Covid-19 Sentry

Contents

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

From Preprints

• Excess Mortality probably due to COVID-19 in Tokyo, Japan between August and October, 2020 -

  Background: As of March, 2021, the COVID-19 outbreak has been record the highest peak in the end of December, 2020. Nevertheless, no remarkable excess mortality attributable to COVID-19 has been observed. Object: We sought to quantify excess mortality in April using the National Institute of Infectious Diseases (NIID) model. Method: We applied the NIID model to deaths of all causes from 1987 up through January, 2021 for the whole of Japan and up through October for Tokyo. Results: Results in Japan show very few excess mortality in August and October, 2020 It was estimated as 12 and 104. Conversely, in Tokyo, 595 excess mortality was detected between August and Octoember, which was 3.1% and 1.7% of baseline. Discussion and Conclusion: We detected substantial excess mortality in Tokyo but a few in Japan. It might be important to continue to monitor excess mortality of COVID-19 carefully hereafter.

  🖺 Full Text HTML: Excess Mortality probably due to COVID-19 in Tokyo, Japan between August and October, 2020
• Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza -
  Infection of certain influenza viruses is triggered when its hemagglutinin (HA) is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, while the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R{downarrow} sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal -helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interact with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.
  🖺 Full Text HTML: Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza
• State anhedonia in young healthy adults: psychometric properties of the German Dimensional Anhedonia Rating Scale (DARS) and effects of the COVID-19 pandemic -
  Healthy reward processing is a complex interplay of several components. Recent self-report measures of anhedonia, the decrease or loss of hedonic capacity, take this complexity into account. The Dimensional Anhedonia Rating Scale (DARS) measures interest, motivation, effort and consummatory pleasure across four domains: hobbies, food/drink, social activities and sensory experiences. In the present cross-sectional survey study, we validated the German version of the DARS in a sample of 557 young healthy adults. Factor structure as well as convergent and divergent validity were assessed. As a secondary aim, we examined the effects of the COVID-19 pandemic on state anhedonia and depression severity. Our results suggest good convergent and divergent validity and high internal consistency of the German DARS. The original differentiation of four factors mapping onto the four domains was confirmed. We conclude that the DARS is a valid instrument to comprehensively assess state anhedonia in German samples. Future studies should further assess the utility of the German DARS in clinical contexts. In line with many previous reports, there were significantly higher levels of depressive symptoms during the pandemic. We found no indication that the COVID-19 pandemic affected state hedonic capacity.
  🖺 Full Text HTML: State anhedonia in young healthy adults: psychometric properties of the German Dimensional Anhedonia Rating Scale (DARS) and effects of the COVID-19 pandemic
• Why dexamethasone can reduce mortality rate among patients with viral infections -
  As an anti-inflammatory hormone, dexamethasone may minimize proton buildup and down-regulate the production of oxalate. The reduced generation of insoluble and stiff calcium oxalate might account for the substantial drop of mortality rates by dexamethasone amid the current COVID-19 pandemic.
  🖺 Full Text HTML: Why dexamethasone can reduce mortality rate among patients with viral infections
• Estimating the increased transmissibility of the B.1.1.7 strain over previously circulating strains in England using fractions of GISAID sequences and the distribution of serial intervals -

  The B.1.1.7 strain, a variant strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is thought to have higher transmissibility than previously circulating strains in England. The fraction of the B.1.1.7 strain among SARS-CoV-2 viruses in England have grown rapidly. In this paper, we propose a method to estimate the selective advantage of a mutant strain over previously circulating strains using the time course of the fraction of B.1.1.7 strains. Our approach is based on the Maynard Smith9s model of allele frequencies in adaptive evolution, which assumes that the selective advantage of a mutant strain over previously circulating strains is constant over time. Applying this method to the sequence data in England using serial intervals of COVID-19, we found that the transmissibility of the B.1.1.7 strain is 40% (with a 95% confidence interval (CI) from 40% to 41%) higher than previously circulating strains in England. The date of the emergence of B.1.1.7 strains in England was estimated to be September 20, 2020 with its 95% CI from September 11 to September 20, 2020. The result indicated that the control measure against the B.1.1.7 strain needs to be strengthened by 40% from that against previously circulating strains. To get the same control effect, contact rates between individuals need to be restricted to 0.71 of the contact rates that have been achieved form the control measure taken for previously circulating strains.

  🖺 Full Text HTML: Estimating the increased transmissibility of the B.1.1.7 strain over previously circulating strains in England using fractions of GISAID sequences and the distribution of serial intervals
• Target Capture Sequencing of SARS-CoV-2 Genomes Using the ONETest Coronaviruses Plus -
  Background Genomic sequencing is important to track and monitor genetic changes in SARS-CoV-2. We introduce a target capture next-generation sequencing methodology, the ONETest Coronaviruses Plus, to sequence SARS-CoV-2 genomes and select genes of other respiratory viruses simultaneously. Methods We applied the ONETest on 70 respiratory samples (collected in Florida, USA between May and July, 2020), in which SARS-CoV-2 had been detected by a qualitative PCR assay. For 48 (69%) of the samples, we also applied the ARTIC protocol for Illumina sequencing. All the libraries were sequenced as 2x150 nucleotide reads on an Illumina instrument. The ONETest data were analyzed using an in-house pipeline and the ARTIC data using a published pipeline to produce consensus SARS-CoV-2 genome sequences, to which lineages were assigned using pangolin. Results Of the 70 ONETest libraries, 45 (64%) had a complete or near-complete SARS-CoV-2 genome sequence (> 29,000 bases and with > 90% of its bases covered by at least 10 reads). Of the 48 ARTIC libraries, 25 (52%) had a complete or near-complete SARS-CoV-2 genome sequence. In 24 out of 34 (71%) samples in which both the ONETest and ARTIC sequences were complete or near-complete and in which lineage could be assigned to both the ONETest and ARTIC sequences, the SARS-CoV-2 lineage identified was the same. Conclusions The ONETest can be used to sequence the SARS-CoV-2 genomes in archived samples and thereby enable detection of circulating and emerging SARS-CoV-2 variants. Target capture approaches, such as the ONETest, are less prone to loss of sequence coverage probably due to amplicon dropouts encountered in amplicon approaches, such as ARTIC. With its added value of characterizing other major respiratory pathogens, although not assessed in this study, the ONETest can help to better understand the epidemiology of infectious respiratory disease in the post COVID-19 era.
  🖺 Full Text HTML: Target Capture Sequencing of SARS-CoV-2 Genomes Using the ONETest Coronaviruses Plus
• Large-scale population analysis of SARS-CoV-2 whole genome sequences reveals host-mediated viral evolution with emergence of mutations in the viral Spike protein associated with elevated mortality rates -

  Background We aimed to further characterize and analyze in depth intra-host variation and founder variants of SARS-CoV-2 worldwide up until August 2020, by examining in excess of 94,000 SARS-CoV-2 viral sequences in order to understand SARS-CoV-2 variant evolution, how these variants arose and identify any increased mortality associated with these variants. Methods and Findings We combined worldwide sequencing data from GISAID and Sequence Read Archive (SRA) repositories and discovered SARS-CoV-2 hypermutation occurring in less than 2% of COVID19 patients, likely caused by host mechanisms involved APOBEC3G complexes and intra-host microdiversity. Most of this intra-host variation occurring in SARS-CoV-2 are predicted to change viral proteins with defined variant signatures, demonstrating that SARS-CoV-2 can be actively shaped by the host immune system to varying degrees. At the global population level, several SARS-CoV-2 proteins such as Nsp2, 3C-like proteinase, ORF3a and ORF8 are under active evolution, as evidenced by their increased πN/πS ratios per geographical region. Importantly, two emergent variants: V1176F in co-occurrence with D614G mutation in the viral Spike protein, and S477N, located in the Receptor Binding Domain (RBD) of the Spike protein, are associated with high fatality rates and are increasingly spreading throughout the world. The S477N variant arose quickly in Australia and experimental data support that this variant increases Spike protein fitness and its binding to ACE2. Conclusions SARS-CoV-2 is evolving non-randomly, and human hosts shape emergent variants with positive fitness that can easily spread into the population. We propose that V1776F and S477N variants occurring in the Spike protein are two novel mutations occurring in SARS-CoV-2 and may pose significant public health concerns in the future.

  🖺 Full Text HTML: Large-scale population analysis of SARS-CoV-2 whole genome sequences reveals host-mediated viral evolution with emergence of mutations in the viral Spike protein associated with elevated mortality rates
• Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants -
  Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.
  🖺 Full Text HTML: Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants
• Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses -
  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease.
  🖺 Full Text HTML: Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses
• Genomic surveillance and phylodynamic analyses reveal emergence of novel mutation and co-mutation patterns within SARS-CoV2 variants prevalent in India -
  Emergence of distinct viral clades has been observed in SARS-CoV2 variants across the world and India. Identification of the genomic diversity and the phylodynamic profiles of the prevalent strains of the country are critical to understand the evolution and spread of the variants. We performed whole-genome sequencing of 54 SARS-CoV2 strains collected from COVID-19 patients in Kolkata, West Bengal during August to October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad available in GISAID database. Spatio-temporal evolutionary dynamics of the pathogen across various regions and states of India over three different time periods in the year 2020 were analyzed. We estimated the clade dynamics of the Indian strains and compared the clade specific mutations and the co-mutation patterns across states and union territories of India over the time course. We observed that GR, GH and G (GISAID) or 20B and 20A (Nextstrain) clades were the prevalent clades in India during middle and later half of the year 2020. However, frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating emergence of newer mutations in the viral population prevailing in the country. Further, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested within the Indian patients.
  🖺 Full Text HTML: Genomic surveillance and phylodynamic analyses reveal emergence of novel mutation and co-mutation patterns within SARS-CoV2 variants prevalent in India
• Freely accessible ready to use global infrastructure for SARS-CoV-2 monitoring -
  The COVID-19 pandemic is the first global health crisis to occur in the age of big genomic data. Although data generation capacity is well established and sufficiently standardized, analytical capacity is not. To establish analytical capacity it is necessary to pull together global computational resources and deliver the best open source tools and analysis workflows within a ready to use, universally accessible resource. Such a resource should not be controlled by a single research group, institution, or country. Instead it should be maintained by a community of users and developers who ensure that the system remains operational and populated with current tools. A community is also essential for facilitating the types of discourse needed to establish best analytical practices. Bringing together public computational research infrastructure from the USA, Europe, and Australia, we developed a distributed data analysis platform that accomplishes these goals. It is immediately accessible to anyone in the world and is designed for the analysis of rapidly growing collections of deep sequencing datasets. We demonstrate its utility by detecting allelic variants in high-quality existing SARS-CoV-2 sequencing datasets and by continuous reanalysis of COG-UK data. All workflows, data, and documentation is available at https://covid19.galaxyproject.org.
  🖺 Full Text HTML: Freely accessible ready to use global infrastructure for SARS-CoV-2 monitoring
• Essential Emergency and Critical Care - a consensus among global clinical experts -

  Background Globally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients can be overlooked in health systems. Essential and Emergency Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low-cost and low-complexity for the identification and timely treatment of critically ill patients across all medical specialities. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19. Methods A Delphi process was conducted to seek consensus (>90% agreement) among a diverse panel of global clinical experts. The panel was asked to iteratively rate proposed treatments and actions based on previous guidelines and the WHO Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent, user-friendly, and feasible EECC package of clinical processes plus a list of hospital resource requirements. Results The 272 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 hospital readiness requirements. The essential diagnosis-specific care of critically ill COVID-19 patients has an additional 7 clinical processes and 9 hospital readiness requirements. Conclusion The study has specified the content of the essential emergency and critical care that should be provided to all critically ill patients. Implementation of EECC could be an effective strategy to reduce preventable deaths worldwide. As critically ill patients have high mortality rates in all hospital settings, especially where trained staff or resources are limited, even small improvements would have a large impact on survival. EECC has a vital role in the effective scale-up of oxygen and other care for critically ill patients in the COVID-19 pandemic. Policy makers should prioritise EECC, increase its coverage in hospitals, and include EECC as a component of universal health coverage.

  🖺 Full Text HTML: Essential Emergency and Critical Care - a consensus among global clinical experts
• COVID-19 symptom frequency comparison: non-hospitalised positively and negatively tested persons with flu-like symptoms in Austria -

  Background. The majority of clinical studies reporting on COVID-19 symptom frequencies focus on patients already hospitalized. Thus, reported symptom frequencies may not be applicable to the general population. Here we report COVID-19 symptom frequencies for the general population in a major European city. Methods. During a scientific collaboration between the Vienna Social Fund (FSW, Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the AI-biotech company Symptoma we recorded symptom frequencies gathered by the COVID-19 chatbot of the city government of Vienna and corresponding SARS-CoV-2 nucleic acid amplification test (NAAT) results. Chatbot users answered 13 yes/no questions about symptoms and provided information about age and sex. Subsequently a medically trained professional came to their address to take a sample and NAAT results were obtained. Findings. Between November 2 and January 5, a total of 3011 persons experiencing flu-like symptoms had completed the chatbot-session and were subsequently tested by a NAAT. NAATs were performed by at home visitations of medical professionals. NAAT analysis was positive in 816 persons (27.1%). We compared the symptom frequencies between COVID-19 positive and negative users, and between male and female users. The symptoms (sorted by frequency) of users with positive NAATs were malaise (81.1%), fatigue (72.9%), headache (64.1%), cough (57.7%), fever (50.7%), sore throat (40.7%), rhinorrhea (31.0%), sneezing (28.4%), dysgeusia (27.1%), hyposmia (26.5%), dyspnea (11.4%) and diarrhea (10.9%) while 34.9% reported a close contact with a COVID-19 case. Among these the frequencies of cough, fever, hyposmia, dysgeusia, malaise, headache, close contact with COVID-19 case and fatigue were significantly (P < 0.01) increased in COVID-19 positive persons while the frequencies of dyspnea, diarrhea and sore throat were significantly (P < 0.01) decreased in COVID-19 positive persons. There was no significant difference for rhinorrhea and sneezing.

  🖺 Full Text HTML: COVID-19 symptom frequency comparison: non-hospitalised positively and negatively tested persons with flu-like symptoms in Austria
• Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor -
  The association of the receptor binding domain (RBD) of SARS-CoV-2 viral spike with human angiotensin converting enzyme (hACE2) represents the first required step for viral entry. Amino acid changes in the RBD have been implicated with increased infectivity and potential for immune evasion. Reliably predicting the effect of amino acid changes in the ability of the RBD to interact more strongly with the hACE2 receptor can help assess the public health implications and the potential for spillover and adaptation into other animals. Here, we introduce a two-step framework that first relies on 48 independent 4-ns molecular dynamics (MD) trajectories of RBD-hACE2 variants to collect binding energy terms decomposed into Coulombic, covalent, van der Waals, lipophilic, generalized Born electrostatic solvation, hydrogen-bonding, {pi}-{pi} packing and self-contact correction terms. The second step implements a neural network to classify and quantitatively predict binding affinity using the decomposed energy terms as descriptors. The computational base achieves an accuracy of 82.2% in terms of correctly classifying single amino-acid substitution variants of the RBD as worsening or improving binding affinity for hACE2 and a correlation coefficient r of 0.69 between predicted and experimentally calculated binding affinities. Both metrics are calculated using a 5-fold cross validation test. Our method thus sets up a framework for effectively screening binding affinity change with unknown single and multiple amino-acid changes. This can be a very valuable tool to predict host adaptation and zoonotic spillover of current and future SARS-CoV-2 variants.
  🖺 Full Text HTML: Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor
• The Role of Testing Availability on Intentions to Isolate during the COVID-19 Pandemic - A Randomized Trial -

  Background: Little information exists on how COVID-19 testing availability influences intentions to engage in risky behavior. Understanding the behavioral effects of testing availability may provide insight into the role of adequate testing on controlling viral transmission. Objective: To evaluate the impact of testing availability on behavioral intention to self-isolate in a simulated scenario with participants who have been clinically diagnosed with COVID-19. Methods: A total of 1400 participants were recruited from Amazon Mechanical Turk (MTurk) through a national, online, opt-in survey. Participants were randomized to one of three hypothetical scenarios. Each scenario asked participants to imagine having symptoms consistent with COVID-19 along with a clinical diagnosis from their physician. However, scenarios differed in their testing result: testing unavailable, positive test, or negative test. The primary outcome was intention to engage in high-risk COVID-19 behaviors, measured using an 11-item mean score (range 1-7) that was pre-registered prior to data collection. The randomized survey was conducted between July 23rd to July 29th, 2020. Results: Out of 1194 respondents (41.6% male, 58.4% female) with a median age of 38.5 years, participants who had no testing available in their clinical scenario showed significantly greater intentions to engage in behavior facilitating COVID-19 transmission compared to those who received a positive confirmatory test result scenario (difference (SE): 0.14 (0.06), P=0.016), equating to an 11.1% increase in mean score risky behavior intentions. Intention to engage in behaviors that can spread COVID-19 were also positively associated with male gender, poor health status, and Republican party affiliation. Conclusion: Testing availability appears to play an independent role in influencing behaviors facilitating COVID-19 transmission. Such findings shed light on the possible negative externalities of testing unavailability.

  🖺 Full Text HTML: The Role of Testing Availability on Intentions to Isolate during the COVID-19 Pandemic - A Randomized Trial

From Clinical Trials

• Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Xuanfei Baidu Granules;   Other: Placebo
  Sponsor:   Darcy Spicer
  Recruiting

• Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19 - Condition:   Covid19
  Interventions:   Drug: Emricasan;   Other: Placebo
  Sponsor:   Histogen
  Recruiting

• Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma - Condition:   Covid19
  Interventions:   Other: Convalescent Plasma with antibody against SARS-CoV-2.;   Other: Standard treatment for COVID-19
  Sponsors:   Hospital Son Llatzer;   Fundació d’investigació Sanitària de les Illes Balears
  Recruiting

• SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition:   Covid19
  Intervention:   Diagnostic Test: Anti-SARS-CoV2 Serology
  Sponsor:   Université de Reims Champagne-Ardenne
  Completed

• ANTIcoagulation in Severe COVID-19 Patients - Condition:   Severe COVID-19 Pneumonia
  Interventions:   Drug: Tinzaparin, Low dose prophylactic anticoagulation;   Drug: Tinzaparin, High dose prophylactic anticoagulation;   Drug: Tinzaparin,Therapeutic anticoagulation
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Neuromodulation in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Device: Transcranial direct-current stimulation;   Device: Sham Transcranial direct-current stimulation
  Sponsors:   D’Or Institute for Research and Education;   Rio de Janeiro State Research Supporting Foundation (FAPERJ);   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition:   COVID-19
  Interventions:   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd
  Recruiting

• Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19 - Condition:   Covid19
  Interventions:   Biological: KDS-1000;   Other: Placebo
  Sponsor:   Kiadis Pharma
  Not yet recruiting

• A Study to Assess if a Medicine Called Bamlanivimab is Safe and Effective in Reducing Hospitalization Due to COVID-19 - Condition:   Covid19
  Interventions:   Biological: Bamlanivimab;   Other: Standard of Care
  Sponsors:   Fraser Health;   Fraser Health Authrority Department of Evaluation and Research Services;   Surrey Memorial Hospital Clinical Research Unit;   Centre for Health Evaluation and Outcome Sciences;   Surrey Hospitals Foundation;   BC Support Unit;   University of British Columbia;   Ministry of Health, British Columbia
  Not yet recruiting

• Effects of Telerehabilitation After Discharge in COVID-19 Survivors - Condition:   Covid19
  Intervention:   Other: Telerehabilitation
  Sponsor:   Hacettepe University
  Recruiting

• Corticosteroids for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Prednisone;   Device: Point of Care testing device for C-reactive protein
  Sponsor:   University of Alberta
  Not yet recruiting

• Post COVID-19 Syndrome and the Gut-lung Axis - Condition:   Covid19
  Interventions:   Dietary Supplement: Omni-Biotic Pro Vi 5;   Dietary Supplement: Placebo
  Sponsors:   Medical University of Graz;   CBmed Ges.m.b.H.
  Not yet recruiting

• Covid-19 Vaccination in Adolescents - Condition:   Covid19
  Interventions:   Biological: Tozinameran;   Biological: Oxford-AstraZeneca COVID-19 vaccine;   Biological: CoronaVac
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• Efficacy of Adaptogens in Patients With Long COVID-19 - Condition:   Covid19
  Interventions:   Dietary Supplement: ADAPT-232 oral solution;   Other: Placebo oral solution
  Sponsors:   Swedish Herbal Institute AB;   National Family Medicine Training Centre, Georgia;   Tbilisi State Medical University;   Phytomed AB
  Not yet recruiting

• Improved Oxygen Therapy in Covid-19 - Condition:   Covid19
  Intervention:   Other: oxygen mask
  Sponsor:   Region Skane
  Recruiting

From PubMed

• A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase - The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several…

• Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment - CONCLUSIONS: Our study established Drosophila as a model for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the potential of Selinexor for inhibiting Orf6 toxicity using an in vivo animal model system.

• Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor - CONCLUSIONS: Our study revealed Orf6 as a highly pathogenic protein from the SARS-CoV-2 genome, identified its key host interacting proteins, and Selinexor as a drug candidate for directly targeting Orf6 host protein interaction that leads to cytotoxicity.

• An overview of some potential immunotherapeutic options against COVID-19 - After the advent of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in the late 2019, the resulting severe and pernicious syndrome (COVID-19) immediately was deployed all around the world. To date, despite relentless efforts to control the disease by drug repurposing, there is no approved specific therapy for COVID-19. Given the role of innate and acquired immune components in the control and elimination of viral infections and inflammatory mutilations during SARS-CoV2…

• Sarbecovirus ORF6 proteins hamper induction of interferon signaling - The presence of an ORF6 gene distinguishes sarbecoviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 from other betacoronaviruses. Here we show that ORF6 inhibits induction of innate immune signaling, including upregulation of type I interferon (IFN) upon viral infection as well as type I and III IFN signaling. Intriguingly, ORF6 proteins from SARS-CoV-2 lineages are more efficient antagonists of innate immunity than their orthologs from SARS-CoV lineages….

• In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase - Since the outbreak emerged in November 2019, no effective drug has yet been found against SARS-CoV-2. Repositioning studies of existing drug molecules or candidates are gaining in overcoming COVID-19. Antiviral drugs such as remdesivir, favipiravir, ribavirin, and galidesivir act by inhibiting the vital RNA polymerase of SARS-CoV-2. The importance of in silico studies in repurposing drug research is gradually increasing during the COVID-19 process. The present study found that especially…

• High-dose ACEi might be harmful in COVID-19 patients with serious respiratory distress syndrome by leading to excessive bradykinin receptor activation - PURPOSE: We aimed to critically review the available information on the potential contribution of excessive kallikrein-kinin systems (KKSs) activation to severe respiratory inflammation in SARS-CoV-2 infection, and the likely consequence of ACE inhibition in seriously affected patients.

• Isatin-based virtual high throughput screening, molecular docking, DFT, QM/MM, MD and MM-PBSA study of novel inhibitors of SARS-CoV-2 main protease - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly growing health care emergency across the world. One of the viral proteases called main protease or Mpro, plays a crucial role in the replication of SARS-CoV-2. As the structure of Mpro of SARS-CoV-2 is similar to the Mpro of SARS-CoV-1 (responsible for SARS outbreak between 2002 and 2004), we hypothesize that the inhibitors of SARS-CoV-1 Mpro can also inhibit the Mpro of…

• Hydroxychloroquine Effects on TLR Signalling: Underexposed but Unneglectable in COVID-19 - The main basis for hydroxychloroquine (HCQ) treatment in COVID-19 is the compound’s ability to inhibit viral replication in vitro. HCQ also suppresses immunity, mainly by interference in TLR signalling, but reliable clinical data on the extent and nature of HCQ-induced immunosuppression are lacking. Here, we discuss the mechanistic basis for the use of HCQ against SARS-CoV-2 in a prophylactic setting and in a therapeutic setting, at different stages of the disease. We argue that the clinical…

• Inhibition of HECT E3 ligases as potential therapy for COVID-19 - SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we…

• Effectiveness and safety review of Chinese herbal sachets for external use in the treatment of COVID-19 pandemic: A protocol for systematic review and meta-analysis - CONCLUSION: This systematic review will provide evidence whether Chinese herbal sachets are effective and safe intervention of COVID-19 Pandemic.

• Heme oxygenase-1 inducer hemin does not inhibit SARS-CoV-2 virus infection - Antiviral agents with different mechanisms of action could induce synergistic effects against SARS-CoV-2 infection. Some reports suggest the therapeutic potential of the heme oxygenase-1 (HO-1) enzyme against virus infection. Given that hemin is a natural inducer of the HO-1 gene, the aim of this study was to develop an in vitro assay to analyze the antiviral potency of hemin against SARS-CoV-2 infection. A SARS-CoV-2 infectivity assay was conducted in Vero-E6 and Calu-3 epithelial cell lines….

• N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2 - The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an…

• Study on the mechanism of active components of Liupao tea on 3CL^pro based on HPLC-DAD fingerprint and molecular docking technique - Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were…

• Interleukin-6 Antagonists: Lessons From Cytokine Release Syndrome to the Therapeutic Application in Severe COVID-19 Infection - Current retrospective data have found up to 20% of COVID-19 infection had developed into severe cases with hyperinflammatory pulmonary symptoms. Interleukin 6 (IL-6) is recognized as a key mediator of hyperinflammation previously mentioned in cytokine release syndrome. This leads to implementing IL-6 pathway inhibition in severe COVID-19. This review aimed to explore the clinical evidences of using IL-6 antagonists in COVID-19 infection based on most recent available data. Relevant studies were…

From Patent Search

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

• Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen -

  Ein Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen, umfassend: ein Bildschirmgerät, das einen Umfang hat; eine UV-Entkeimungslampe, die sich am Umfang des Bildschirmgeräts befindet; eine Stromquelle, die elektrisch mit der UV-Entkeimungslampe verbunden ist; eine Steuerschaltung, die elektrisch mit der UV-Entkeimungslampe verbunden ist; und eine Befestigungsvorrichtung, durch die die UV-Entkeimungslampe am Umfang des Bildschirmgeräts befestigbar ist, wobei die Befestigungsvorrichtung einen Sitzkörper, eine erste Klemmplatte und eine zweite Klemmplatte aufweist, wobei der Sitzkörper mit der UV-Entkeimungslampe versehen ist, wobei die erste Klemmplatte und die zweite Klemmplatte beabstandet am Sitzkörper gleitbar angeordnet sind, wodurch ein Klemmabstand zwischen der ersten Klemmplatte und der zweiten Klemmplatte besteht, wobei ein elastisches Element zwischen der zweiten Klemmplatte und dem Sitzkörper angeordnet ist, um die zweite Klemmplatte dazu zu zwingen, sich der ersten Klemmplatte zu nähern.

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• Schublade mit antiepidemischer Wirkung -

  Schublade mit antiepidemischer Wirkung, mit einem Schrank (1); mindestens einer Schublade (2), die in dem Schrank (1) angeordnet ist, wobei jede Schublade (2) einen Schubladenraum (25) aufweist; einer UV-Sterilisationsvorrichtung (3), die an der Schublade (2) angeordnet ist; einer Stromquelle (4), die elektrisch mit der UV-Sterilisationsvorrichtung (3) verbunden ist; einer Steuerschaltung (5), die elektrisch mit der Stromquelle (4) und der UV-Sterilisationsvorrichtung (3) verbunden ist; und einem Sensor (6), der elektrisch mit der Steuerschaltung (5) verbunden ist.

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• Gerät zur Unterstützung und Verstärkung natürlicher Lüftung -

  Lüftungssystem für einen mit öffnbaren Fenstern (16) ausgestatteten Gebäuderaum, gekennzeichnet dadurch, dass es ein Gehäuse (18) und einen Ventilator (20) aufweist, wobei durch das Gehäuse eine vom Ventilator erzeugte Luftströmung strömen kann, wobei das Gehäuse dafür eine Einströmöffnung (24) für Luft und eine Ausströmöffnung (22) für Luft enthält, wobei eine der beiden Öffnungen der Form eines Öffnungsspalts (26) zwischen einem Fensterflügel (12) und einem Blendrahmen (14) des Fensters (16) angepasst ist.

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• X射线图像识别方法、装置、计算机设备及存储介质 - 本申请涉及一种X射线图像识别方法、装置、计算机设备和存储介质。通过获取X射线图像，将X射线图像作为训练样本；构建多注意力交互网络，多注意力交互网络包括卷积批处理标准化网络、特征提取网络和输出网络；其中特征提取网络包括多注意力交互特征提取模块和批标准化模块，特征提取网络通过学习通道之间的相关性，多通道之间的信息交互来达到增强模型的识别能力。利用训练样本对多注意力交互网络进行训练，得到X射线图像识别模型；获取待测X射线图像；将待测X射线图像输入到X射线图像识别模型中，得到X射线图像的类别。本方法减少了网络的参数量和计算量，提高了模型的泛化能力。 - link

• 利用HEK293细胞制备新型冠状病毒核衣壳蛋白的方法 - 本发明提供一种利用HEK293细胞制备新型冠状病毒核衣壳蛋白的方法，包括：1）构建新冠病毒核衣壳蛋白（N蛋白）重组表达载体；2）用重组表达载体转染HEK293细胞；3）体外培养细胞，从培养上清中分离纯化N蛋白。利用HEK293表达系统可在短时间内获得大量新冠病毒N蛋白，通过一步亲和层析法可获得纯度高达98%以上的N蛋白。与大肠杆菌相比，采用HEK293表达系统制备的N蛋白在与抗体的结合活性及新冠抗体胶体金检测方面均表现出极大优势，且HEK293表达系统制备的N蛋白其蛋白空间构象接近于病毒N基因在宿主体内的蛋白表达构象，具有更高的免疫诊断和抗体制备的准确性，将其用于制作诊断试剂和疫苗前景广阔。 - link

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link