Covid-19 Sentry

Contents

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

From Preprints

• The rise and fall of SARS-CoV-2 variants and the emergence of competing Omicron lineages -
  In late December of 2019, high throughput sequencing technologies enabled rapid identification of SARS-CoV-2 as the etiological agent of COVID-19, and global sequencing efforts are now a critical tool for monitoring the ongoing spread and evolution of this virus. Here, we analyze a subset (n=83,204) of all publicly available SARS-CoV-2 genomes (n=~5.6 million) that were randomly selected, but equally distributed over the course of the pandemic. We plot the emergence and extinction of new variants of concern (VOCs) over time and show how this corresponds to the ongoing accumulation of mutations in SARS-CoV-2 genomes and individual proteins. While the accumulation of mutations generally follows a linear regression, non-synonymous mutations are significantly greater in Omicron viruses than in previous variants-especially in the spike and nucleoproteins-and these differences are more pronounced in a recently identified sub-lineage (BA.2) of Omicron.
  🖺 Full Text HTML: The rise and fall of SARS-CoV-2 variants and the emergence of competing Omicron lineages
• Cell delivery peptides for small interfering RNAs targeting SARS-CoV-2 new variants through a bioinformatics and deep learning design -
  Nucleic acid technologies with designed delivery systems have surged as one the most promising therapies of the future, due to their contribution in combating SARS-CoV-2 severe disease. Nevertheless, the emergence of new variants of concern still represents a real threat in the years to come. It is here that the use of small interfering RNA sequences to inhibit gene expression and, thus, protein synthesis, may complement the already developed vaccines, with faster design and production. Here, we have designed new sequences targeting COVID-19 variants and other related viral diseases through bioinformatics, while also addressing the limited number of delivery peptides by a deep learning approach. Two sequences databases were produced, from which 62 were able to target the virus mRNA, and ten displayed properties present in delivery peptides, which we compared to the broad use TAT delivery peptide.
  🖺 Full Text HTML: Cell delivery peptides for small interfering RNAs targeting SARS-CoV-2 new variants through a bioinformatics and deep learning design
• SARS-CoV-2 Nsp1 N-terminal and linker regions as a platform for host translational shutoff -
  In the early stages of SARS-CoV-2 infection, non-structural protein 1 (Nsp1) inhibits the innate immune response by inserting its C-terminal helices into the mRNA entry channel of the ribosome and promoting mRNA degradation. Nevertheless, the mechanism by which Nsp1 achieves host translational shutoff while allowing for viral protein synthesis remains elusive. We set out to characterize the interactome of full-length Nsp1 and its topology by crosslinking mass spectrometry in order to investigate the role of the N-terminal domain and linker regions in host translational shutoff. We find that these regions are in contact with 40S proteins lining the mRNA entry channel and detect a novel interaction with the G subunit of the eIF3 complex. The crosslink-derived distance restraints allowed us to derive an integrative model of full-length Nsp1 on the 40S subunit, reporting on the dynamic interface between Nsp1, the ribosome and the eIF3 complex. The significance of the Nsp1-eIF3G interaction is supported by further evidence that Nsp1 predominantly binds to 40-43S complexes. Our results point towards a mechanism by which Nsp1 is preferentially recruited to canonical initiation complexes, leading to selective inhibition of host-translating ribosomes and subsequent mRNA degradation.
  🖺 Full Text HTML: SARS-CoV-2 Nsp1 N-terminal and linker regions as a platform for host translational shutoff
• Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants -
  Genetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern or interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV, VEKLURY(R)) is a nucleoside analog prodrug and the first FDA- approved antiviral treatment of COVID-19. Here we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein ELISA and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with EC50 values 0.31 to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.15 to 2.3-fold of the observed EC50 values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.
  🖺 Full Text HTML: Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants
• Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors -
  Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust systemic inflammation may trigger persistent changes in hematopoietic cells and innate immune memory through epigenetic mechanisms. We reveal that rare circulating hematopoietic stem and progenitor cells (HSPC), enriched from human blood, match the diversity of HSPC in bone marrow, enabling investigation of hematopoiesis and HSPC epigenomics. Following COVID-19, HSPC retain epigenomic alterations that are conveyed, through differentiation, to progeny innate immune cells. Epigenomic changes vary with disease severity, persist for months to a year, and are associated with increased myeloid cell differentiation and inflammatory or antiviral programs. Epigenetic reprogramming of HSPC may underly altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.
  🖺 Full Text HTML: Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors
• Lyophilized mRNA-lipid nanoparticles vaccine with long-term stability and high antigenicity against SARS-CoV-2 -
  Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to the poor stability, most current mRNA delivery platforms need to be stored at -20 {degrees}C or -70 {degrees}C. Here we present lyophilized thermostable mRNA loaded lipid nanoparticles, which could be stored at room temperature with long-term stability. We demonstrate the applicability of lyophilization techniques to different mRNA sequences and lipid components. Three lyophilized vaccines targeting wild-type, Delta and Omicron SARS-CoV-2 variant were prepared and demonstrated to be able induce high-level of IgG titer and neutralization response. In the Delta challenge in vivo experiment, the lyophilized mRNA vaccine successfully protected the mice from infection and clear the virus. This lyophilization platform could significantly improve the accessibility of mRNA vaccine or therapeutics, particularly in remote regions.
  🖺 Full Text HTML: Lyophilized mRNA-lipid nanoparticles vaccine with long-term stability and high antigenicity against SARS-CoV-2
• Engineering Defensin α-helix to produce high-affinity SARS-CoV-2 Spike protein binding ligands. -
  The binding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein to the Angiotensin- Converting Enzyme 2 (ACE2) receptor expressed on the host cells is a critical initial step for viral infection. This interaction is blocked through competitive inhibition by soluble ACE2 protein. Therefore, developing high-affinity and cost-effective ACE2 peptidomimetic ligands that disrupt this protein-protein interaction is a promising strategy for viral diagnostics and therapy. We employed human and plant defensins, a class of small and highly stable proteins, and engineered the amino acid residues on its conformationally constrained alpha-helices to mimic the critical residues on the ACE2 helix 1 that interacts with the Spike-protein. The engineered proteins were soluble and purified to homogeneity with high yield from a bacterial expression system. The proteins demonstrated exceptional thermostability, high- affinity binding to the Spike protein with dissociation constants in the low nanomolar range, and were used in a diagnostic assay that detected SARS-CoV-2 neutralizing antibodies. This work addresses the challenge of developing helical peptidomimetics by demonstrating that defensins provide promising scaffolds to engineer alpha-helices in a constrained form for designing high-affinity ligands.
  🖺 Full Text HTML: Engineering Defensin α-helix to produce high-affinity SARS-CoV-2 Spike protein binding ligands.
• Predicting Epitope Candidates for SARS-CoV-2 -
  Epitopes are short amino acid sequences that define the antigen signature to which an antibody binds. In light of the current pandemic, epitope analysis and prediction is paramount to improving serological testing and developing vaccines. In this paper, we leverage known epitope sequences from SARS-CoV, SARS-CoV-2 and other Coronaviridae and use those known epitopes to identify additional antigen regions in 62k SARS-CoV-2 genomes. Additionally, we present epitope distribution across SARS-CoV-2 genomes, locate the most commonly found epitopes, discuss where epitopes are located on proteins, and how epitopes can be grouped into classes. We also discuss the mutation density of different regions on proteins using a big data approach. We find that there are many conserved epitopes between SARS-CoV-2 and SARS-CoV, with more diverse sequences found in Nucleoprotein and Spike Glycoprotein.
  🖺 Full Text HTML: Predicting Epitope Candidates for SARS-CoV-2
• Distinct Core Glycan and O-Glycoform Utilization of SARS-CoV-2 Omicron Variant Spike Protein RBD Revealed by Top- Down Mass Spectrometry -
  The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations that enhance transmissibility and evasion of neutralizing antibodies, making it a serious threat to existing COVID-19 vaccines and therapies. Accurately distinguishing emerging S variants and revealing their post-translational glycosylation changes can provide new insights for rational design and development of vaccines and therapeutics. Here we report the first comprehensive elucidation of the molecular variations and O-glycoform changes of the Omicron, Delta (B.1.617.2), and wild-type (WA1/2020) S receptor-binding domains (S-RBDs) using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings provide high resolution detail of Omicron O-glycoform and utilization, providing new insights into how this variant escapes immunological protection and informing strategies for developing Omicron-directed vaccines, diagnostics, and therapeutics.
  🖺 Full Text HTML: Distinct Core Glycan and O-Glycoform Utilization of SARS-CoV-2 Omicron Variant Spike Protein RBD Revealed by Top-Down Mass Spectrometry
• COVID Testing in the Workplace: Return to Work Testing in an Occupational Cohort -

  Background. The Omicron SARS-CoV-2 variant resulted in significant community-based transmission. Numerous occupational settings have employed surveillance testing strategies to minimize occupational exposure and return workers safely to work following isolation. Methods. From an occupational COVID-19 testing program, we obtained longitudinal (February 2021-January 2022) saliva-based RT-qPCR results and starting December 27th, 2021, daily on-site molecular over-the-counter (OTC) nasal swab-based isothermal nucleic acid amplification test (molecular OTC; Cue Health COVID-19 test) results. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30 on each day post detection from suspected and confirmed Omicron infections (n=37), compared results to molecular OTC testing, and measured workplace and household transmission. We evaluated return-to-work timing using a post-isolation, two-test threshold of Ct >30, or two negative molecular OTC tests over a 24 hour period, or a single PCR test >30 plus negative molecular OTC test. Results. From the paired testing cohort, 37 (48%) individuals tested positive; all 37 were vaccinated. All individuals tested positive ≤1 day after a previous negative test, and 19 (51.3%) remained PCR-positive with Ct values <30 at day 5. While 3 (8.1%) remained PCR-positive with a Ct value <30 on day 10, no individuals remained PCR-positive on day 12. The average time to PCR clearance/return-to-work was 7.94 days (median=9.5 days). Time to clearance for those boosted (n=8; 7.75 days) and those not yet boosted (8.04 days) did not differ (p=0.49). Peak viral load measured by PCR was 1.97 days from the initial positive test. There were no cases of transmission after returning to work. Conclusions. A large percentage of individuals remain contagious at day 5 post first positive test based on serial PCR testing and can continue until day 12. Early discontinuation of isolation can utilize a two test framework separated by 24 hours. Rapid onsite tests may be useful.

  🖺 Full Text HTML: COVID Testing in the Workplace: Return to Work Testing in an Occupational Cohort
• Cov2MS: an automated matrix-independent assay for mass spectrometric detection and measurement of SARS-CoV-2 nucleocapsid protein in infectious patients -

  INTRODUCTION The pandemic readiness toolbox needs to be extended, providing diagnostic tools that target different biomolecules, using orthogonal experimental setups and fit-for-purpose specification of detection. Here we build on a previous Cov-MS effort that used liquid chromatography-mass spectrometry (LC-MS) and describe a method that allows accurate, high throughput measurement of SARS-CoV-2 nucleocapsid (N) protein. MATERIALS and METHODS We used Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA) technology to enrich and quantify proteotypic peptides of the N protein from trypsin-digested samples from COVID-19 patients. RESULTS The Cov2MS assay was shown to be compatible with a variety of sample matrices including nasopharyngeal swabs, saliva and blood plasma and increased the sensitivity into the attomole range, up to a 1000-fold increase compared to direct detection in matrix. In addition, a strong positive correlation was observed between the SISCAPA antigen assay and qPCR detection up to a quantification cycle (Cq) of 30. The automatable addition only sample preparation, digestion protocol, peptide enrichment and subsequent reduced dependency upon LC allow analysis of up to 500 samples per day per MS instrument. Importantly, peptide enrichment allowed detection of N protein in a pooled sample containing a single PCR positive sample mixed with 31 PCR negative samples, without loss in sensitivity. MS can easily be multiplexed and we also propose target peptides for Influenza A and B virus detection. CONCLUSIONS The Cov2MS assay described is agnostic with respect to the sample matrix or pooling strategy used for increasing throughput and can be easily multiplexed. Additionally, the assay eliminates interferences due to protein-protein interactions including those caused by anti-virus antibodies. The assay can be adapted to test for many different pathogens and could provide a tool enabling longitudinal epidemiological monitoring of large numbers of pathogens within a population, applied as an early warning system.

  🖺 Full Text HTML: Cov2MS: an automated matrix- independent assay for mass spectrometric detection and measurement of SARS-CoV-2 nucleocapsid protein in infectious patients
• Implementation and economic effects of local non-pharmaceutical interventions -

  In this paper, we analyze economic costs and consequences of local non-pharmaceutical interventions (NPIs) aimed at containing the COVID-19 pandemic. Using comprehensive data on municipal and regional policies in Norway, we implement a difference-in-differences framework identifying impacts of local NPIs from discontinuous differential shifts in outcomes following the implementation of new policies. In treated municipalities, local NPIs lead to persistent reductions in mobility, persistent increases in unemployment, and transient reductions in consumer spending. Analyses of spatial spillovers show that the implementation of local NPIs increases retail mobility in non-treated neighboring municipalities. Overall, our findings suggest that local NPIs have economic consequences for local economies and induce residents to shift their consumption of goods and services to neighboring municipalities.

  🖺 Full Text HTML: Implementation and economic effects of local non-pharmaceutical interventions
• Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection -

  In the present study, we were interested in the decline over time of anti SARS-CoV-2 antibodies and SARS-CoV-2 specific T-cell responses after two doses of mRNA vaccines in total and by age group and comorbidity. The second goal was to suggest an immunological correlate for protection on an individual basis and to describe the probability of protection over time after second vaccination. We analysed blood samples from 228 residents (median age 83.8 years) and from 273 Health Care Workers (HCW; median age 49.7 years) of five nursing homes and one home for the elderly with assisted living support. Participants had received two vaccinations. The blood samples were analysed for SARS-CoV-2 specific antibody and T-cell responses. We compared outcomes in the HCW and residents in the respective institutions. No breakthrough infections occurred during the study period. The initial immune responses in the younger participants were about 30 % higher than in the older ones. Over time, all parameters dropped continuously in all groups within the maximum observation period of 232 days. Comorbidities such as coronary heart disease or diabetes mellitus reduced the initial immune responses, regardless of age. In contrast to an almost linear decline in antibody levels, we observed that the interferon-gamma response remained at a constant level between about day 120 and 180, only to decline further thereafter. Based on our data, we propose on an individual level a correlate of protection: Persons who have a neutralizing capacity of 75 % (which would correspond to approx. 200 BAU/ml) and an interferon-gamma response above 200 mIU/ml should be considered to be protected resp. sufficiently immunized.

  🖺 Full Text HTML: Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection
• The COVID-19 Community Research Partnership: Objectives, Study Design, Baseline Recruitment, and Retention -

  The COVID-19 Community Research Partnership (CCRP) is a multisite surveillance platform designed to characterize the epidemiology of the SARS-CoV-2 pandemic. This manuscript describes the CCRP study design and methodology. The CCRP includes two prospective cohorts, one with six health systems in the mid-Atlantic and southern United States, and the other with six health systems in North Carolina. With enrollment beginning April 2020, sites invited persons within their healthcare systems as well as community members to participate in daily surveillance for symptoms of COVID-like illnesses, testing and risk behaviors. Participants with electronic health records were also asked to volunteer data access. Subsets of participants, representative of the general population and including oversampling of populations of interest, were selected for repeated at home serology testing. By October 2021, 65,739 participants (62,261 adult and 3,478 pediatric) were enrolled with 89% providing syndromic data, 74% providing EHR data, and 70% participating in one of two serology sub-studies. An average of 62% of participants completed a daily survey at least once a week, and 55% of serology kits were returned. The CCRP provides rich regional epidemiologic data and opportunities to more fully characterize the risks and sequelae of SARS-CoV-2 infection.

  🖺 Full Text HTML: The COVID-19 Community Research Partnership: Objectives, Study Design, Baseline Recruitment, and Retention
• Machine Learning Generalizability Across Healthcare Settings: Insights from multi-site COVID-19 screening -

  As patient health information is highly regulated due to privacy concerns, the majority of machine learning (ML)-based healthcare studies are unable to test on external patient cohorts, resulting in a gap between locally reported model performance and cross-site generalizability. Different approaches have been introduced for developing models across multiple clinical sites, however no studies have compared methods for translating ready-made models for adoption in new settings. We introduce three methods to do this - (1) applying a ready-made model as-is; (2) readjusting the decision threshold on the output of a ready-made model using site-specific data; and (3) finetuning a ready-made model using site-specific data via transfer learning. Using a case study of COVID-19 diagnosis across four NHS Hospital Trusts, we show that all methods achieve clinically-effective performances (NPV >0.959), with transfer learning achieving the best results (mean AUROCs between 0.870-0.925). Our models demonstrate that site-specific customization improves predictive performance when compared to other ready-made approaches.

  🖺 Full Text HTML: Machine Learning Generalizability Across Healthcare Settings: Insights from multi-site COVID-19 screening

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

• European Respiratory Society Statement on Long COVID-19 Follow-Up - Patients diagnosed with COVID-19 associated with SARS-CoV-2 infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aim to identify optimal strategies for follow-up care that may positively impact the patient’s quality-of-life (QOL).A European Respiratory Society (ERS) Task Force (TF) convened and prioritised eight clinical questions. A targeted search of the literature defined the time line of long COVID-19 as one to six months post infection and…

• Ruxolitinib attenuates secondary injury after traumatic spinal cord injury - Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were…

• 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…

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