Covid-19 Sentry

Contents

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

From Preprints

• Deploying wearable sensors for pandemic mitigation -

  Wearable sensors can continuously and passively detect potential respiratory infections, before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada9s second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we found that deploying wearable sensors could have averted 9% of second wave SARS-CoV-2 infections, though 29% of this reduction is attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized incorrect quarantines and associated costs. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensor deployment can meaningfully contribute to pandemic mitigation; in the case of COVID-19, technology improvements or supporting measures are required to reduce social and economic costs to acceptable levels.

• First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France -

  The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here we describe the first cases diagnosed with this variant in south-eastern France. We identified thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers returning from Tanzania. Overall, viral genomes displayed a mean (+/-standard deviation) number of 65.9+/-2.5 (range, 61-69) nucleotide substitutions and 31.0+/-8.3 (27-50) nucleotide deletions, resulting in 49.6+/-2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4+/-1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

  🖺 Full Text HTML: First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France
• Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study -

  Background: To partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear. Methods: Decentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged >70 years) and 375 younger (30-50 years) recruits. Findings: Local and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose. Interpretation: We report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies. Funding: Supported by the Public Health Agency of Canada and the University Health Network Foundation.

  🖺 Full Text HTML: Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study
• Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example -

  In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals. Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a model-based approach that accounts for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence of SARS-CoV-2 infection among HCWs. Over a total follow-up of 6,064 person-days (PD), we estimated an incidence rate (per 100 PD) of 1.05 (95% CrI: 0.58-1.65) at Hospital 1, 1.92 (95% CrI: 0.93-3.28) at Hospital 2 and 7.62 (95% CrI: 3.47-13.70) at Hospital 3. The probability for an HCW to be infected at the end of a shift was 13.7% (95% CrI: 7.8%-20.8%) and 23.8% (95% CrI: 12.2%-37.3%) for a 2-week shift at Hospital 1 and Hospital 2, respectively, which lies within the range of risk levels previously documented in standard healthcare settings, whereas it was >3-fold higher for a 7-day shift at Hospital 2 (42.6%, 95%CrI: 21.9%-64.4%). Our model-based estimates unveil a proportion of undiagnosed infections among HCWs of 46.4% (95% CrI: 18.8%-66.7%), 45.0% (95% CrI: 5.6%-70.8%) and 59.2% (95% CrI: 34.8%-78.8%), for Hosp1 to 3, respectively. The large variation in SARS-CoV-2 incidence we document here suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient anticipation and infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.

  🖺 Full Text HTML: Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example
• Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus -
  Background: The Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity. Findings: Here, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gbp, similar to the 2.50 Gbp length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where approximately 17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0 in which the number of unresolved bases is reduced to 3.00%. Conclusions: Access to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models. Keywords: Syrian hamster, Mesocricetus auratus, genome, disease model, COVID-19
  🖺 Full Text HTML: Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus
• N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus -
  Several compounds have been tested against SARS-CoV-2; at present, COVID-19 treatments decrease the deleterious inflammatory response and acute lung injury. However, the best therapeutic response would be expected by combining anti- inflammatory properties, while concomitantly blocking viral replication. These combined effects should drastically reduce both infection rate and severe complications induced by novel SARS-CoV-2 variants. Therefore, we explored the antiviral potency of a class of anti-inflammatory compounds that inhibit the N-Acylethanolamine acid amidase (NAAA). This enzyme catalyzes the hydrolysis of palmitoylethanolamide (PEA), a bioactive lipid that mediates anti-inflammatory and analgesic activity through the activation of peroxisome proliferator receptor- (PPAR-). Similarly, this pathway is likely to be a significant target to impede viral replication since PPAR- activation leads to dismantling of lipid droplets, where viral replication of Flaviviruses and Coronaviruses occurs.
  🖺 Full Text HTML: N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus
• SARS-CoV-2 ORF6 disrupts innate immune signalling by inhibiting cellular mRNA export -
  SARS-CoV-2 is a betacoronavirus and the etiological agent of COVID-19, a devastating infectious disease. Due to its far-reaching effect on human health, there is an urgent and growing need to understand the viral molecular biology of SARS-CoV-2 and its interaction with the host cell. SARS-CoV-2 encodes 9 predicted accessory proteins, which are presumed to be dispensable for in vitro replication, most likely having a role in modulating the host cell environment to aid viral replication. Here we show that the ORF6 accessory protein interacts with cellular Rae1 to inhibit cellular protein production by blocking mRNA export. We utilised cell fractionation coupled with mRNAseq to explore which cellular mRNA species are affected by ORF6 expression and show that ORF6 can inhibit the export of many mRNA including those encoding antiviral factors such as IRF1 and RIG-I. We also show that export of these mRNA is blocked in the context of SARS-CoV-2 infection. Together, our studies identify a novel mechanism by which SARS-CoV-2 can manipulate the host cell environment to supress antiviral responses, providing further understanding to the replication strategies of a virus that has caused an unprecedented global health crisis.
  🖺 Full Text HTML: SARS-CoV-2 ORF6 disrupts innate immune signalling by inhibiting cellular mRNA export
• Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System -
  The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P [≤] 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research.
  🖺 Full Text HTML: Auto- Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System
• Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat -
  The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
  🖺 Full Text HTML: Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat
• Aerosol Formation During Processing of Potentially Infectious Samples on Roche Immunochemistry Analyzers (cobas e analyzers) and in an End-to-End Laboratory Workflow to Model SARS-CoV-2 Infection Risk for Laboratory Operators -
  Background: This study assessed formation of potentially infectious aerosols during processing of infectious samples in a real-world laboratory setting, which could then be applied in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This two-part study assessed aerosol formation when using cobas e analyzers only and in an end-to-end laboratory workflow. To estimate aerosol formation, recombinant hepatitis B surface antigen (HBsAg) was used as a surrogate marker for infectious virus particles to evaluate the potential risk of SARS- CoV-2 infection to laboratory operators. Using the HBsAg model, air sampling was performed at different positions around the cobas e analyzers and in four scenarios reflecting critical handling and/or transport locations in an end-to-end laboratory workflow. Aerosol formation of HBsAg was quantified using the Elecsys(R) HBsAg II quant II assay. The model was then applied to a SARS-CoV-2 context using SARS-CoV-2 infection-specific parameters to calculate viral RNA copies. Results: Following application to SARS-CoV-2, the mean HBsAg uptake per hour when recalculated into viral RNA copies was 1.9 viral RNA copies across the cobas e analyzers and 0.87 viral RNA copies across all tested scenarios in an end-to- end laboratory workflow. This corresponds to a maximum aspiration rate of <16 viral RNA copies during an 8-hour shift when using cobas e analyzers and/or in an end-to-end laboratory workflow. Conclusions: The low production of marker- containing aerosol when using cobas e analyzers and in an end-to-end laboratory workflow is consistent with a remote risk of laboratory-acquired SARS-CoV-2 infection for laboratory operators.
  🖺 Full Text HTML: Aerosol Formation During Processing of Potentially Infectious Samples on Roche Immunochemistry Analyzers (cobas e analyzers) and in an End-to-End Laboratory Workflow to Model SARS-CoV-2 Infection Risk for Laboratory Operators
• Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release -
  The Omicron variant has become dominant in the U.S. and around the world. This variant is found to be 2-fold more infectious than the Delta variant, posing a significant threat of severe cases and death. We and others have recently reported that the N-terminus domain (NTD) of the SARS-CoV-2 of various variants is responsible for inducing cytokine release in human PBMCs. Here, we demonstrate that the NTD of the Omicron variant remains highly effective at inducing cytokine release in human PBMCs. Furthermore, we show that Ponatinib and a novel compound, Olverembatinib, are potent Omicron NTD-mediated cytokine release inhibitors. Target profiling revealed that Olverembatinib blocks most of the previously identified kinases responsible for cytokine release. Together, we propose that Ponatinib and Olverembatinib may represent an attractive therapeutic option for treating moderate to severe COVID-19 cases.
  🖺 Full Text HTML: Olverembatinib inhibits SARS- CoV-2-Omicron variant-mediated cytokine release
• The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters -
  A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs.
  🖺 Full Text HTML: The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters
• Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein -
  Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by 3-4 different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein-protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced co-assembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.
  🖺 Full Text HTML: Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein
• Designing effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains: an in silico approach -
  Background: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a highly transmissible and pathogenic coronavirus that first emerged in late 2019 and has since triggered a pandemic of acute respiratory disease named “coronavirus disease 2019” (COVID-19), poses a significant threat to all public health institutions in the absence of specific antiviral treatment. Methods: The innate RNA interference (RNAi) pathway, on the other hand, allows for the development of nucleic acid-based antiviral drugs. It is a cellular gene-silencing event in which complementary small interfering RNA (siRNA) molecules cause sequence-specific degradation of target mRNA. Hence, in this current study, the potential of RNAi was utilized to construct siRNA molecules against specific target genes of SARS-CoV-2 structural proteins, such as the envelope protein gene (E), membrane protein gene (M), nucleocapsid phosphoprotein gene (N), and surface glycoprotein gene (S). Results: Conserved sequence from 811 SARS-CoV-2 strains from around India was collected to construct 157 siRNAs that can inactivate E, M, N and S genes. The proposed siRNA molecules possessed sufficient nucleotide-based and other features for effective gene silencing and siRNAs’ targets revealed no significant matches across the whole human genome and hence, siRNAs were found to have no off-target effects on the genome, ruling out the possibility of off-target silencing. Conclusions: Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and molecular docking analysis, 4 effective siRNA molecules were selected for each target gene which is proposed to exert the best action. Our engineered siRNA candidates could be used as a genome-level therapeutic treatment against various sequenced SARS-CoV-2 strains in India. However, future applications will necessitate additional validations in vitro and in vivo animal models.
  🖺 Full Text HTML: Designing effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains: an in silico approach
• The mechanism of RNA capping by SARS-CoV-2 -
  The SARS-CoV-2 RNA genome contains a 5’-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made is not completely understood. Here, we reconstitute the SARS-CoV-2 7MeGpppA2’-O-Me-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain of nsp12 transfers RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers RNA to GDP, forming the cap core structure GpppA-RNA. The nsp14 and nsp16 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system that the N-terminus of nsp9 and the kinase- like active site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.
  🖺 Full Text HTML: The mechanism of RNA capping by SARS- CoV-2

From Clinical Trials

• Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV). - Condition:   COVID-19
  Interventions:   Biological: Tozinameran - Standard dose;   Biological: Tozinameran - fractional dose;   Biological: Elasomeran - standard dose;   Biological: Elasomeran - fractional dose
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   PATH;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Zofin to Treat COVID-19 Long Haulers - Condition:   COVID-19
  Interventions:   Drug: Zofin;   Other: Placebo
  Sponsors:  
  Organicell Regenerative Medicine;   Proxima Clinical Research, Inc.
  Not yet recruiting

• Effect of Daily Oral Administration of Food Supplement NLC-V in Patients Diagnosed With COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: NLC-V
  Sponsor:  
  Todos Medical, Ltd.
  Completed

• Fourth COVID-19 Vaccine Dose- mRNA1273 - Condition:   COVID-19 Pandemic
  Intervention:   Biological: mRNA1273 vaccine
  Sponsor:   Sheba Medical Center
  Active, not recruiting

• Study Design of the Diacerein in Patients With Covid-19 - Condition:   COVID-19
  Interventions:   Drug: Diacerein;   Drug: placebo capsules
  Sponsors:   University of Campinas, Brazil;   Fundação de Amparo à Pesquisa do Estado de São Paulo
  Not yet recruiting

• HEART Rate Variability Biofeedback in LOng COVID-19 (HEARTLOC) - Condition:   COVID-19
  Intervention:   Behavioral: Heart Rate Variability Biofeedback (HRV-B)
  Sponsors:   University of Leeds;   University of Manchester;   Leeds Comunity Healthcare NHS Trust
  Recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of MVC-COV1901 or MVC-COV1901(Beta) Against COVID-19 - Condition:   COVID-19 Vaccine
  Interventions:   Biological: MVC-COV1901(Beta);   Biological: MVC- COV1901
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Fourth BNT162b2 COVID-19 Vaccine Dose - Condition:   COVID-19 Pandemic
  Intervention:   Biological: BNT162b2 vaccine
  Sponsor:   Sheba Medical Center
  Active, not recruiting

• Effects of Aerobic Exercise in Patients With Post COVID-19 - Condition:   COVID-19
  Interventions:   Other: High-intensity interval aerobic exercise training;   Other: Control Group
  Sponsor:   Gazi University
  Not yet recruiting

• Evaluate the Efficacy and Safety of TF0023 in Treatments for COVID-19 in Hospitalized Adults - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: TF0023
  Sponsor:  
  Techfields Inc
  Not yet recruiting

• Immunogenicity and Safety of the SpikoGen COVID-19 Vaccine in Children Aged 5 to <12 Years and 12 to <18 Years Compared With Adults Aged 18 to 40 Years - Condition:   COVID-19
  Interventions:   Biological: Low-dose SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant
  Sponsors:  
  Cinnagen;   Vaxine Pty Ltd
  Not yet recruiting

• Safety and Immunogenicity of COVI-VAC as a Booster Dose in Adults Previously Vaccinated Against COVID-19 - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Biological: COVI-VAC
  Sponsor:  
  Codagenix, Inc
  Not yet recruiting

• Effects of Inspiratory Muscle Training in Patients With Post COVID-19 - Condition:   COVID-19
  Interventions:   Other: Inspiratory Muscle Training Group;   Other: Control Group
  Sponsor:   Gazi University
  Not yet recruiting

• Short Daily Versus Conventional Hemodialysis for COVID-19 Patients - Condition:   COVID-19
  Intervention:   Other: Short daily dialysis
  Sponsor:  
  Shahid Beheshti University of Medical Sciences
  Completed

• Ivermectin for Post Exposure Prophylaxis of Covid-19 - Condition:   COVID-19
  Interventions:   Drug: Ivermectin;   Other: Placebo
  Sponsors:  
  Clinical Research Centre, Malaysia;   Hovid Berhad
  Recruiting

From PubMed

• Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro - The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed…

• Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection - The spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We have developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determine the neutralization titers (defined as the maximal serum dilution that inhibited 50% of infectious virus) of patient sera collected at 1-…

• Reconstruction of the unbinding pathways of noncovalent SARS-CoV and SARS-CoV-2 3CLpro inhibitors using unbiased molecular dynamics simulations - The main protease (3CLpro) is one of the essential components of the SARS-CoVs viral life cycle, which makes it an interesting target for overpowering these viruses. Although many covalent and noncovalent inhibitors have been designed to inhibit this molecular target, none have gained FDA approval as a drug. Because of the high rate of COVID-19 pandemic development, in addition to laboratory research, we require in silico methods to accelerate rational drug design. The unbinding pathways of two…

• Centrifugal Microfluidic Method for Enrichment and Enzymatic Extraction of Severe Acute Respiratory Syndrome Coronavirus 2 RNA - The diversification of analytical tools for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is imperative for effective virus surveillance and transmission control worldwide. Development of robust methods for rapid, simple isolation of viral RNA permits more expedient pathogen detection by downstream real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) to minimize stalled containment and enhance treatment efforts. Here, we describe an automatable…

• Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19 - CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.

• A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant - The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on long term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We here have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma and Epsilon, at…

• Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID-19 context - Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the…

• A randomized, controlled, feasibility study of RD-X19 in subjects with mild-to-moderate COVID-19 in the outpatient setting - The RD-X19 is an investigational, handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses shown to be non-cytotoxic in an in vitro 3-dimensional human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of immune stimulating cytokines IL-1α and IL-1β, with corresponding inhibition of SARS-CoV-2 replication. A single exposure of 425 nm blue…

• Risk Factors for COVID-19: Diabetes, Hypertension, and Obesity - CONCLUSION: Overall, diabetes, hypertension, and obesity seem to negatively affect the clinical course and disease outcome in patients with COVID-19. However, these data need further confirmation by studies with more accurate data registration.

• Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking - SARS-CoV-2 (COVID-19) is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papain-like protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through…

• Disulfiram inhibits neutrophil extracellular trap formation protecting rodents from acute lung injury and SARS-CoV-2 infection - Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram -an FDA-approved drug for alcohol use disorder- dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in…

• The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs - CONCLUSIONS: XC8 acts against cough evoked by the activation of TRPA1 (citric acid/cinnamaldehyde) but not TRPV1 (capsaicin) channels. XC8 inhibits the cough reflex and suppresses the cough potentiation by IFN-γ. XC8 might be of significant therapeutic value for patients suffering from chronic cough associated with inflammation.

• Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibody - The SARS-CoV-2 Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own or in complex with ACE2 or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein, which change binding epitopes to many current antibodies. In the ACE2 binding site, compensating mutations strengthen RBD binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An…

• Cytokine Storm and Failed Resolution in COVID-19: Taking a Cue from Multiple Sclerosis - CONCLUSION: Given the fact that current treatment for COVID-19 is only supportive, global research is aimed at developing safe and effective therapeutic options that can result in a better clinical course in patients with comorbid conditions. Accordingly, taking a cue from our experiences in controlling robust inflammatory response in MS and diabetes by simultaneously inhibiting inflammatory process and stimulating its resolution, combinatorial therapy of metformin and SPM in COVID-19 holds…

• Anticoronavirus Activity of Water-Soluble Pristine C₆₀ Fullerenes: In Vitro and In Silico Screenings - CONCLUSION: Pioneer in vitro study to identify the anticoronavirus activity of water-soluble pristine C(60) fullerenes indicates that they are highly promising for further preclinical studies, since a significant inhibition of the infectious activity of swine coronavirus of transmissible gastroenteritis in BHK-21 cell culture was found. According to molecular modeling results, it was shown that C(60) fullerene can create the stable complexes with 3CLpro and RdRp proteins of SARS-CoV-2…

From Patent Search

• IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link

• ANTIMICROBIAL SANITIZING FORMULATION - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - link

• A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - link

• RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 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

• 黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用 - 本发明公开了黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用。所述黄芩黄酮活性成分选自下述至少一种：黄芩素、汉黄芩素和千层纸素A。炎症风暴是一种机体对外界刺激的过度免疫反应和炎症反应，以炎症细胞因子的快速大量释放为特征。炎症风暴可由许多感染或非感染性疾病引起，并与疾病的严重程度和多器官功能障碍综合征的发生密切相关。减少炎症风暴的发生有助于降低器官损伤和减缓疾病进程，尤其对危重症患者的治疗至关重要。本发明发现，黄芩素、汉黄芩素、千层纸素A均具有不同程度抑制小鼠细胞因子风暴的作用。黄芩素能改善炎症风暴引发的肺损伤和炎性细胞浸润。因此黄芩黄酮活性成分可用于制备防治炎症风暴的药物。 - link

• 一种预防和/或治疗炎症风暴的药物组合物及其制剂与应用 - 本发明公开了一种预防和/或治疗炎症风暴的药物组合物、制剂及其应用。该药物组合物，由黄芩素、汉黄芩素和千层纸素A组成，其中，黄芩素、汉黄芩素、千层纸素A的质量比为0.25_1.5：0.57：1。本发明提供的自微乳包括下述组分：药物磷脂复合物、油相、乳化剂和助乳化剂；其中，所述药物磷脂复合物由上述药物组合物和磷脂材料复合而成。本发明的实验结果表明在LPS诱导的系统性炎症风暴小鼠模型中，黄芩素、汉黄芩素和千层纸素A的组合物及其自微乳制剂均具有不同程度抑制小鼠细胞因子风暴的作用。本发明为炎症风暴的临床治疗提供了一种安全、有效、经济的解决方案。 - link

• 用于核酸检测的微流控芯片及检测方法 - 本发明提供一种用于核酸检测的微流控芯片及检测方法。所述微流控芯片包括依次叠放在一起并相互密封的三层结构，由上至下分别为气道层、中间层和流道层；所述气道层包含两个独立的气道，所述中间层为弹性薄膜，用于控制流道层上微阀的开启和关闭，所述流道层包含四个进样口，两个出样口，四个微阀，一个LAMP反应室、一个CRISPR反应室以及若干条流道，所述微阀通过弹性薄膜与气道层的气道相连，并通过气道层气压的改变来实现微阀的开关，实现不同进样口的顺序进样。本发明将微流控与LAMP扩增技术以及CRISPR检测技术相结合，在单个芯片上实现高灵敏，高特异性的检测病毒核酸。 - link

• REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - link

• 基于引物设计和铜纳米簇的SARS-CoV-2德尔塔变异株检测方法 - 本发明公开了一种基于引物设计和铜纳米簇的SARS‑CoV‑2德尔塔变异株检测方法。该方法结合DPO引物和AT引物成功区分了单碱基缺失的SARS‑CoV‑2德尔塔变异株和SARS‑CoV‑2野生菌株。并且DPO引物和AT引物的PCR产物可以作为CuNCs的生成模板，在紫外照射下实现SARS‑CoV‑2德尔塔变异株的可视化检测。本申请利用常规实验条件，借助PCR仪将DPO引物和AT引物结合扩增，使其SARS‑CoV‑2德尔塔变异株检测具有特异性、高灵敏、可视化的优势。 - link

• REDUCING AND STOPPING OXYGEN WASTAGE IN HOSPITAL - In an aspect, the present invention discloses a system (200) for prevention and reduction of oxygen wastage from oxygen mask (202). The system (200) includes the oxygen mask (202) having straps; a tension sensor (204), the tension sensor being sensitive towards tension produced in the straps as the oxygen gets leakage through sides of the mask (202); a processor configured in alignment with the tension sensor (204); and a buzzer (206) in alignment with processor. - link