Covid-19 Sentry

Contents

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

From Preprints

• Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk -
  The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is an extremely complex with nutritional composition to nourish infants and protect them from different kinds of infection diseases and also SARS-CoV-2 infection. Previous studies have found that breastmilk exhibited potent antiviral activity against SARS-CoV-2 infection. However, it is still unknown which component(s) in the breastmilk is responsible for its antiviral activity. Here, we identified Lactoferrin (LF), MUC1 and -Lactalbumin (-LA) from human breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in vitro confirmation that inhibited SARS-CoV-2 infection and analyzed their antiviral activity using the SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like- particles (trVLP) in the Huh7.5, Vero E6 and Caco-2-N cell lines. Additionally, we found that LF and MUC1 could inhibit viral attachment, entry and post-entry replication, while -LA just inhibit viral attachment and entry. Importantly, LF, MUC1 and -LA possess potent antiviral activities towards not only wild-type but also variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Moreover, LF from other species (e.g., bovine and goat) is still capable of blocking viral attachment to cellular heparan sulfate. Taken together, our study provided the first line of evidence that human breastmilk components (LF, MUC1 and -LA) are promising therapeutic candidates warranting further development or treatingVID-19 given their exceedingly safety levels.
  🖺 Full Text HTML: Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk
• Visceral Fat Inflammation and Fat Embolism are associated with Lung’s Lipidic Hyaline Membranes in COVID-19 patients -
  Background: Visceral obesity is a critical determinant of severe coronavirus disease-2019 (COVID-19). Methods: In this study, we performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissues (VAT), lungs and livers of 19 COVID-19 and 23 non-COVID-19 subjects. Results: Although there were no between-groups differences in body- mass-index and adipocytes size, higher prevalence of CD68+ macrophages in COVID-19 subjects VAT was detected (p=0.005) and accompanied by crown-like structures presence, signs of adipocytes stress and death. Consistently, human adipocytes were successfully infected by SARS-CoV2 in vitro and displayed lower cell viability. Being VAT inflammation associated with lipids spill-over from dead adipocytes, we studied lipids distribution employing Oil-Red-O staining (ORO). Lipids were observed within lungs and livers interstitial spaces, macrophages, endothelial cells, and vessels lumen, features suggestive of fat embolism syndrome, more prevalent among COVID-19 individuals (p<0.001). Notably, signs of fat embolism were more prevalent among obese (p=0.03) independently of COVID-19 diagnosis, suggesting that such condition may be an obesity complication, exacerbated by SARS-CoV2 infection. Importantly, all infected subjects lungs presented lipids-rich (ORO+) hyaline membranes, formations associated with COVID-19-related pneumonia, present only in one control with non-COVID-19 pneumonia. Conclusions: This study describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in obese SARS-CoV2-infected- subjects.
  🖺 Full Text HTML: Visceral Fat Inflammation and Fat Embolism are associated with Lung’s Lipidic Hyaline Membranes in COVID-19 patients
• A biosafety level 2 surrogate for studying SARS-CoV-2 survival in food processing environmental biofilms -
  Meat processing plants have been at the center of the SARS-CoV-2 pandemic. There are several factors that contribute to the persistence of SARS-CoV-2 in meat processing plants and one of the factors is the formation of a multi-species biofilm with virus. Biofilm can act as a reservoir in protecting, harboring, and dispersing SARS-CoV-2 from biofilm to the meat processing facility environment. We used Murine Hepatitis Virus (MHV) as a surrogate for SARS- CoV-2 virus and meat processing facility drain samples to develop mixed-species biofilms on commonly found materials in processing facilities (Stainless-Steel (SS), PVC and tiles). The results showed that MHV was able to integrate into the environmental biofilm and survived for a period of 5 days at 7C. There was no significate difference between the viral- environmental biofilm biovolumes developed on different materials SS, PVC, and tiles. There was a 2-fold increase in the virus-environmental biofilm biovolume when compared to environmental biofilm by itself. These results indicate a complex virus-environmental biofilm interaction which is providing enhanced protection for the survival of viral particles with the environmental biofilm community.
  🖺 Full Text HTML: A biosafety level 2 surrogate for studying SARS-CoV-2 survival in food processing environmental biofilms
• Multiple spillovers and onward transmission of SARS-Cov-2 in free-living and captive White-tailed deer (Odocoileus virginianus) -
  Many animal species are susceptible to SARS-CoV-2 and could potentially act as reservoirs, yet transmission in non- human free-living animals has not been documented. White-tailed deer (Odocoileus virginianus), the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns transmit the virus to other captive deer. To test the hypothesis that SARS-CoV-2 may be circulating in deer, we evaluated 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through December of 2020 for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 deer (33.2%; 95% CI: 28, 38.9) samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, between Nov 23, 2020, and January 10, 2021, 80 of 97 (82.5%; 95% CI 73.7, 88.8) RPLN samples had detectable SARS-CoV-2 RNA by RT-PCR. Whole genome sequencing of the 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%), and B.1.311 (n = 19; 20%) accounting for ~75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple zooanthroponotic spillover events and deer-to-deer transmission. The discovery of sylvatic and enzootic SARS-CoV-2 transmission in deer has important implications for the ecology and long-term persistence, as well as the potential for spillover to other animals and spillback into humans. These findings highlight an urgent need for a robust and proactive One Health approach to obtaining a better understanding of the ecology and evolution of SARS-CoV-2.
  🖺 Full Text HTML: Multiple spillovers and onward transmission of SARS-Cov-2 in free-living and captive White-tailed deer (Odocoileus virginianus)
• Comparative genomics and characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern (VOC) from Amazonas, Brazil -

  Background: P.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies. Methods: The samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples. Results: Forty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage. Conclusion: P.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

  🖺 Full Text HTML: Comparative genomics and characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern (VOC) from Amazonas, Brazil
• Comparison of Antibody Levels in Response to SARS-CoV-2 Infection and Vaccination Type in a Midwestern Cohort -

  We present preliminary data in an ongoing observational study reporting SARS-CoV-2 spike protein reactive antibody levels from a convenience cohort of over 200 individuals in Kansas City. We observe stable antibody levels over a year in individuals who recovered from COVID19 infection caused by SARS-CoV-2. Our data revealed higher-than recovered levels from naïve individuals vaccinated with Pfizer or Moderna vaccines and similar-to recovered levels from Johnson & Johnson (J&J) recipients. For all vaccines, inoculation after recovery resulted in higher antibody levels than vaccination alone. Responses to Pfizer and Moderna vaccines decreased over time from high initial levels but at the time of publication remain higher than those for recovered or J&J recipients. Within our limited cohort we only see slight demographic trends including higher antibody levels in recovered female vs. male individuals. Booster doses and breakthrough infections both result in rapid increases in antibody levels.

  🖺 Full Text HTML: Comparison of Antibody Levels in Response to SARS-CoV-2 Infection and Vaccination Type in a Midwestern Cohort
• A Bayesian approach to reveal the key role of mask wearing in modulating interpersonal distance during the COVID-19 outbreak -
  Creating and maintaining bonds in humans typically comes with interactions occurring at close social distances which are usually shorter than the one (of at least 1.5 meters) recommended as a relevant measure of COVID-19 contagion containment. In a web-based experimental study conducted during the first pandemic wave (mid-April 2020), we asked 242 participants to regulate their preferred distance towards confederates who did or did not wear protective mask/gloves and who could have tested positive or negative to COVID-19 or whose test results are unknown. Information concerning the dispositional factors (perceived vulnerability to disease, moral attitudes and prosocial tendencies) and situational factors (perceived severity of the situation in the country, frequency of physical and virtual social contacts and attitudes toward quarantine) that may modulate compliance with safety prescriptions was also acquired. A bayesian analysis approach was adopted. Individual differences did not modulate the interpersonal distance. We found strong evidence in favor of a reduction of interpersonal distance towards characters wearing protective equipment and who tested negative to Covid-19. Importantly, shorter interpersonal distances were kept towards confederates wearing protections, even when their test result was unknown or turned out positive to Covid-19. The protective equipment- related regulation of interpersonal distance may reflect an underestimation of the perceived vulnerability to the infection, which has to be discouraged when pursuing individual and collective safety.
  🖺 Full Text HTML: A Bayesian approach to reveal the key role of mask wearing in modulating interpersonal distance during the COVID-19 outbreak
• Validation of a Novel IoT and AI based Point-of-Care Testing Laboratory: Analytical Accuracy and Clinical Agreement -

  Point-of-care testing (POCT) offers several advantages over traditional laboratory testing. Offering less invasive testing with a faster turnaround time is not enough if not associated with an acceptable level of accuracy. Here, we show the analytical validation behind the multi-analyte POCT immunochromatography analyser, Hilab Flow (HiF). Analyses from 4,518 clinical samples were compared to College of American Pathologists accredited laboratories for ten quantitative and thirteen qualitative exams. Compatibility between methods was evaluated in terms of association/correlation and clinical agreement. Strong correlation/ concordance was observed between quantitative (CHOL, HDL-c, TG, HbA1c, Glycemia, 25-Hydroxy Vitamin D, TSH, Uric Acid, Creatinine, Urea) and qualitative methods (COVID-19 IgG/ IgM, Beta-hCG, Syphilis, Anti-HBsAg, Zika IgG/ IgM, Influenza A/B, HIV, HCV, HBsAg, Dengue NS1, COVID-19 Ag, Dengue IgG/ IgM, PSA). Approval criteria was obtaining a kappa agreement > 0.8 or a Pearson correlation > 0.9 depending on the exam. Overall percentage agreement was greater than 95% for all exams, indicating a good clinical agreement to gold-standard laboratory-based tests. Results indicate all exams are suitable for POCT and present a reliable performance. Data support the analyser is a useful tool to aid decision-making at the clinical setting, with potential to contribute with healthcare solutions in diagnostic medicine worldwide.

  🖺 Full Text HTML: Validation of a Novel IoT and AI based Point-of-Care Testing Laboratory: Analytical Accuracy and Clinical Agreement
• Allosteric modulation of the SARS-CoV-2 spike conformation -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding to angiotensin- converting enzyme 2 (ACE2), which is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural data and real-time analysis of conformational dynamics have shown that S can adopt multiple conformations, which mediate the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Forster resonance energy transfer (smFRET) imaging we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and the B.1 variant (D614G). We found that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicated antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.
  🖺 Full Text HTML: Allosteric modulation of the SARS-CoV-2 spike conformation
• Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent behind the current COVID-19 pandemic having emerged in Wuhan China in late 2019 from a yet to be determined animal reservoir. SARS-CoV-2 B.1.1.7, a variant identified in the UK in late 2020, contains a higher than typical level of point mutants across its genome, including P681H in the spike S1/S2 cleavage site. Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from Wuhan-Hu1 and B.1.1.7 and observed no definitive difference in furin cleavage between Wuhan-Hu1 and B.1.1.7 in vitro. We performed functional assays using pseudo-typed particles harboring SARS-CoV-2 spike proteins and observed no significant differences between Wuhan-Hu1, Wuhan-Hu1 P681H or B.1.1.7 spike-carrying pseudo-typed particles in VeroE6 or Vero-TMPRSS2 cells, despite the spikes containing P681H being more efficiently cleaved. Likewise, we or show no differences in cell-cell fusion assays using the spike P681H-expressing cells. Our findings suggest that while the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC).
  🖺 Full Text HTML: Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike
• Glycopeptide antibiotic teicoplanin inhibits cell entry of SARS-CoV-2 by suppressing the proteolytic activity of cathepsin L -
  Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanism and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the Spike of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on Spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of authentic SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 M for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 M for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.
  🖺 Full Text HTML: Glycopeptide antibiotic teicoplanin inhibits cell entry of SARS-CoV-2 by suppressing the proteolytic activity of cathepsin L
• Detailed Overview of the Buildout and Integration of an Automated High-Throughput CLIA Laboratory for SARS-CoV-2 Testing on a Large Urban Campus -

  In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for Covid-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University, created an on-campus Covid-19 screening protocol as part of planning for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand. The Boston University Clinical Testing Laboratory was operational at the start of the fall 2020 academic year. The lab performed over 1 million SARS-CoV-2 RT- PCR tests during the 2020-2021 academic year.

  🖺 Full Text HTML: Detailed Overview of the Buildout and Integration of an Automated High-Throughput CLIA Laboratory for SARS-CoV-2 Testing on a Large Urban Campus
• Underlying factors that influence the acceptance of COVID-19 vaccine in a country with a high vaccination rate -

  Control of the COVID-19 pandemic largely depends on the effectiveness of the vaccination. Several factors including vaccine hesitancy can affect the vaccination process. Understanding the factors that underlie the willingness to accept vaccination brings pivotal information to control the pandemic. We analyzed the association between the willingness level to accept the COVID-19 vaccine, and vaccine determinants amidst the Chilean vaccination process. Individual-level survey data was collected from nationally representative samples of 744 respondents, and multivariate regression models used to estimate the association between outcome and explanatory variables. Trust in the COVID-19 vaccine, scientists, and medical professionals were found to increase the willingness to: accept the vaccine, a booster dose, annual vaccination, and children vaccination. Our results are critical to understanding the acceptance of COVID-19 vaccines in the context of a country with one of the highest vaccination rates in the world. We provide information for decision-making, policy design and communication of vaccination programs.

  🖺 Full Text HTML: Underlying factors that influence the acceptance of COVID-19 vaccine in a country with a high vaccination rate
• Modelling COVID-19 Pandemic Dynamics Using Transparent, Interpretable, Parsimonious and Simulatable (TIPS) Machine Learning Models: A Case Study from Systems Thinking and System Identification Perspectives -

  Since the outbreak of COVID-19, an astronomical number of publications on the pandemic dynamics appeared in the literature, of which many use the susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR) models, or their variants, to simulate and study the spread of the coronavirus. SIR and SEIR are continuous-time models which are a class of initial value problems (IVPs) of ordinary differential equations (ODEs). Discrete-time models such as regression and machine learning have also been applied to analyze COVID-19 pandemic data (e.g. predicting infection cases), but most of these methods use simplified models involving a small number of input variables pre-selected based on a priori knowledge, or use very complicated models (e.g. deep learning), purely focusing on certain prediction purposes and paying little attention to the model interpretability. There have been relatively fewer studies focusing on the investigations of the inherent time-lagged or time-delayed relationships e.g. between the reproduction number (R number), infection cases, and deaths, analyzing the pandemic spread from a systems thinking and dynamic perspective. The present study, for the first time, proposes using systems engineering and system identification approach to build transparent, interpretable, parsimonious and simulatable (TIPS) dynamic machine learning models, establishing links between the R number, the infection cases and deaths caused by COVID-19. The TIPS models are developed based on the well-known NARMAX (Nonlinear AutoRegressive Moving Average with eXogenous inputs) model, which can help better understand the COVID-19 pandemic dynamics. A case study on the UK COVID-19 data is carried out, and new findings are detailed. The proposed method and the associated new findings are useful for better understanding the spread dynamics of the COVID-19 pandemic.

  🖺 Full Text HTML: Modelling COVID-19 Pandemic Dynamics Using Transparent, Interpretable, Parsimonious and Simulatable (TIPS) Machine Learning Models: A Case Study from Systems Thinking and System Identification Perspectives
• Quantifying the effects of non-pharmaceutical and pharmaceutical interventions against COVID-19 epidemic in the Republic of Korea: Mathematical model-based approach considering age groups and the Delta variant -

  Background: Early vaccination efforts and non-pharmaceutical interventions were insufficient to prevent a surge of coronavirus disease 2019 (COVID-19) cases triggered by the Delta variant. This study aims to understand how vaccination and variants contribute to the spread of COVID-19 so that appropriate measures are implemented. Methods: A compartment model that includes age, vaccination, and infection with the Delta or non-Delta variants was developed. We estimated the transmission rates using maximum likelihood estimation and phase-dependent reduction effect of non- pharmaceutical interventions (NPIs) according to government policies from 26 February to 8 October 2021. We extended our model simulation until 31 December considering the initiation of eased NPIs. Furthermore, we also performed simulations to examine the effect of NPIs, arrival timing of Delta variant, and speed of vaccine administration. Results: The estimated transmission rate matrices show distinct pattern, with the transmission rates of younger age groups (0~39 years) much larger than non-Delta. Social distancing (SD) level 2 and SD4 in Korea were associated with transmission reduction factors of 0.64 to 0.69 and 0.70 to 0.78, respectively. The easing of NPIs to a level comparable to SD2 should be initiated not earlier than 16 October to keep the number of severe cases below the capacity of Korean healthcare system. Simulation results also showed that a surge prompted by the spread of the Delta variant can be prevented if the number of people vaccinated daily was larger. Conclusions: Simulations showed that the timing of easing and intensity of NPIs, vaccination speed, and screening measures are key factors in preventing another epidemic wave.

  🖺 Full Text HTML: Quantifying the effects of non- pharmaceutical and pharmaceutical interventions against COVID-19 epidemic in the Republic of Korea: Mathematical model- based approach considering age groups and the Delta variant

From Clinical Trials

• COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition:   COVID-19
  Intervention:   Drug: casirivimab+imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca);   Biological: CoronaVac (Sinovac Biotech);   Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   Instituto Fernandes Figueira
  Not yet recruiting

• Tocilizumab Versus Baricitinib in Patients With Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tocilizumab;   Drug: Baricitinib
  Sponsor:   University Hospital of Patras
  Recruiting

• The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients (Phase3) - Condition:   COVID-19
  Interventions:   Drug: Pyramax;   Drug: Placebo
  Sponsor:  
  Shin Poong Pharmaceutical Co. Ltd.
  Recruiting

• JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: JINZHEN Granules for Oral Solution;   Drug: Placebo
  Sponsor:   Lianyungang Kanion Group, Ltd.
  Not yet recruiting

• Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition:   COVID-19
  Intervention:   Device: Chatbot
  Sponsor:   Sun Yat- sen University
  Recruiting

• Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care - Condition:   COVID-19
  Intervention:   Drug: Apixaban
  Sponsors:  
  Scotmann Pharmaceuticals;   Rawalpindi Medical College
  Not yet recruiting

• Clinical Validation of Breath Analyser Tests for Diagnosis of COVID-19. - Condition:   COVID-19
  Intervention:   Diagnostic Test: Breath Sample analysis
  Sponsor:   Tera Group
  Recruiting

• Efficacy, Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 DNA Vaccine;   Biological: Matching placebo
  Sponsors:   The University of Hong Kong;   Immuno Cure 3 Limited
  Not yet recruiting

• Safety and Efficacy of KOVIR (TD0068) in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR (TD0068) oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Vietstar Biomedical Research
  Recruiting

• Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Biological: Ad5-triCoV/Mac;   Biological: ChAd-triCoV/Mac
  Sponsors:   McMaster University;   Canadian Institutes of Health Research (CIHR)
  Not yet recruiting

• Effect of PBM on Functional Capacity and Fatigability in Post Covid-19 Elderly - Condition:   Post Covid-19 Elderly
  Interventions:   Radiation: photobiomodulation;   Other: placebo intervention by photobiomodulation device
  Sponsor:   Cairo University
  Recruiting

• Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Study - Condition:   COVID-19 Pandemic
  Interventions:   Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01);   Biological: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Not yet recruiting

• Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC) - Condition:   Post-Acute Sequelae of COVID-19
  Interventions:   Device: Active tDCS;   Device: Sham tDCS
  Sponsor:   Massachusetts General Hospital
  Not yet recruiting

From PubMed

• Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study - CONCLUSIONS: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms.

• Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection - Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial…

• Biphasic effect of mechanical stress on lymphocyte activation - Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C-Jun, and increased the expression of early activation marker CD69 in resting…

• Feasibility of Remote Performance Assessment Using the Free Research Executive Evaluation Test Battery in Adolescents - Lockdowns and other preventive measures taken to curb the spread of diseases such as COVID-19 have restricted the use of face-to-face cognitive assessment. Remote testing may be an alternative, but it should first be shown to be comparable to in-person assessment before being used more widely, during and after the pandemic. Our aim was to evaluate the suitability of online, examiner-mediated administration of an open-access battery of executive function tests (the Free Research Executive…

• Effect of Prophylactic Use of Intranasal Oil Formulations in the Hamster Model of COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in the upper respiratory tract, leading to coronavirus disease 2019 (COVID-19). Severe COVID-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting the entry of the virus or its internalization in the upper respiratory tract are of interest. Herein, we report the prophylactic application of two intranasal formulations provided by the…

• Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2 - COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (M^(pro)), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were…

• Effective inhibition of coronavirus replication by Polygonum cuspidatum - Background: The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have…

• Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence - Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early….

• Therapeutic mTOR blockade in systemic autoimmunity: Implications for antiviral immunity and extension of lifespan - The mechanistic target of rapamycin (mTOR) pathway integrates metabolic cues into cell fate decisions. A particularly fateful event during the adaptive immune response is the engagement of a T cell receptor by its cognate antigen presented by an antigen-presenting cell (APC). Here, the induction of adequate T cell activation and lineage specification is critical to mount protective immunity; at the same time, inadequate activation, which could lead to autoimmunity, must be avoided. mTOR forms…

• Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2 - Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and…

• Short-term immune response after inactivated SARS-CoV-2 (CoronaVac, Sinovac) and ChAdOx1 nCoV-19 (Vaxzevria, Oxford- AstraZeneca) vaccinations in health care workers - CONCLUSIONS: A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.

• Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Currently, there are no particular antivirals available to battle with COVID-19. The RNA-dependent RNA polymerase (RdRp) has emerged as a novel drug target due to its essential role in virus replication. In this study, turmeric-derived compounds were chosen and subjected to in-silico analysis to evaluate their binding affinity against the RdRp-RNA complex of SARS-CoV-2. Our in-silico…

• Dysregulation of RNA interference components in COVID-19 patients - OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as…

• APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis - The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with…

• Specific delivering of RNAi using Spike’s aptamer-functionalized lipid nanoparticles for targeting SARS-CoV-2: A strong anti-Covid drug in a clinical case study - Coronavirus (SARS-CoV-2) as a global pandemic has attracted the attention of many scientific centers to find the right treatment. We expressed and purified the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, and specific RBD aptamers were designed using SELEX method. RNAi targeting nucleocapsid phosphoprotein was synthesized and human lung cells were inoculated with aptamer-functionalized lipid nanoparticles (LNPs) containing RNAi. The results demonstrated that RBD…

From Patent Search

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link

• 多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - link