Covid-19 Sentry

Contents

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

From Preprints

• Clinical observation of high-flow nasal cannula (HFNC) with non-rebreather mask (NRM) use on severe or critically ill COVID-19 diabetic patients -

  Objective: Diabetes prevalence is a vital factor in COVID-199s clinical prognosis. This study aimed to investigate and compare the efficacy of High-flow Nasal Cannula (HFNC) with/without non-rebreather mask (NRM) on critical COVID-19 patients with/without diabetes. Materials and methods: For analysis and comparison, epidemiological, biochemical, and clinical data were collected from 240 HFNC±NRM treated severe and critical COVID-19 ICU patients (diabetic = 136; non-diabetic = 104) of five hospitals in Chattogram, Bangladesh. Results and Discussion: 59.1% patients with fever had diabetes (p=0.012). ICU stay was longer for diabetic patients (9.06±5.70) than non-diabetic ones (7.41±5.11) (p=0.020). Majority of hypertensive patients were diabetic (68.3%; p<0.001). Most of the diabetic patients (70.4%; p<0.005) had elevated creatinine levels. The partial pressure of oxygen after HFNC (only) was significantly (p=0.031) higher in non-diabetic patients (69.30±23.56) than diabetic ones (61.50±14.49). Diabetic (62.64±13.05) and non-diabetic patients (59.40±13.22) had similar partial pressure of oxygen from HFNC+NRM. Majority of the diabetic patients who required HFNC+NRM had elevated RBS (73.8%; p=0.001) and creatinine (75.7%; p=0.009). Factors affecting the HFNC only treated patients were fever and impaired glucose tolerance. Besides, increased plasma glucose level, age, and hypertension affected the HFNC + NRM treated diabetic patients. Conclusion: The results of this study imply that oxygen supply with HFNC+NRM may be beneficial for the elderly/hypertensive diabetic patients with COVID-19 associated AHRF; and that IGT and increased blood glucose levels could be determinants for COVID-19 severity. However, further experiments to substantiate these claims are required on a larger sample and among different clinical cohorts.

  🖺 Full Text HTML: Clinical observation of high-flow nasal cannula (HFNC) with non-rebreather mask (NRM) use on severe or critically ill COVID-19 diabetic patients
• THE US MIDLIFE MORTALITY CRISIS CONTINUES: INCREASED EXCESS CAUSE-SPECIFIC MORTALITY DURING 2020 -

  COVID-19 prematurely ended many lives, particularly among the oldest Americans, but the pandemic also had an indirect effect on health and non-COVID mortality among the working-age population, who suffered the brunt of the economic consequences. This analysis investigates whether monthly excess mortality in the US during 2020 varied by age and cause of death. Based on national-level death counts and population estimates for 1999-2020, negative binomial regression models–fit separately by sex–were used to estimate monthly cause-specific excess mortality by age group during 2020. Among males, 71% non-COVID excess deaths occurred at working ages (25-64), but those ages accounted for only 36% of non-COVID excess deaths in females. The results revealed substantial numbers of excess deaths from external causes (particularly among males), heart disease, diabetes, Alzheimer9s disease (particularly among women), and cerebrovascular disease. For males, the largest share of non-COVID excess deaths resulted from external causes, nearly 80% of which occurred at working ages. Although incorrectly classified COVID-19 deaths may explain some excess non-COVID mortality, misclassification is unlikely to explain the increase in external causes of mortality. Auxiliary analyses suggested that drug-related mortality may be driving the rise in external mortality, but drug overdoses were already increasing for a full year prior to the pandemic. The oldest Americans bore the brunt of COVID-19 mortality, but working-age Americans, particularly men, suffered substantial numbers of excess non-COVID deaths, most commonly from external causes and heart disease.

  🖺 Full Text HTML: THE US MIDLIFE MORTALITY CRISIS CONTINUES: INCREASED EXCESS CAUSE-SPECIFIC MORTALITY DURING 2020
• Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory programming and continual clearance of apoptotic cells -

  COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV2-infected apoptotic cells (AC) exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppress macrophage anti-inflammation and efficient tissue repair programs and provide mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

  🖺 Full Text HTML: Efferocytosis of SARS- CoV-2-infected dying cells impairs macrophage anti-inflammatory programming and continual clearance of apoptotic cells
• Allosteric regulation of 3CL protease of SARS-CoV-2 and SARS-CoV observed in the crystal structure ensemble -
  The 3C-like protease (3CLpro) of SARS-CoV-2 is a potential therapeutic target for COVID-19. Importantly, it has an abundance of structural information solved as a complex with various drug candidate compounds. Collecting these crystal structures (83 Protein Data Bank (PDB) entries) together with those of the highly homologous 3CLpro of SARS-CoV (101 PDB entries), we constructed the crystal structure ensemble of 3CLpro to analyze the dynamic regulation of its catalytic function. The structural dynamics of the 3CLpro dimer observed in the ensemble were characterized by the motions of four separate loops (the C-loop, E-loop, H-loop, and Linker) and the C-terminal domain III on the rigid core of the chymotrypsin fold. Among the four moving loops, the C-loop (also known as the oxyanion binding loop) causes the order (active)-disorder (collapsed) transition, which is regulated cooperatively by five hydrogen bonds made with the surrounding residues. The C-loop, E-loop, and Linker constitute the major ligand binding sites, which consist of a limited variety of binding residues including the substrate binding subsites. Ligand binding causes a ligand size dependent conformational change to the E-loop and Linker, which further stabilize the C-loop via the hydrogen bond between the C-loop and E-loop. The T285A mutation from SARS-CoV 3CLpro to SARS-CoV-2 3CLpro significantly closes the interface of the domain III dimer and allosterically stabilizes the active conformation of the C-loop via hydrogen bonds with Ser1 and Gly2; thus, SARS-CoV-2 3CLpro seems to have increased activity relative to that of SARS-CoV 3CLpro.

• A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features -
  The recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viral-host interactions. By temporally tracking 527,988 SARS-CoV-2 genomes, we identified invariant and hypervariable regions within the spike protein. We evaluated combination of mutations from SARS-CoV-2 lineages and found that maximum number of lineage-defining mutations were present in the N-terminal domain (NTD). Based on mutant 3D-structural models of known Variants of Concern (VOCs), we found that structural properties such as accessibility, secondary structural type, and intra-protein interactions at local mutation sites are greatly altered. Further, we observed significant differences between intra-protein networks of wild-type and Delta mutant, with the latter showing dense intra-protein contacts. Extensive molecular dynamics simulations of D614G mutant spike structure with hACE2 further revealed dynamic features with 47.7% of mutations mapping on flexible regions of spike protein. Thus, we propose that significant changes within spike protein structure have occurred that may impact SARS-CoV-2 pathogenesis, and repositioning of vaccine candidates is required to contain the spread of COVID-19 pathogen.
  🖺 Full Text HTML: A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
• Variant-driven multi-wave pattern of COVID-19 via a Machine Learning analysis of spike protein mutations -

  Never before such a vast amount of data, including genome sequencing, has been collected for any viral pandemic than for the current case of COVID-19. This offers the possibility to trace the virus evolution and to assess the role mutations play in its spread within the population, in real time. To this end, we focused on the Spike protein for its central role in mediating viral outbreak and replication in host cells. Employing the Levenshtein distance on the Spike protein sequences, we designed a machine learning algorithm yielding a temporal clustering of the available dataset. From this, we were able to identify and define emerging persistent variants that are in agreement with known evidences. Our novel algorithm allowed us to define persistent variants as chains that remain stable over time and to highlight emerging variants of epidemiological interest as branching events that occur over time. Hence, we determined the relationship and temporal connection between variants of interest and the ensuing passage to dominance of the current variants of concern. Remarkably, the analysis and the relevant tools introduced in our work serve as an early warning for the emergence of new persistent variants once the associated cluster reaches 1% of the time-binned sequence data. We validated our approach and its effectiveness on the onset of the Alpha variant of concern. We further predict that the recently identified lineage AY.4.2 (`Delta plus`) is causing a new emerging variant. Comparing our findings with the epidemiological data we demonstrated that each new wave is dominated by a new emerging variant, thus confirming the hypothesis of the existence of a strong correlation between the birth of variants and the pandemic multi-wave temporal pattern. The above allows us to introduce the epidemiology of variants that we described via the Mutation epidemiological Renormalisation Group (MeRG) framework.

  🖺 Full Text HTML: Variant-driven multi- wave pattern of COVID-19 via a Machine Learning analysis of spike protein mutations
• Vaccine Effectiveness for the COVID-19 in Japan -

  Background: As of the end of September , 2021, the rate of completion for second dose administration was higher than 55% in Japan. Object: We evaluated vaccine effectiveness for COVID-19 in Japan, controlling mutated strains , the Olympic Games and counter measures. Method: The effective reproduction number R(t) was regressed on vaccine coverage, shares of mutated strains, and an Olympic Games dummy variable along with data of temperature, humidity, mobility, and countermeasures. The study period was February, 2020 through September 28, as of October 18, 2021. Results: Estimation results indicate that vaccine coverage reduced R(t) significantly. The infectiousness of mutated strain N501Y decreased significantly, but that of L452R was not significant. The Olympic Games did not affect infectiousness significantly. Discussion and Conclusion: Results indicate a negative association between infectiousness and vaccine coverage. Moreover, some evidence exists of herd immunity attributable to vaccination.

  🖺 Full Text HTML: Vaccine Effectiveness for the COVID-19 in Japan
• Power Law in COVID-19 Cases in China -

  The novel coronavirus (COVID-19) was first identified in China in December 2019. Within a short period of time, the infectious disease has spread far and wide. This study focuses on the distribution of COVID-19 confirmed cases in China—the original epicenter of the outbreak. We show that the upper tail of COVID-19 cases in Chinese cities is well described by a power law distribution, with exponent around one in the early phases of the outbreak (when the number of cases was growing rapidly) and less than one thereafter. This finding is significant because it implies that (i) COVID-19 cases in China is heavy-tailed and disperse; (ii) a few cities account for a disproportionate share of COVID-19 cases; and (iii) the distribution generally has no finite mean or variance. We find that a proportionate random growth model predicated by Gibrat9s law offers a plausible explanation for the emergence of a power law in the distribution of COVID-19 cases in Chinese cities in the early phases of the outbreak.

  🖺 Full Text HTML: Power Law in COVID-19 Cases in China
• Gramicidin S and Melittin - Potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection -
  The COVID19 pandemic has resulted in multipronged approaches for treatment of the disease. Since de novo discovery of drugs is time consuming, repurposing of molecules is now considered as one of the alternative strategies to treat COVID19. Antibacterial peptides are being recognized as attractive candidates for repurposing to treat viral infections. In this study, we describe the anti-SARS-CoV-2 activity of gramicidin S and melittin peptides obtained from Bacillus brevis and bee venom respectively. Our in vitro antiviral assay results showed significant decrease in the viral load compared to the untreated group with no/very less cytotoxicity. The EC50 values for gramicidin S and melittin are calculated as 1.571g and 0.656g respectively. Both the peptides treated to the SARS-CoV-2 infected Vero cells showed viral clearance from 12 hours onwards with a maximal clearance after 24 hours post infection. Based on proteome analysis it was found that more than 250 proteins were found to be differentially regulated in the gramicidin S and melittin treated SARS-CoV-2 infected Vero cells against control SARS-CoV-2 infected Vero cells after 24 and 48 hours post infection. The identified proteins were found to be associated in the metabolic and mRNA processing of the Vero cells post-treatment and infection. Both these peptides could be attractive candidates for repurposing to treat SARS-CoV-2 infection.
  🖺 Full Text HTML: Gramicidin S and Melittin - Potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection
• Underlying selection for the diversity of Spike protein sequences of SARS-CoV-2 -
  The global spread of SARS-CoV-2 is fast moving and has caused a worldwide public health crisis. In the present manuscript we analyzed spike protein sequences of SARS-CoV-2 genomes to assess the impact of mutational diversity. We observed from amino acid usage patterns that spike proteins are associated with a diversity of mutational changes and most important underlying cause of variation of amino acid usage is the changes in hydrophobicity of spike proteins. The changing patterns of hydrophobicity of spike proteins over time and its influence on the receptor binding affinity provides crucial information on the SARS-CoV-2 interaction with human receptor. Our results also show that spike proteins have evolved to prefer more hydrophobic residues over time. The present study provides a comprehensive analysis of molecular sequence data to consider that mutational variants might play a crucial role in modulating the virulence and spread of the virus and has immediate implications for therapeutic strategies.
  🖺 Full Text HTML: Underlying selection for the diversity of Spike protein sequences of SARS-CoV-2
• Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination -
  Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Since mucosal immunity is critical for nasal prevention, we investigated an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved nasal prevention. Our results demonstrated that intranasal influenza-based boost vaccination is required for inducing mucosal and systemic immunity for effective SARS- CoV-2 prevention in both upper and lower respiratory systems.
  🖺 Full Text HTML: Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination
• What Are the Kids Doing? Exploring Young Children’s Activities at Home and Relations with Externally Cued Executive Function and Child Temperament -
  Time in less-structured activities is associated with children’s developing executive function, but it is unclear why. Prior research suggests less-structured time specifically benefits self-directed executive function, by allowing children to practice making choices. We tested another hypothesis: that less-structured time also benefits externally- cued executive function, which develops earlier than self-directed executive function, theorizing that less-structured time can provide children with opportunities to acquire knowledge that supports emerging control skills. Caregivers of 93 3- to 5-year-olds reported their child’s activities on a typical day at home during the COVID-19 pandemic, and children completed a widely-used cued executive function task, the Dimensional Change Card Sort. Time and variety in less-structured activities predicted successful switching on the card sort, controlling for age, family income, caregiver education, and verbal knowledge. Caregivers were more involved in less-structured versus structured activities. Children’s temperament, as rated by caregivers, predicted how they spent their time. Findings provide a more nuanced picture of how less-structured time and executive function are related, consistent with less-structured time affording opportunities for children, particularly those higher in effortful control, to acquire diverse knowledge that supports engaging control in various ways.
  🖺 Full Text HTML: What Are the Kids Doing? Exploring Young Children’s Activities at Home and Relations with Externally Cued Executive Function and Child Temperament
• Mobile Apps for COVID-19 Surveillance: Balancing Public Health Needs with the Privacy of Personal Data under the Saudi Arabian Laws -
  Privacy of personal information is a protected human right both under the international human rights and the Saudi Arabian constitution (Basic Law of Governments) and other statutes and regulations, subject to so exceptions that include protecting public health. The COVID-19 pandemic has challenged and overwhelmed the status quo in every human sphere, including the conventional surveillance of infectious diseases, contact tracing, isolation, reporting and vaccination while simultaneously protecting the privacy of personal data. The pandemic had led national governments, institutions and agencies to adopt mobile applications for collecting, analysing, managing and sharing critical personal data of individuals infected with or exposed to COVID-19. These data may be centralized at a central database, or localized in individuals’ phones. While the benefits of sharing private information for achieving public health needs may not be disputed, the risk of breach of personal privacy is, also, enormous. Consequently, it forced the national governments into a dilemma of either succumbing to public health needs, or strictly respecting and protecting the privacy of individuals, or balancing the two conflicting demands. There is a massive body of literature on the security and privacy of such mobile applications, but none has adequately explored and discussed the public interest justifications under the Saudi Arabian laws for the alleged privacy breaches. This paper explored the COVID-18 surveillance mobile app technologies in use in Saudi Arabia for their potential risks of data breaches under the prevailing data protection laws and regulations with a view to understanding if such breaches are obligated, allowed, or justified under the laws. Our findings suggest that any potential risk of a breach to the individuals’ privacy of personal information under the law would seem to have been properly balanced against (justified by) the public health needs to protect the society during the COVID-19 pandemic.
  🖺 Full Text HTML: Mobile Apps for COVID-19 Surveillance: Balancing Public Health Needs with the Privacy of Personal Data under the Saudi Arabian Laws
• Differences in COVID-19 Risk by Race and County-Level Social Determinants of Health Among Veterans -

  COVID-19 disparities by area-level social determinants of health (SDH) may be impacting U.S. Veterans. This retrospective analysis utilized COVID-19 data from the U.S. Department of Veterans Affairs (VA)s EHR and geographically linked county-level data from 18 area-based socioeconomic measures. The risk of testing positive with Veterans county- level SDHs adjusting for demographics, comorbidities, and facility characteristics was calculated using generalized linear models. We found an exposure-response relationship whereby individual COVID-19 infection risk increased with each increasing quartile of adverse county-level SDH such as the percentage of residents in a county without a college degree, eligible for Medicaid, and living in crowded housing.

  🖺 Full Text HTML: Differences in COVID-19 Risk by Race and County-Level Social Determinants of Health Among Veterans
• High prevalence of an alpha variant lineage with a premature stop codon in ORF7a in Iraq, winter 2020-2021 -

  Background: Since the first reported case of coronavirus disease 2019 (COVID-19) in China, SARS-CoV-2 has been spreading worldwide. Genomic surveillance of SARS-CoV-2 has had a critical role in tracking the emergence, introduction, and spread of new variants, which may affect transmissibility, pathogenicity, and escape from infection or vaccine- induced immunity. As anticipated, the rapid increase in COVID-19 infections in Iraq in February 2021 is due to the introduction of variants of concern during the second wave of the COVID-19 pandemic. Aim: To understand the molecular epidemiology of SARS-CoV-2 during the second wave in Iraq (2021), Methods: We sequenced 76 complete SARS-CoV-2 genomes using NGS technology and identified genomic mutations and proportions of circulating variants among these. Also, we performed an in silico study to predict the effect of the truncation of NS7a protein (ORF7a) on its function Results: We detected nine different lineages of SARS-CoV-2. The B.1.1.7 lineage was predominant (78.9%) from February to May 2021, while only one B.1.351 strain was detected. Interestingly, the phylogenetic analysis showed that multiple strains of the B.1.1.7 lineage clustered closely with those from European countries. A high frequency (88%) of stop codon mutation (NS7a Q62stop) was detected among the B.1.1.7 lineage sequences. In silico analysis of NS7a with Q62stop found that this stop codon had no significant effect on the function of NS7a. Conclusion: This work provides molecular epidemiological insights into the spread variants of SARS-CoV-2 in Iraq, which are most likely imported from Europe.

  🖺 Full Text HTML: High prevalence of an alpha variant lineage with a premature stop codon in ORF7a in Iraq, winter 2020-2021

From Clinical Trials

• Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care - Condition:   COVID-19
  Intervention:   Drug: Apixaban
  Sponsors:  
  Scotmann Pharmaceuticals;   Rawalpindi Medical College
  Not yet recruiting

• Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca);   Biological: CoronaVac (Sinovac Biotech);   Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   Instituto Fernandes Figueira
  Not yet recruiting

• Tocilizumab Versus Baricitinib in Patients With Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tocilizumab;   Drug: Baricitinib
  Sponsor:   University Hospital of Patras
  Recruiting

• The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients (Phase3) - Condition:   COVID-19
  Interventions:   Drug: Pyramax;   Drug: Placebo
  Sponsor:  
  Shin Poong Pharmaceutical Co. Ltd.
  Recruiting

• Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition:   Covid19
  Intervention:   Device: Inspiratory muscle training
  Sponsor:  
  Universidade Federal do Rio Grande do Norte
  Recruiting

• Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition:   COVID-19
  Intervention:   Device: Chatbot
  Sponsor:   Sun Yat- sen University
  Recruiting

• Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial - Condition:   COVID-19
  Interventions:   Behavioral: Self-Benefit/Social Norm;   Behavioral: Self- Benefit/No Social Norm;   Behavioral: Other Benefit/Social Norm;   Behavioral: Other Benefit/No Social Norm
  Sponsors:   University of Pennsylvania;   Pennsylvania Department of Health
  Completed

• Efficacy, Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• Cardiovascular Assessment in Patient Recovered From COVID-19 and Recovery of Autonomic Nervous System in Association With the Severity of the Disease - Condition:   COVID-19
  Intervention:   Other: Non invasive cardiovascular monitoring with CNAP device of arterial pressure, ECG and respiratory activity
  Sponsor:   IRCCS Policlinico S. Donato
  Recruiting

• Safety and Efficacy of KOVIR (TD0068) in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR (TD0068) oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Vietstar Biomedical Research
  Recruiting

• A Safety and Tolerability Study of BDB-001 in Mild, Moderate COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: BDB-001 injection
  Sponsors:  
  Staidson (Beijing) Biopharmaceuticals Co., Ltd;   Beijing Defengrui Biotechnology Co. Ltd
  Completed

• 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

• Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition:   COVID-19
  Intervention:   Diagnostic Test: diaphragm ultrasonography
  Sponsor:   University Hospital, Limoges
  Not yet recruiting

• Safety and Immunogenicity Study of Booster Vaccination With Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: High-dosage SARS-CoV-2 vaccine;   Biological: Medium-dosage SARS-CoV-2 vaccine
  Sponsor:   Sinovac Biotech Co., Ltd
  Not yet recruiting

From PubMed

• SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy - Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened…

• Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry - Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures effective against SARS-CoV-2 variants and future spillovers of other sarbecoviruses. Here we describe the isolation and characterization of a human monoclonal antibody, designated S2K146, broadly neutralizing viruses belonging to all three sarbecovirus clades known to utilize ACE2 as entry receptor and protecting therapeutically against SARS-CoV-2 beta challenge in hamsters. Structural and…

• Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? - Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism…

• COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2 - Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients’ susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin’s expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues…

• Receptor-binding domain of SARS-CoV-2 spike protein efficiently inhibits SARS-CoV-2 infection and attachment to mouse lung - COVID-19, caused by a novel coronavirus, SARS-CoV-2, poses a serious global threat. It was first reported in 2019 in China and has now dramatically spread across the world. It is crucial to develop therapeutics to mitigate severe disease and viral spread. The receptor-binding domains (RBDs) in the spike protein of SARS-CoV and MERS-CoV have shown anti- viral activity in previous reports suggesting that this domain has high potential for development as therapeutics. To evaluate the potential…

• Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies - SARS coronavirus 2 (SARS-CoV-2) has spread rapidly around the world and continues to have a massive global health effect, contributing to an infectious respiratory illness called coronavirus infection-19 (COVID-19). TMPRSS2 is an emerging molecular target that plays a role in the early stages of SARS-CoV-2 infection; hence, inhibiting its activity might be a target for COVID-19. This study aims to use many computational approaches to provide compounds that could be optimized into clinical…

• Transparent Air Filters with Active Thermal Sterilization - The worldwide proliferation of COVID-19 poses the urgent need for sterilizable and transparent air filters to inhibit virus transmission while retaining ease of communication. Here, we introduce copper nanowires to fabricate transparent and self-sterilizable air filters. Copper nanowire air filter (CNAF) allowed visible light penetration, thereby can exhibit facial expressions, helpful for better communication. CNAF effectively captured particulate matter (PM) by mechanical and electrostatic…

• Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy - Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc…

• Current treatment strategies for COVID-19 (Review) - The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo…

• Niclosamide for Covid-19: bridging the gap - CONCLUSIONS: NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

• A review on protective roles and potential mechanisms of metformin in diabetic patients diagnosed with COVID-19 - The novel coronavirus disease 2019 (COVID-19), is currently the leading threat to public health and a huge challenge to the healthcare systems across the globe and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity, a state of chronic inflammation, and diabetes mellitus are risk factors for severe SARS-CoV-2. Metformin is one of the most commonly used antidiabetic medications that displayed immunomodulatory activity through AMP-activated protein kinase. Metformin has…

• SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated…

• Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue - The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that…

• Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19 - COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to…

• Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort - No abstract

From Patent Search

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 广谱抗冠状病毒和流感病毒及口腔致病菌复合IgY及其制剂 - 本发明提供一种广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂。本发明提供制备广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂的方法。广谱抗冠状病毒IgY和广谱抗流感病毒IgY可结合保守的抗原表位，达到广谱中和效果，解决新冠病毒和流感病毒变异的问题。本发明将广谱抗新冠病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体制成系列制剂，包括牙膏和口含片以及潄口水和其它日用品、口鼻喷雾剂、消毒剂、洗手液、粉剂、片剂、糖果、滴鼻剂、滴眼剂、口服剂、胶囊剂，应用于防治新冠和流感以及口腔疾病的药物、消毒产品、保健品和医疗器械中。 - link

• 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

• SARS-CoV2潜在突变位点的筛选方法及其应用 - 本发明涉及生物信息学和生物医药技术领域，尤其是SARS‑CoV2潜在突变位点的筛选方法，包括：1）下载得到SARS‑CoV2的基因序列，对下载的序列进行快速注释文件和序列比对，从全基因组序列中提取出所有编码基因的序列；2）计算出每个位点的突变频率，筛选出高频率的突变热点，再结合毒株的采样时间和地理分布信息，筛选出在种群中具有显著选择优势的突变位点；3）下载已有的编码基因对应蛋白质的三级结构信息；4）根据预测的B细胞和T细胞表位，筛选位于免疫表位上或其附近的突变位点，评估其对宿主免疫反应的可能影响，鉴定出SARS‑CoV‑2在流行传播中基因组上潜在的可能和病毒感染及宿主适应相关的关键变异位点。 - 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