Covid-19 Sentry

Contents

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

From Preprints

• Accessibility, inclusivity, and implementation of COVID-19 clinical management guidelines early in the pandemic: a global survey -

  Background: With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found that most lacked methodological rigour, overlooked many at-risk populations, and had variations in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. The aim of this study was to evaluate access to, inclusivity of, and implementation of Covid-19 CMGs in different settings. Methods: A cross-sectional survey of clinicians worldwide from 15 June to 20 July 2020, to explore access to and implementation of Covid-19 CMGs and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs. were analyzed by geographic location. Results: Seventy-six clinicians, from 27 countries responded, 82% from high-income countries, 17% from low-middle income countries. Most respondents reported access to Covid-19 CMG and confidence in implementation of these. However, many respondents, particularly from LMICs reported barriers to implementation, including limited access to treatments and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women and 50% for older adults (>65 years). Themes emerging were for CMGs to include recommendations for different at-risk populations, and settings, include supportive care guidance, be readily updated as evidence emerges, and CMG implementation supported by training, and access to treatments recommended. Conclusion: Our findings highlight important gaps in Covid-19 CMG development and implementation challenges during a pandemic, particularly affecting different at-risk populations and lower resourced settings. The findings highlight a need for a new, harmonized evidence-based, that is inclusive and adaptable for different context, incorporating implementation support, to improve access in evidence-based care recommendations during an emergency.

  🖺 Full Text HTML: Accessibility, inclusivity, and implementation of COVID-19 clinical management guidelines early in the pandemic: a global survey
• Short-term antibody response and tolerability of one dose of BNT162b2 vaccine in patients receiving hemodialysis -

  Background: Patients with end-stage kidney disease receiving in-center hemodialysis are at high risk of exposed to, and dying from, SARS-CoV-2. As impairments in both humoral and cellular immunity are common in this population, their response to vaccination against SARS-CoV-2 is uncertain. Methods: We have followed in-center hemodialysis patients in the Réseau Rénal Québécois since March 2020 with serial PCRs for COVID-19 and clinical outcomes. Plasma samples were taken from 58 patients from one center before, and 4 weeks after, vaccination with one dose of the BNT162b2 mRNA vaccine. Anti-RBD (region binding domain of the SARS-CoV-2 Spike protein) IgG levels were measured using ELISA and compared to levels in 32 health care worker (HCW) controls, as well as levels in convalescent plasma taken from 12 hemodialysis patients 4-12 weeks after COVID-19 infection. Patients were stratified based on evidence of previous infection with COVID-19 (positive PCR or antiRBD detectable at baseline). Results: Compared with health-care workers, hemodialysis patients without prior COVID-19 exhibited significantly lower anti-RBD IgG levels 4 weeks after vaccination (p=0.0007). Anti-RBD IgG was non-detectable in 1/16 (6%) of HCWs, and 25/46 (54%) of dialysis patients (p=0.0008). In dialysis patients previously infected with COVID-19, mean anti-RBD levels were significantly lower than their HCW controls (p=0.0031), but not signficantly different than those in convalescent plasma of recently infected dialysis patients (p=NS). No patients reported any symptoms 7 days after vaccination on a standardized questionnaire. Conclusion: The BNT162b2 vaccine was well-tolerated in hemodialysis patients, but failed to elicit a humoral immune response in >50% patients by 4 weeks. Whether these patients develop antibodies or T-cell responses after prolonged observation requires further study. Until then, we recommend that rigorous infection prevention and control measures in the dialysis unit and outside of it be continued to prevent SARS-CoV-2 infection in this susceptible population.

  🖺 Full Text HTML: Short-term antibody response and tolerability of one dose of BNT162b2 vaccine in patients receiving hemodialysis
• Estimating the strength of selection for new SARS-CoV-2 variants -

  A challenge to controlling the SARS-CoV-2 pandemic is the ability of the virus to adapt to its new human hosts, with novel and more transmissible strains of the virus being continually identified. Yet there are no generally accepted methods to consistently estimate the relative magnitude of the change in transmissiblity of newly emerging variants. In this paper we consider three methods for examining and quantifying positive selection of new and emerging strains of SARS-CoV-2 over an existing wild-type strain. We consider replication at the level of countries and allow for the action of other processes that can change variants9 frequencies, specifically migration and drift. We apply these methods to the D614G spike mutation and the variant designated B.1.1.7, in every country where there is sufficient sequence data. For each of D614G and B.1.1.7, we find evidence for strong selection (greater than 25% increased contagiousness) in more than half of countries analyzed. Our results also shows that the selective advantages of these strains are highly heterogeneous at the country level, suggesting the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.

  🖺 Full Text HTML: Estimating the strength of selection for new SARS-CoV-2 variants
• Role of Immunity and Inflammation Mediators in Early COVID-19 Management: Genetic Results Interpretations Versus Real-life Practice. -
  Pairo-Castineira et al. have recently demonstrated that altered expression of certain genes related to the immune and inflammatory systems reduced the odds of severe COVID-19 and protected against it; we agree with their results from a clinical perspective. However, they have suggested some drugs, including barictinib, to be of priority to be tested basing on their results. We present a concise analysis of these results according to our real-life and academic experience that disagree with some of their recommendations from a clinical and pharmacovigilant point of view. Further, we confirm that the important results released Pairo-Castineira et al. confirm the validity to our recommended real-life used protocol using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin to manage COVID-19 patients.
  🖺 Full Text HTML: Role of Immunity and Inflammation Mediators in Early COVID-19 Management: Genetic Results Interpretations Versus Real-life Practice.
• Non-steroidal Anti-inflammatory Drugs (NSAIDs)/nitazoxanide/azithromycin Potential Beneficial COVID-19 Effects: Preventing the Cytokine Storm via Mitigation of the Interleukin-6 Amplifier and Monocytic Immunological Dysrhythmia. -
  Introduction Recent genetic results demonstrated the important role that mediators of immunity and inflammation are playing in COVID-19 pathogenesis and complications. Interestingly, a weak early interferon response to SARS CoV-2 infection was shown to trigger an exaggerated inflammatory response, to be noted that the unconstrained immunoinflammatory response is responsible for the COVID-19 associated mortality. Areas covered We present a concise analysis and interpretations of the mentioned genetic results that correlated COVID-19 with interferons and inflammatory genes and present our experience which disagrees with some described recommendations. Expert opinion Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response in our body as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs have been hypothesized and practiced by the author to prevent COVID-19 complications and mortality due to their ability to prevent, constrain or reverse COVID-19 associated dysregulated immuno-inflammatory response and to mitigate the formation of several inflammatory cytokines and pathways including interleukin-6 amplifier, as well as prevention or amelioration of described monocytic immunological dysrhythmia, both of which are known to be vital to develop the cytokine storm.
  🖺 Full Text HTML: Non-steroidal Anti-inflammatory Drugs (NSAIDs)/nitazoxanide/azithromycin Potential Beneficial COVID-19 Effects: Preventing the Cytokine Storm via Mitigation of the Interleukin-6 Amplifier and Monocytic Immunological Dysrhythmia.
• Linking Diabetes mellitus to SARS-CoV-2 infection through differential targeting of the microRNAs in the Pancreas tissue -
  Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. The plus-sense single-stranded RNA (+ssRNA) genome of the SARS-CoV-2 virus can be targeted and suppressed by the host cell’s microRNAs (miRNAs). Using the differential gene expression analysis between the mock-infected and the SARS-CoV-2-infected pancreatic tissue, we report five Diabetes-associated genes that are upregulated due to SARS-CoV-2 infection in the hESC pancreas tissues. Ten miRNAs regulating these five genes can potentially target the SARS-CoV-2 genome. We hypothesize that the SARS-CoV-2 genome copies in the infected human pancreas cell compete with the host cell native genes in being regulated by the native miRNAs. It leads to the reduced miRNA-regulation and, thus, the upregulation of the Diabetes-associated native genes. Thus, the resultant new-onset or elevated Diabetic symptoms may worsen the condition of COVID-19 patients.
  🖺 Full Text HTML: Linking Diabetes mellitus to SARS-CoV-2 infection through differential targeting of the microRNAs in the Pancreas tissue
• A spatial multi-scale fluorescence microscopy toolbox discloses entry checkpoints of SARS-CoV-2 variants in VeroE6 cells -
  We developed a multi-scale microscopy imaging toolbox to address some major issues related to SARS-CoV-2 interactions with host cells. Our approach harnesses both conventional and super-resolution fluorescence microscopy (Airyscan, STORM, and STED) and easily matches the spatial scale of single virus-cell checkpoints. We deployed this toolbox to characterize subtle issues related to the entry phase of SARS-CoV-2 variants in VeroE6 cells. Our results suggest that the variant of concern B.1.1.7, currently on the rise in several countries by a clear transmission advantage, in these cells outcompetes its ancestor B.1 in terms of a much faster kinetics of entry. Given the molecular scenario (entry by the late pathway and similar fraction of pre-cleaved S protein for B.1.1.7 and B.1), the faster entry of B.1.1.7 could be directly related to the N501Y mutation in the S protein, which is known to strengthen the binding of Spike RBD with ACE2. Remarkably, we also observed directly the significant role of clathrin as mediator of late entry endocytosis, which had been previously suggested in analogy with other CoVs and from experiments on pseudotyped virus models. On overall, we believe that our fluroescence microscopy-based approach is valuable for future studies addressing of how SARS-CoV-2 and its variants interact with cells.
  🖺 Full Text HTML: A spatial multi-scale fluorescence microscopy toolbox discloses entry checkpoints of SARS-CoV-2 variants in VeroE6 cells
• A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY -

  Background. Effective simple, home-treatment algorithms implemented on the basis of a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalization of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health care providers. Methods. This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians from October 2020 to January 2021 according to the proposed recommendation algorithm with those of 90 age-, sex-, and comorbidities- matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalization. Analyses were by intention-to-treat. Findings. All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the recommended schedule cohort and 14 [7-30] days in the matched control cohort (p=0.033). Minor symptoms persisted in a lower percentage of patients in the recommended than in the control cohort (23.3% versus 73.3%, respectively, p<0.0001) and for a shorter period (p=0.0107). Two patients in the recommended cohort were hospitalized compared to 13 (14.4%) controls (Log-rank test, p=0.0038). Prevention algorithm abated the days and cumulative costs of hospitalization by >90% (from 481 to 44 days and from 296 to 28 thousand Euros, respectively. 1.2 patients had to be treated to save one hospitalization event. Interpretation. Implementation of an early, home-treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but almost blunted the risk of hospitalization and related treatment costs.

  🖺 Full Text HTML: A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY
• Quantifying the impact of test-trace-isolate-quarantine (TTIQ) strategies on COVID-19 transmission -

  Background: The test-trace-isolate-quarantine (TTIQ) strategy is used to break chains of transmission during a disease outbreak and is one of the key pillars of the non-pharmaceutical interventions to suppress the ongoing SARS-CoV-2 pandemic. Here we quantify how the probability of detecting and isolating a case, the fraction of contacts identified and quarantined, and the delays that are inherent to these processes impact the reduction of disease transmission by TTIQ. Methods: We develop an analytical model of disease transmission that is based on empirical distributions of the timing of SARS-CoV-2 transmission. The isolation of confirmed cases and quarantine of their contacts is implemented by truncating their respective infectious periods. Using this model we quantify how the parameters describing the coverage of the TTIQ intervention and the inherent delays impact the level of disease transmission. We provide an online application to assess the efficacy of TTIQ as a function of these parameters. Findings: Increasing the coverage of testing and isolating index cases has the largest effect on transmission reduction, followed by reducing the delay between symptom onset and index case isolation. The impacts of these two changes are substantially greater than the effect of increasing the fraction of contacts which are traced and subsequently quarantined or reducing the delay to quarantine. We find that, on average, increasing testing and isolation coverage and reducing the delay to isolation have four-fold and three-fold greater impacts, respectively, on transmission reduction compared to increasing contact tracing coverage. Increasing the duration of lookback in which contacts are identifiable has limited impact on TTIQ efficacy. Interpretation: To be a successful intervention strategy, TTIQ requires intensive testing. The majority of transmission is prevented by isolating symptomatic individuals, and doing so in a short amount of time. Despite the lesser impact, adding contact tracing and quarantine to testing and isolation increases the parameter space in which an epidemic is controllable, and is necessary to control epidemics with a high reproductive number. Our results show how TTIQ can be improved and optimised.

  🖺 Full Text HTML: Quantifying the impact of test-trace-isolate-quarantine (TTIQ) strategies on COVID-19 transmission
• Genetic associations with severe COVID-19 -

  Identification of host genetic factors that predispose individuals to severe COVID-19 is important, not only for understanding the disease and guiding the development of treatments, but also for risk prediction when combined to form a polygenic risk score (PRS). Using population controls, Pairo-Castineira et al. identified 12 SNPs (a panel of 8 SNPs and a panel of 6 SNPs, with two SNPs in both panels) associated with severe COVID-19. Using controls with asymptomatic or mild COVID-19, we were able to replicate the association with severe COVID-19 for only three of their SNPs and found marginal evidence for an association for one other. When combined as an 8-SNP PRS and a 6-SNP PRS, we found no evidence of association with severe COVID-19. The difference in our results and the results of Pairo-Castineira et al. might be the choice of controls: population controls vs controls with asymptomatic or mild COVID-19.

  🖺 Full Text HTML: Genetic associations with severe COVID-19
• Use of portable air cleaners to reduce aerosol transmission on a hospital COVID-19 ward -

  Objective To study the airflow, transmission and clearance of aerosols in the clinical spaces of a hospital ward that had been used to care for patients with COVID-19, and to examine the impact of portable air cleaners on aerosol clearance. Design Observational study Setting A single ward of a tertiary public hospital in Melbourne Australia Intervention Glycerine-based aerosol was used as a surrogate for respiratory aerosols. The transmission of aerosols from a single patient room into corridors and a nurses station in the ward was measured. The rate of clearance of aerosols was measured over time from the patient room, nurses station and ward corridors with and without air cleaners (also called portable HEPA filters). Results Aerosols rapidly travelled from the single patient room into other parts of the ward. Air cleaners were effective in increasing the clearance of aerosols from the air in clinical spaces and reducing their spread to other areas. Conclusion Air cleaners may be useful in clinical spaces to help reduce the risk of healthcare acquired acquisition of respiratory viruses that are transmitted via aerosols.

  🖺 Full Text HTML: Use of portable air cleaners to reduce aerosol transmission on a hospital COVID-19 ward
• Mitigating the identity and health threat of COVID-19: Perspectives of Middle-Class South Asians living in the UK -

  The recognition and representation of BAME community as 9high risk9 of Covid-19 in the UK presents both a health and an identity threat to this ethnic group. This study employed thematic analysis to explore response to these threats as related by a sample of thirteen middle class members of the South Asian community. This work advances both health and identity psychological theory by recognising the affinity between expressions of health efficacy and identity. Our findings identify South Asian intragroup stigmatisation and commonalities that have implications for the promotion of health behaviour and health communications for minority groups.

  🖺 Full Text HTML: Mitigating the identity and health threat of COVID-19: Perspectives of Middle-Class South Asians living in the UK
• Arrayed multicycle drug screens identify broadly acting chemical inhibitors for repurposing against SARS CoV 2 -
  Coronaviruses (CoVs) circulate in humans and animals, and expand their host range by zoonotic and anthroponotic transmissions. Endemic human CoVs, such as 229E and OC43 cause limited respiratory disease, and elicit short term anti-viral immunity favoring recurrent infections. Yet, severe acute respiratory syndrome (SARS)-CoV-2 spreads across the globe with unprecedented impact on societies and economics. The world lacks broadly effective and affordable anti-viral agents to fight the pandemic and reduce the death toll. Here, we developed an image-based multicycle replication assay for focus formation of -coronavirus hCoV-229E-eGFP infected cells for screening with a chemical library of 5440 compounds arrayed in 384 well format. The li-brary contained about 39% clinically used compounds, 26% in phase I, II or III clinical trials, and 34% in preclinical development. Hits were counter-selected against toxicity, and challenged with hCoV-OC43 and SARS-CoV-2 in tissue culture and human bronchial and nasal epithelial explant cultures from healthy donors. Fifty three compounds inhibited hCoV-229E-GFP, 39 of which at 50% effective concentrations (EC50) < 2M, and were at least 2-fold separated from toxicity. Thirty nine of the 53 compounds inhibited the replication of hCoV-OC43, while SARS-CoV-2 was inhibited by 11 compounds in at least two of four tested cell lines. Six of the 11 compounds are FDA-approved, one of which is used in mouth wash formulations, and five are systemic and orally available. Here, we demonstrate that methylene blue (MB) and myco-phenolic acid (MPA), two broadly available low cost compounds, strongly inhibited shedding of infectious SARS-CoV-2 at the apical side of the cultures, in either pre- or post-exposure regimens, with somewhat weaker effects on viral RNA release indicated by RT-qPCR measurements. Our study illustrates the power of full cycle screens in repurposing clinical compounds against SARS-CoV-2. Importantly, both MB and MPA reportedly act as immunosuppressants, making them interesting candidates to counteract the cytokine storms affecting COVID-19 patients.
  🖺 Full Text HTML: Arrayed multicycle drug screens identify broadly acting chemical inhibitors for repurposing against SARS CoV 2
• A protective broadly cross-reactive human antibody defines a conserved site of vulnerability on beta-coronavirus spikes -
  We recently described CC40.8 bnAb from a COVID-19 donor that exhibits broad reactivity with human {beta}-CoVs. Here, we show that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 A resolution and found that the peptide adopts a mainly helical structure. Conserved residues in {beta}-CoVs interact with the antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibits in vivo protective efficacy against SARS-CoV-2 challenge in a hamster model with reduction in weight loss and lung viral titers. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational vaccine strategies. Overall, our study describes a new target on CoV spikes for protective antibodies that may facilitate the development of pan-{beta}-CoV vaccines.
  🖺 Full Text HTML: A protective broadly cross-reactive human antibody defines a conserved site of vulnerability on beta-coronavirus spikes
• Exploring the role of glycans in the interaction of SARS-CoV-2 RBD and human receptor ACE2 -
  COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2, enabling the virus to enter the host cell. Both the Spike and ACE2 are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD-ACE2 complex without glycans, (ii) RBD-ACE2 with oligomannose MAN9 glycans in ACE2, and (iii) RBD-ACE2 with complex FA2 glycans in ACE2. These simulations identify the key residues at the RBD-ACE2 interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD-ACE2 contact signature is not altered by the presence of different glycoforms, suggesting that RBD-ACE2 interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 glycans on ACE2 decrease RBD-ACE2 affinity, while FA2 glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus.
  🖺 Full Text HTML: Exploring the role of glycans in the interaction of SARS-CoV-2 RBD and human receptor ACE2

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

• 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

• Study to Evaluate the Viral Load Reduction of a Single Dose of Plitidepsin in Adult Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Plitidepsin;   Drug: Symptomatic Treatment
  Sponsors:   PharmaMar;   Apices Soluciones S.L.
  Not yet recruiting

• 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

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Elderly Adults - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901 (High-Dose);   Biological: MVC-COV1901(Mid-Dose)
  Sponsor:   Medigen Vaccine Biologics Corp.
  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

• STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19 - Condition:   Covid19
  Interventions:   Drug: Brensocatib;   Drug: Placebo
  Sponsors:   University of Dundee;   NHS Tayside;   Insmed Incorporated
  Completed

• 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

• Respiratory Tele Monitoring COVID 19 (TMR COVID-19) - Condition:   Covid19
  Interventions:   Device: Radius PPG Tetherless Pulse Oximetry (Masimo);   Device: usual monitoring
  Sponsor:   Assistance Publique Hopitaux De Marseille
  Recruiting

• Monitoring of COVID-19 Seroprevalence Among GHdC Staff Members - Condition:   Covid19
  Intervention:   Diagnostic Test: Serology to determine SARS-CoV-2 infection
  Sponsor:   Grand Hôpital de Charleroi
  Recruiting

• Favipiravir in High-risk COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Favipiravir
  Sponsor:   Penang Hospital, Malaysia
  Recruiting

• Efficacy of Psidii Guava’s Extract For COVID-19 - Condition:   Covid19
  Interventions:   Drug: Extract Psidii guava;   Combination Product: Standard therapy for Covid-19 patient
  Sponsor:   Faculty of Medicine Baiturrahmah University
  Completed

• Essential Amino Acid Supplementation in Older Adult COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: Essential amino acids;   Dietary Supplement: Maltodextrin
  Sponsor:   University of Arkansas
  Not yet recruiting

• Tele-rehabilitation Program After Hospitalization for COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Other: TR;   Other: TSu
  Sponsors:   Istituti Clinici Scientifici Maugeri SpA;   Istituto Auxologico Italiano
  Recruiting

From PubMed

• Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir - Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell…

• Activation of STING signaling pathway effectively blocks human coronavirus infection - The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the HCoV-OC43 model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway,…

• Antiviral Drug Ivermectin at Nanomolar Concentrations Inhibits Glycine-Induced Chloride Current in Rat Hippocampal Neurons - Ivermectin (IVM) belongs to the class of macrocyclic lactones, which is used as an antiparasitic agent. At present, the researchers focus on possibility to use IVM in treatment of certain forms of cancer and viral diseases such as COVID-19. The mechanisms of IVM action are not clear. It is assumed that IVM affects chloride channels and increases cytoplasmic concentration of chloride. This study examines the effect of IVM on chloride currents induced by glycine (I(Gly)). Experiments were carried…

• A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells - Host-cell cysteine proteases play an essential role in the processing of the viral spike protein of SARS coronaviruses. K777, an irreversible, covalent inactivator of cysteine proteases that has recently completed phase 1 clinical trials, reduced SARS-CoV-2 viral infectivity in several host cells: Vero E6 (EC(50)< 74 nM), HeLa/ACE2 (4 nM), Caco-2 (EC(90) = 4.3 μM), and A549/ACE2 (<80 nM). Infectivity of Calu-3 cells depended on the cell line assayed. If Calu-3/2B4 was used, EC(50) was 7 nM, but…

• Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry - Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. In addition to a role in cancer, NRP-1 is a reported entry point for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19). The furin cleavage product of SARS-CoV-2 Spike protein takes advantage of the vascular endothelial growth factor A (VEGF-A) binding site on NRP-1…

• Multiple Sites on SARS-CoV-2 Spike Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V - SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the virus’s capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein…

• Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors - Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the…

• New Decade, Old Debate: Blocking the Cytokine Pathways in Infection-Induced Cytokine Cascade - CONCLUSIONS: As ongoing clinical trials determine the efficacy and safety of anticytokine therapy in patients with coronavirus disease 2019, clinicians should uphold caution when incorporating it into treatment protocols, while maintaining focus on established evidence-based practices and the mantra of “less is more.”

• An in silico analysis of effective siRNAs against COVID-19 by targeting the leader sequence of SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a retrovirus having genome size of around 30 kb. Its genome contains a highly conserved leader sequence at its 5’ end, which is added to all subgenomic mRNAs at their 5’ terminus by a discontinuous transcription mechanism and regulates their translation. Targeting the leader sequence by RNA interference can be an effective approach to inhibit the viral replication. In the present study an in-silico prediction of highly effective…

• Drug Repurposing of Itraconazole and Estradiol Benzoate against COVID-19 by Blocking SARS-CoV-2 Spike Protein-Mediated Membrane Fusion - SARS-CoV-2 caused the emerging epidemic of coronavirus disease in 2019 (COVID-19). To date, there are more than 82.9 million confirmed cases worldwide, there is no clinically effective drug against SARS-CoV-2 infection. The conserved properties of the membrane fusion domain of the spike (S) protein across SARS-CoV-2 make it a promising target to develop pan-CoV therapeutics. Herein, two clinically approved drugs, Itraconazole (ITZ) and Estradiol benzoate (EB), are found to inhibit viral entry by…

• Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2 - Hexavalent sulfoglycodendrimers (SGDs) are synthesized as mimics of host cell heparan sulfate proteoglycans (HSPGs) to inhibit the early stages in viral binding/entry of HIV-1 and SARS-CoV-2. Using an HIV neutralization assay, the most promising of the seven candidates are found to have sub-micromolar anti-HIV activities. Molecular dynamics simulations are separately implemented to investigate how/where the SGDs interacted with both pathogens. The simulations revealed that the SGDs: 1) develop…

• Recent Advances on Nanomaterials to COVID-19 Management: A Systematic Review on Antiviral/Virucidal Agents and Mechanisms of SARS-CoV-2 Inhibition/Inactivation - The current pandemic of coronavirus disease 2019 (COVID-19) is recognized as a public health emergency of worldwide concern. Nanomaterials can be effectively used to detect, capture/inactivate or inhibit coronavirus cell entry/replication in the human host cell, preventing infection. Their potential for nanovaccines, immunoengineering, diagnosis, repurposing medication, and disinfectant surfaces targeting the novel coronavirus (SARS-CoV-2) is highlighted. In this systematic review the aim is to…

• Effect of coronavirus lockdowns on the ambient seismic noise levels in Gujarat, northwest India - The Covid-19 pandemic created havoc and forced lockdowns in almost all the countries worldwide, to inhibit social spreading. In India as well, as a precautionary measure, complete and partial lockdowns were announced in phases during March 25 to May 31, 2020. The restricted human activities led to a drastic reduction in seismic background noise in the high frequency range of 1-20 Hz, representative of cultural noise. In this study, we analyse the effect of anthropogenic activity on the Earth…

• Multidisciplinary Approaches Identify Compounds that Bind to Human ACE2 or SARS-CoV-2 Spike Protein as Candidates to Block SARS-CoV-2-ACE2 Receptor Interactions - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged virus that causes coronavirus infectious disease 2019 (COVID-19). SARS-CoV-2 spike protein, like SARS-CoV-1, uses the angiotensin converting enzyme 2 (ACE2) as a cellular receptor to initiate infection. Compounds that interfere with the SARS-CoV-2 spike protein receptor binding domain protein (RBD)-ACE2 receptor interaction may function as entry inhibitors. Here, we used a dual strategy of molecular docking and…

• Therapeutic Potential of Metformin in COVID-19: Reasoning for Its Protective Role - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections present with increased disease severity and poor clinical outcomes in diabetic patients compared with their nondiabetic counterparts. Diabetes/hyperglycemia-triggered endothelial dysfunction and hyperactive inflammatory and immune responses are correlated to twofold to threefold higher intensive care hospitalizations and more than twice the mortality among diabetic coronavirus disease 2019 (COVID-19) patients. While…

From Patent Search

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

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

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

• IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - 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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