Covid-19 Sentry

Contents

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

From Preprints

• Prе-Rеcordеd Lеcturеs, Livе Onlinе Lеcturеs, аnd Studеnt Аcаdеmic Аchiеvеmеnt -
  In thе midst of thе COVID-19 Pаndеmic, univеrsitiеs throughout thе world аrе еmbrаcing onlinе lеаrning, oftеn dеpеnding on synchronous аnd аsynchronous digitаl communicаtions. In this pаpеr, wе compаrе thе impаcts of livе onlinе (synchronous) аnd prе-rеcordеd (аsynchronous) lеcturеs on studеnt аchiеvеmеnt using а rаndomizеd еxpеrimеnt. Wе discovеrеd thаt thе prе-rеcordеd lеcturеs rеducе lowеr аbility studеnts’ аcаdеmic аchiеvеmеnt but hаvе no еffеct on highеr аbility studеnts’ аcаdеmic аchiеvеmеnt. In pаrticulаr, bеing tаught viа thе prе-rеcordеd lеcturеs, аs opposеd to thе livе onlinе lеcturеs, dеcrеаsеs thе likеlihood of аnswеring еxаm quеstions corrеctly by 1.6 pеrcеntаgе points for studеnts in thе bottom 50th pеrcеntilе of thе аbility distribution (mеаsurеd by GPА аt thе bеginning of thе sеmеstеr). Furthеrmorе, bеing tаught viа thе prе-rеcordеd lеcturеs in thе stаrting wееks of thе sеmеstеr tеnd to bе morе hаrmful to studеnts’ аcаdеmic аchiеvеmеnt, compаrеd to thе lаtеr onеs. Thеsе findings hаvе importаnt implicаtions for thе еffеctivе dеsign of еducаtion policiеs.
  🖺 Full Text HTML: Prе-Rеcordеd Lеcturеs, Livе Onlinе Lеcturеs, аnd Studеnt Аcаdеmic Аchiеvеmеnt
• Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period -
  Understanding immune memory to Common Cold Coronaviruses (CCCs) is relevant for assessing its potential impact on the outcomes of SARS-CoV-2 infection, and for the prospects of pan-corona vaccines development. We performed a longitudinal analysis, of pre-pandemic samples collected from 2016-2019. CD4+ T cells and antibody responses specific for CCC and to other respiratory viruses, and chronic or ubiquitous pathogens were assessed. CCC-specific memory CD4+ T cells were detected in most subjects, and their frequencies were comparable to those for other common antigens. Notably, responses to CCC and other antigens such as influenza and Tetanus Toxoid (TT) were sustained over time. CCC-specific CD4+ T cell responses were also associated with low numbers of HLA-DR+CD38+ cells and their magnitude did not correlate with yearly changes in the prevalence of CCC infections. Similarly, spike RBD-specific IgG responses for CCC were stable throughout the sampling period. Finally, high CD4+ T cell reactivity to CCC, but not antibody responses, was associated with high pre-existing SARS-CoV-2 immunity. Overall, these results suggest that the steady and sustained CCC responses observed in the study cohort are likely due to a relatively stable pool of CCC- specific memory CD4+ T cells instead of fast decaying responses and frequent reinfections.
  🖺 Full Text HTML: Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period
• Decoding COVID-19 mRNA Vaccine Immunometabolism in Central Nervous System: human brain normal glial and glioma cells by Raman imaging -
  The paper presents the effect of COVID-19 mRNA (Pfizer/BioNT) vaccine on in vitro glial cells of the brain studied by means of Raman spectroscopy and imaging.. The results obtained for human brain normal and tumor glial cells of astrocytes, astrocytoma, glioblastoma incubated with the Covid-19 mRNA vaccine Pfizer/BioNT vaccine show alterations in the reduction-oxidation pathways associated with Cytochrome c. We found that the Pfizer/BioNT vaccine down regulate the concentration of cytochrome c in mitochondria upon incubation with normal and tumorous glial cells. Concentration of oxidized form of cytochrome c in brain cells has been shown to decrease upon incubation the mRNA vaccine. Lower concentration of oxidized cytochrome c results in lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis and lessened ATP production. Alteration of Amide I concentration, which may reflect the decrease of mRNA adenine nucleotide translocator. Moreover, mRNA vaccine leads to alterations in biochemical composition of lipids that suggest the increasing role of signaling. mRNA vaccine produce statistically significant changes in cell nucleus due to histone alterations. The results obtained for mitochondria, lipid droplets, cytoplasm may suggest that COVID-19 mRNA (Pfizer/BioNT) vaccine reprograms immune responses. The observed alterations in biochemical profiles upon incubation with COVID-19 mRNA in the specific organelles of the glial cells are similar to those we observe for brain cancer vs grade of aggressiveness.
  🖺 Full Text HTML: Decoding COVID-19 mRNA Vaccine Immunometabolism in Central Nervous System: human brain normal glial and glioma cells by Raman imaging
• Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters -
  With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.
  🖺 Full Text HTML: Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters
• Comparative pathogenicity of SARS-CoV-2 Omicron and Delta variants in Syrian hamsters mirrors the attenuated clinical outlook of Omicron in COVID-19 irrespective of age -
  Coronavirus disease 2019 continues to batter the world with the unceasing introduction of new variants of the causative virus, SARS-CoV-2. In order to understand differences in disease caused by variants of concern and to develop variant-specific vaccines, suitable small animal models are required that mimic disease progression in humans at various stages of life. In this study, we compared the dynamics of infection with two SARS-CoV-2 variants of concern (Delta and Omicron) in aged (>1 year 3 months old) and young (<5 weeks old) Syrian hamsters (Mesocricetus auratus). We show that no weight loss occurred in Omicron infected groups regardless of age, while infection with the Delta variant caused weight loss of up to 10% by day 7 post-infection with slower and incomplete recovery in the aged group. Omicron replicated to similar levels as Delta in the lungs, trachea and nasal turbinates, with no significant differences in the tissue viral loads of aged versus young animals for either variant. In contrast to rare necrosis observed in Omicron- infected animals regardless of age, severe necrosis was observed in the olfactory epithelium in Delta-infected animals. Omicron infection also resulted in mild pulmonary disease in both young and aged animals compared to the moderate acute necrotizing bronchointerstitial pneumonia seen in Delta-infected animals. These results suggest that Omicron infection results in an attenuated clinical disease outlook in Syrian hamsters compared to infection with the Delta variant irrespective of age.
  🖺 Full Text HTML: Comparative pathogenicity of SARS- CoV-2 Omicron and Delta variants in Syrian hamsters mirrors the attenuated clinical outlook of Omicron in COVID-19 irrespective of age
• Remdesivir, Zidovudine (AZT) and Nevirapine inhibit Chandipura virus replication through high energy interactions with the RdRp domain of the polymerase protein L -
  Chandipura Virus (CHPV), a rhabdovirus belonging to mononegavirales, is an emerging pathogen in Indian subcontinent. The virus infection causes fever, brain encephalitis among the young children below 14 yrs of age. In recent past, several outbreaks and deaths among children were reported from in India. There are no targeted drugs or vaccines available against CHPV and symptomatic treatments are the only option. In this background, we aimed to investigate the inhibitory effects of some priviously known viral RNA polymerase inhibitor drugs on CHPV replication. First, we examined remdesivir, which is known to inhibit HCV, Ebola and SARS-CoV-2 replication and close structural similarity along with conserved residues in the finger region of RNA dependent RNA polymerase (RdRp) domain is the basis of replication inhibition. Our results showed that remdesivir inhibits CHPV replication in vero E6 cells to a significant level. In this study we have also included non-nucleoside anti-retroviral inhibitor (NNRTI) drug nevirapine, and nucleoside inhibitor (NRTI) drug AZT (Zidovudine) to determine if these are also able to inhibit CHPV replication. Interestingly, we observed inhibition of CHPV replication by both nevirapine and AZT (in the order nevirapine>AZT), albeit to a lesser extent compared to remdesivir. We next performed molecular docking and modeling study to get an insight about the interactions of these drugs with CHPV polymerase protein. Modeling study predicts that remdesivir has most favourable CHPV polymerase binding energy among these three drugs. Both remdesivor and AZT binds near the polymerase active site through interctions with residues in finger and palm regions of RdRp. In contrast, nevirapine binds to the N-terminal domain (NTD) of the RdRp. In summary, we found remdesivir as a potent inhibitor of CHPV. A combination therapy including remdesivir, nevirapine and AZT may be a better drug cocktail to treat CHPV disease. Our findings warrant further studies of these drugs against CHPV in animal models for clinical use in near future.

• Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination -
  High antibody affinity against the ancestral SARS-CoV-2 strain seems to be necessary (but not always sufficient) for the control of emerging immune-escape variants. Therefore, aiming at strong B cell somatic hypermutation - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naive, but also antigen- experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the booster, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.

• Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening -
  The emergence of several zoonotic viruses in the last twenty years, especially the pandemic outbreak of SARS-CoV-2, has exposed a dearth of antiviral drug therapies for viruses with pandemic potential. Developing a diverse drug portfolio will be critical for our ability to rapidly respond to novel coronaviruses (CoVs) and other viruses with pandemic potential. Here we focus on the SARS-CoV-2 conserved macrodomain (Mac1), a small domain of non-structural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that cleaves mono-ADP-ribose (MAR) from target proteins, protects the virus from the anti-viral effects of host ADP-ribosyltransferases, and is critical for the replication and pathogenesis of CoVs. In this study, a luminescent-based high-throughput assay was used to screen ~38,000 small molecules for those that could inhibit Mac1-ADP-ribose binding. We identified 5 compounds amongst 3 chemotypes that inhibit SARS-CoV-2 Mac1-ADP-ribose binding in multiple assays with IC50 values less than 100M, inhibit ADP-ribosylhydrolase activity, and have evidence of direct Mac1 binding. These chemotypes are strong candidates for further derivatization into highly effective Mac1 inhibitors.
  🖺 Full Text HTML: Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening
• Flipped Over U: Structural Basis for dsRNA Cleavage by the SARS-CoV-2 Endoribonuclease -
  Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base- flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.
  🖺 Full Text HTML: Flipped Over U: Structural Basis for dsRNA Cleavage by the SARS-CoV-2 Endoribonuclease
• Fine-scale variation in the effect of national border on COVID-19 spread: A case study of the Saxon-Czech border region -

  The global extent and temporally asynchronous pattern of COVID-19 spread have repeatedly highlighted the role of international borders in the fight against the pandemic. Additionally, the deluge of high resolution, spatially referenced epidemiological data generated by the pandemic provides new opportunities to study disease transmission at heretofore inaccessible scales. Existing studies of cross-border infection fluxes, for both COVID-19 and other diseases, have largely focused on characterizing overall border effects. Here, we couple fine-scale incidence data with localized regression models to quantify spatial variation in the inhibitory effect of an international border. We take as a case study the border region between the German state of Saxony and the neighboring regions in northwestern Czechia, where municipality-level COVID-19 incidence data are available on both sides of the border. Consistent with past studies, we find an overall inhibitory effect of the border, but with a clear asymmetry, where the inhibitory effect is stronger from Saxony to Czechia than vice versa. Furthermore, we identify marked spatial variation along the border in the degree to which disease spread was inhibited. In particular, the area around Loebau in Saxony appears to have been a hotspot for cross-border disease transmission. The ability to identify infection flux hotspots along international borders may help to tailor monitoring programs and response measures to more effectively limit disease spread.

  🖺 Full Text HTML: Fine-scale variation in the effect of national border on COVID-19 spread: A case study of the Saxon-Czech border region
• The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization -

  Background: In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and to develop, validate, improve, and implement serological testing and associated technologies. SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. Methods: To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. SARS- CoV-2 serology standard reference material and First WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. Results: SeroNet institutions reported development of a total of 27 ELISA methods, 13 multiplex assays, 9 neutralization assays, and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. Conclusions: SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 virus and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons.

  🖺 Full Text HTML: The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization
• Impact of COVID-19 on alcohol use disorder recovery: A qualitative study -
  In March 2020, restrictions on in-person gatherings were introduced due to the coronavirus disease (COVID-19) pandemic, requiring alcohol use disorder (AUD) recovery resources to migrate to virtual platforms. This study investigated how these restrictions impacted recovery attempts and explored participant experiences with virtual resources using a qualitative approach. Participants attempting recovery from AUD (N = 62;Mage = 48.2; F = 53.2%; 71% White) completed virtual semistructured interviews from July 2020 to August 2020 on their experience during the COVID-19 lockdown, impacts on recovery, and experiences with online resources. Interviews were recorded, transcribed, and analyzed using a thematic coding process. Three overarching themes were identified: Effect on Recovery, Virtual Recovery Resources, and Effect on General Life. Within each overarching theme, lower order parent themes and subthemes reflected varied participant experiences. Specifically, one group of participants cited negative impacts due to COVID-19, a second group reported positive impacts, and a third group reported experiencing both positive and negative impacts. Participants reported both positive and negative experiences with virtual resources, identifying suggestions for improvement and other resources. Findings suggest that while individuals in AUD recovery experienced significant hardships, a proportion experienced positive impacts as well, and the positive and negative consequences were not mutually exclusive. Additionally, the results highlight the limitations of existing virtual resources.

• Development and validation of a quantitative instrument for measuring temporal and social disorientation in the Covid-19 crisis -

  We developed a quantitative Instrument for measuring Temporal and Social Disorientation (ITSD), aimed at major crises such as the Covid-19 pandemic. Disorientation has been identified as one of the central elements of the psychological impact of the Covid-19 era on the general public, but so far, the question has only been approached qualitatively. This paper offers an empirical, quantitative approach to the multi-faceted disorientation of the Covid-19 pandemic by operationalising the issue with the help of the ITSD. The ITSD was developed through multiple stages involving a preliminary open-ended questionnaire followed by a coder-based thematic analysis. This paper establishes the reliability and validity of the resulting ITSD using a 3-step validation process on a sample size of 3306.

• DECREASED BREADTH OF THE ANTIBODY RESPONSE TO THE SPIKE PROTEIN OF SARS-CoV-2 AFTER REPEATED VACCINATION -

  The rapid development of vaccines to prevent infection by SARS-CoV-2 virus causing COVID-19 makes necessary to compare the capacity of the different vaccines in terms of development of a protective humoral response. Here, we have used a highly sensitive and reliable flow cytometry method to measure the titers of antibodies of the IgG1 isotype in blood of healthy volunteers after receiving one or two doses of the vaccines being administered in Spain. We took advantage of the multiplexed capacity of the method to measure simultaneously the reactivity of antibodies with the S protein of the original strain Wuhan and the variants B.1.1.7 (Alpha), B.1.617.2 (Delta) and B.1.617.1 (Kappa). We found significant differences in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech and Ad26.COV.S/Janssen. Most important, we found a relative reduction in the reactivity of the sera with the Alpha, Delta and Kappa variants, versus the Wuhan one, after the second boosting immunization. These data allow to make a comparison of different vaccines in terms of anti-S antibody generation and cast doubts about the convenience of repeatedly immunizing with the same S protein sequence.

  🖺 Full Text HTML: DECREASED BREADTH OF THE ANTIBODY RESPONSE TO THE SPIKE PROTEIN OF SARS-CoV-2 AFTER REPEATED VACCINATION
• Descriptive and Narrative Study of Long Covid Cases in General Practice and Diagnostic Value of Single Photon Emission Computed Tomography -

  The issue of Long Covid, its diagnosis and therapeutic approach are discussed here in detail. The Long Covid is described on the basis of a review of the literature and also on the basis of clinical experience in general practice. The main characteristics of thirty four cases (twenty five women) of Long Covid encountered in 2021 and early 2022 are outlined. The experience of six of them is reported on the basis of notes from their medical records. These six patients were interviewed and each was asked to reread and correct the texts concerning them. This is therefore a descriptive study based on clinical and narrative experience, verified by the patients. Long Covid, the first disease in the history of medicine to be described first by patients themselves on social networks, is not yet precisely defined and the multi-systemic symptoms may be non-specific or vary according to the organs affected. Diagnosis is based on careful listening to the patients history. Previously unknown irrepressible fatigue, brain fog, working memory disorders with possible anomia, anosmia, dysgeusia or other muli-systemic symptoms occurring after an acute Covid are varying characteristics of Long Covid. Biological evidence of Covid is missing in fourteen patients as PCRs may have been not done or came back negative in the acute phase of the disease. Anti-SARS-CoV-2 antibodies are not always present or are indistinguishable from post-vaccine antibodies. In fourteen severe cases presented, Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m (Tc-99m HM-PAO) were able to demonstrate a disorder of cerebral perfusion. Two follow-up brain SPECT at three months showed significant improvement. Further genetic and immunologic study is ongoing for all patient with the help of the international consortium COVID Human Genetic Effort. A patient who presents after a Covid with medically unexplained symptoms may well be a Long Covid. Despite some interesting hypothesis, there is no known specific treatment. Neurocognitive revalidation and physiotherapy may help those patients who need long-term empathic support to cope with their condition.

  🖺 Full Text HTML: Descriptive and Narrative Study of Long Covid Cases in General Practice and Diagnostic Value of Single Photon Emission Computed Tomography

From Clinical Trials

• 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

• EPIC-Peds: Study of Oral PF-07321332 (Nirmatrelvir)/Ritonavir in Nonhospitalized COVID-19 Pediatric Patients at Risk for Severe Disease - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir;   Drug: ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• Anti-inflammatory Drug Algorithm for COVID-19 Home Treatment - Condition:   COVID-19
  Interventions:   Drug: Recommended treatment schedule;   Drug: Usual care
  Sponsors:   Mario Negri Institute for Pharmacological Research;   Family physicians
  Not yet recruiting

• Transcranial Direct Stimulation for Persistent Fatigue Treatment Post-COVID-19 - Condition:   COVID-19
  Interventions:   Device: Active tDCS;   Device: Sham tDCS
  Sponsor:   Hospital San Carlos, Madrid
  Not yet recruiting

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

• Effect of Combined Use of Ivermectin and Colchicine in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Ivermectin + colchicine;   Drug: Colchicine
  Sponsor:   Ain Shams University
  Recruiting

• Vale+ Tu Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID 19 - Condition:   COVID-19
  Interventions:   Behavioral: COVID-19 Group Problem Solving;   Behavioral: Control Group-standard of care
  Sponsors:   The University of Texas Health Science Center, Houston;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• A Phase III, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of TD0069 Capsule as a Combination Regimen With Standard Treatment for Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: TD0069 hard capsule;   Drug: TD0069 Placebo
  Sponsors:   Sao Thai Duong Joint Stock Company;   Clinical Training Company
  Recruiting

• Efficacy of the Infusion of Donor Plasma in SARS CoV 2 Infection - Condition:   COVID-19
  Intervention:   Biological: convalescent plasma infusion covid 19
  Sponsor:   Hospital Galdakao-Usansolo
  Terminated

• Nebulised Heparin in Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Unfractionated heparin
  Sponsor:   Lady Reading Hospital, Pakistan
  Not yet recruiting

• Nutrition and LOComotoric Rehabilitation in Long COVID-19 - Condition:   COVID-19
  Intervention:   Other: Intervention group
  Sponsors:  
  Universitair Ziekenhuis Brussel;   Vrije Universiteit Brussel
  Not yet recruiting

• Immuno-bridging and Broadening Study of a Whole, Inactivated COVID-19 Vaccine BBV152 in Healthy Adults - Condition:   COVID-19
  Intervention:   Biological: BBV152
  Sponsor:   Ocugen
  Active, not recruiting

• Reparixin as add-on Therapy to Standard of Care to Limit Disease Progression in Adult Patients With COVID-19. - Conditions:   COVID-19 Pneumonia;   Sars-CoV-2 Infection
  Interventions:   Drug: Reparixin;   Other: Placebo
  Sponsor:   Dompé Farmaceutici S.p.A
  Not yet recruiting

• COVID-19 Prevention Trial: Effect of Prophylactic Use of TAFFIX™ on Infection Rate by SARS-COV-2 VIRUS (COVID-19). - Conditions:   COVID-19;   Upper Respiratory Tract Infections
  Intervention:   Device: TaffiX™
  Sponsor:   Nasus Pharma
  Completed

• A Phase III Trial to Assess the Safety and Immunogenicity of a HIPRA’s Candidate Booster Vaccination Against COVID-19. - Conditions:   COVID-19;   SARS-CoV-2 Acute Respiratory Disease
  Intervention:  
  Biological: COVID-19 Vaccine 40 ug/dose
  Sponsor:   Hipra Scientific, S.L.U
  Recruiting

From PubMed

• Complement Activation via the Lectin and Alternative Pathway in Patients With Severe COVID-19 - Complement plays an important role in the direct defense to pathogens, but can also activate immune cells and the release of pro-inflammatory cytokines. However, in critically ill patients with COVID-19 the immune system is inadequately activated leading to severe acute respiratory syndrome (SARS) and acute kidney injury, which is associated with higher mortality. Therefore, we characterized local complement deposition as a sign of activation in both lungs and kidneys from patients with severe…

• Modulation of Innate Antiviral Immune Response by Porcine Enteric Coronavirus - Host’s innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity. The porcine enteric coronaviruses (PECs) consist of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis coronavirus (TGEV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV), which cause lethal diarrhea in neonatal pigs and threaten the swine industry worldwide. PECs…

• Correlated sequence signatures are present within the genomic 5’UTR RNA and NSP1 protein in coronaviruses - The 5’UTR part of coronavirus genomes plays key roles in the viral replication cycle and the translation of the viral mRNAs. The first 75-80 nucleotides, also called the leader sequence, are identical for the genomic mRNA and for the subgenomic mRNAs. Recently, it was shown that cooperative actions of a 5’UTR segment and the non-structural protein NSP1 are essential for both the inhibition of host mRNAs and for specific translation of viral mRNAs. Here, sequence analyses of both the 5’UTR RNA…

• SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells - Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte…

• Missense variants in human ACE2 strongly affect binding to SARS-CoV-2 Spike providing a mechanism for ACE2 mediated genetic risk in Covid-19: A case study in affinity predictions of interface variants - SARS-CoV-2 Spike (Spike) binds to human angiotensin-converting enzyme 2 (ACE2) and the strength of this interaction could influence parameters relating to virulence. To explore whether population variants in ACE2 influence Spike binding and hence infection, we selected 10 ACE2 variants based on affinity predictions and prevalence in gnomAD and measured their affinities and kinetics for Spike receptor binding domain through surface plasmon resonance (SPR) at 37°C. We discovered variants that…

• Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells - Porcine epidemic diarrhea virus (PEDV) is the main cause of diarrhea, vomiting, and mortality in pigs, which results in devastating economic loss to the pig industry around the globe. In recent years, the advent of RNA-sequencing technologies has led to delineate host responses at late stages of PEDV infection; however, the comparative analysis of host responses to early-stage infection of virulent and avirulent PEDV strains is currently unknown. Here, using the BGI DNBSEQ RNA-sequencing, we…

• Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions - The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing…

• Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection - Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and…

• Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model - The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity, identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta…

• VE607 Stabilizes SARS-CoV-2 Spike In the “RBD-up” Conformation and Inhibits Viral Entry - SARS-CoV-2 infection of host cells starts by binding of the Spike glycoprotein (S) to the ACE2 receptor. The S-ACE2 interaction is a potential target for therapies against COVID-19 as demonstrated by the development of immunotherapies blocking this interaction. Here, we present the commercially available VE607, comprised of three stereoisomers, that was originally described as an inhibitor of SARS-CoV-1. We show that VE607 specifically inhibits infection of SARS-CoV-1 and SARS-CoV-2 S-expressing…

• Phytocompounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro through computational studies - The inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) and papain-like protease (PLpro) prevents viral multiplications; these viral enzymes have been recognized as one of the most favorable targets for drug discovery against SARS-CoV-2. In the present study, we screened 225 phytocompounds present in 28 different Indian spices to identify compounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro. Molecular docking, molecular dynamics simulation,…

• Evaluating the structural and immune mechanism of Interleukin-6 for the investigation of Goat Milk peptides as potential treatments for COVID-19 - The function of Immune control, haematopoiesis, and inflammation all depend on the cytokine Interleukin 6 (IL-6), and higher expression of IL-6 is seen in COVID-19 and other diseases. The immune protein IL-6 activation is dependent on binding interactions with IL-6Rα, mIL-6R, and sIL-6R for its cellular function. Termination of these reaction could benefit for controlling the over-expression in COVID-19 patients and that may arise as inhibitors for controlling COVID-19. Traditionally, the goat…

• The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression - SARS-CoV-2, responsible for the ongoing global pandemic, must overcome a conundrum faced by all viruses. To achieve its own replication and spread, it simultaneously depends on and subverts cellular mechanisms. At the early stage of infection, SARS-CoV-2 expresses the viral nonstructural protein 1 (NSP1), which inhibits host translation by blocking the mRNA entry tunnel on the ribosome; this interferes with the binding of cellular mRNAs to the ribosome. Viral mRNAs, on the other hand, overcome…

• Enhancing the prediction of hospitalization from a COVID-19 agent-based model: A Bayesian method for model parameter estimation - Agent-based models (ABMs) have become a common tool for estimating demand for hospital beds during the COVID-19 pandemic. A key parameter in these ABMs is the probability of hospitalization for agents with COVID-19. Many published COVID-19 ABMs use either single point or age-specific estimates of the probability of hospitalization for agents with COVID-19, omitting key factors: comorbidities and testing status (i.e., received vs. did not receive COVID-19 test). These omissions can inhibit…

• Immunomodulatory effects of pharmaceutical opioids and antipyretic analgesics: Mechanisms and relevance to infection - Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive…

From Patent Search

• METHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGES - ABSTRACTMETHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGESThe present invention provides a new approach is proposed that includes fuzzy-based approach and similarity function for filtering the mixed noise. In a peer group, the similarity function was adaptive to edge information and local noise level, which was utilized for detecting the similarity among pixels. In addition, a new filtering method Modified Trilateral Filter (MTF) with Improved Generalized Fuzzy Peer Group (IGFPG) is proposed to remove mixed impulse and Adaptive White Gaussian Noise from Color Images. The modified trilateral filter includes Kikuchi algorithm and loopy belief propagation to solve the inference issues on the basis of passing local message. In this research work, the images were collected from KODAK dataset and a few real time multimedia images like Lena were also used for testing the effectiveness of the proposed methodology. - link

• A STUDY ON MENTAL HEALTH, STRESS AND ANXIETY AMONG COLLEGE STUDENTS DURING COVID-19 - SARS-Cov-2 virus causes an infectious disease coronavirus(COVID-19).The Students life is made harder by COVID-19.The human reaction that happens normally to everyone through physical or emotional tension is stress. Feeling of angry, nervous and frustration caused through any thought or events leads to stress. As college closures and cancelled events, students are missing out on some of the biggest moments of their young lives as well as everyday moments like chatting with friend, participating in class and cultural programme. For students facing life changes due to the outbreak are feeling anxious, isolated and disappointed which lead them to feel all alone. We like to take the help of expert adolescent psychologist to find out the techniques to practice self-care and look after their mental health. We would like to find out whether techniques used reduce the anxiety and stress among Engineering Students. - link

• A METHOD FOR THE TREATMENT OF COVID-19 INFECTIONS WITH PALMITOYLETHANOLAMIDE - - link

• A CENTRAL TRANSACTION AUTHENTIC SYSTEM FOR OTP VERIFICATION - The present invention relates to a central transaction authentic system (100) for OTP verification. The system (100) comprises one or more user display units (102), one or more financial units (104), an account deposit unit (106), an OTP authentication unit (108) and a service server unit (110). The central transaction authentic system (100) for OTP verification work as Anti-money laundering measure. The system (100) also helpful for minimizing rate of cybercrime. The central transaction authentic system (100) for OTP verification that can neutralize digital financial fraud. The present invention provides a central transaction authentic system (100) for OTP verification that can monitor and analyze every transaction and customer interaction across its customer base for suspicious and potentially criminal activity. - link

• FORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAP - ABSTRACTFORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAPThe present invention provides formulations for herbal medicated transparent soaps and method of preparation of the same. Transparent soaps are prepared by saponification of mixture of non-edible oils to get the desired consistency and cleaning action. Nonvolatile alcohols and other transparency promoters are used to get good transparency and binding properties. Herbal extracts of different herbs are added to get medicated properties. - link

• 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 MACHINE LEARNING BASED SYSTEM FOR DETECTING OMICRON VARIANT FROM A GENOME SEQUENCE AND METHOD THEREOF - The present invention discloses a machine learning based system for detecting omicron variant from a genome sequence and method thereof. The system includes, but not limited to, a processing unit having a memory unit and a machine learning interface embedded on it for validating a variant-induced changes in the one or more condition-specific cell variables are combined to output a single numerical variant score for each of the one or more variants, the variant score computed by one of outputting the score for a fixed condition; summing the variant-induced changes across conditions; computing the maximum of the absolute variant-induced changes across conditions. - 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

• 用于体外诊断的新型冠状病毒核衣壳蛋白抗体 - 本发明提供了一种用于体外诊断的新型冠状病毒核衣壳蛋白抗体或抗原结合片段。所提供的抗体包括重链可变区和轻链可变区，重链可变区包括SEQ ID NO:11、12和13所示的CDR序列，轻链可变区包括SEQ ID NO:14、15和16所示的CDR序列。所提供的抗体用于新型冠状病毒的体外检测，具有极高的灵敏度和特异性。 - link

• 用于体外诊断的新型冠状病毒核衣壳蛋白抗体 - 本发明提供了一种用于体外诊断的新型冠状病毒核衣壳蛋白抗体或抗原结合片段。所提供的抗体包括重链可变区和轻链可变区，重链可变区包括SEQ ID NO:1、2和3所示的CDR序列，轻链可变区包括SEQ ID NO:4、5和6所示的CDR序列。所提供的抗体用于新型冠状病毒的体外检测，具有极高的灵敏度和特异性。 - link