Covid-19 Sentry

Contents

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

From Preprints

• Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains -
  The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics that are effective against a variety of strains of the virus. Herein, we characterize a human VH domain, F6, which we generated by sequentially panning large phage displayed VH libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized VH domain, resulted in a construct (F6-ab8-Fc) that neutralized Omicron pseudoviruses with a half-maximal neutralizing concentration (IC50) of 4.8 nM in vitro. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 VOCs - including the recently emerged Omicron variant - and highlight a vulnerable epitope within the spike protein RBD that may be exploited to achieve broad protection against circulating variants.
  🖺 Full Text HTML: Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains
• Mosaic receptor-binding domain nanoparticles induce protective immunity against SARS-CoV-2 challenges -
  Recurrent spillovers of - and {beta}-coronaviruses (CoV) such as acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-2, and possibly human CoV (NL63, 229E, OC43, and HKU1) have caused serious morbidity and mortality worldwide. Six receptor binding domains (RBDs) derived from - and {beta}-CoV that are considered to have originated from animals and cross-infected humans were linked to proliferating cell nuclear antigen (PCNA) heterotrimeric subunits, PCNA1, PCNA2, and PCNA3. These were used to form a scaffold-based mosaic multivalent antigen, 6RBD-np. Electron microscopic and atomic force microscopic images show a ring-shaped disk with six protruding RBDs, like jewels in a crown, with a size of 40 nm. Prime-boost immunizations with 6RBD-np in BALB/c mice elicited strong, dose- dependent antibody responses. In human angiotensin converting enzyme 2-transgenic mice, the same immunization induced full-protection against SARS-CoV-2 wild type and Delta challenges, resulting in a 100% survival rate. The mosaic 6RBD-np provides a potential platform for developing a pan-CoV vaccine against newly emerging SARS-CoV-2 variants and future CoV spillovers.
  🖺 Full Text HTML: Mosaic receptor-binding domain nanoparticles induce protective immunity against SARS-CoV-2 challenges
• Genomic Characterization of Sars-Cov-2 from Islamabad Pakistan by Rapid Nanopore Sequencing -
  Since the start of COVID-19 pandemic, Pakistan has experienced four waves of pandemic. The fourth wave ended in October, 2021 while the fifth wave of pandemic starts in January, 2022. The data regarding the circulating strains after the fourth wave of pandemic from Pakistan is not available. The current study explore the genomic diversity of SARS- CoV-2 after fourth wave and before fifth wave of pandemic through whole genome sequencing. The results showed the circulation of different strains of SARS-CoV-2 during November-December, 2021. We have Omicron BA.1 (n=4), Lineage A (n=2) and delta AY.27 (n=1) variants of SARS-CoV-2 in the population of Islamabad. All the isolates harbors characteristics mutations of omicron and delta variant in the genome. The lineage A isolate harbors a nine amino acid (68-76) and a ten amino acid (679-688) deletion in the genome. The circulation of omicron in the population before the fifth wave of pandemic and subsequent upsurges of COVID-19 positive cases in Pakistan highlights the importance of genomic surveillance.
  🖺 Full Text HTML: Genomic Characterization of Sars- Cov-2 from Islamabad Pakistan by Rapid Nanopore Sequencing
• Metagenomic analysis reveals the abundance and diversity of opportunistic fungal pathogens in the nasopharyngeal tract of COVID-19 patients -
  The nasopharyngeal tract (NT) of human is a habitat of a diverse microbial community that work together with other gut microbes to maintain the host immunity. In our previous study, we reported that SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome (bacteria, archaea and commensal respiratory viruses) but increases the abundance of pathobionts. This study aimed to assess the possible changes in the resident fungal diversity by the inclusion of opportunistic fungi due to the infection of SARS-CoV-2 in the NT of humans. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 = 8, Recovered = 7, and Healthy = 7) were collected for RNAseq-based metagenomics analyses. Our results indicate that SARS-CoV-2 infection significantly increased (p < 0.05, Wilcoxon test) the population and diversity of NT fungi with a high inclusion of opportunistic pathogens. We detected 863 fungal species including 533, 445, and 188 species in COVID-19, Recovered, and Healthy individuals, respectively that indicate a distinct microbiome dysbiosis due to the SARS-CoV-2 infection. Remarkably, 37% of the fungal species were exclusively associated with SARS-CoV-2 infection, where Saccharomyces cerevisiae (88.62%) and Phaffia rhodozyma (10.30%) were two top abundant species in the NT of COVID-19 patients. Importantly, 16% commensal fungal species found in the Healthy control were not detected in either COVID-19 patients or when they were recovered from the COVID-19. Pairwise Spearman’s correlation test showed that several altered metabolic pathways had significant positive correlations (r > 0.5, p < 0.01) with dominant fungal species detected in three metagenomes. Taken together, our results indicate that SARS- CoV-2 infection causes significant dysbiosis of fungal microbiome and alters some metabolic pathways and expression of genes in the NT of human. Findings of our study might be helpful for developing microbiome-based diagnostics, and also devising appropriate therapeutic regimens including antifungal drugs for prevention and control of concurrent fungal coinfections in COVID-19 patients.
  🖺 Full Text HTML: Metagenomic analysis reveals the abundance and diversity of opportunistic fungal pathogens in the nasopharyngeal tract of COVID-19 patients
• SARS-CoV-2 has not emerged in roe, red or fallow deer in Germany or Austria during the COVID 19 pandemic -
  Spillover of SARS-CoV-2 to North American white tailed deer (Odocoileus virginianus) has been documented. We evaluated pre and pandemic exposure of German and Austrian deer species using a SARS-CoV-2 pseudoneutralization assay. In stark contrast to North American white tailed deer, we found no evidence of SARS-CoV-2 exposure.
  🖺 Full Text HTML: SARS-CoV-2 has not emerged in roe, red or fallow deer in Germany or Austria during the COVID 19 pandemic
• Ideological responses to the breaking of COVID-19 social distancing recommendations -
  COVID-19 has plagued the globe since January 2020, infecting millions and claiming the lives of several hundreds of thousands (at the time of writing). Despite this, many individuals have ignored public health guidance and continued to socialize in groups. Emergent work has highlighted the potential role that ideology plays in such behavior, and judgements of it. In response to this contemporary cultural phenomenon, we tested whether judgements of those allegedly flouting the guidance on social distancing were influenced by an interaction between the ideologies of those providing judgements, and those allegedly breaking the rules. Our data suggest that judgements of those flouting social distancing guidance are influenced by ideology in a symmetrical way. That is, both liberals and conservatives condemn outgroup flouting more than ingroup flouting. We discuss this finding in the context of theoretical work into ideological symmetries, and the implications of growing ideological polarization in contemporary Western democracies.
  🖺 Full Text HTML: Ideological responses to the breaking of COVID-19 social distancing recommendations
• On Correlation between Structural Properties and Viral Escape Measurements from Deep Mutational Scanning -
  Encouraged by recent efforts to map responses of SARS-CoV-2 mutations to various antibody treatments with deep mutational scanning, we explored the possibility of tying measurable structural contact information from the binding complexes of antibodies and their targets to experimentally determined viral escape responses. With just a single crystal structure for each binding complex, we find that the average correlation coefficient R is surprisingly high at 0.76. Our two methods for calculating contact information use binary contacts measured between all residues of two proteins. By varying the parameters to obtain binary contacts, we find that 3.6 A and 7 A are pivotal distances to toggle the binary step function when tallying the contacts for each method. The correlations are improved by short simulations (~25 ns), which increase average R to 0.78. With blind tests using the random forest model, we can further improve average R to 0.84. These easy-to-implement measurements can be utilized in computational screening of viral mutations that escape antibody treatments and potentially other protein-protein interaction problems.
  🖺 Full Text HTML: On Correlation between Structural Properties and Viral Escape Measurements from Deep Mutational Scanning
• Tensor decomposition reveals coordinated multicellular patterns of transcriptional variation that distinguish and stratify disease individuals -
  Tissue- and organism-level biological processes often involve coordinated action of multiple distinct cell types. Current computational methods for the analysis of single-cell RNA-sequencing (scRNA-seq) data, however, are not designed to capture co-variation of cell states across samples, in part due to the low number of biological samples in most scRNA-seq datasets. Recent advances in sample multiplexing have enabled population-scale scRNA-seq measurements of tens to hundreds of samples. To take advantage of such datasets, here we introduce a computational approach called single- cell Interpretable Tensor Decomposition (scITD). This method extracts multicellular gene expression patterns that vary across different biological samples. These patterns capture how changes in one cell type are connected to changes in other cell types. The multicellular patterns can be further associated with known covariates (e.g., disease, treatment, or technical batch effects) and used to stratify heterogeneous samples. We first validated the performance of scITD using in vitro experimental data and simulations. We then applied scITD to scRNA-seq data on peripheral blood mononuclear cells (PBMCs) from 115 patients with systemic lupus erythematosus and 56 healthy controls. We recapitulated a well-established pan-cell-type signature of interferon-signaling that was associated with the presence of anti-dsDNA autoantibodies and a disease activity index. We further identified a novel multicellular pattern that appears to potentiate renal involvement for patients with anti-dsDNA autoantibodies. This pattern was characterized by an expansion of activated memory B cells along with helper T cell activation and is predicted to be mediated by an increase in ICOSLG-ICOS interaction between monocytes and helper T cells. Finally, we applied scITD to two PBMC datasets from patients with COVID-19 and identified reproducible multicellular patterns that stratify patients by disease severity. Overall, scITD is a flexible method for exploring co-variation of cell states in multi-sample single-cell datasets, which can yield new insights into complex non-cell-autonomous dependencies that define and stratify disease.
  🖺 Full Text HTML: Tensor decomposition reveals coordinated multicellular patterns of transcriptional variation that distinguish and stratify disease individuals
• Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) is a host factor for RNA viruses including SARS-CoV-2 -
  Viruses with an RNA genome are the main causes of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid insertion-mutagenized mouse embryonic cell library for clones that rendered them resistant to the zoonotic Rift Valley fever virus (RVFV; family Phleboviridae, order Bunyavirales). This screen returned the Low Density Lipoprotein Receptor-Related protein 1 (LRP1, or CD91) as top hit, a 600 kDa plasma membrane protein known to be involved in a wide variety of cell activities. Inactivation of LRP1 expression in human cells reduced RVFV infection at the early stages of infection, including the particle attachment to the cell. In the highly LRP1-positive human HuH-7 cell line, LRP1 was required for the early infection stages also of Sandfly fever Sicilian virus (SFSV; family Phleboviridae, order Bunyavirales), vesicular stomatitis (VSV; family Rhabdoviridae, order Mononegavirales), Encephalomyocarditis virus (EMCV, family Picornaviridae), and the coronaviruses MERS-CoV, SARS-CoV-1, and SARS-CoV-2. While for RVFV, EMCV, and MERS-CoV the replication cycle could eventually catch up, LRP1 requirement for the late infection stage in HuH-7 cells was observed for SFSV, La Crosse virus (LACV; family Peribunyaviridae, order Bunyavirales), VSV, SARS-CoV-1, and SARS-CoV-2. For SARS-CoV-2, the absence of LRP1 stably reduced viral RNA levels in human lung Calu-3 cells, and both RNA levels and particle production in the hepatic HuH-7 cells. Thus, we identified LRP1 as a host factor that supports various infection cycle stages of a broad spectrum of RNA viruses.
  🖺 Full Text HTML: Low Density Lipoprotein Receptor- Related Protein 1 (LRP1) is a host factor for RNA viruses including SARS-CoV-2
• Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19 -

  Background. The identification of effective strategies capable of reducing the case mortality rate of high-risk COVID-19 is an urgent and unmet medical need. We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). Here we report data from a pilot clinical study (RPI-015) which examined the safety, tolerability, and feasibility of using RJX in combination with clinical standard of care (SOC) in hospitalized COVID-19 patients with pneumonia (ClinicalTrials.gov Identifier: NCT04708340). In addition to our early clinical proof of concept (POC) data, we also present non-clinical POC from a mouse model of CRS and ARDS that informed the design of the reported clinical study. Methods. 13 patients, who were hospitalized with COVID-19 pneumonia and abnormally elevated serum inflammatory biomarkers markers ≥3 months prior to the identification of the first confirmed U.S case of the Omicron variant, were treated with IV RJX (daily x 7 days) plus SOC. Non-clinical POC study examined the ability of RJX plus dexamethasone (DEX) to improve the survival outcome in the lipopolysaccharide (LPS)-Galactosamine (GalN) mouse model of fatal cytokine release syndrome (CRS), sepsis and acute respiratory distress syndrome (ARDS). Findings. In the Phase 1 clinical study, none of the 13 patients developed a treatment-related DLT, SAE, or Grade 3-5 AEs. Nine (9) of the 12 evaluable patients, including 3 patients with hypoxemic respiratory failure, showed rapid clinical recovery. In the non-clinical POC study in LPS-GalN challenged mice, the combination of RJX plus DEX was more effective than RJX alone or DEX alone, reversed the CRS as well as inflammatory tissue damage in the lungs and liver, and improved the survival outcome. Taken together, these findings provide the early clinical and non-clinical POC for the development of RJX as an adjunct to the SOC in the multi-modality management of high-risk COVID-19.

  🖺 Full Text HTML: Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19
• Increased household transmission and immune escape of the SARS-CoV-2 Omicron variant compared to the Delta variant: evidence from Norwegian contact tracing and vaccination data -

  Understanding the rapid epidemic growth of the novel SARS-CoV-2 Omicron variant is critical for public health management. We compared the secondary attack rate (SAR) of the Omicron and Delta variants in households using Norwegian contact tracing data from December 2021 to January 2022. Omicron SAR was higher (51%) than Delta (36%), with a relative risk (RR) of 1.41 (95% CI 1.27-1.56). We observed increased susceptibility to Omicron infection in household contacts compared to Delta independent of vaccination status; however, considering booster vaccinated contacts, the mean SAR was lower for both variants. We found increased Omicron transmissibility in all vaccination groups of primary cases, except partially vaccinated, compared to Delta. In particular, Omicron SAR for boosted primary cases was high, 46% vs 11 % for Delta (RR 4.34; 95% CI 1.52-25.16). In conclusion, booster doses decrease the infection risk of Delta and Omicron but have limited effect in preventing Omicron transmission.

  🖺 Full Text HTML: Increased household transmission and immune escape of the SARS-CoV-2 Omicron variant compared to the Delta variant: evidence from Norwegian contact tracing and vaccination data
• Adolescent vaccination with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine and effectiveness against COVID-19: national test-negative case-control study, England -

  Adolescents in the UK were recommended to have their first dose of mRNA vaccine during a period of high community transmission due to the highly transmissible Delta variant, followed by a second dose at an extended interval of 8-12 weeks. We used national SARS-CoV-2 testing, vaccination and hospitalisation data to estimate vaccine effectiveness (VE) using a test-negative case-control design, against PCR-confirmed symptomatic COVID-19 in England. BNT162b2 vaccination in 12-15-year-olds and 16-17-year-olds was associated with lower VE against symptomatic COVID-19 caused by Omicron compared to Delta. Data shows a rapid increase in VE against symptomatic COVID-19 after the second dose for both Delta and Omicron, although this declines to 23% against Omicron after 70+ days. Very high protection was achieved for Delta against hospitalisation after one dose. Our data highlight the importance of the second vaccine dose for protection against symptomatic COVID-19 and raise important questions about the objectives of an adolescent immunisation programme. If prevention of infection is the primary aim, then regular COVID-19 vaccine boosters will be required.

  🖺 Full Text HTML: Adolescent vaccination with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine and effectiveness against COVID-19: national test-negative case-control study, England
• The Achilles’ heel of coronaviruses: targeting the 5’ Polyuridines tract of the antigenome to inhibit Mouse coronavirus-induced cell death -
  The current coronavirus pandemic situation is worsened by the rapidly-spreading SARS-CoV-2 virus variants. Identification of viral targets that are indispensable for the virus can be targeted to inhibit mutation-based new escape variant development. The 5’-polyU tract of the antigenome offers such a target. Host cells do not harbor 5’-polyU tracts on any of their transcripts, making the tract an attractive, virus-specific target. Inhibiting the 5’-polyU can limit the use of the tract as template to generate 3’ polyA tails of +RNAs of coronaviruses. Here, a modified DNA oligo with 3’ polyAs is used to target the 5’-polyU tract in mouse coronavirus (MHV-A59). The oligo treatment in mouse 17CL-1 cells infected with MHV-A59 significantly prevented virus-induced cell deaths. This proof-of-concept result shows a unique mode of action against mouse coronavirus without affecting host cells, and can be used for the development of novel classes of drugs that inhibit coronavirus infection in host cells, specifically by the COVID-19-causing virus SARS-CoV-2. In addition, as the 5’-polyU tract is immediately generated upon infection, the tag can also be targeted for reliable early detection of viral infection.
  🖺 Full Text HTML: The Achilles’ heel of coronaviruses: targeting the 5’ Polyuridines tract of the antigenome to inhibit Mouse coronavirus-induced cell death
• The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2 -
  Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sotrovimab and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an LS mutation in the Fc region to prolong serum half-life. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. Sotrovimab and VIR-7832 potently neutralize wild-type and variant pseudotyped viruses and authentic virus in vitro. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs. The sotrovimab/VIR-7832 epitope continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with sotrovimab had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that sotrovimab and VIR-7832 are key agents in the fight against COVID-19.
  🖺 Full Text HTML: The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS- CoV-2
• Clonal chromosomal mosaicism and loss of chromosome Y in men are risk factors for SARS-CoV-2 vulnerability in the elderly -

  The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome events (CME) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (CME and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, CME and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.

  🖺 Full Text HTML: Clonal chromosomal mosaicism and loss of chromosome Y in men are risk factors for SARS-CoV-2 vulnerability in the elderly

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

• Pulmonary Rehabilitation Implemented With Virtual Reality for Post-COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Pulmonary rehabilitation
  Sponsor:  
  The Opole University of Technology
  Not yet recruiting

• Pulmonary Rehabilitation Implemented With VR for Post-COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Pulmonary Rehabilitation Program
  Sponsor:   The Opole University of Technology
  Recruiting

• COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsors:   DreamTec Research Limited;   Middle East Cell and Gene Therapy;   National Institute of Genetic Engineering and Biotechnology
  Completed

• 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

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

• A Phase II Study of the Immunogenicity and Safety of SCTV01C in Population Aged ≥12 Years and Previously Vaccinated With Inactivated COVID-19 Vaccine - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Biological: SCTV01C;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet 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

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01E in Population Aged ≥18 Years Previously Fully Vaccinated With mRNA COVID-19 Vaccine - Conditions:   COVID-19;   Sars-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E in Population Aged ≥12 Years Previously Fully Vaccinated With Inactivated COVID-19 Vaccine - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C in Population Aged ≥18 Years and Previously Fully Vaccinated With Either Inactivated or mRNA COVID-19 Vaccine or Previously Diagnosed With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

From PubMed

• Validation and Invalidation of SARS-CoV-2 Papain-like Protease Inhibitors - SARS-CoV-2 encodes two viral cysteine proteases, the main protease (M^(pro)) and the papain-like protease (PL^(pro)), both of which are validated antiviral drug targets. PL^(pro) is involved in the cleavage of viral polyproteins as well as immune modulation by removing ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins. Therefore, targeting PL^(pro) might be a two-pronged approach. Several compounds including YM155, cryptotanshinone, tanshinone I, dihydrotanshinone I,…

• Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes - Complements and neutrophils are two key players of the innate immune system that are widely implicated as drivers of severe COVID-19 pathogenesis, as evident by the direct correlation of respiratory failure and mortality with elevated levels of terminal complement complex C5b-9 and neutrophils. In this study, we identified a feed-forward loop between complements and neutrophils that could amplify and perpetuate the cytokine storm seen in severe SARS-CoV-2-infected patients. We observed for the…

• Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung - The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2,…

• Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine - CONCLUSIONS: The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full…

• Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12 - Complex glycans decorate viral surface proteins and play a critical role in virus-host interactions. Viral surface glycans shield vulnerable protein epitopes from host immunity yet can also present distinct “glycoepitopes” that can be targeted by host antibodies such as the potent anti-HIV antibody 2G12 that binds high-mannose glycans on gp120. Two recent publications demonstrate 2G12 binding to high mannose glycans on SARS-CoV-2 and select Influenza A (Flu) H3N2 viruses. Previously, our lab…

• Microsecond molecular dynamics simulations revealed the inhibitory potency of amiloride analogs against SARS-CoV-2 E viroporin - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes small envelope protein (E) that plays a major role in viral assembly, release, pathogenesis, and host inflammation. Previous studies demonstrated that pyrazine ring containing amiloride analogs inhibit this protein in different types of coronavirus including SARS-CoV-1 small envelope protein E (SARS-CoV-1 E). SARS-CoV-1 E has 93.42% sequence identity with SARS-CoV-2 E and shared a conserved domain NS3/small envelope protein…

• Bat coronaviruses related to SARS-CoV-2 and infectious for human cells - The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats^(1-4), including the closest virus from R. affinis, RaTG13^(5,6) and in pangolins^(7-9). SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host…

• Differing pan-coronavirus antiviral potency of boceprevir and GC376 in vitro despite discordant molecular docking predictions - Given the structural similarities of the viral enzymes of different coronaviruses (CoVs), we investigated the potency of the anti-SARS-CoV-2 agents boceprevir and GC376 for counteracting seasonal coronavirus infections. In contrast to previous findings that both boceprevir and GC376 are potent inhibitors of the main protease (Mpro) of SARS-CoV-2, we found that GC376 is much more effective than boceprevir in inhibiting SARS-CoV-2 and three seasonal CoVs (NL63, 229E, and OC43) in cell culture…

• A Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19 - SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allowed for rapid movement of existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells when…

• 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…

• Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice - The B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and…

• SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19 - SARS-CoV-2 variants of concern (VOC) have triggered distinct infection waves in the coronavirus disease 2019 (COVID-19) pandemic, culminating in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals such as molnupiravir promise to improve disease management and limit SARS-CoV-2 spread. However, molnupiravir efficacy against VOC delta was questioned based on clinical trial results and its potency against omicron is unknown. This study evaluates…

• Identification of a conserved drug binding pocket in TMEM16 proteins - The TMEM16 family of calcium-activated membrane proteins includes ten mammalian paralogs (TMEM16A-K) playing distinct physiological roles with some implicated in cancer and airway diseases. Their modulators with therapeutic potential include 1PBC, a potent inhibitor with anti-tumoral properties, and the FDA-approved drug niclosamide that targets TMEM16F to inhibit syncytia formation induced by SARS-CoV-2 infection. Here, we report cryo-EM structures of TMEM16F associated with 1PBC and…

• Inhaled heparin polysaccharide nanodecoy against SARS-CoV-2 and variants - The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

• Non-covalent SARS-CoV-2 M(pro) inhibitors developed from in silico screen hits - M^(pro), the main protease of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for the viral life cycle. Accordingly, several groups have performed in silico screens to identify M^(pro) inhibitors that might be used to treat SARS-CoV-2 infections. We selected more than five hundred compounds from the top-ranking hits of two very large in silico screens for on-demand synthesis. We then examined whether these compounds could bind to M^(pro) and inhibit its protease…

From Patent Search

• SOCIAL NAVIGATION SYSTEM FOR MOBILE ROBOTS IN THE EMERGENCY DEPARTMENT TECHNOLOGY - The emergency department (ED) is a safety-critical environment in which healthcare workers (HCWs) are overburdened, overworked, and have limited resources, especially during the COVID-19 pandemic. One way to address this problem is to explore the use of robots that can support clinical teams, e.g., to deliver materials or restock supplies. However, due to EDs being overcrowded, and the cognitive overload HCWs experience, robots need to understand various levels of patient acuity so they avoid disrupting care delivery. In this invention, we introduce the Safety-Critical Deep Q-Network (SafeDQN) system, a new acuity-aware navigation system for mobile robots. SafeDQN is based on two insights about care in EDs: high-acuity patients tend to have more HCWs in attendance and those HCWs tend to move more quickly. We compared SafeDQN to three classic navigation methods, and show that it generates the safest, quickest path for mobile robots when navigating in a simulated ED environment. We hope this work encourages future exploration of social robots that work in safety-critical, human-centered environments, and ultimately help to improve patient outcomes and save lives. Figure 1. - link

• A SYSTEM BASED ON DEEP LEARNING FOR ANALYZING DELAYED ENHANCEMENT MAGNETIC RESONANCE IMAGING TO IDENTIFY COVID 19 AND METHOD THEREOF - The present invention discloses a system based on deep learning for analyzing delayed enhancement magnetic resonance imaging to identify COVID 19 and method thereof. The method and system include, but not limited to, a processing unit adapted to process the data based on deep learning data modelling in the magnetic resonance imaging associated with the digital image scanning system for diagnosis COVID 19 with the spatial resolution that each frame is deposited is 256 * 256, and being creating that level and vertical resolution respectively are 256 pixels (pixel), the read/write address that the read/write address of each image element, which is controlled by processing unit and forms circuit and finishes; And the data that will be stored in memory are input to a real-time microcontroller, it is characterized in that: analyze and compare by the Multi-source Information Fusion analytical system by using the real-time microcontroller to deliver the D/A changer then, digital signal is become analogue signal output. - link

• FOLDABLE KIDS NEST - The objective of the present invention is to provide a bird’s nest bag which allows a kid to sleep or sit inside. According to the embodiment of the present invention, the bird nest bag is used to isolate kids below 2 years, who are affected by COVID-19. The netted portion of the bag allows a clear visibility to check on the user by the medical assistants, during emergency situations. The children below two years of age can be isolated in the bags for a shorter duration. (Refer Fig. 1) - link

• 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

• 胸部CT图像识别方法、装置、计算机设备和存储介质 - 本申请涉及一种胸部CT图像识别方法、装置、计算机设备和存储介质。所述方法针对CT图像特点，设计轻量级的胸部CT图像识别网络更快速准确地识别出胸部CT图像。引入X‑DMFF模块，提升模型性能且降低计算成本。在DMS模块中引入Swin‑Transformer与残差学习，提取更多尺度的空间特征信息并对特征信息不断重用，提升模型分类效果。 - link