Covid-19 Sentry

Contents

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

From Preprints

• Integrative analysis of multi-omics reveals gene regulatory networks across brain regions from risk variants to phenotypes of Alzheimer’s disease and Covid-19 -
  Background: Genome-wide association studies have found many genetic risk variants associated with Alzheimer’s disease (AD). However, how these risk variants affect deeper phenotypes such as disease progression and immune response remains elusive. Also, our understanding of cellular and molecular mechanisms from disease risk variants to various phenotypes is still limited. To address these problems, we performed integrative multi-omics analysis from genotype, transcriptomics, and epigenomics for revealing gene regulatory mechanisms from disease variants to AD phenotypes. Method: First, we cluster gene co-expression networks and identify gene modules for various AD phenotypes given population gene expression data. Next, we predict the transcription factors (TFs) that significantly regulate the genes in each module and the AD risk variants (e.g., SNPs) interrupting the TF binding sites on the regulatory elements. Finally, we construct a full gene regulatory network linking SNPs, interrupted TFs, and regulatory elements to target genes for each phenotype. This network thus provides mechanistic insights of gene regulation from disease risk variants to AD phenotypes. Results: We applied our analysis to predict the gene regulatory networks in three major AD-relevant regions: hippocampus, dorsolateral prefrontal cortex (DLPFC), and lateral temporal lobe (LTL). These region networks provide a comprehensive functional genomic map linking AD SNPs to TFs and regulatory elements to target genes for various AD phenotypes. Comparative analyses further revealed cross-region-conserved and region-specific regulatory networks. For instance, AD SNPs rs13404184 and rs61068452 disrupt the bindings of TF SPI1 that regulates AD gene INPP5D in the hippocampus and lateral temporal lobe. However, SNP rs117863556 interrupts the bindings of TF REST to regulate GAB2 in the DLPFC only. Furthermore, driven by recent discoveries between AD and Covid-19, we found that many genes from our networks regulating Covid-19 pathways are also significantly differentially expressed in severe Covid patients (ICU), suggesting potential regulatory connections between AD and Covid. Thus, we used the machine learning models to predict severe Covid and prioritized highly predictive genes as AD-Covid genes. We also used Decision Curve Analysis to show that our AD-Covid genes outperform known Covid-19 genes for predicting Covid severity and deciding to send patients to ICU or not. In short, our results provide a deeper understanding of the interplay among multi-omics, brain regions, and AD phenotypes, including disease progression and Covid response. Our analysis is open-source available at https://github.com/daifengwanglab/ADSNPheno.
  🖺 Full Text HTML: Integrative analysis of multi-omics reveals gene regulatory networks across brain regions from risk variants to phenotypes of Alzheimer’s disease and Covid-19
• The polarity and specificity of SARS-CoV2 -specific T lymphocyte responses determine disease susceptibility -

  Optimal vaccination and immunotherapy against coronavirus disease COVID-19 relies on the in-depth comprehension of immune responses determining the individual susceptibility to be infected by SARS-CoV-2 and to develop severe disease. We characterized the polarity and specificity of circulating SARS-CoV-2-specific T cell responses against whole virus lysates or 186 unique peptides derived from the SARS-CoV-2 or SARS-CoV-1 ORFeome on 296 cancer-bearing and 86 cancer-free individuals who were either from the pre-COVID-19 era (67 individuals) or contemporary COVID-19-free (237 individuals) or who developed COVID-19 (78 individuals) in 2020/21. The ratio between the prototypic T helper 1 (TH1) cytokine, interleukin-2, and the prototypic T helper 2 (TH2) cytokine, interleukin-5 (IL-5), released from SARS-CoV-2-specific memory T cells measured in early 2020, among SARS-CoV-2-negative persons, was associated with the susceptibility of these individuals to develop PCR-detectable SARS-CoV-2 infection in late 2020 or 2021. Of note, T cells from individuals who recovered after SARS-CoV-2 re-infection spontaneously produced elevated levels of IL-5 and secreted the immunosuppressive TH2 cytokine interleukin-10 in response to SARS-CoV-2 lysate, suggesting that TH2 responses to SARS-CoV-2 are inadequate. Moreover, individuals susceptible to SARS-CoV-2 infection exhibited a deficit in the TH1 peptide repertoire affecting the highly mutated receptor binding domain (RBD) amino acids (331-525) of the spike protein. Finally, current vaccines successfully triggered anti-RBD specific TH1 responses in 88% healthy subjects that were negative prior to immunization. These findings indicate that COVID-19 protection relies on TH1 cell immunity against SARS-CoV-2 S1-RBD which in turn likely drives the phylogenetic escape of the virus. The next generation of COVID-19 vaccines should elicit high-avidity TH1 (rather than TH2)-like T cell responses against the RBD domain of current and emerging viral variants.

  🖺 Full Text HTML: The polarity and specificity of SARS-CoV2 -specific T lymphocyte responses determine disease susceptibility
• Drug offence detection during the pandemic: a spatiotemporal study of drug markets -
  Research on COVID-19 and crime has so far shown that most crime types declined, especially in the early months of the pandemic. Illicit drug offences were a notable exception, however few studies have considered changes at specific drug market locations. This study documents how key drug markets were affected during the lockdown. Using a spatiotemporal generalised additive model (GAM), this study examines the pattern of drug offence detection throughout the city of Brisbane, Australia and identifies areas of change during lockdown. Statistical meshblock analysis is used to illustrate discrete changes at key market locations. Contrary to aggregate-level analysis, we show that several of the major drug markets experienced a significant decline in drug offence detections, but that these local changes were offset by a displacement to neighbouring areas. We also find some preliminary evidence of the emergence of new outer-urban markets. Existing drug markets were adversely affected by the COVID-19 lockdown, however drug market activity was likely displaced rather than diminished.
  🖺 Full Text HTML: Drug offence detection during the pandemic: a spatiotemporal study of drug markets
• Archiving Dossier Narrative: Transcribing “Le Pelerinage de Damoiselle Sapience” -
  The archived documents were created for Transcribing “Le Pelerinage de Damoiselle Sapience”: Scholarly Editing Covid19-Style, a digital transcription, edition creation and writing project in November 2020 as part of the 13th Annual (Virtual) Schoenberg Symposium on Manuscript Studies in the Digital Age. International teams of medieval scholars and paleographers divided into three teams the first of which transcribed a unique manuscript copy of Le Pelerinage de Damoiselle Sapience, a previously unedited French-language text that survives in f. 86r-95v of UPenn MS Codex 660. The second team reviewed the work and the third team provided final editorial sign off and created a micro-edition with commentary that was submitted to the journal Digital Medievalist.
  🖺 Full Text HTML: Archiving Dossier Narrative: Transcribing “Le Pelerinage de Damoiselle Sapience”
• Depression symptoms mediate mismatch between perceived severity of the COVID-19 pandemic and preventive motives -
  The present study monitored changes in beliefs about the COVID-19 pandemic, depressive symptoms, and preventive motives between the first wave and the second wave in South Korea using an online survey administered to 1144 individuals nationally representative for age, gender, and areas of residence. While participants correctly updated their beliefs about the worsening pandemic situations, perceived importance of social distancing did not change, and their motives to follow prevention measures shifted toward compulsory rather than voluntary motives. This inconsistency appeared to be mediated by depressive symptoms, such that negative belief changes followed by increased depressive symptoms were associated with decreased perceived importance of social distancing and decreased voluntary motives. Our data highlights the importance of psychological responses to the dynamically evolving pandemic situations in promoting preventive behaviors.
  🖺 Full Text HTML: Depression symptoms mediate mismatch between perceived severity of the COVID-19 pandemic and preventive motives
• Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection -
  A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows that spatially dispersed infections lead to increased viral loads. The model shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection, and the magnitude and timing of the T cell immune response. When the branching airway structure is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed ODE model. These results illustrate how realistic spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.
  🖺 Full Text HTML: Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection
• Moxidectin and ivermectin inhibit SARS-CoV-2 replication in Vero E6 cells but not in human primary airway epithelium cells -
  Antiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 micromolar. These in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: “the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive”. It is speculated that the in vivo concentration of ivermectin is too low to exert a strong antiviral effect. Here, we performed a head-to head comparison of the antiviral activity of ivermectin and a structurally related, but metabolically more stable, moxidectin in multiple in vitro models of SARS-CoV-2 infection, including physiologically relevant human respiratory epithelial cells. Both moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Subsequent experiments revealed that the compounds predominantly act on a step after virus cell entry. Surprisingly, however, in human airway-derived cell models, moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection, even at a concentration of 10 micromolar. These disappointing results calls for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on Vero cells. Altogether, these findings suggest that, even by using a high-dose regimen of ivermectin or switching to another drug in the same class are unlikely to be useful for treatment against SARS-CoV-2 in humans.
  🖺 Full Text HTML: Moxidectin and ivermectin inhibit SARS-CoV-2 replication in Vero E6 cells but not in human primary airway epithelium cells
• Poliovirus Vaccination Induces a Humoral Immune Response that Cross Reacts with SARS-CoV-2 -

  Background: Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2. Methods: Publicly available data were analyzed for possible correlations between national median ages and epidemiological outbreak patterns across 100 countries. Sera from 204 adults and children, who were immunized with the poliovirus vaccine, were analyzed using an enzyme-linked immunosorbent assay. The effects of polio-immune serum on SARS-CoV-2-induced cytopathology in cell culture were then evaluated. Results: Analyses of median population age demonstrated a positive correlation between median age and SARS-CoV-2 prevalence and death rates. Countries with effective poliovirus immunization protocols and younger populations have fewer and less pathogenic cases of COVID-19. Antibodies to poliovirus and SARS-CoV-2 were found in pediatric sera and in sera from adults recently immunized with polio. Western blot demonstrated antibodies recognized the RNA-dependent-RNA-polymerase (RdRp) of either virus. Sera from polio-immunized individuals inhibited SARS-CoV-2 infection of Vero cell cultures. These results suggest the anti-D3-pol-antibody, induced by poliovirus vaccination, may provide a similar degree of protection from SARS-CoV-2 to adults as to children. Conclusions: Poliovirus vaccination induces an adaptive humoral immune response. Antibodies created by poliovirus vaccination bind the RdRp protein of both poliovirus and SARS-CoV-2, thereby preventing SARS-CoV-2 infection. These findings suggest proteins other than spike proteins may be suitable targets for immunity and vaccine development.

  🖺 Full Text HTML: Poliovirus Vaccination Induces a Humoral Immune Response that Cross Reacts with SARS-CoV-2
• Increased Risk of Severe COVID-19 Disease in Pregnancy in a Multicenter Propensity Score-Matched Study. -

  Background: Respiratory infections have long been associated with higher maternal and perinatal morbidity. Early data did not report an increased risk of SARS-CoV-2 infection or disease severity in pregnancy. However, surveillance data from the Center for Disease Control and Prevention (CDC) indicates a higher risk of severe disease and death in pregnant women with symptomatic SARS-CoV-2 infection, although this data is subject to ascertainment bias. Objective: To explore the association between COVID-19 disease severity and pregnancy in our university-based hospital system using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death. Study design: We conducted a retrospective, multicenter case-control study to understand the association between COVID-19 disease severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory-confirmed SARS-CoV-2 infection in six months between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death. Results: A higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than nonpregnant women (25% vs. 16.1%, p=0.04, respectively). While there was a higher rate of hospitalization (25.6% vs. 17.2%), ICU admission (8.9% vs. 4.4%), need for vasoactive substances (5.0% vs. 2.8%), and invasive mechanical ventilation (5.6% vs. 2.8%) in the pregnant group, this difference was not significant after the propensity score matching was applied. We found a high rate of pregnancy complications in our population (40.7%). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1%). Conclusions: In our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and an increased risk of pregnancy complications.

  🖺 Full Text HTML: Increased Risk of Severe COVID-19 Disease in Pregnancy in a Multicenter Propensity Score-Matched Study.
• Plasma gradient of soluble urokinase-type plasminogen activator receptor is linked to pathogenic plasma proteome and immune transcriptome and stratifies outcomes in severe COVID-19 -

  Disease caused by SARS-CoV-2 coronavirus (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with ARDS. Plasma sUPAR level was found to be linked to a characteristic proteomic signature of plasma, linked to coagulation disorders and complement activation. Receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 1996.809 pg/ml that could predict survival in our cohort (Odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower sUPAR level than this threshold concentration was associated with a differential expression of the immune transcriptome as well as favourable clinical outcomes, both in terms of survival benefit (Hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus we identified sUPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.

  🖺 Full Text HTML: Plasma gradient of soluble urokinase-type plasminogen activator receptor is linked to pathogenic plasma proteome and immune transcriptome and stratifies outcomes in severe COVID-19
• Excellent negative predictive value (99.8%) of two rapid molecular COVID-19 tests compared to conventional RT-PCR for SARS-CoV-2 (COVID-19) in 2,011 tests performed in a single centre. -

  Conventional Reverse Transcription Polymerase Chain Reaction (RT-PCR) remains the gold standard for testing SARS-CoV-2. Since their availability, two rapid molecular COVID-19 tests were performed in parallel with RT-PCR in all urgent and emergency admissions, as the negative predictive value was not yet ascertained. In this study, we present the data of 2011 test results using either ID Now COVID-19 (Abbott) (Abbott ID NOW) or Xpert Xpress SARS-CoV-2 (Cepheid) (GeneXpert) tests comparing to conventional RT-PCR results. The negative predictive value is 99.8%(3 false negatives out of 1,964 tests) using a cut-off CT value of 40. Using a cut-off of RT-PCR CT value of 30 (predicting infectivity), the negative predictive value is reduced to 99.9% (1 out of 1,964 tests). With these results, we feel confident to recommend the immediate use of the rapid PCR tests alone and to use conventional RT-PCR for confirmation testing after.

  🖺 Full Text HTML: Excellent negative predictive value (99.8%) of two rapid molecular COVID-19 tests compared to conventional RT-PCR for SARS-CoV-2 (COVID-19) in 2,011 tests performed in a single centre.
• Role of physiotherapy team in critically ill COVID-19 patients pronation: can a multidisciplinary management reduce the complications rate? -

  Objectives: During the pandemic, critically ill COVID-19 patients9 management presented an increased workload for Intensive Care Unit (ICU) nursing staff, particularly during pronation maneuvers, with high risk of complications. In this scenario, a support during pronation by the ICU Physiotherapy Team was introduced. Research methodology: Retrospective analysis. Consecutive critically ill COVID-19 patients. Setting: A COVID-19 Center in southern Switzerland, between March 16th and April 30th, 2020. Main Outcome Measures: Rates and characteristics of pronation-related complications. Results: Forty-two patients on mechanical ventilation (MV) were treated; 296 standard prone/supine positioning were performed, with 3.52 cycles/patient. One (0.3%) major complication was observed, while fourteen (33.3%) patients developed minor complications, e.g. pressure injuries. The incidence of pressure sores was related to ICU length-of-stay (LOS) (p = 0.029) and MV days (p = 0.015), while their number (n = 27) further correlated with ICU LOS (p = 0.001) and MV days (p = 0.001). The propensity matching score analysis did not show any protective factor of pronation regarding pressure injuries (p = 0.448). No other significant correlation was found. Conclusion: The specific pronation team determined a low rate of major complications in critically ill COVID19 patients. The high rate of minor complications appeared to be related to disease severity, rather than from pronation.

  🖺 Full Text HTML: Role of physiotherapy team in critically ill COVID-19 patients pronation: can a multidisciplinary management reduce the complications rate?
• Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States -

  The SARS-CoV-2 variant of concern B.1.617.2 displaced B.1.1.7 as the dominant variant in England and other countries. This study aimed to determine whether B.1.617.2 was also displacing B.1.1.7 in the United States. We analyzed PCR testing results and viral sequencing results of samples collected across the United States, and showed that B.1.1.7 was rapidly being displaced and is no longer responsible for the majority of new cases. The percentage of SARS-CoV-2 positive cases that are B.1.1.7 dropped from 70% in April 2021 to 42% in just 6 weeks. Our analysis showed rapid growth of variants B.1.617.2 and P.1 as the primary drivers for this displacement. Currently, the growth rate of B.1.617.2 was higher than P.1 in the US (0.61 vs. 0.22), which is consistent with reports from other countries. Lastly, we showed that B.1.617.2 was growing faster in counties with a lower vaccination rate.

  🖺 Full Text HTML: Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States
• Determining a novel feature-space for SARS-CoV-2 sequence data -
  The pandemicity & the ability of the SARS-COV-2 to reinfect a cured subject, among other damaging characteristics of it, took everybody by surprise. A global collaborative scientific effort was direly required to bring learned people from different niches of medicine & data science together. Such a platform was provided by COVID19 Virtual BioHackathon, organized from the 5th to the 11th of April, 2020, to ponder on the related pressing issues varying in their diversity from text mining to genomics. Under the “Machine learning” track, we determined optimal k-mer length for feature extraction, constructed continuous distributed representations for protein sequences to create phylogenetic trees in an alignment-free manner, and clustered predicted MHC class I and II binding affinity to aid in vaccine design. All the related work in available in a Github repository under an MIT license for future research.
  🖺 Full Text HTML: Determining a novel feature-space for SARS-CoV-2 sequence data
• Book Review of “Implementation of Online Learning in The Era of Covid-19” -
  Online learning is implemented during Covid-19 era to reduce the risk of transmission to the community. Online learning is carried out not only in Indonesia, but also in various other countries. Online Learning does not only provide advantages and benefits but also there are some risk, impacts and obstacles faced during online learning. The implementation of online learning also has factors that support success in implementing it.
  🖺 Full Text HTML: Book Review of “Implementation of Online Learning in The Era of Covid-19”

From Clinical Trials

• Ivermectin Treatment Efficacy in Covid-19 High Risk Patients - Condition:   COVID-19
  Intervention:   Drug: Ivermectin 0.4mg/kg/day for 5 days
  Sponsor:   Clinical Research Centre, Malaysia
  Recruiting

• MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MP1032;   Drug: Placebo
  Sponsors:   MetrioPharm AG;   Syneos Health, LLC
  Not yet recruiting

• Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: XAV-19;   Drug: Placebo
  Sponsor:   Xenothera SAS
  Recruiting

• Study of Codivir in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: One Step Test;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: RT-PCR SARS-CoV-2;   Diagnostic Test: Screening blood test;   Diagnostic Test: ECG;   Diagnostic Test: Medical evaluation;   Diagnostic Test: NEWS-2 score;   Diagnostic Test: WHO score
  Sponsors:   Code Pharma;   Zion Medical
  Active, not recruiting

• In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection - Condition:   COVID-19
  Intervention:   Drug: tPA
  Sponsor:   Grupo Mexicano para el Estudio de la Medicina Intensiva
  Completed

• Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition:   COVID-19 Virus Disease
  Interventions:   Biological: MAD0004J08;   Other: Placebo
  Sponsors:   Toscana Life Sciences Sviluppo s.r.l.;   Cross Research S.A.
  Active, not recruiting

• Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Vitamin C;   Drug: N-acetylcysteine (NAC);   Drug: NAC + Bromhexine (BMX)
  Sponsors:   Universidade Federal do Ceara;   Paulista School of Medicine-EPM, UNIFESP;   Health Surveillance Secretariat - SVS;   Central Laboratory of Public Health of Ceara - LACEN-CE;   Leonardo da Vinci Hospital - HLV;   São José Hospital for Infectious Diseases - HSJ;   Ceará Health Secretariat - SESA;   Municipal Health Secretary - SMS-Fortaleza
  Not yet recruiting

• Augmentation of Immune Response to COVID-19 mRNA Vaccination Through OMT With Lymphatic Pumps - Condition:   Covid19
  Intervention:   Other: Osteopathic Manipulative Treatment (OMT)
  Sponsors:   Western University of Health Sciences;   American College of Osteopathic Physicians;   American Osteopathic Foundation;   Osteopathic Physicians and Surgeons of California;   Xavier-Nichols Foundation
  Recruiting

• Nervous System Symptoms Associated With COVID 19 - Condition:   Covid19
  Interventions:   Other: NEURO +;   Other: NEURO -
  Sponsor:   University Hospital, Toulouse
  Completed

• Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
  Sponsor:   Peking Union Medical College Hospital
  Recruiting

• Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test - Condition:   Covid-19 Testing
  Intervention:   Diagnostic Test: Biozek Covid-19 Antigen Rapid Test (Saliva)
  Sponsor:   Mach-E B.V.
  Recruiting

• Community-based Post-exposure Prophylaxis for COVID-19 - Condition:   Covid19
  Interventions:   Other: Guduchi Ghanvati;   Other: Standard guidelines
  Sponsors:   NMP Medical Research Institute;   Aarogyam UK;   Dr. Sarvepalli Radhakrishnan Rajasthan Ayurved University;   Samta Ayurveda Prakoshtha, India;   Padmanabhama Ayurveda Hospital and Research Centre
  Completed

• Vitamin A Supplementation in Children With Moderate to Severe COVID-19 - Condition:   Covid19
  Intervention:   Dietary Supplement: Vitamin A supplement
  Sponsor:   Shiraz University of Medical Sciences
  Not yet recruiting

• Cerebral Autoregulation and COVID-19 - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   COVID-19 Pneumonia
  Intervention:   Other: NIRS (Near-Infrared Spectroscopy)
  Sponsor:   University of Athens
  Not yet recruiting

• Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19 - Condition:   Covid19
  Interventions:   Drug: Favipiravir;   Drug: Nitazoxanide;   Other: Nitazoxanide Placebo
  Sponsors:   Coordinación de Investigación en Salud, Mexico;   University College, London;   Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV);   Universidad Autonoma de Guadalajara;   Siegfried Rhein S.A. de C.V.;   Strides Pharma Science Limited;   Hakken Enterprise
  Not yet recruiting

From PubMed

• SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals - Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy…

• Design of optical cavity for air sanification through ultraviolet germicidal irradiation - The transmission of airborne pathogens represents a major threat to worldwide public health. Ultraviolet light irradiation can contribute to the sanification of air to reduce the pathogen transmission. We have designed a compact filter for airborne pathogen inactivation by means of UVC LED sources, whose effective irradiance is enhanced thanks to high reflective surfaces. We used ray-tracing and computational fluid dynamic simulations to model the device and to maximize the performance inside…

• Coronaviruses, cholesterol and statins: Involvement and application for Covid-19 - The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can…

• Potential for the Repurposing of Adamantane Antivirals for COVID-19 - Several adamantanes have established actions against coronaviruses. Amantadine, rimantadine, bananins and the structurally related memantine are effective against human respiratory coronavirus HCoV-OC43, bovine coronavirus and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and a spiroadamantane amine is effective against the coronavirus strain 229E. Molecular docking studies suggest that amantadine may block the viral E protein channel, leading to impaired viral propagation….

• Virtual screenings of the bioactive constituents of tea, prickly chaff, catechu, lemon, black pepper, and synthetic compounds with the main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE 2) of SARS-CoV-2 - CONCLUSION: Therefore, the selected compounds could be considered a potential herbal treatment source against SARS-CoV-2.

• Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies - Bruton’s tyrosine kinase (BTK) was discovered due to its importance in B cell development, and it has a critical role in signal transduction downstream of the B cell receptor (BCR). Targeting of BTK with small molecule inhibitors has proven to be efficacious in several B cell malignancies. Interestingly, recent studies reveal increased BTK protein expression in circulating resting B cells of patients with systemic autoimmune disease (AID) compared with healthy controls. Moreover, BTK…

• Exploring the Psychological Effects of COVID-19 Home Confinement in China: A Psycho-Linguistic Analysis on Weibo Data Pool - CONCLUSION: Home confinement caused a decline in the use of positive emotion words. This indicates that home confinement can increase the frequency of negative emotions. The changes of exclusion words and inhibition words in high-endemic areas may be related to the high epidemic threat and the urgent need for social distancing in these areas.

• Discovery of New Potent anti-MERS CoV Fusion Inhibitors - Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong…

• “Surfactants - compounds for inactivation of SARS-CoV-2 and other enveloped viruses” - We provide here a general view on the interactions of surfactants with viruses, with a particular emphasis on how such interactions can be controlled and employed, for inhibiting the infectivity of enveloped viruses, including coronaviruses. The aim is to provide to interested scientists from different fields, including chemistry, physics, biochemistry, and medicine, an overview over the basic properties of surfactants and (corona)viruses, which are relevant to understanding the interactions…

• COVID-19: In silico identification of potent alpha-ketoamide inhibitors targeting the main protease of the SARS-CoV-2 - The COVID-19 has been creating a global crisis, causing countless deaths and unbearable panic. Despite the progress made in the development of the vaccine, there is an urge need for the discovery of antivirals that may better work at different stages of SARS-CoV-2 reproduction. The main protease (M^(pro)) of the SARS-CoV-2 is a crucial therapeutic target due to its critical function in virus replication. The α-ketoamide derivatives represent an important class of inhibitors against the M^(pro)…

• Fragment-based in silico design of SARS CoV-2 main protease inhibitors - 3CLpro is essential for SARS-CoV-2 replication and infection; its inhibition using small molecules is a potential therapeutic strategy. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. All small molecules co-crystallized with SARS-CoV-2 3CLpro with structures deposited in the Protein Data Bank were used as inputs. Fragments sitting in the binding pocket (87) were grouped into eight…

• Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors - The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic coronavirus disease (COVID-19), but no specific antiviral drug has been proven effective for controlling this pandemic to date. In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors. After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized,…

• Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial - BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.

• TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous…

• From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions - Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix. HS interacts with numerous proteins to mediate a vast array of biological and pathological processes. Inhibition of HS-protein interactions is thus an attractive approach for new therapeutic development for cancer and infectious diseases, including COVID-19; however, synthesis of well-defined native HS oligosaccharides remains challenging. This has aroused…

From Patent Search

• SARS-CoV-2 anti-viral therapeutic - - link

• 폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link

• COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19 - - link

• METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link

• Erweiterbare Desinfektionsvorrichtung -

  Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.

• link

• Einfache Sterilisationsvorrichtung -

  Einfache Sterilisationsvorrichtung, mit einem Hauptkörper (11), der in Längsrichtung einen ersten Plattenabschnitt (111) und in Querrichtung einen zweiten Plattenabschnitt (112) aufweist, wobei der erste Plattenabschnitt (111) und der zweite Plattenabschnitt (112) L-förmig miteinander verbunden sind; und einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist.

• link

• Klemmarme aufweisende Desinfektionsvorrichtung -

  Klemmarme aufweisende Desinfektionsvorrichtung, umfassend: einen Hauptkörper; eine Desinfektionslampe, die im Hauptkörper angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; einen Klemmabschnitt, der auf einer Seite des Hauptkörpers angeordnet ist, wobei der Klemmabschnitt zwei gegenüberliegende Greifbacken umfasst, wobei mindestens eine der beiden Greifbacken mit einer Schwenkachse versehen ist, wobei ein Klemmraum durch passgenaues Schließen der beiden Greifbacken entsteht und die beiden Greifbacken jeweils mit einem Durchgangsloch versehen sind; einen Befestigungsabschnitt, der durch die Durchgangslöcher der beiden Greifbacken hindurchgeführt ist;und ein Schild, das auf einer Seite des Klemmabschnitts angeordnet und mit einem Aufnahmeloch versehen ist.

• link

• Aufhängbare Sterilisationsvorrichtung -

  Aufhängbare Sterilisationsvorrichtung, mit einem Hauptkörper (11); einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist; einem Klemmabschnitt (13), der an einer Seite des Hautpkörpers (11) angeordnet ist und zwei gegenüberliegend angeordnete Klemmbacken (131) aufweist, wobei mindestens eine der beiden Klemmbacken (131) mit einem Achsbolzen (132) versehen ist, wobei die beiden Klemmbacken (131) beim Schließen einen Klemmraum (134) bilden, und wobei die beiden Klemmbacken (131) jeweils mit einem Durchgangsloch (135) versehen sind; und einem Befestigungselement (14), das durch die Durchgangslöcher (135) der beiden Klemmbacken (131) hindurchgeführt wird.

• link

• Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung -

  Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung, umfassend: einen Hauptkörper, der eine erste Oberfläche, eine von der ersten Oberfläche abgewandte zweite Oberfläche und ein Aufnahmeloch aufweist, wobei die zwei Seiten des Hauptkörpers jeweils mit einem Durchgangsloch versehen sind, wobei die Durchgangslöcher mit dem Aufnahmeloch durchgängig verbunden sind; eine Desinfektionslampe, die auf der zweiten Oberfläche des Hauptkörpers angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; und ein Befestigungsteil, das durch die Durchgangslöcher und das Aufnahmeloch des Hauptkörpers hindurchgeführt ist.

• link

• IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link