Covid-19 Sentry

Contents

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

From Preprints

• What Happened to MSMEs During the Pandemic? -
  The Covid-19 pandemic causes a huge impact to global economy including people’s income and purchasing power. This has brought deflation which triggered by falling prices in several sectors. Some of the biggest affected sectors are food, beverages and also transportation. With this pandemic that affects in both microeconomics and macroeconomics, government should take control so that Covid-19 cases can be minimalized and gain public trust for economic recovery.
  🖺 Full Text HTML: What Happened to MSMEs During the Pandemic?
• Pathogenic neutrophilia drives acute respiratory distress syndrome in severe COVID-19 patients -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing COVID-19 pandemic have caused ~33 million cases and over 585,000 deaths in the United States alone. Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths being Black/African-American (AA) patients in some areas, yet targeted studies to delineate features of disease severity within this demographic are scant. Our multi-omics single-cell analyses of immune profiles from airways and matching blood samples of Black/AA patients revealed pronounced pulmonary neutrophilia and low viral burden as a hallmark of severe disease, where neutrophil phenotypes display advanced features of cytokine release syndrome and acute respiratory distress syndrome (ARDS). Cell-cell communication and trajectory analysis reveal a subset of circulating S100A12+/CXCR4+ mature neutrophils that infiltrate the lung via the IL-8/CXCR2 axis. Recruited neutrophils progress toward a transcriptionally active and pathogenic state characterized by exacerbated production of IL-8, IL-1{beta}, IL-6, and CCL3/4 along with elevated levels of neutrophil elastase and myeloperoxidase. Inflammatory monocytes recruited via neutrophil-derived CCL3/4 also produce elevated neutrophil chemotactic factor IL-8, potentiating the sustained neutrophilia in the airways. The IL-8/CXCR2 axis emerges as a potential therapeutic target to reduce pathogenic neutrophilia and constrain ARDS in severe COVID-19.
  🖺 Full Text HTML: Pathogenic neutrophilia drives acute respiratory distress syndrome in severe COVID-19 patients
• CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent -
  Lymphopenia is common in severe COVID-19 disease, yet the mechanisms are poorly understood. In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to recovered, mild disease (p<0.0001). In severe disease, immunodominant CD4+ T cell responses to Spike-1(S1) produced increased in vitro TNF-, but impaired proliferation and increased susceptibility to activation-induced cell death (AICD). CD4+TNF-+ T cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.744, P<0.0001). TNF- blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ proliferation and abrogated S1-AICD in severe COVID-19 patients (P<0.001). Single-cell RNAseq demonstrated downregulation of Type-1 cytokines and NF{kappa}B signaling in S1-stimulated CD4+ cells with infliximab treatment. Lung CD4+ T cells in severe COVID-19 were reduced and produced higher TNF- versus PBMC. Together, our findings show COVID-19-associated CD4+ lymphopenia and dysfunction is autocrine TNF-/TNFRI-dependent and therapies targeting TNF- may be beneficial in severe COVID-19.
  🖺 Full Text HTML: CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent
• The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner -
  The rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.
  🖺 Full Text HTML: The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner
• Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip -
  Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PMBCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.
  🖺 Full Text HTML: Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip
• Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19. -

  Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found; although several new candidates including ivermectin, dutasteride, baricitinib, budesonide and colchicine are being studied with some early promising results. Safe and effective treatments will need to be both affordable and widely available globally. Objectives This analysis will estimate and compare potential generic production costs of a selection of COVID-19 drug candidates with international list prices. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from $2.58 for IV dexamethasone (or $0.19 orally) to $0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Analysed drugs are widely available and affordable, whilst IV treatment courses are more expensive.

  🖺 Full Text HTML: Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19.
• Virologic features of SARS-CoV-2 infection in children -

  Background: Data on viral factors causing pediatric disease and guidance for pediatric-specific considerations have lagged behind adults throughout the COVID-19 pandemic. As COVID-19 infections and deaths increase in the pediatric population, characterization of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. Methods: Nasal swabs collected from children with COVID-19 were analyzed. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age or symptom duration were analyzed. SARS-CoV-2 whole genome amplification was compared with contemporaneous Massachusetts sequences to assess for clustering patterns. Results: Ninety-seven children with COVID-19 (median age 10 years, range 2 weeks-22 years) were included in this study. Age did not impact SARS-CoV-2 viral load in nasal secretions: children of all ages were equally likely to carry live, replicating virus. Children within the first five days of illness had higher viral loads and rates of culture positivity, and viral load in hospitalized children (n=30) did not differ from hospitalized adults (n=21) with similar duration of symptoms. While pediatric SARS-CoV-2 sequences were representative of those in the community, novel variants were identified. Conclusions: Children can carry high quantities of live, replicating virus, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

  🖺 Full Text HTML: Virologic features of SARS-CoV-2 infection in children
• Why is non-suicidal self-injury more prevalent among women? Mediation and moderation analyses of psychological distress, emotion dysregulation, and impulsivity -

  OBJECTIVE Non-suicidal self-injury (NSSI) appears to be more common among women than men, though the underlying reasons for this remain unclear. In a community sample of young adults (n=996, aged 18-30) assessed during the COVID-19 pandemic, we investigated gendered patterns in NSSI etiology. METHODS Mediation and moderation analyses considered associations between past-year NSSI prevalence, gender, and putative mechanistic variables: self-reported psychological distress (K10), emotion dysregulation (DERS), and impulsivity (UPPS-P). RESULTS Nearly twice as many women as men reported past-year NSSI (14.47% versus 7.78%). Women reported significantly higher psychological distress and significantly lower sensation seeking and positive urgency than men. Psychological distress partially statistically mediated the relationship between gender and past-year NSSI. Gender did not significantly moderate associations between self-reported distress, emotion dysregulation, or impulsivity and past-year NSSI. Past-year NSSI prevalence did not significantly decrease with age and we found no significant age by gender interaction. CONCLUSIONS Greater levels of NSSI in young women are explained by their greater levels of emotional distress. Women do not appear to be more likely than men to report NSSI due to differences in how they manage emotional distress: gender did not moderate the association between psychological distress and past-year NSSI, and there were no gender differences in emotion dysregulation or negative urgency. Furthermore, we show that NSSI remains prevalent beyond adolescence. Early interventions which reduce distress or improve distress tolerance, strengthen emotion regulation skills, and provide alternative coping strategies merit investigation for NSSI.

  🖺 Full Text HTML: Why is non-suicidal self-injury more prevalent among women? Mediation and moderation analyses of psychological distress, emotion dysregulation, and impulsivity
• Implementing Mandatory Testing and a Public Health Commitment to Control COVID-19 on a College Campus -

  The COVID-19 pandemic has greatly impacted US colleges and universities. As The George Washington University (GWU), a large urban university, prepared to reopen for the Fall 2020 semester, GWU established protocols to protect the health and wellness of all members of campus community. Reopening efforts included a cadre of COVID-19 surveillance systems including development of a public health COVID-19 laboratory, weekly and symptomatic SARS-CoV-2 testing and daily risk screening and symptom monitoring. Other activities included completion of a mandatory COVID-19 training and influenza vaccination for the on-campus population, quarantining of students returning to campus, campus-focused case investigations and quarantining of suspected close contacts, clinical follow-up of infected persons, and regular communication and monitoring. A smaller on-campus population of 4,435 students, faculty and staff returned to campus with later expansion of testing to accommodate GWU students living in the surrounding area. Between August 17 and December 4, 2020, 38,288 tests were performed; 220 were positive. The surveillance program demonstrated a relatively low positivity rate, with temporal clustering of infected persons mirroring community spread, and little evidence for transmission among the GWU on-campus population. These efforts demonstrate the feasibility of safely partially reopening a large urban college campus by applying core principles of public health surveillance, infectious disease epidemiology, behavioral measures, and increased testing capacity, while continuing to promote educational and research opportunities. GWU will continue to monitor the program as the pandemic evolves and periodically reassess to determine if these strategies will be successful upon a full return to in-person learning.

  🖺 Full Text HTML: Implementing Mandatory Testing and a Public Health Commitment to Control COVID-19 on a College Campus
• Physical integrity of medical exam gloves with repeated applications of disinfecting agents: evidence for extended use -

  Background: The COVID-19 pandemic has created global shortages of personal protective equipment (PPE) such as medical exam gloves, forcing healthcare workers to either forgo or reuse PPE to keep themselves and patients safe from infection. In severely resource-constrained situations, limited cycles of disinfection and extended use of gloves is recommended by the U.S. Centers for Disease Control and Prevention (CDC) to conserve supplies. However, these guidelines are based on limited evidence. Methods: Serial cycles of hand hygiene were performed on gloved hands using alcohol-based hand rub (ABHR) (six and ten cycles), 0.1% sodium hypochlorite (bleach) solution (ten cycles), or soap and water (ten cycles) on three types of latex and three types of nitrile medical exam gloves, purchased in the United States and India. A modified FDA-approved water-leak test was performed to evaluate glove integrity after repeated applications of these disinfecting agents. 80 gloves per disinfectant-glove type combination were tested. Within each glove type the proportion of gloves that failed the water-leak test for each disinfectant was compared to that of the control using a non-inferiority design with a non-inferiority margin of five percentage points. Results were also aggregated by glove material, and combined for overall results. Findings: When aggregated by glove material, the dilute bleach exposure demonstrated the lowest difference in proportion failed between treatment and control arms: -2.5 percentage points (95% CI: -5.3 to 0.3) for nitrile, 0.6 percentage points (95% CI: -2.6 to 3.8) for non-powdered latex. For US-purchased gloves tested with six and ten applications of ABHR, the mean difference in failure risk between treatment and control gloves was within the prespecified non-inferiority margin of five percentage points or less, though some findings were inconclusive because confidence intervals extended beyond the non-inferiority margin. The aggregated difference in failure risk between treatment and control gloves was 3.5 percentage points (0.6 to 6.4) for soap and water, and 2.3 percentage points (-0.5 to 5.0) and 5.0 percentage points (1.8 to 8.2) for 10 and 6 applications of ABHR, respectively. The majority of leaks occurred in the interdigital webs (35%) and on the fingers (34%). Conclusion: Current guidelines do not recommend extended use of a single-use PPE under normal supply conditions. However, our findings indicate that some combinations of glove types and disinfection methods may allow for extended use under crisis conditions. We found that ten applications of dilute bleach solution have the least impact on glove integrity, compared to repeated applications of ABHR and soap and water. However, the majority of glove and exposure combinations were inconclusive with respect to non-inferiority with a 5 percentage point non-inferiority margin. Testing specific glove and disinfectant combinations may be worthwhile for settings facing glove shortages during which extended use is necessary. The modified water-leak testing method used here is a low-resource method that could easily be reproduced in different contexts.

  🖺 Full Text HTML: Physical integrity of medical exam gloves with repeated applications of disinfecting agents: evidence for extended use
• Development of a rapid SARS-CoV-2 neutralisation test by detecting antibodies that block interaction of spike protein receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) -

  The urgent need for a rapid and reliable Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising antibody detection test compatible with routine clinical laboratory testing currently exists. This is necessary to provide accurate estimates of immunity and to monitor vaccine effectiveness. Utilising Biochip Array Technology (BAT), the Randox SARS-CoV-2 Biochip proxy virus neutralisation test (pVNT) has been developed. Immobilising SARS-CoV-2 Spike RBD on the Biochip surface, innovative assay design enables direct sample addition to the Biochip well without the need for off-board sample pre-incubation step. Results are reported within 1.5 hours and testing is carried out without the prerequisite of live virus or biosafety level 3 (BSL3) laboratory facilities. In this study, assay validation is performed using recombinant antibodies and clinical samples and an excellent correlation against conventional virus neutralisation methods is established (100% clinical specificity and 98% clinical sensitivity). Serial dilution of samples with high neutralising antibody levels demonstrate end-point sample dilutions comparable with those obtained using the SARS-CoV-2 microneutralisation test. Species independent neutralising antibody detection capacity of the SARS-CoV-2 Biochip pVNT is also demonstrated. The findings of this study exemplifying the utility of the SARS-CoV-2 Biochip pVNT as a robust and reliable method for the accurate measurement of neutralising antibodies against SARS-CoV-2 and the availability of this test can now positively impact current testing deficiencies in this area.

  🖺 Full Text HTML: Development of a rapid SARS-CoV-2 neutralisation test by detecting antibodies that block interaction of spike protein receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2)
• SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern. -

  In this investigation we examined the magnitude, breadth, and durability of SARS-CoV-2 specific antibodies in two distinct B-cell compartments: long-lived plasma cell-derived antibodies in the plasma, and peripheral memory B-cells along with their associated antibody profiles elicited after in vitro stimulation. We found that magnitude varied amongst individuals, but was the highest in hospitalized subjects. Variants of concern (VoC) -RBD-reactive antibodies were found in the plasma of 72% of samples in this investigation, and VoC-RBD-reactive memory B-cells were found in all but 1 subject at a single time-point. This finding, that VoC-RBD-reactive MBCs are present in the peripheral blood of all subjects including those that experienced asymptomatic or mild disease, provides a reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to limit disease severity and transmission of variants of concern as they continue to arise and circulate.

  🖺 Full Text HTML: SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern.
• The COVID-19 pandemic storm in India subsides, but the calm is still far away -

  In May 2021, the number of new COVID-19 patients in India began to decline, as predicted by the generalized SIR-model (susceptible-infected-removed). The calculations of the final size of this pandemic wave and its duration probably were too pessimistic. New SIR simulations with the use of fresher datasets are necessary in order to update the predictions and to calculate the difference between the registered (laboratory-confirmed) and real number of cases.

  🖺 Full Text HTML: The COVID-19 pandemic storm in India subsides, but the calm is still far away
• Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan -
  To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.
  🖺 Full Text HTML: Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan
• Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir -
  Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3CL main protease inhibitor in vitro (IC50 value of 29 uM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3CL main protease inhibitor in vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.
  🖺 Full Text HTML: Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir

From Clinical Trials

• Study of Intravenous COVI-MSC for Treatment of COVID-19-Induced Acute Respiratory Distress - Condition:   Covid19
  Interventions:   Biological: COVI-MSC;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Treatment of COVID-19 Acute Respiratory Distress - Condition:   Covid19
  Interventions:   Biological: COVI-MSC;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study to Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 (US) - Condition:   Covid19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study to Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 (UK) - Condition:   Covid19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise - Condition:   Covid19
  Intervention:   Biological: COVI-MSC
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Intramuscular VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19 - Condition:   Covid19
  Intervention:   Biological: VIR-7831
  Sponsors:   Vir Biotechnology, Inc.;   GlaxoSmithKline
  Not yet recruiting

• CISCO-21 Prevent and Treat Long COVID-19. - Condition:   Covid19
  Intervention:   Other: Resistance Exercise
  Sponsors:   NHS Greater Glasgow and Clyde;   University of Glasgow;   Chief Scientist Office of the Scottish Government
  Not yet recruiting

• Leronlimab in Moderatelly Ill Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Leronlimab;   Drug: Placebo
  Sponsors:   Hospital Israelita Albert Einstein;   CytoDyn, Inc.
  Not yet recruiting

• Collecting Respiratory Sound Samples From Corona Patients to Extend the Diagnostic Capability of VOQX Electronic Stethoscope to Diagnose COVID-19 Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: Electronic stethoscope
  Sponsor:   Sanolla
  Recruiting

• To Evaluate the Safety and Efficacy of TQ Formula in Covid-19 Participants - Condition:   Covid19
  Intervention:   Drug: Black Seed Oil Cap/Tab
  Sponsor:   Novatek Pharmaceuticals
  Recruiting

• Leronlimab in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Leronlimab;   Drug: Placebo
  Sponsors:   Hospital Israelita Albert Einstein;   CytoDyn, Inc.
  Not yet recruiting

• CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19 - Condition:   Covid19
  Intervention:   Device: CRP-apheresis
  Sponsor:   University Hospital, Essen
  Recruiting

• A Proof of Concept Study for the DNA Repair Driven by the Mesenchymal Stem Cells in Critical COVID-19 Patients - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Mesenchymal Stem Cells Transplantation
  Sponsors:   SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi;   Istinye University;   Liv Hospital (Ulus)
  Completed

• Antigen Rapid Test Screening to Prevent SARS-CoV-2 Transmission (COVID-19) at Mass Gathering Events. - Condition:   Covid19
  Intervention:   Diagnostic Test: SARS-CoV-2 antigen rapid test
  Sponsors:   Norwegian Institute of Public Health;   University of Oslo
  Not yet recruiting

• Evaluation of the INDICAID™ COVID-19 Rapid Antigen Test - Condition:   Covid19
  Interventions:   Device: Rapid antigen testing and offsite PCR testing;   Device: Rapid antigen testing and onsite PCR testing
  Sponsor:   University of California, Los Angeles
  Completed

From PubMed

• Essential sufficiency of zinc, omega-3 polyunsaturated fatty acids, vitamin D and magnesium for prevention and treatment of COVID-19, diabetes, cardiovascular diseases, lung diseases and cancer - Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention and…

• SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment - Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry…

• SARS-CoV-2 infection and cancer: Evidence for and against a role of SARS-CoV-2 in cancer onset - Despite huge efforts towards understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis, little is known about the long-term consequences of the disease. Here, we critically review existing literature about oncogenesis as a potential long-term effect of SARS-CoV-2 infection. Like other viral infections, SARS-CoV-2 may promote cancer onset by inhibiting tumor suppressor genes. We conclude that, although unlikely, such hypothesis cannot be excluded a priori and we…

• A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2 - The COVID-19 pandemic calls for rapid development of effective treatments. Although various drug repurpose approaches have been used to screen the FDA-approved drugs and drug candidates in clinical phases against SARS-CoV-2, the coronavirus that causes this disease, no magic bullets have been found until now. In this study, we used directed message passing neural network to first build a broad-spectrum anti-beta-coronavirus compound prediction model, which gave satisfactory predictions on newly…

• An Integrated Computational and Experimental Approach to Identifying Inhibitors for SARS-CoV-2 3CL Protease - The newly evolved SARS-CoV-2 has caused the COVID-19 pandemic, and the SARS-CoV-2 main protease 3CLpro is essential for the rapid replication of the virus. Inhibiting this protease may open an alternative avenue toward therapeutic intervention. In this work, a computational docking approach was developed to identify potential small-molecule inhibitors for SARS-CoV-2 3CLpro. Totally 288 potential hits were identified from a half-million bioactive chemicals via a protein-ligand docking protocol….

• Marine Sponge is a Promising Natural Source of Anti-SARS-CoV-2 Scaffold - The current pandemic caused by SARS-CoV2 and named COVID-19 urgent the need for novel lead antiviral drugs. Recently, United States Food and Drug Administration (FDA) approved the use of remdesivir as anti-SARS-CoV-2. Remdesivir is a natural product-inspired nucleoside analogue with significant broad-spectrum antiviral activity. Nucleosides analogues from marine sponge including spongouridine and spongothymidine have been used as lead for the evolutionary synthesis of various antiviral drugs…

• Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2 - CONCLUSION: The presented RKI/ZBS1 SARS-CoV-2 protocol represents a cost-effective alternative in times of shortages when commercially available ready-to-use kits may not be available or affordable.

• Evaluation of Dual Inhibitory Effect of Anagliptin, Ramipril, and Lisinopril on Angiotensin-Converting Enzyme and DPP-4 Activities - CONCLUSION: It seems that while most ACE inhibitors cannot affect DPP-4 activity, inhibitors of DPP-4 vary in their effect on ACE activity. The selection of DPP-4 inhibitors under different clinical situations should take into account the action of these drugs on ACE.

• Identifying the molecular targets and mechanisms of xuebijing injection for the treatment of COVID-19 via network parmacology and molecular docking - Xuebijing Injection have been found to improve the clinical symptoms of COVID-19 and alleviate disease severity, but the mechanisms are currently unclear. This study aimed to investigate the potential molecular targets and mechanisms of the Xuebijing injection in treating COVID-19 via network pharmacology and molecular docking analysis. The main active ingredients and therapeutic targets of the Xuebijing injection, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt,…

• SARS-CoV-2 infection induces the activation of tissue factor-mediated coagulation by activation of acid sphingomyelinase - SARS-CoV-2 infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced…

• Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization - Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3…

• Combination of a Sindbis-SARS-CoV-2 spike vaccine and alphaOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity - The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world’s population at record speeds. However, there is still demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the…

• Evidence of neutralizing antibodies against SARS-CoV-2 in domestic cats living with owners with a history of COVID-19 in Lima - Peru - SARS-CoV-2 can infect a variety of wild and domestic animals worldwide. Of these, domestic cats are highly susceptible species and potential viral reservoirs. As such, it is important to investigate disease exposure in areas with active community transmission and high disease prevalence. In this report we demonstrate the presence of serum neutralizing antibodies against the receptor binding-domain (RBD) of the SARS-CoV-2 in cats whose owners had been infected with SARS-CoV-2 in Lima, Peru, using…

• Single-Molecule Dynamics of SARS-CoV-2 5’ Cap Recognition by Human eIF4F - Coronaviruses initiate translation through recognition of the viral RNA 5’ m ⁷ GpppA (m) cap by translation factor eIF4F. eIF4F is a heterotrimeric protein complex with cap-binding, RNA-binding, and RNA helicase activities. Modulating eIF4F function through cellular regulation or small-molecule inhibition impacts coronavirus replication, including for SARS-CoV-2. Translation initiation involves highly coordinated dynamics of translation factors with messenger or viral RNA. However, how the eIF4F…

• SARS-CoV-2 Nsp14 activates NF-kappaB signaling and induces IL-8 upregulation - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation…

From Patent Search

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

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

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

• DEEP LEARNING BASED SYSTEM FOR DETECTION OF COVID-19 DISEASE OF PATIENT AT INFECTION RISK - The present invention relates to Deep learning based system for detection of covid-19 disease of patient at infection risk. The objective of the present invention is to solve the problems in the prior art related to technologies of detection of covid-19 disease using CT scan image processing. - link

• A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link

• UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19 - - link

• 一种预判重症新冠肺炎（COVID-19）的标志物及其产品和用途 - 本发明提供了一种预判重症疾病的标志物，所述的预判重症疾病的标志物为S100A12，序列为SEQ ID NO.1，所述的重症疾病为重症新冠肺炎、重症感染中的一种。S100A12基因作为标志物，在预判重症疾病时对全血中的S100A12基因的表达水平进行检测即可，无需对白细胞进行分离，简化检测流程。S100A12的表达水平可以指导感染类疾病包括新冠肺炎重症的预判，从而及早施治，降低病死率，具有很好的临床应用前景。 - link

• INDICATING SYSTEM - A visual indicating system for use with a hospital bed, the hospital bed comprising a bed frame extending between a head end and a foot end of the bed frame, the visual indicating system comprising: an indicating member adapted to be coupled with the bed frame wherein the indicating member comprises an indicia for indicating one of a plurality of pre-determined health conditions.

  FIGURE 1 - link

• USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link

• 一种高灵敏SARS-CoV-2中和抗体的检测方法、检测试剂盒 - 本发明公开了一种高灵敏SARS‑CoV‑2中和抗体的检测方法、检测试剂盒，属于生物医学检测技术领域，本发明试剂盒包括层析试纸、卡壳和样本稀释液，所述层析试纸包括底板、样品垫、结合垫、NC膜和吸水垫，所述NC膜上依次设置有捕获线、检测线和质控线，所述捕获线包被有ACE2蛋白，所述检测线包被有RBD蛋白，所述结合垫设置有RBD蛋白标记物；本发明采用阻断法加夹心法原理提高检测中和抗体的灵敏度，通过添加捕获线的方式，将靶向RBD的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。 - link