArcGIS. Methods: The ToxPiGIS Toolkit is a collection of methods for creating interactive feature layers that contain ToxPi diagrams. It currently includes an ArcGIS Toolbox (ToxPiToolbox.tbx) for drawing geographically located ToxPi diagrams onto a feature layer, a collection of modular Python scripts that create predesigned layer files containing ToxPi feature layers from the command line, and a collection of Python routines for useful data manipulation and preprocessing. We present workflows documenting ToxPi feature layer creation, sharing, and embedding for both novice and advanced users looking for additional customizability. Results: Map visualizations created with the ToxPiGIS Toolkit can be made freely available on public URLs, allowing users without ArcGIS Pro access or expertise to view and interact with them. Novice users with ArcGIS Pro access can create de novo custom maps, and advanced users can exploit additional customization options. The ArcGIS Toolbox provides a simple means for generating ToxPi feature layers. We illustrate its usage with current COVID-19 data to compare drivers of pandemic vulnerability in counties across the United States. Significance: Development of new features, which will advance the interests of the scientific community in many fields, is ongoing for the ToxPiGIS Toolkit, which can be accessed from www.toxpi.org.

  🖺 Full Text HTML: ToxPi*GIS Toolkit: Creating, viewing, and sharing integrative visualizations for geospatial data using ArcGIS
• Decline in prenatal buprenorphine/naloxone fills during the COVID-19 pandemic in the United States -

  Background and Aims: Pregnancy provides a critical opportunity to engage women with substance use disorder in care. Buprenorphine/naloxone treatment is associated with improved pregnancy and fetal outcomes, but prior to the COVID-19 pandemic, there were multiple barriers to accessing buprenorphine/naloxone during pregnancy. Care disruptions during the pandemic may have further exacerbated these already existing barriers. To quantify these changes, we examined trends in the number of individuals filling prescriptions for prenatal buprenorphine/naloxone prescriptions during the COVID-19 pandemic. Methods: We estimated an interrupted time series model using linked national pharmacy claims and medical claims data from May 2019 to December 2020. We estimated changes in the level and trend in the monthly number of individuals filling prescriptions for prenatal buprenorphine/naloxone during the COVID-19 pandemic. We then stratified our analyses by payer. Results: We identified 2,947 pregnant patients filling buprenorphine/naloxone prescriptions. Before the pandemic, there was positive growth in the monthly number of individuals filling prescriptions for prenatal buprenorphine/naloxone (4.83% (95% confidence interval (CI): 3.40% to 6.26%). During the pandemic, the monthly growth rate in individuals filling prescriptions for prenatal buprenorphine/naloxone declined for both patients on commercial insurance and patients on Medicaid (all payers: -5.53% (95% CI: -7.28% to -3.78%); Medicaid: -7.66% (95% CI: -10.42% to -4.90%); Commercial: -3.59% (95% CI: -5.53% to -1.66%)). Conclusion: The number of pregnant individuals filling buprenorphine/naloxone prescriptions was increasing prior to the pandemic, but this growth has been lost during the pandemic.

  🖺 Full Text HTML: Decline in prenatal buprenorphine/naloxone fills during the COVID-19 pandemic in the United States
• Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection -

  Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. This study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan - T cell subsets decrease less than 2-fold - and is lower in males than in females. After accounting for effects of age and sex, ILCs, but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, the abundance of ILCs, but not of T cells, correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and the numbers of these cells did not recover during follow-up. In contrast, children with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked closely with ILCs from lung. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis, and the percentage of amphiregulin-producing ILCs was higher in females than in males. These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS- CoV-2 infection, and that lower ILC abundance accounts for increased COVID-19 severity with age and in males.

• Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex -
  Corona Virus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has caused a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha variant, B.1.1.7 lineage, reported from the United Kingdom (UK), is of great significance in that it contains several mutations that increase its infection and transmission rates as evident from clinical reports. Specifically, the N501Y mutation in the SARS-CoV-2 spike S1 receptor binding domain (S1-RBD) has been shown to possess an increased affinity for ACE2, although the basis for this is not entirely clear yet. Here, we dissect the mechanism underlying the increased affinity using molecular dynamics (MD) simulations of the available ACE2-S1-RBD complex structure (6M0J) and show a prolonged and stable interfacial interaction of the N501Y mutant S1-RBD with ACE2 compared to the wild type S1-RBD. Additionally, we find that the N501Y mutant S1-RBD displays altered dynamics that likely aids in its enhanced interaction with ACE2. By elucidating a mechanistic basis for the increased affinity of the N501Y mutant S1-RBD for ACE2, we believe that the results presented here will aid in developing therapeutic strategies against SARS-CoV-2 including designing drugs targeting the ACE2-S1-RBD interaction.
  🖺 Full Text HTML: Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex
• An insight into SARS-CoV-2 Membrane protein interaction with Spike, Envelope, and Nucleocapsid proteins -
  Intraviral protein-protein interactions are crucial for replication, pathogenicity, and viral assembly. Among these, virus assembly is a critical step as it regulates the arrangements of viral structural proteins and helps in the encapsulation of genomic material. SARS-CoV-2 structural proteins play an essential role in the self-rearrangement, RNA encapsulation, and mature virus particle formation. In SARS-CoV, the membrane protein interacts with the envelope and spike protein in Endoplasmic Reticulum Golgi Intermediate Complex (ERGIC) to form an assembly in the lipid bilayer, followed by membrane-ribonucleoprotein (nucleocapsid) interaction. In this study, we tried to understand the interaction of membrane protein’s interaction with envelope, spike, and nucleocapsid proteins using protein-protein docking. Further, simulation studies performed up to 100 ns to examine the stability of protein-protein complexes of Membrane- Envelope, Membrane-Spike, and Membrane-Nucleocapsid. Prime MM-GBSA showed high binding energy calculations than the docked complex. The interactions identified in our study will be of great importance, as it provides valuable insight into the protein-protein complex, which could be the potential drug targets for future studies.
  🖺 Full Text HTML: An insight into SARS-CoV-2 Membrane protein interaction with Spike, Envelope, and Nucleocapsid proteins
• Novel Investigation of SARS-CoV-2 in COVID-19 Survivors’ Semen in Surabaya, Indonesia -

  The emergence and the widespread of Coronavirus disease 2019 (COVID-19) demands an accurate detection method to establish a diagnosis. Real-time polymerase chain reaction (real-time PCR) is accounted for the perfect point of reference in detecting this virus. The notion that this virus also invades the male reproductive tract requires further investigation to prove the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the semen. This investigation was designed to detect SARS-CoV-2 in COVID-19 survivors semen. This study design was a cross-sectional examination and conducted between November 2020 and March 2021 in the Andrology Unit of Dr. Soetomo General Hospital and Professor Nidom Foundation, both located in the City of Surabaya, Indonesia. The sample was 34 male participants aged above 18 years old and had been confirmed COVID-19 by nasopharyngeal swab PCR test. Part of the semen was taken for real-time PCR testing with the QuantStudio 5 Applied Biosystem (AB) PCR machine and the kits utilized were the STANDARD M nCOV Real-Time Detection Kit and mBioCov-19 RT-PCR Kit. Furthermore, the mean of participants ages was 35.74 years old with 25% of them had had a history of primary infertility and 21.8% of secondary infertility. From the real-time PCR COVID-19 of the semen examination, this investigation found that 27 participants had been negatives (74.4%), six inconclusive (17.6%), and one positive (3%) of SARS CoV-2. In summary, SARS-CoV-2 could be found in the semen of COVID-19 survivors. This should be a concern for the potential impact of COVID-19 in male fertility and the possibility of transmission reproductively.

  🖺 Full Text HTML: Novel Investigation of SARS-CoV-2 in COVID-19 Survivors’ Semen in Surabaya, Indonesia
• Super.Complex: A supervised machine learning pipeline for molecular complex detection in protein-interaction networks -
  Characterization of protein complexes, i.e. sets of proteins assembling into a single larger physical entity, is important, as such assemblies play many essential roles in cells such as gene regulation. From networks of protein- protein interactions, potential protein complexes can be identified computationally through the application of community detection methods, which flag groups of entities interacting with each other in certain patterns. Most community detection algorithms tend to be unsupervised and assume that communities are dense network subgraphs, which is not always true, as protein complexes can exhibit diverse network topologies. The few existing supervised machine learning methods are serial and can potentially be improved in terms of accuracy and scalability by using better-suited machine learning models and parallel algorithms. Here, we present Super.Complex, a distributed, supervised AutoML-based pipeline for overlapping community detection in weighted networks. We also propose three new evaluation measures for the outstanding issue of comparing sets of learned and known communities satisfactorily. Super.Complex learns a community fitness function from known communities using an AutoML method and applies this fitness function to detect new communities. A heuristic local search algorithm finds maximally scoring communities, and a parallel implementation can be run on a computer cluster for scaling to large networks. On a yeast protein-interaction network, Super.Complex outperforms 6 other supervised and 4 unsupervised methods. Application of Super.Complex to a human protein-interaction network with ~8k nodes and ~60k edges yields 1,028 protein complexes, with 234 complexes linked to SARS-CoV-2, the COVID-19 virus, with 111 uncharacterized proteins present in 103 learned complexes. Super.Complex is generalizable with the ability to improve results by incorporating domain-specific features. Learned community characteristics can also be transferred from existing applications to detect communities in a new application with no known communities. Code and interactive visualizations of learned human protein complexes are freely available at: https://sites.google.com/view/supercomplex/super-complex-v3-0.
  🖺 Full Text HTML: Super.Complex: A supervised machine learning pipeline for molecular complex detection in protein-interaction networks
• Defining the analytical and clinical sensitivity of the ARTIC method for the detection of SARS-CoV-2 -

  The SARS-CoV-2 ARTIC amplicon protocol is the most widely used genome sequencing method for SARS-CoV-2, accounting for over 43% of publicly-available genome sequences. The protocol utilises 98 primers to amplify ~400bp fragments of the SARS-CoV-2 genome covering all 30,000 bases. Understanding the analytical performance metrics of this protocol will improve how the data is used and interpreted. Different concentrations of SARS-CoV-2 control material were used to establish the limit of detection (LoD) of the ARTIC protocol. Results demonstrated the LoD was a minimum of 25-50 virus particles per mL. The sensitivity of ARTIC was comparable to the published sensitivities of commercial diagnostics assays and could therefore be used to confirm diagnostic testing results. A set of over 3,600 clinical samples from three UK regions were then evaluated to compare the protocols performance to clinical diagnostic assays (Roche Lightcycler 480 II, AusDiagnostics, Roche Cobas, Hologic Panther, Corman RdRp, Roche Flow, ABI QuantStudio 5, Seegene Nimbus, Qiagen Rotorgene, Abbott M2000, Thermo TaqPath, Xpert). We developed a Python tool, RonaLDO, to perform this validation (available under the GNU GPL3 open-source licence from https://github.com/quadram-institute- bioscience/ronaldo). Positives detected by diagnostic platforms were generally supported by sequencing data; platforms that used RT-qPCR were the best predictors of whether the sample would subsequently sequence successfully. To maximise success of sample sequencing for phylogenetic analysis, samples with Ct <31 should be chosen. For diagnostic tests that do not provide a quantifiable Ct value, adding a quantification step is recommended. The ARTIC SARS-CoV-2 sequencing protocol is highly sensitive, capable of detecting SARS-CoV-2 in samples with Cts in the high 30s. However, to routinely obtain whole genome coverage, samples with Ct <31 are recommended. Comparing different virus detection methods close to their LoD was challenging and significant discordance was observed.

  🖺 Full Text HTML: Defining the analytical and clinical sensitivity of the ARTIC method for the detection of SARS- CoV-2

From Clinical Trials

• Prophylaxis of COVID-19 Disease With Ivermectin in COVID-19 Contact Persons [German: Prophylaxe Der COVID-19-Erkrankung Mit Ivermectin Bei COVID-19 Kontaktpersonen] - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsors:  
  Infectopharm Arzneimittel GmbH;   GKM Gesellschaft für Therapieforschung mbH
  Not yet recruiting

• Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: AD17002;   Biological: Placebo (Formulation buffer)
  Sponsor:   Advagene Biopharma Co. Ltd.
  Not yet recruiting

• Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition:   COVID-19
  Interventions:   Other: Lymphatic OMM;   Other: Light Touch
  Sponsor:   Rowan University
  Not yet recruiting

• “Efesovir” (FS-1) for COVID-19, Phase 2 - Condition:   Covid19
  Intervention:   Drug: Efesovir
  Sponsor:   Scientific Center for Anti-infectious Drugs, Kazakhstan
  Not yet recruiting

• SARS-CoV-2 Infection in COVID-19 Vaccinated Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 vaccinated people
  Sponsor:   Hospices Civils de Lyon
  Recruiting

• Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine;   Biological: SARS-CoV-2 Inactivated Vaccine
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Not yet recruiting

• A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Drug: VXA-CoV2-1.1-S;   Other: Placebo Tablets
  Sponsor:   Vaxart
  Recruiting

• RCT on the Efficacy of Dexamethasone Versus Methyl Prednisolone in Covid-19 Infected Patients With High Oxygen Flow - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Dexamethasone;   Drug: Methylprednisolone
  Sponsor:   Cairo University
  Recruiting

• Acetylsalicylic Acid in COVID-19 (ASA-SARS) - Conditions:   SARS-CoV2 Infection;   Covid19
  Interventions:   Drug: Low-dose acetylsalicylic acid;   Drug: Placebo
  Sponsors:   Barcelona Institute for Global Health;   Hospital Universitario de Torrejón,Madrid;   Hospital Universitario Infanta Leonor;   Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau;   Hospital del Mar;   Hopsital Central de Maputo, Mozambique
  Not yet recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08);   Biological: COVID-19 vaccine (Vero cells);   Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• EFFECTIVENESS, SAFETY AND IMMUNOGENICITY OF THE HALF DOSE OF THE VACCINE ChadOx1 nCoV-19 (AZD1222) for COVID-19 - Condition:   SARS-CoV-2
  Interventions:   Biological: Half dose of ChAdOx1 nCoV-19 (AZD1222);   Biological: Standard dose of ChAdOx1 nCoV-19 (AZD1222)
  Sponsors:   Federal University of Espirito Santo;   Instituto René Rachou/Fiocruz;   Escola Nacional de Saúde Pública Sérgio Arouca/Fiocruz;   Programa de Computação Científica/Fiocruz;   Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória
  Recruiting

• Study on COVID-19 Vaccine Effectiveness Among Health Workers in Azerbaijan - Conditions:   Vaccine Refusal;   Covid19
  Intervention:   Biological: COVID-19 vaccine Observation of individuals who receive the COVID-19 vaccine
  Sponsors:   Public health and reforms Center of Ministry of Health;   World Health Organization;   Ministry of Health of Azerbaijan Republic
  Recruiting

• Pulmonary Rehabilitation After Pregnancy in COVID-19 Infection: A Case Report - Conditions:   COVID-19 Pneumonia;   Pulmonary Rehabilitation;   Pregnancy
  Intervention:  
  Other: pulmonary rehabilitation
  Sponsor:   Dr. Lutfi Kirdar Kartal Training and Research Hospital
  Not yet recruiting

• Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） - Condition:   SARS-CoV-2 Infection
  Interventions:   Biological: MT-2766 High dose;   Drug: Placebo;   Biological: MT-2766 Low dose
  Sponsors:   Medicago;   Mitsubishi Tanabe Pharma Corporation
  Enrolling by invitation

• The School SPIT Study - COVID-19 Testing in Secondary Schools - Condition:   SARS-CoV2 Infection
  Intervention:   Diagnostic Test: Take home saliva kit
  Sponsor:   The Hospital for Sick Children
  Active, not recruiting

From PubMed

• A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells - The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally…

• Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity - CONCLUSIONS: Our data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.

• A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases - Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small…

• SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both…

• MOXIDECTIN AND IVERMECTIN INHIBIT SARS-COV-2 REPLICATION IN VERO E6 CELLS BUT NOT IN HUMAN PRIMARY AIRWAY EPITHELIUM CELLS - Antiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 μM. These limited in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: "the current evidence on the use of ivermectin to…

• Mechanisms of instantaneous inactivation of SARS-CoV-2 by silicon nitride bioceramic - The hydrolytic processes occurring at the surface of silicon nitride (Si(3)N(4)) bioceramic have been indicated as a powerful pathway to instantaneous inactivation of SARS-CoV-2 virus. However, the virus inactivation mechanisms promoted by Si(3)N(4) remain yet to be elucidated. In this study, we provide evidence of the instantaneous damage incurred on the SARS-CoV-2 virus upon contact with Si(3)N(4). We also emphasize the safety characteristics of Si(3)N(4) for mammalian cells. Contact between…

• The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery - Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated…

• 6-Thioguanine Blocks SARS-CoV-2 Replication by Inhibition of PLpro - The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2…

• Prompt Reduction in CRP, IL-6, IFN-gamma, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19 - Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy…

• Regulatory T cells in COVID-19 - The outbreak of coronavirus disease 2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to the disruption of immune system, exacerbated inflammation, and even multiple organ dysfunction syndrome. Regulatory T cells (Tregs) are an important subpopulation of T cells that exert immunosuppressive effects. Recent studies have demonstrated that the number of Tregs is significantly reduced in COVID-19 patients, and this reduction may…

• Fighting coronaviruses with natural polyphenols - Few licensed drugs and vaccines are available concerning COVID-19, a disease caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Furthermore, numerous recent SARS-COV-2 variants of have arisen globally, demonstrating the need to develop broadly protective interventions for different coronavirus strains. Polyphenols are the largest class of natural bioactive compounds, categorized as flavonoids (catechins, quercetin and kaempferol) and non-flavonoids (gallic acid and…

• Will Auranofin Become a Golden New Treatment Against COVID-19? - Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression via inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that…

• Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease - BACKGROUND: Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture.

• Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico - The ongoing pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV 2) has led to more than 168 million confirmed cases with 3.5 million deaths as at 28th May, 2021 across 218 countries. The virus has a cysteine protease called main protease (Mpro) which is significant to it life cycle, tagged as a suitable target for novel antivirals. In this computer-assisted study, we designed 100 novel molecules through an artificial neural network-driven platform called LigDream…

• Differential roles of interferons in innate responses to mucosal viral infections - Interferons (IFNs) are among the first vertebrate immune pathways activated upon viral infection and are crucial for control of viral replication and dissemination, especially at mucosal surfaces as key locations for host exposure to pathogens. Inhibition of viral establishment and spread at and from these mucosal sites is paramount for preventing severe disease, while concomitantly limiting putative detrimental effects of inflammation. Here, we compare the roles of type I, II, and III IFNs in…

From Patent Search

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• 健康智能检测方法、装置、电子设备及可读存储介质 - 本申请公开了一种健康智能检测方法、装置、电子设备及可读存储介质，其方法包括获取音频信号，并对所述音频信号进行预处理，得到检测信号；将所述检测信号转化为矩阵数字矩阵；将得到的矩阵数字矩阵作为检测样本，输入健康智能检测模型中，以获取检测结果；其中，所述健康智能检测模型是采用迁移学习和卷积神经网络对训练样本进行训练得到的。本申请由于卷积神经网络各组件或部分组件基于迁移学习进行了重新训练，显著提升了对人们健康检测的准确度；且本申请中的健康智能检测模型为分类模型，计算量小，可将其部署于人们的移动终端中，使用方便，极大程度上提升了用户的使用感受。 - link

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• 单克隆抗体32C7及其制备方法和用途 - 本发明公开了单克隆抗体32C7及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体32C7，在体外通过表面等离子共振检测抗体32C7可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体32C7的中和能力，测定了中和抗体32C7对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体32C7抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• 单克隆抗体35B5及其制备方法和用途 - 本发明公开了单克隆抗体35B5及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体35B5，在体外通过表面等离子共振检测抗体35B5可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体35B5的中和能力，测定了中和抗体35B5对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体35B5抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - link

• 以痘苗病毒为载体的新冠疫苗 - 本申请涉及一种基于经过基因工程改造的痘苗病毒为载体的新型冠状病毒南非突变株疫苗。所述疫苗以A46R缺陷的痘苗病毒为载体携带新冠病毒南非突变株S基因核酸序列，所述痘苗病毒载体还可以携带IL‑21，该疫苗在免疫小鼠后可以产生针对新冠病毒南非突变株的抗体。 - link

• 氧化钛负载银单原子的材料在病毒消杀中的应用 - 本发明属于生物医药领域，尤其涉及一种负载银单原子的材料在病毒消杀中的应用，所述氧化钛负载银单原子材料具有以下的结构：银单原子以单分散的形式，稳定地锚定于氧化钛的表面和/或骨架中，键合方式为Ti‑O‑Ag；银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙范围为2.9‑3.2

eV；氧化钛负载银单原子材料具有较银纳米颗粒更加优异的催化活性，具有过氧化物酶活性，利用羟基自由基可高效破坏核酸和蛋白质的原理来实现广谱消杀病毒，银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙变小，对可见光的敏感性更强，可将光照射下的光催化诱导光动力杀伤病毒。 - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link