Covid-19 Sentry

Contents

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

From Preprints

• An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants -
  The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations, posing significant challenges to the effectiveness of vaccines and therapeutic antibodies. Although several neutralizing antibodies were authorized for emergency clinical use, natural antibodies isolated from convalescent patients are vulnerable to SARS-CoV-2 Spike mutations. Here, we describe the screen of a panel of SARS-CoV-2 receptor-binding domain (RBD) targeted nanobodies (Nbs) from a synthetic library and the design of a biparatopic Nb dimer, named Nb1-Nb2, with tight affinity and super wide neutralization breadth against multiple SARS-CoV-2 variants of concern or interest. Deep- mutational scanning experiments identify the potential binding epitopes of the monomeric Nb1 and Nb2 on the RBD and demonstrate that bivalent Nb1-Nb2 has a strong escape resistant feature against more than 60 tested RBD amino acid substitutions. Using pseudovirion-based and trans-complementation SARS-CoV-2 tools, we determine that Nb1-Nb2 broadly neutralizes SARS-CoV-2, including variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), Kappa (B.1.617.1) and Mu (B.1.621). Furthermore, a heavy chain antibody is constructed by fusing the human IgG1 Fc to the biparatopic Nb (designated as Nb1-Nb2-Fc) to improve its neutralization potency, yield, stability and potential half-life extension. For the new Omicron variant (B.1.1.529) that harbors unprecedented multiple RBD mutations, Nb1-Nb2-Fc keeps a firm affinity (KD < 1.0*10E-12 M) and neutralizing activity (IC50 = 0.0017 nM). Together, we developed a biparatopic human heavy chain antibody with ultrapotent and broad-spectrum SARS-CoV-2 neutralization activity which highlights the potential clinical applications.
  🖺 Full Text HTML: An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants
• Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19 -
  Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients’ leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.
  🖺 Full Text HTML: Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19
• SARS-CoV-2 comes up with a perfect recipe for disaster: Each mutation plays a specific role in the evolution of variants of concern -
  COVID-19 pandemic has extended for close to two years with the continuous emergence of new variants. Mutations in the receptor binding domain (RBD) are of prime importance in dictating the SARS-CoV-2 spike protein function. By studying a series of single, double and triple RBD mutants, we have delineated the individual and collective effects of RBD mutations in a variant of concern (VOC) containing multiple mutations (Gamma variant; K417T/E484K/N501Y) on binding to angiotensin converting enzyme 2 (ACE2) receptor, antibody escape and protein stability. Our results show that each mutation in the VOC serves a distinct function that improves virus fitness landscape supporting its positive selection, even though individual mutations have deleterious effects that make them prone to negative selection. K417T contributes to increased expression, increased stability and escape from class 1 antibodies; however, it has decreased ACE2 binding. E484K contributes to escape from class 2 antibodies; however, it has decreased expression, decreased stability, and decreased ACE2 binding affinity. N501Y increases receptor binding affinity; however, it has decreased stability and decreased expression. But when these mutations come together, the deleterious effects are mitigated in the triple mutant due to the presence of compensatory effects, which improves the chances of selection of mutations together. These results show the implications of presence of multiple mutations on virus evolution and indicate the emergence of future SARS-CoV-2 variants with multiple mutations that enhance viral fitness on different fronts by balancing both positive and negative selection.
  🖺 Full Text HTML: SARS-CoV-2 comes up with a perfect recipe for disaster: Each mutation plays a specific role in the evolution of variants of concern
• Designing multi-epitope based peptide vaccine targeting spike protein SARS-CoV-2 B1.1.529 (Omicron) variant using computational approaches. -
  Since the SARS-CoV-2 outbreak in 2019, millions of people have been infected with the virus, and due to its high human-to-human transmission rate, there is a need for a vaccine to protect people. Although some vaccines are in use, due to the high mutation rate in the SARS-CoV-2 multiple variants, the current vaccines may not be sufficient to immunize people against new variant threats. One of the emerging variants of concern is B1.1.529 (Omicron), which carries ~30 mutations in the Spike protein of SARS-CoV-2 is predicted to evade antibodies recognition even from vaccinated people. We used a structure-based approach along with an epitope prediction server to develop a Multi-Epitope based Subunit Vaccine (MESV) involving SARS-CoV-2 B1.1.529 variant spike glycoprotein. The predicted epitope with better antigenicity and non-toxicity were used for designing and predicting vaccine construct features and structure models. The MESV construct In-silico cloning in pET28a expression vector predicted the construct to be highly translational. The proposed MESV vaccine construct was also subjected to immune simulation prediction and was found to be highly antigenic and elicit a cell-mediated immune response. The proposed MESV in the present study has the potential to be evaluated further for vaccine production against the newly identified B1.1.529 (Omicron) variant of concern.
  🖺 Full Text HTML: Designing multi-epitope based peptide vaccine targeting spike protein SARS-CoV-2 B1.1.529 (Omicron) variant using computational approaches.
• Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening. -
  Experiments with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited by the need for biosafety level 3 (BSL3) conditions. A SARS-CoV-2 replicon system rather than an in vitro infection system is suitable for antiviral screening since it can be handled under BSL2 conditions and does not produce infectious particles. However, the reported replicon systems are cumbersome because of the need for transient transfection in each assay. In this study, we constructed a bacterial artificial chromosome vector (the replicon-BAC vector) including the SARS-CoV-2 replicon and a fusion gene encoding Renilla luciferase and neomycin phosphotransferase II, examined the antiviral effects of several known compounds, and then established a cell line stably harboring the replicon-BAC vector. Several cell lines transiently transfected with the replicon-BAC vector produced subgenomic replicon RNAs (sgRNAs) and viral proteins, and exhibited luciferase activity. In the transient replicon system, treatment with remdesivir or interferon-{beta} but not with camostat or favipiravir suppressed the production of viral agents and luciferase, indicating that luciferase activity corresponds to viral replication. VeroE6/Rep3, a stable replicon cell line based on VeroE6 cells, was successfully established and continuously produced viral proteins, sgRNAs and luciferase, and their production was suppressed by treatment with remdesivir or interferon-{beta}. Molnupiravir, a novel coronavirus RdRp inhibitor, inhibited viral replication more potently in VeroE6/Rep3 cells than in VeroE6-based transient replicon cells. In summary, our stable replicon system will be a powerful tool for the identification of SARS-CoV-2 antivirals through high-throughput screening.
  🖺 Full Text HTML: Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening.
• Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19 -

  COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic, antiviral, and anti-inflammatory effect of BromAc in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Method: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine storm analysis was performed. Results: BromAc displayed a robust mucolytic effect in a dose dependent manner. BromAc showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1RA and total reduction for IL-9 compared to NAC alone and control. BromAc acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250ug. Conclusion: These results indicate robust mucolytic and anti-inflammatory effect of BromAc in tracheal aspirates from critically ill COVID-19 patients, indicating its potential as a therapeutic strategy to COVID-19.

  🖺 Full Text HTML: Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19
• Genomic diversification of long polynucleotide fragments is a signature of emerging SARS-CoV-2 variants of concern -

  Highly transmissible or immuno-evasive SARS-CoV-2 variants have intermittently emerged and outcompeted previously circulating strains, resulting in repeated COVID-19 surges, reinfections, and breakthrough infections in vaccinated individuals. With over 5 million SARS-CoV-2 genomes sequenced globally over the last 2 years, there is unprecedented data to decipher how competitive viral evolution results in the emergence of fitter SARS-CoV-2 variants. Much attention has been directed to studying how specific mutations in the Spike protein impact its binding to the ACE2 receptor or viral neutralization by antibodies, but there is limited knowledge of genomic signatures shared primarily by dominant variants. Here we introduce a methodology to quantify the genome-wide distinctiveness of polynucleotide fragments of various lengths (3- to 240-mers) that constitute SARS-CoV-2 lineage genomes. Compared to standard phylogenetic distance metrics and overall mutational load, the quantification of distinctive 9-mer polynucleotides provides a higher resolution of separation between variants of concern (Reference = 89, IQR: 65-108; Alpha = 166, IQR: 150-182; Beta 130, IQR: 113-147; Gamma = 165, IQR: 152-180; Delta = 234, IQR: 216-253; and Omicron = 294, IQR: 287-315). The similar scoring of the Alpha and Gamma variants by our methodology is consistent with these strains emerging at approximately the same time and circulating in distinct geographical regions as dominant strains. Furthermore, evaluation of genomic distinctiveness for 1,363 lineages annotated in GISAID highlights that polynucleotide diversity has increased over time (R2 = 0.37) and that VOCs show high distinctiveness compared to non-VOC contemporary lineages. To facilitate similar real-time assessments on the competitive fitness potential of future variants, we are launching a freely accessible resource for infusing pandemic preparedness with genomic inference (“GENI” — https://academia.nferx.com/GENI). This study demonstrates the value of characterizing new SARS-CoV-2 variants by their genome-wide polynucleotide distinctiveness and emphasizes the need to go beyond a narrow set of mutations at known functionally salient sites.

  🖺 Full Text HTML: Genomic diversification of long polynucleotide fragments is a signature of emerging SARS-CoV-2 variants of concern
• Are COVID-19 data reliable? The case of the European Union -

  Previous studies have used Benford9s distribution to assess whether there is misreporting of COVID-19 cases and deaths. Data inaccuracies provide false information to the media, undermine global response and hinder the preventive measures taken by countries worldwide. In this study, we analyze daily new cases and deaths from all the countries of the European Union and estimate the conformance to Benford9s distribution. For each country, two statistical tests and two measures of deviations are calculated to determine whether the reported statistics comply with the expected distribution. Four country-level developmental indexes are also included, the GDP per capita, health expenditures, the Universal Health Coverage index, and full vaccination rate. Regression analysis is implemented to show whether the deviation from Benford9s distribution is affected by the aforementioned indexes. The findings indicate that only three countries were in line with the expected distribution, Bulgaria, Croatia, and Romania. For daily cases, Denmark, Greece, and Ireland, showed the greatest deviation from Benford9s distribution, and for deaths, Malta, Cyprus, Greece, Italy, and Luxemburg had the highest deviation from Benford9s law. Furthermore, it was found that the vaccination rate is positively associated with deviation from Benford9s distribution. These results suggest that overall official data provided by authorities are not confirming Benford9s law, yet this approach acts as a preliminary tool for data verification. More extensive studies should be made with a more thorough investigation of countries that showed the greatest deviation.

  🖺 Full Text HTML: Are COVID-19 data reliable? The case of the European Union
• A novel methodology for the synchronous collection and multimodal visualisation of continuous neurocardiovascular and neuromuscular physiological data in adults with long COVID -

  Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e. self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. To accomplish such an investigation, a wide range of continuous non-invasive biomedical technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. With the novel technique described and exemplified in this paper, we were able to integrate signals from all instruments used in the assessment in a precisely synchronized fashion. We demonstrate that it is possible to visualize the interactions between all different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. The proposed multimodal data visualization can offer an overview of the functioning of the muscle pump during both supine rest and orthostatic recovery and can conduct comparison studies with signals from multiple participants at any given time in the assessment. This could help researchers and clinicians generate and test hypotheses based on the multimodal inspection of raw data, in long COVID and other clinical cohorts.

  🖺 Full Text HTML: A novel methodology for the synchronous collection and multimodal visualisation of continuous neurocardiovascular and neuromuscular physiological data in adults with long COVID
• Relative Importance of Various Inflammatory Markers and Their Critical Thresholds for COVID-19 Mortality -

  Background: Various inflammatory markers are commonly assessed in many patients to help in the management of COVID-19 patients. It is not clear, though, how much risk of mortality their different levels of elevations entail, and which marker signifies more risk than others and how much. This study was undertaken to describe their levels and to answer these questions regarding eight inflammatory markers, namely, CRP, D-dimer, ferritin, IL-6, LDH, CPK, troponin-I. Methods: The data were retrieved from the electronic records of 19852 CoViD-19 patients admitted to a chain of hospitals in north India from March 2020 to July 2021. Levels for most markers were available for more than 10,000 patients. In view of widely different ranges of values of different markers, we divided their values into quintiles (Qs) and studied the pattern of mortality and for running the logistic regression. In addition, logarithm transformation was also tried. The statistical distribution of the values was compared by Mann-Whitney test. Relative importance was judged by the mortality rates, area under the ROC curves (AUROCs), and the odds ratios. Results: Although the mortality increased with decreasing ALC and increasing level of all the other markers, more than 70% survived even with levels in the extreme quintile. The adjusted odds ratio was the highest (7.62) for the Q5 levels of IL-6, closely followed by D-dimer (OR = 6.04). The AUROC was the highest (0.817) for LDH and the least (0.612) for CPK. However, the optimal cut-off for any marker could correctly classify not more than 80% deaths and the multivariable logistic regression could correctly classify patients with mortality in less than 24% cases. Conclusion: Although elevated levels of all the markers and low values of ALC were significant risk factor but no firm evidence was available for any of the eight markers to be a major indicator of the mortality in COVID-19 unless they reach to a critical threshold. Among those studied, D-Dimer (>192 ng/mL) followed by IL-6 (>4.5 pg/mL) had stronger association with mortality even with moderate and higher end of the normal levels and LDH (>433 U/L) and troponin-I (>0.002ng/mL) with only steeply increased levels. Ferritin had modest association, and CPK, CRP and ALC were a relatively poor risk of mortality.

  🖺 Full Text HTML: Relative Importance of Various Inflammatory Markers and Their Critical Thresholds for COVID-19 Mortality
• Risk of myocarditis following sequential COVID-19 vaccinations by age and sex -

  In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy.

  🖺 Full Text HTML: Risk of myocarditis following sequential COVID-19 vaccinations by age and sex
• Genomic surveillance reveals the emergence of SARS-CoV-2 Lineage A from Islamabad Pakistan -

  The lineage A of SARS-CoV-2 has been around the world since the start of the pandemic. In Pakistan the last case of lineage A was reported in April, 2021 since then no case has been reported. In November, 2021 during routine genomic surveillance at National Institute of Health we have found 07 cases of lineage A from Islamabad, Pakistan. The study reports two novel deletions in the spike glycoprotein. One 09 amino acid deletion (68-76 a.a) is found in the S1 subunit while another 10 amino acid deletion (679-688 a.a) observed at the junction of S1/S2 referred as furin cleavage site. The removal of furin cleavage site may result in impaired virus replication thus decreasing its pathogenesis. The actual impact of these two deletions on the virus replication and disease dynamics needs to be studied in detail. Moreover, the enhanced genomic surveillance will be required to track the spread of this lineage in other parts of the country.

  🖺 Full Text HTML: Genomic surveillance reveals the emergence of SARS-CoV-2 Lineage A from Islamabad Pakistan
• COMPARATIVE ANALYSIS OF ANTIBODY RESPONSES FROM COVID-19 CONVALESCENTS RECEIVING VARIOUS VACCINES REVEALS CONSISTENT HIGH NEUTRALIZING ACTIVITY FOR SARS-CoV-2 VARIANT OF CONCERN OMICRON. -

  The novel SARS-CoV-2 Omicron variant of concern (VOCs), with its escape from unboosted vaccines and monoclonal antibodies, is demanding for a return to COVID19 convalescent plasma therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and using high nAb-titer units in early disease stages. In this systematic analysis, we show that CCP from unvaccinated donors is not effective against Omicron, while CCP from vaccinees convalescents from previous VOCs or third-dose uninfected vaccinees is likely to remain effective against Omicron. countries. CCP remains the only antibody-based therapy that keeps up with the variants and provides an effective tool to combat the emergence of variants that defeat monoclonal antibodies. Consequently, there is a need for continue study of the variables that determine CCP efficacy.

  🖺 Full Text HTML: COMPARATIVE ANALYSIS OF ANTIBODY RESPONSES FROM COVID-19 CONVALESCENTS RECEIVING VARIOUS VACCINES REVEALS CONSISTENT HIGH NEUTRALIZING ACTIVITY FOR SARS- CoV-2 VARIANT OF CONCERN OMICRON.
• Serial interval and basic reproduction number of SARS-CoV-2 Omicron variant in South Korea -

  South Korea is experiencing the community transmission of the SARS-CoV-2 Omicron variant (B.1.1.529). We estimated that the mean of the serial interval was 2.22 days, and the basic reproduction number was 1.90 (95% Credible Interval, 1.50-2.43) for the Omicron variant outbreak in South Korea.

  🖺 Full Text HTML: Serial interval and basic reproduction number of SARS-CoV-2 Omicron variant in South Korea
• Paxlovid and Molnupiravir Approved to Manage COVID-19: A Countdown for SARS CoV-2 Variant Apocalypse. -
  I wish to recommend not to approve either Paxlovid or molnupiravir in those countries that are still considering their license, to revoke the emergency use authorization in those countries that issued it, and it is very unfortunate for humanity that safe, generic and highly effective Kelleni’s African protocol used to manage pediatric, adult and pregnant COVID-19 patients is not, yet, adopted by those countries where COVID-19 is wasting thousands of lives daily and I humbly suggest the reasons for this long-lasting ignorance are not medical or scientific.
  🖺 Full Text HTML: Paxlovid and Molnupiravir Approved to Manage COVID-19: A Countdown for SARS CoV-2 Variant Apocalypse.

From Clinical Trials

• Trial to Evaluate Nitazoxanide for Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Drug: Placebo;   Dietary Supplement: Vitamin Super-B Complex
  Sponsor:   Romark Laboratories L.C.
  Not yet recruiting

• Trial to Evaluate Nitazoxanide for Treatment of Mild or Moderate COVID-19 in Subjects at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Dietary Supplement: Vitamin Super-B Complex;   Drug: Placebo;   Other: Standard of Care
  Sponsor:  
  Romark Laboratories L.C.
  Not yet recruiting

• A Double-blind Randomized Controlled Trial of Ivermectin With Favipiravir in Mild-to-moderate COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Other: Placebo
  Sponsors:   Mahidol University;   Prince of Songkla University
  Not yet recruiting

• A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: IBI314;   Other: Placebo
  Sponsor:   Innovent Biologics (Suzhou) Co. Ltd.
  Not yet recruiting

• Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial - Condition:   COVID-19
  Interventions:   Biological: Adrecizumab (HAM 8101);   Drug: Placebo
  Sponsor:   Universitätsklinikum Hamburg-Eppendorf
  Not yet recruiting

• Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Belnacasan;   Drug: Placebo
  Sponsor:  
  MedStar Health
  Recruiting

• A Study Evaluating Tocilizumab in Pediatric Patients Hospitalized With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tocilizumab
  Sponsor:   Hoffmann- La Roche
  Not yet recruiting

• Immunogenicity Study of the Covid-19 (Recombinante) Vaccine With a 4 or 8 Week Interval Between the First Doses. - Condition:   COVID-19
  Intervention:   Biological: Covid-19 (recombinante) vaccine
  Sponsor:   The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  Active, not recruiting

• A Study to Evaluate Efficacy and Safety of the Combination of SCTA01 & SCTA01C in Outpatients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SCTA01 and SCTA01C;   Drug: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Efficacy,Immunogenicity and Safety of COVID-19 Vaccine , Inactivated Booster Dose in Adults Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: Medium-dosage COVID-19 Vaccine,Inactivated;   Biological: High-dosage COVID-19 Vaccine,Inactivated;   Biological: Placebo-comparator group
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Safety and Immunogenicity Study of Booster Vaccination in Different Doses of COVID-19 Vaccine (Vero Cell),Inactivated for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: High-dosage of COVID-19 vaccine (Vero cell), Inactivated;   Biological: Medium-dose COVID-19 Vaccine(Vero Cell),Inactivated
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Active, not recruiting

• Clinical Trial for Oral Formula of Vanillin and Wheat Germ Oil for Treatment of Mild and Moderate COVID-19 Viral Disease - Condition:   Mild-to-moderate COVID-19
  Intervention:   Drug: Oral Capsule
  Sponsors:  
  Alexandria University;   Assoc. Prof. Ayman Baeis;   Dr. Noha Alaa Eldine Hassan Hamdy;   Ph. Hanya Hesham Sweilam
  Recruiting

• Safety and Immunogenicity Study of Booster Vaccination With COVID-19 Vaccine (Vero Cell),Inactivated From Different Manufactures for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Experimental vaccine 1;   Biological: Experimental vaccine 2;   Biological: Experimental vaccine 3
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Combination Assessment Trial of COVID-19 Vaccines (COMBAT-COVID) - Condition:   COVID 19 Vaccine
  Interventions:   Biological: BIBP (CNBG, Sinopharm) WIV;   Biological: CanSinoBIO;   Biological: AstraZeneca ChAdOx
  Sponsors:  
  Aga Khan University Hospital, Pakistan;   Coalition for Epidemic Preparedness Innovations;   University of Oxford;   International Vaccine Institute;   Harvard Medical School (HMS and HSDM);   Chughtai Lab;   National Institute of Health, Pakistan
  Not yet recruiting

• Oral Neutralizing Antibody Booster for Post-vaccinated People With COVID19 Vaccine - Condition:   COVID-19 Pandemic
  Intervention:   Dietary Supplement: Bacillus subtilis spore extract
  Sponsors:   DreamTec Research Limited;   Hong Kong Metropolitan University;   DreamTec Cytokine Limited
  Recruiting

From PubMed

• mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses - Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes…

• Adsorption of benzalkonium chlorides onto polyethylene microplastics: Mechanism and toxicity evaluation - Usage of disposable plastic products and disinfectants has been skyrocketing due to the COVID-19 pandemic. The random disposal of plastic products may result in greater microplastic pollution. Benzalkonium chloride is known as one of the most common ingredients of disinfectants. In this study, the adsorption behavior of benzalkonium chlorides (BAC(12), BAC(14), BAC(16)) on polyethylene microplastics (PE-MPs) and the combined toxic effects were investigated using batch adsorption experiment and…

• The JAK inhibitor ruxolitinib abrogates immune hepatitis instigated by concanavalin A in mice - Therapeutics that impair the innate immune responses of the liver during the inflammatory cytokine storm like that occurring in COVID-19 are greatly needed. Much interest is currently directed toward Janus kinase (JAK) inhibitors as potential candidates to mitigate this life-threatening complication. Accordingly, this study investigated the influence of the novel JAK inhibitor ruxolitinib (RXB) on concanavalin A (Con A)-induced hepatitis and systemic hyperinflammation in mice to simulate the…

• Anti-CD20 monoclonal antibodies inhibit seropositive response to Covid-19 vaccination in Non-Hodgkin lymphoma patients within six months after treatment - The Covid-19 pandemic caused millions of death worldwide. Vaccines have been developed but patients on immunosuppressive therapy are less likely to respond. This study aimed to investigate the efficacy of Covid-19 vaccine (Pfizer-BioNTech) in patients with non-Hodgkin lymphoma, treated with anti-CD20 monoclonal antibodies. Only one of 28 lymphoma patients (3.6%) developed a seropositive response compared to 100% (28 of 28) of the healthy volunteers. The low levels of CD19+ lymphocytes among the…

• SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells - The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2…

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and has infected more than 250 million people. A typical feature of COVID-19 is the lack of type I interferon (IFN-I)-mediated antiviral immunity in patients. However, the detailed molecular mechanisms by which SARS-CoV-2 evades the IFN-I-mediated antiviral response remain elusive. Here, we performed a comprehensive screening and identified a set of SARS-CoV-2…

• Impairment of T cells’ antiviral and anti-inflammation immunities may be critical to death from COVID-19 - Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate…

• Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury - Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from…

• Polyethylene Films Containing Plant Extracts in the Polymer Matrix as Antibacterial and Antiviral Materials - Low density polyethylene (LDPE) films covered with active coatings containing mixtures of rosemary, raspberry, and pomegranate CO(2) extracts were found to be active against selected bacterial strains that may extend the shelf life of food products. The coatings also offer antiviral activity, due to their influence on the activity of Φ6 bacteriophage, selected as a surrogate for SARS-CoV-2 particles. The mixture of these extracts could be incorporated into a polymer matrix to obtain a foil with…

• Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta - The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently…

• Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets - COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus-host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a…

• Polyphenols as Potential Inhibitors of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp) - An increasing number of studies have demonstrated the antiviral nature of polyphenols, and many polyphenols have been proposed to inhibit SARS-CoV or SARS-CoV-2. Our previous study revealed the inhibitory mechanisms of polyphenols against DNA polymerase α and HIV reverse transcriptase to show that polyphenols can block DNA elongation by competing with the incoming NTPs. Here we applied computational approaches to examine if some polyphenols can also inhibit RNA polymerase (RdRp) in SARS-CoV-2,…

• Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study - (1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a…

• Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril - Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect…

• COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling - COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing…

From Patent Search

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• METHODS OF TREATING SARS-COV-2 INFECTION - - link

• REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link

• P2P 네트워크를 이용한 내장된 화상회의 시스템 - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - link

• 小分子化合物肌醇六磷酸酯钠水合物在制备抗SARS-CoV-2药物中的应用 - 本发明公开了小分子化合物肌醇六磷酸酯钠水合物在制备抗严重急性呼吸综合征冠状病毒2(SARS‑CoV‑2)药物中的应用，所述抗SARS‑CoV‑2药物是以肌醇六磷酸酯钠水合物为唯一的活性成份，或包含肌醇六磷酸酯钠水合物的药物组合物，所述抗SARS‑CoV‑2药物是指预防或治疗SARS‑CoV‑2感染的药物。本发明利用SARS‑CoV‑2的易感细胞系，包括非洲绿猴肾细胞Vero

E6以及人肺腺癌细胞Calu‑3，检测肌醇六磷酸酯钠水合物的抗SARS‑CoV‑2活性。实验结果显示，肌醇六磷酸酯钠水合物能有效抑制SARS‑CoV‑2对上述易感细胞的感染，且细胞毒性较小，有希望作为有效抗SARS‑CoV‑2感染的药物，具有应用前景。 - link

• A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link

• Schnelltestsystem -

  Schnelltestsystem, aufweisend: eine Testkassette (11), die ein Testfeld (111) und einen einem bestimmten Benutzer entsprechenden Identifikationsstrichcode (113) aufweist, wobei das Testfeld (111) eine Probe (115) empfängt, um eine Testreaktion (R) zu bewirken, wodurch sich ein der Testreaktion (R) entsprechendes Muster (G) ergibt; und ein tragbares elektronisches Gerät (13), das eine Bildaufnahmeeinheit (131) aufweist, wobei die Bildaufnahmeeinheit (131) das Muster

7. und den Identifikationsstrichcode (113) liest und anschließend an einen Server (15) sendet.

• link

• A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link

• 靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗 - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - link

• 跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途 - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - link