Covid-19 Sentry

Contents

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

From Preprints

• The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodium yoelii infection -
  Background: Malaria, caused by Plasmodium, is a global life-threatening infection disease especially during the COVID-19 pandemic. However, it is still unclear about the dynamic change and the interactions between intestinal microbiota and host immunity. Here, we investigated the change of intestinal microbiome and transcriptome during the whole Plasmodium infection process in mice to analyze the dynamic landscape of parasitaemia dependent intestinal microbiota shifting and related to host immunity. Results: There were significant parasitaemia dependent changes of intestinal microbiota and transcriptome, and the microbiota was significantly correlated to the intestinal immunity. We found that (i) the diversity and composition of the intestinal microbiota represented a significant correlation along with the Plasmodium infection in family, genus and species level; (ii) the up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways along with the malaria development, particularly, naive CD4+ T cells differentiation; (iii) the abundance of the parasitaemia phase-specific microbiota represented a high correlation with the phase-specific immune cells development, particularly, Th1 cell with family Bacteroidales BS11 gut group, genera Prevotella 9, Ruminococcaceae UCG 008, Moryella and specie Sutterella, Th2 cell with specie Sutterella, Th17 cell with family Peptococcaceae , genus Lachnospiraceae FCS020 group and spices Ruminococcus 1, Ruminococcus UGG 014 and Eubacterium plexicaudatum ASF492, Tfh and B cell with genera Moryella and species Erysipelotrichaceae bacterium canine oral taxon 255. Conclusion: There was a remarkable dynamic landscape of the parasitaemia dependent shifting of intestinal microbiota and immunity, and a notable correlation between the abundance of intestinal microbiota.
  🖺 Full Text HTML: The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodium yoelii infection
• SARS-CoV-2 spike protein interacts with and activates TLR4 -
  The onset of sepsis is an important feature of COVID19 and a main cause of death. It is unknown how SARS-CoV-2 infection results in viral sepsis in human. We recently found that SARS-CoV-2 provoked an anti-bacterial like response and activation of TLR4 pathway at the very early stage of infection in animal models. This abnormal immune response led to emergency granulopoiesis and sepsis. However, the original trigger of TLR4 signaling by SARS-CoV-2 is unknown. We here identified that the trimeric spike protein of SARS-CoV-2 could bind to TLR4 directly and robustly activate downstream signaling in monocytes and neutrophils. Moreover, specific TLR4 or NFKB inhibitor, or knockout of MyD88 could significantly block IL-1B induction by spike protein. We thus reveal that spike protein of SARS-CoV-2 functions as a potent stimulus causing TLR4 activation and sepsis related abnormal responses.
  🖺 Full Text HTML: SARS-CoV-2 spike protein interacts with and activates TLR4
• Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19 -
  Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
  🖺 Full Text HTML: Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
• SNPnexus COVID: Facilitating the analysis of COVID-19 host genetics -
  The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented a crisis for global healthcare systems. Human SARS-CoV-2 infection can result in coronavirus disease 2019 (COVID-19), which has been characterised as an acute respiratory illness, with most patients displaying flu-like symptoms, such as a fever, cough and dyspnoea. However, the range and severity of individual symptoms experienced by patients can vary significantly, indicating a role for host genetics in impacting the susceptibility and severity of COVID-19 disease. Whilst most symptomatic infections are known to manifest in mild to moderate respiratory symptoms, severe pneumonia and complications including cytokine release syndrome, which can lead to multi-organ dysfunction, have also been observed in cases worldwide. Global initiatives to sequence the genomes of patients with COVID-19 have driven an expanding new field of host genomics research, to characterise the genetic determinants of COVID-19 disease. The functional annotation and analysis of incoming genomic data, within a clinically relevant turnaround time, is therefore imperative given the importance and urgency of research efforts to understand the biology of SARS-CoV-2 infection and disease. To address these requirements, we developed SNPnexus COVID. This is a web-based variant annotation tool, powered by the SNPnexus software.
  🖺 Full Text HTML: SNPnexus COVID: Facilitating the analysis of COVID-19 host genetics
• assayM: a web application to monitor mutations in COVID-19 diagnostic assays. -
  Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) is the gold standard as diagnostic assays for the detection of COVID-19 and the specificity and sensitivity of these assays depend on the complementarity of the RT-PCR primers to the genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the virus mutates over time during replication cycles, there is an urgent need to continuously monitor the virus genome for appearances of mutations and mismatches in the PCR primers used in these assays. Here we present assayM, a web application to explore and monitor mutations introduced in the primer and probe sequences published by the World Health Organisation (WHO) or in any custom-designed assay primers for SARS-CoV-2 detection assays in globally available SARS-CoV-2 genome datasets.
  🖺 Full Text HTML: assayM: a web application to monitor mutations in COVID-19 diagnostic assays.
• Covid-19 pandemic lessons: Uncritical communication of test results can induce more harm than benefit and raises questions on standardized quality criteria for communication and liability -

  Background: The COVID-19 pandemic is characterized by both health and economic risks. A "safety loop" model postulates risk-related decisions are not based on objective and measurable risks but on the subjective perception of those risks. We here illustrate a quantification of the difference between objective and subjective risks. Method: The objective risks (or chances) can be obtained from traditional 2 x 2 tables by calculating the positive (+LR) and negative (-LR) likelihood ratios. The subjective perception of objective risks is calculated from the same 2 x 2 tables by exchanging the X- and Y-axes. The traditional 2 x 2 table starts with the hypothesis, uses a test and a gold standard to confirm or exclude the investigated condition. The 2 x 2 table with inverted axes starts with the communication of a test result and presumes that the communication of bad news (whether right or false) will induce "perceived anxiety" while good news will induce "perceived safety". Two different functions (confirmation and exclusion) of both perceptions (perceived anxiety and safety) can be quantified with those calculations. Results: The analysis of six published tests and of one incompletely reported test on COVID-19 polymerase chain reactions (completed by four assumptions on high and low sensitivities and specificities) demonstrated that none of these tests induces "perceived safety". Eight of the ten tests confirmed the induction of perceived anxiety with +LRs (range 3.1 - 5900). In two of these eight tests a -LR (0.25 and 0.004) excluded the induction of perceived safety. Conclusions: Communication of test results caused perceived anxiety but not perceived safety in 80% of the investigated tests. Medical tests, whether right or false, generate strong psychological messages. In the case of COVID-19 tests may induce more perceived anxiety than safety.

  🖺 Full Text HTML: Covid-19 pandemic lessons: Uncritical communication of test results can induce more harm than benefit and raises questions on standardized quality criteria for communication and liability
• The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19: Evidence from a multi-country survey -

  Physical distancing measures are intended to mitigate the spread of COVID-19, even though their impact on social contacts and disease transmission remains unclear. Obtaining timely data on social contact patterns can help to assess the impact of such protective measures. We conducted an online opt-in survey based on targeted Facebook advertising campaigns across seven European countries (Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom (UK)) and the United States (US), achieving a sample of 53,708 questionnaires in the period March 13-April 13, 2020. Post-stratification weights were produced to correct for biases. Data on social contact numbers, as well as on protective behavior and perceived level of threat were collected and used to the expected net reproduction number by week, Rt, with respect to pre-pandemic data. Compared to social contacts reported prior to COVID-19, in mid-April daily social contact numbers had decreased between 49% in Germany and 83% in Italy, ranging from below three contacts per day in France, Spain, and the UK up to four in Germany and the Netherlands. Such reductions were sufficient to bring Rt to one or even below in all countries, except Germany. Evidence from the US and the UK showed that the number of daily social contacts mainly decreased after governments issued the first physical distancing guidelines. Finally, although contact numbers decreased uniformly across age groups, older adults reported the lowest numbers of contacts, indicating higher levels of protection. We provided a comparable set of statistics on social contact patterns during the COVID-19 pandemic for eight high-income countries, disaggregated by week. As these estimates offer a more grounded alternative to the theoretical assumptions often used in epidemiological models, the scientific community could draw on this information for developing more realistic epidemic models of COVID-19.

  🖺 Full Text HTML: The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19: Evidence from a multi-country survey
• Temporal kinetics of RNAemia and associated systemic cytokines in hospitalized COVID-19 patients -
  COVID-19 is associated to a wide range of extra-respiratory complications, of which the pathogenesis is currently not fully understood. In this study we report the temporal kinetics of viral RNA and inflammatory cytokines and chemokines in serum during the course of COVID-19. We show that a RNAemia occurs more frequently and lasts longer in patients that develop critical disease compared to patients that develop moderate or severe disease. Furthermore we show that concentrations of IL-10 and MCP-1-but not IL-6-are associated with viral load in serum. However, higher levels of IL-6 were associated with the development of critical disease. The direct association of inflammatory cytokines with viral load or disease severity highlights the complexity of systemic inflammatory response and the role of systemic viral spread.
  🖺 Full Text HTML: Temporal kinetics of RNAemia and associated systemic cytokines in hospitalized COVID-19 patients
• An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by COVID-19 patient antibodies -
  SARS-CoV-2 infection causes severe symptoms in a subset of patients, suggesting the presence of certain unknown risk factors. Although antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike have been shown prevent SARS-CoV-2 infection, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from COVID-19 patients, and found that some of antibodies against the N-terminal domain (NTD) dramatically enhanced the binding capacity of the spike protein to ACE2, and thus increased SARS-CoV2 infectivity. Surprisingly, mutational analysis revealed that all the infectivity-enhancing antibodies recognized a specific site on the surface of the NTD. The antibodies against this infectivity-enhancing site were detected in all samples of hospitalized COVID-19 patients in the study. However, the ratio of infectivity-enhancing antibodies to neutralizing antibodies differed among patients. Furthermore, the antibodies against the infectivity-enhancing site were detected in 3 out of 48 uninfected donors, albeit at low levels. These findings suggest that the production of antibodies against SARS-CoV-2 infectivity-enhancing site could be considered as a possible exacerbating factors for COVID-19 and that a spike protein lacking such antibody epitopes may be required for safe vaccine development, especially for individuals with pre-existing enhancing antibodies.
  🖺 Full Text HTML: An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by COVID-19 patient antibodies
• Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro -
  Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with severe acute respiratory syndrome coronavirus-1 (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo models. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 microg/ml). The results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.
  🖺 Full Text HTML: Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro
• A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples -
  Rationale: COVID -19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. Objective: This study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. Methods: rfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. Measurements and Main Results: In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5 micro M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 micro M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5 micro M rfhSP-D. Conclusions: These results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.
  🖺 Full Text HTML: A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples
• A new concept on anti-SARS-CoV-2 vaccines: strong CD8+ T-cell immune response in both spleen and lung induced in mice by endogenously engineered extracellular vesicles -
  Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is spreading rapidly in the absence of validated tools to control the growing epidemic besides social distancing and masks. Many efforts are ongoing for the development of vaccines against SARS-CoV-2 since there is an imminent need to develop effective interventions for controlling and preventing SARS-CoV-2 spread. Essentially all vaccines in most advanced phases are based on the induction of antibody response against either whole or part of spike (S) protein. Differently, we developed an original strategy to induce CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). We exploited this technology with the aim to identify a clinical candidate defined as DNA vectors expressing SARS-CoV-2 antigens inducing a robust CD8+ T-cell response. This is a new vaccination approach employing a DNA expression vector encoding a biologically inactive HIV-1 Nef protein (Nefmut) showing an unusual efficiency of incorporation into EVs even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nefmut-fused antigens released by muscle cells are internalized by antigen-presenting cells leading to cross-presentation of the associated antigens thereby priming of antigen-specific CD8+ T-cells. To apply this technology to a design of anti-SARS-CoV-2 vaccine, we recovered DNA vectors expressing the products of fusion between Nefmut and four viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. All fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8+ T cell immunity was generated. Most important, high levels of virus-specific CD8+ T cells were found in bronchoalveolar lavages of immunized mice. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lung. EVs engineered with SARS-CoV-2 antigens were proven immunogenic also in the human system through cross-priming assays carried out with ex vivo human cells. Hence, DNA vectors expressing Nefmut-based fusion proteins can be proposed as anti-SARS-CoV-2 vaccine candidates.
  🖺 Full Text HTML: A new concept on anti-SARS-CoV-2 vaccines: strong CD8+ T-cell immune response in both spleen and lung induced in mice by endogenously engineered extracellular vesicles
• International Comparisons of Harmonized Laboratory Value Trajectories to Predict Severe COVID-19: Leveraging the 4CE Collaborative Across 342 Hospitals and 6 Countries: A Retrospective Cohort Study -

  Objectives: To perform an international comparison of the trajectory of laboratory values among hospitalized patients with COVID-19 who develop severe disease and identify optimal timing of laboratory value collection to predict severity across hospitals and regions. Design: Retrospective cohort study. Setting: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), an international multi-site data-sharing collaborative of 342 hospitals in the US and in Europe. Participants: Patients hospitalized with COVID-19, admitted before or after PCR-confirmed result for SARS-CoV-2. Primary and secondary outcome measures: Patients were categorized as ″ever-severe″ or ″never-severe″ using the validated 4CE severity criteria. Eighteen laboratory tests associated with poor COVID-19-related outcomes were evaluated for predictive accuracy by area under the curve (AUC), compared between the severity categories. Subgroup analysis was performed to validate a subset of laboratory values as predictive of severity against a published algorithm. A subset of laboratory values (CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin) was compared between North American and European sites for severity prediction. Results: Of 36,447 patients with COVID-19, 19,953 (43.7%) were categorized as ever-severe. Most patients (78.7%) were 50 years of age or older and male (60.5%). Longitudinal trajectories of CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin showed association with disease severity. Significant differences of laboratory values at admission were found between the two groups. With the exception of D-dimer, predictive discrimination of laboratory values did not improve after admission. Sub-group analysis using age, D-dimer, CRP, and lymphocyte count as predictive of severity at admission showed similar discrimination to a published algorithm (AUC=0.88 and 0.91, respectively). Both models deteriorated in predictive accuracy as the disease progressed. On average, no difference in severity prediction was found between North American and European sites. Conclusions: Laboratory test values at admission can be used to predict severity in patients with COVID-19. There is a need for prediction models that will perform well over the course of the disease in hospitalized patients.

  🖺 Full Text HTML: International Comparisons of Harmonized Laboratory Value Trajectories to Predict Severe COVID-19: Leveraging the 4CE Collaborative Across 342 Hospitals and 6 Countries: A Retrospective Cohort Study
• Soap, Water, and SARS-CoV-2: An Ancient Handwashing Strategy for Preventing Dissemination of a New Virus -
  Public Health Agencies worldwide (World Health Organization, U.S. Centers for Disease Prevention and Control, Chinese Center for Disease Control and Prevention, European Centre for Disease Prevention and Control, etc.) are recommending hand washing with soap and water for preventing the dissemination of SARS-CoV-2 infections. In this review, we have discussed the mechanism of decontamination by soap and water (involving both removal and inactivation), described the contribution of the various components of formulated soaps to performance as cleansers and to pathogen inactivation, explained why adherence to recommended contact times is critical, evaluated the possible contribution of water temperature to inactivation, discussed the advantages of antimicrobial soaps versus basic soaps, discussed the differences between use of soap and water versus alcohol-based hand sanitizers for hand decontamination, and evaluated the limitations and advantages of different methods of drying hands following washing. While the paper emphasizes data applicable to SARS-CoV-2, the topics discussed are germane to most emerging and re-emerging enveloped and non-enveloped viruses and other pathogens.
  🖺 Full Text HTML: Soap, Water, and SARS-CoV-2: An Ancient Handwashing Strategy for Preventing Dissemination of a New Virus
• COVID-19 restrictions and recreational fisheries in Ontario, Canada: preliminary insights from an online angler survey -
  The COVID-19 pandemic and corresponding public health mitigation strategies have altered many facets of human life. And yet, little is known about how public health measures have impacted complex socio-ecological systems such as recreational fisheries. Using a web-based online snowball survey, we targeted resident anglers in Ontario, Canada, to obtain preliminary insight on how the pandemic has impacted recreational fishing and related activity. We also explored angler perspectives on pandemic-related restrictions and other aspects of fisheries management. Our results point to the value of recreational fisheries for the mental and physical well-being of participants, as well as the value and popularity of outdoor recreation during a pandemic. Although angling effort and fish consumption appeared to decline during the early phases of the pandemic, approximately 20% of the anglers who responded to our survey self-identified as new entrants who had begun or resumed fishing in that time. Self-reported motivations to fish during the pandemic suggest that free time, importance to mental and physical health, and desires for self-sufficiency caused some anglers to fish more, whereas a lack of free time, poor or uncertain accessibility, and perceived risks caused some anglers to fish less. Respondents also expressed their desires for more clear and consistent communication about COVID-19 fishing restrictions from governments, and viewed angling as a safe pandemic activity. Information on recreational angler behaviours, motivations, and perspectives during the pandemic may prove valuable to fisheries managers and policy makers looking to optimize their strategies for facing this and other similar crises.
  🖺 Full Text HTML: COVID-19 restrictions and recreational fisheries in Ontario, Canada: preliminary insights from an online angler survey

From Clinical Trials

• Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Silmitasertib;   Drug: SOC
  Sponsor:   Chris Recknor, MD
  Recruiting

• Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients - Condition:   Covid19
  Intervention:   Drug: Methylprednisolone, Placebo
  Sponsor:   Azienda Unità Sanitaria Locale Reggio Emilia
  Not yet recruiting

• Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19) - Condition:   COVID-19
  Interventions:   Biological: Group A (AG0302-COVID19);   Biological: Group A (Placebo);   Biological: Group B (AG0302-COVID19);   Biological: Group B (Placebo)
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Recruiting

• Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BCG vaccine
  Sponsors:   Universidade Federal do Rio de Janeiro;   Ministry of Science and Technology, Brazil
  Recruiting

• At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19 - Condition:   Covid19
  Intervention:   Drug: bamlanivimab
  Sponsors:   Daniel Griffin, MD PhD;   Eli Lilly and Company;   Optum, Inc.
  Not yet recruiting

• Changes in Viral Load in COVID-19 After Probiotics - Condition:   COVID-19
  Intervention:   Dietary Supplement: Dietary supplementation in patients with covid disease admitted to hospital
  Sponsors:   Hospital de Sagunto;   Biopolis S.L.;   Laboratorios Heel España
  Recruiting

• Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Hydroxychloroquine;   Behavioral: personal protective Measures
  Sponsor:   Benha University
  Completed

• Phase 3 Inhaled Novaferon Study in Hospitalized Patients With Moderate to Severe COVID-19 - Condition:   Covid19
  Interventions:   Biological: Novaferon;   Biological: Placebo
  Sponsor:   Genova Inc.
  Not yet recruiting

• Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19) - Condition:   COVID-19
  Interventions:   Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment
  Sponsor:   Xi'an International Medical Center Hospital
  Active, not recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection - Condition:   Covid19
  Intervention:   Biological: AT-100
  Sponsor:   Airway Therapeutics, Inc.
  Not yet recruiting

• Mushroom-based Product for COVID-19 - Condition:   COVID-19
  Intervention:   Drug: FoTv
  Sponsors:   Gordon Saxe;   University of California, Los Angeles;   University of California, Irvine
  Recruiting

• Urine Alkalinisation to Prevent AKI in COVID-19 - Condition:   Covid19
  Intervention:   Drug: Sodium Bicarbonate 150Meq/L/D5W Inj
  Sponsor:   Guy's and St Thomas' NHS Foundation Trust
  Not yet recruiting

• COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol - Condition:   Covid19
  Interventions:   Drug: Acebilustat;   Drug: Camostat
  Sponsor:   Stanford University
  Not yet recruiting

• COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Camostat Sub-Protocol - Condition:   Covid19
  Interventions:   Drug: Camostat;   Drug: Placebo
  Sponsor:   Stanford University
  Not yet recruiting

From PubMed

• Lymphocyte Changes in Severe COVID-19: Delayed Over-Activation of STING? - Upon recognition of microbial DNA or self-DNA, the cyclic-GMP-AMP synthase (cGAS) of the host catalyzes the production of the cyclic dinucleotide cGAMP. cGAMP is the main activator of STING, stimulator of interferon genes, leading to interferon synthesis through the STING-TBK1-IRF3 pathway. STING is also a hub for activation of NF-κB and autophagy. The present review details the striking similarities between T and B cell responses in severe coronavirus disease 2019 (COVID-19) and both animal or...

• SARS-CoV-2 and Viral Sepsis: Immune Dysfunction and Implications in Kidney Failure - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), first emerged in Wuhan, China. The clinical manifestations of patients infected with COVID-19 include fever, cough, and dyspnea, up to acute respiratory distress syndrome (ARDS) and acute cardiac injury. Thus, a lot of severe patients had to be admitted to intensive care units (ICU). The pathogenic mechanisms of SARS-CoV-2 infection are mediated by the binding of SARS-CoV-2...

• Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19 - There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency use authorized drugs do not result in significant and widespread patient improvement. The food and drug administration-approved drug ivermectin has long been shown to be both antihelmintic agent and a potent inhibitor of viruses such as Yellow Fever Virus. In this study, we highlight the potential of ivermectin packaged in an orally administrable...

• Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019? - Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its...

• Thalidomide Combined with Short-term Low-Dose Glucocorticoid Therapy for the Treatment of Severe COVID-19: A Case-Series Study - CONCLUSIONS: Thalidomide plus short-term glucocorticoid therapy is an effective and safe regimen for the treatment of severely ill COVID-19 patients. The mechanism of action is most likely inhibition of inflammatory cytokine production.

• Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses - The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach...

• Acute Effects of an Afterschool Running and Reading Program on Executive Functioning in Children: An Exploratory Study - Objective: Emerging research within school settings suggests acute forms of physical activity and exercise lead to improvements in executive functioning among children. However, research pertaining to these effects within the afterschool setting remains limited. The primary purpose of this study was to investigate the acute effects of a community-based afterschool running and reading program on executive functioning in 8 to 12-year-old children. Method: Fifty participants were initially...

• Understanding Views of Patients on Biologics for Psoriasis Amid the COVID-19 Pandemic - Biologics target and inhibit specific cytokines, thereby suppressing the immune system and manifestation of psoriasis. Currently, there exist limited data on the impact of biologics on the coronavirus disease of 2019 (C19). The public may obtain information from many sources which may affect their understanding of biologic use during this pandemic. This study assessed psoriasis patients' understanding of the safety of biologic use during the C19 pandemic and their perception of various...

• Diverse Functional Autoantibodies in Patients with COVID-19 - COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses ^(1-8) . While pathological innate immune activation is well documented in severe disease ¹ , the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare...

• SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential - Coronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2'-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1,...

• Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies - Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the SARS-CoV-2 spike protein is an envelope glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor. The capacity of enveloped viruses to infect host cells depends on a precise thiol/disulfide balance in their surface glycoprotein complexes. To determine if cystines in the SARS-CoV-2 spike protein maintain a native binding interface that can be disrupted by...

• Paradoxical effects of cigarette smoke and COPD on SARS-CoV2 infection and disease - CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection.

• Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors - Among the drug targets being investigated for SARS-CoV-2, the viral main protease (M^(pro)) is one of the most extensively studied. M^(pro) is a cysteine protease that hydrolyzes the viral polyprotein at more than 11 sites. It is highly conserved and has a unique substrate preference for glutamine in the P1 position. Therefore, M^(pro) inhibitors are expected to have broad-spectrum antiviral activity and a high selectivity index. Structurally diverse compounds have been reported as M^(pro)...

• Development of a High-Throughput Homogeneous AlphaLISA Drug Screening Assay for the Detection of SARS-CoV-2 Nucleocapsid - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in urgent need of therapeutic options. High-throughput screening (HTS) offers an opportunity to rapidly identify such compounds. In this work, we have developed a homogeneous cell-based HTS system using AlphaLISA detection technology for the SARS-CoV-2 nucleocapsid protein (NP). Our assay measures both recombinant and endogenous NP from viral lysates and tissue culture...

• Probing the Dynamic Structure-Function and Structure-Free Energy Relationships of the Coronavirus Main Protease with Biodynamics Theory - The SARS-CoV-2 main protease (M^(pro)) is of major interest as an antiviral drug target. Structure-based virtual screening efforts, fueled by a growing list of apo and inhibitor-bound SARS-CoV/CoV-2 M^(pro) crystal structures, are underway in many laboratories. However, little is known about the dynamic enzyme mechanism, which is needed to inform both assay development and structure-based inhibitor design. Here, we apply biodynamics theory to characterize the structural dynamics of...

From Patent Search

• Covid 19 - Chewing Gum -

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof -

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms -

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms -

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex.

• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.

• SARS-CoV-2 RBD共轭纳米颗粒疫苗 - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。

• Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил.

• Anordnung zur Visualisierung von angebotenen Waren und Dienstleistungen -

  Anordnung zur Visualisierung von angebotenen Waren und Dienstleistungen, insbesondere in der Gastronomie, gekennzeichnet durch einen pyramidenartigen Gegenstand (10), der eine flache Unterseite (14) und mehrere in einem Winkel von der flachen Unterseite (14) aufragende Seitenflächen (11,12,13) aufweist, gekennzeichnet durch einen zweidimensionalen Code (15), insbesondere einen QR-Code, der auf mindestens einer der Seitenflächen (11,12,13) aufgebracht ist, gekennzeichnet durch ein elektronisches Gerät (20), das mit einer Kamera (21) und mit einem Display (22) zur Anzeige von zur Verfügung gestellten Informationen versehen und mit dem Internet verbindbar ist, gekennzeichnet durch eine Website (30) im Internet, der das mit der Kamera (21) aufgenommene Bild zugänglich ist, wobei die Website (30) so aufgebaut und ausgestattet ist, dass sie den zweidimensionalen Code (15), insbesondere QR-Code, erkennt und entschlüsselt und abhängig davon, dem elektronischen Gerät (20) eine digitale Abbildung einer Information zu den angebotenen Waren und Dienstleistungen zur Darstellung auf dem Display (22) zur Verfügung stellt.