Covid-19 Sentry

Contents

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

From Preprints

• PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship -

  Abstract Background The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLE9s first finding was that azithromycin and doxycycline were not effective. Aim To explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice. Design and Setting We compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). Methods We used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI). Results Azithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%. Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, p<0.0001), for every unit rise in confirmed COVID there was an associated 3% rise in prescription (IRR=1.026, 95%CI 1.024-1.0285, p<0.0001); whereas these measures were static for doxycycline. Conclusion PRINCIPLE trial flags scope for improvement in antimicrobial stewardship.

  🖺 Full Text HTML: PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship
• Estimation of infection rate and the population size potentially exposed to SARS-CoV-2 in Japan during 2020 -

  Background: The infectious respiratory disease COVID-19, caused novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached pandemic status during 2020. The primary statistic data are important to survey the actual circumstances of COVID-19. Here, we report the analysis of the primary data of COVID-19 in Japan during 2020. Methods: Data were collected and released systematically under Japan domestic law. Machine learning was conducted to estimate the positive rate in Japan and four prefectures (Tokyo, Osaka, Chiba, and Fukuoka). Results: Primary data analysis revealed there were at least two peaks of infection in Japan; the first one was during April 2020 and the second one started from November 1, 2020. Estimating the positive rate in Japan as well as in the four prefectures reinforced the above observations. The positive rate in Japan during 2020 was estimated to be around 6% to 8%. We also estimated that 1.95 million people were possibly exposed to the novel virus on October 31, 2020. The numbers of related deaths were over 3,000 people at the end of 2020. Conclusion: We estimated the infection rate of SARS-CoV-2 in Japan to be 6 and 8% in 2020. We also concluded that Japan had at least two infection-spreading periods, the first one being from Jan 19, 2020 until May 2020, and the second one beginning from November 1, 2020. Importantly, our analysis supports the need for clear definition of the criteria for conducting confirmation tests before embarking on data analysis.

  🖺 Full Text HTML: Estimation of infection rate and the population size potentially exposed to SARS-CoV-2 in Japan during 2020
• Usability of saliva collection devices for SARS-CoV-2 diagnostics -

  There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems because it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. These devices enabled the safe collection of saliva that was acceptable for SARS-CoV-2 diagnostic testing.

  🖺 Full Text HTML: Usability of saliva collection devices for SARS-CoV-2 diagnostics
• Point-of-care evaluation of a rapid antigen test (CLINITEST Rapid COVID-19 Antigen Test) for diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals -

  Rapid antigen assays (RAD) based on lateral flow immunochromatography (LFIC) technology have emerged as a valuable tool for the control of COVID-19 pandemic. Manufacturer‐independent, real‐world evaluation of these assays is crucial given the considerable heterogeneity reported in their clinical and analytical performances. Here, we report for the first time on the point-of-care performance of the CLINITEST Rapid COVID-19 Antigen Test (Siemens, Healthineers, Erlangen, Germany) to detect SARS-CoV-2 infection in presumptive COVID-19 cases or asymptomatic close contacts of COVID-19 patients. When compared to RT-PCR, the overall sensitivity of the assay was 80.2 (95% CI, 70.9-87.1) for symptomatic patients sampled (nasopharyngeal specimens) within five days after the onset of symptoms and 60% (95% CI, 40.7-76.6%) for asymptomatic participants. The overall specificity was 100% in both population groups.

  🖺 Full Text HTML: Point-of-care evaluation of a rapid antigen test (CLINITEST Rapid COVID-19 Antigen Test) for diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals
• COVID-19 Can Exacerbate Pattern Hair Loss and Trigger Telogen Effluvium – The Role of Proteoglycan Replacement Therapy with Nourkrin® in Clinical Treatment of COVID-19 Associated Hair Loss -
  The unfolding coronavirus disease 2019 (COVID-19) has increased the incidence of several dermatological disorders, including diffuse hair loss. Observational studies revealed an escalated incidence of pattern hair loss (PHL) and telogen effluvium (TE) in COVID-19 patients. Psychological stress, systemic inflammation and oxidative stress are potential culprits. Reduced anagenic expression of proteoglycans is a potential mediating mechanism that connects hair loss to critical health conditions such as COVID-19. Proinflammatory cytokines and stress hormones negatively affect the normal metabolism of proteoglycans, which are known regulators of the hair growth cycle. Anagen shortening and hair miniaturisation are thus conceivable consequences of a resultant hypofunctional follicular matrix. In this review, we discuss the association between COVID-19 and diffuse hair loss and elucidate the position of proteoglycan replacement therapy (PRT) using Nourkrin® with Marilex® in addressing the dysmetabolism of proteoglycans in COVID-19. PRT with Nourkrin® is a hair loss treatment with ‘anti-inflammatory’ and ‘hair growth cycle normalising’ effects. This treatment is shown to improve the histological severity of inflammation, suppress several proinflammatory cytokines and expand regulatory T-cell lineages in-vivo. Accordingly, Nourkrin® has potential in treating new-onset or aggravated PHL in COVID-19 survivors. In addition, bioactive proteoglycans in Marilex®, e.g., decorin and versican, exhibit anagen inducing and catagen suppressing properties, which help to reverse anagen shortening in stress-induced TE. Further clinical investigation of PRT in COVID-19 survivors through controlled trials and real-world studies is warranted. In conclusion, Nourkrin® can be considered as a safe treatment to prevent and treat COVID-19 related PHL and TE.
  🖺 Full Text HTML: COVID-19 Can Exacerbate Pattern Hair Loss and Trigger Telogen Effluvium – The Role of Proteoglycan Replacement Therapy with Nourkrin® in Clinical Treatment of COVID-19 Associated Hair Loss
• Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats -
  An explosion of recent findings firmly demonstrated that brain activity and cognitive function in rodents and humans are modulated synchronously with nasal respiration. Rhythmic respiratory (RR) coupling of wide-spread forebrain activity was confirmed using advanced techniques, including current source density analysis, single unit firing, and phase modulation of local gamma activity, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) allowing dynamic PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (~2 Hz) at rest, outside of the short sniffing bouts. We found strong and stable OB-PFC coherence, contrasting OB-HC coherence which was low but highly variable. PFC-HC coupling, however, primarily correlated with the latter, indicating that HC access to the PFC output is dynamically regulated by the responsiveness of HC to the common rhythmic drive. This pattern was present in both theta and non-theta states of waking, whereas PFC-HC communication appeared protected from RR synchronization in sleep states. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the OB epithelium due to infections, such as in COVID-19.
  🖺 Full Text HTML: Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats
• Several SARS-Cov2 variants with large (72, 89, 96) deletions in the spike protein, circulating globally since Covid19 began - B.1.351 mutations accumulate on top of this, explaining poor results of J&J vaccine in South Africa -
  The Covid19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov2 [1,2]) has caused significant mortality globally [3], along with severe socio-economic damage [4,5]. Many vaccines have been given emergency authorization in different countries [6,7]. Mutations raise concerns about these vaccines efficiencies [8] and re-infections [9]. Researchers lately have identified variants (with multiple single mutations, like N501Y and E484K) from different countries (B.1.1.7, B.1.351 and P.1) which are assumed to be more transmissible [10]. There have been reports of small deletions [11]. Here, I report large deletions in multiple parts of the spike protein - these exact protein sequences occur in different countries in different time-frames, (sometimes as early as Jan 2020), making it very unlikely that these are sequencing artifacts. This has probably escaped detection since sometimes sequencing fails to generate the complete genome - filling the missing parts with ”N”, which translates in ”X” as a protein. When there are stretches of this, computational programs looking for mutations ignore these. Also, this happens if one assembles based on a reference genome. A denovo assembly would have given the correct genome, with deletions.
  🖺 Full Text HTML: Several SARS-Cov2 variants with large (72, 89, 96) deletions in the spike protein, circulating globally since Covid19 began - B.1.351 mutations accumulate on top of this, explaining poor results of J&J vaccine in South Africa
• Highlighting COVID-19 Racial Disparities Reduces Fear and Support for Safety Precautions -
  U.S. media has extensively covered racial disparities in COVID-19 infections and deaths. In two preregistered studies, we examined how the association between people of color and COVID-19 impacts White U.S. residents’ attitudes toward COVID-19 and people of color. Utilizing a correlational design (N = 498), we found that awareness of COVID-19 racial disparities predicted reduced fear of COVID-19 and race-related social distancing. Next, we manipulated exposure to information about COVID-19 racial disparities (N = 1,505). Reading about the systemic causes of COVID-19 racial disparities reduced support for COVID-19 safety precautions and empathy for those vulnerable to COVID-19, reduced fear of COVID-19, and increased bias against people of color. These findings have important implications for understanding how public health information may perpetuate systemic racial inequalities.
  🖺 Full Text HTML: Highlighting COVID-19 Racial Disparities Reduces Fear and Support for Safety Precautions
• Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike glycoprotein S1 and its inhibition by dexamethasone -
  An understanding of the pathological inflammatory mechanisms involved in SARS CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 spike glycoprotein. In this study, the effects of a recombinant SARS CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNF, IL-6, IL-1{beta} and IL-8. However, pre-treatment with dexamethasone (100 nM) caused a significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-{kappa}B p65 and I{kappa}B, while increasing I{kappa}B degradation. DNA binding of NF-{kappa}B p65 was also significantly increased following stimulation with S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 M) resulted in inhibition of S1-induced NF-{kappa}B activation. Activation of p38 MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment produced significant inhibition of S1-induced activation of NLRP3/caspase 1. Further experiments revealed that S1-induced increase in the production of TNF, IL-6, IL-1{beta} and IL-8 was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1{beta} production. These results suggest that SARS-CoV-2 spike glycoprotein S1 stimulate PBMCs to release pro inflammatory cytokines through mechanisms involving activation of NF-{kappa}B, p38 MAPK and NLRP3 inflammasome. It is proposed that clinical benefits of dexamethasone in COVID-19 is possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.
  🖺 Full Text HTML: Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike glycoprotein S1 and its inhibition by dexamethasone
• Variation in predicted COVID-19 risk among lemurs and lorises -
  The novel coronavirus SARS-CoV-2, which in humans leads to the disease COVID-19, has caused global disruption and more than 1.5 million fatalities since it first emerged in late 2019. As we write, infection rates are currently at their highest point globally and are rising extremely rapidly in some areas due to more infectious variants. The primary viral target is the cellular receptor angiotensin-converting enzyme-2 (ACE2). Recent sequence analyses of the ACE2 gene predicts that many nonhuman primates are also likely to be highly susceptible to infection. However, the anticipated risk is not equal across the Order. Furthermore, some taxonomic groups show high ACE2 amino acid conservation, while others exhibit high variability at this locus. As an example of the latter, analyses of strepsirrhine primate ACE2 sequences to date indicate large variation among lemurs and lorises compared to other primate clades despite low sampling effort. Here, we report ACE2 gene and protein sequences for 71 individual strepsirrhines, spanning 51 species and 19 genera. Our study reinforces previous results and finds additional variability in other strepsirrhine species, and suggests several clades of lemurs have high potential susceptibility to SARS-CoV-2 infection. Troublingly, some species, including the rare and Endangered aye-aye (Daubentonia madagascariensis), as well as those in the genera Avahi and Propithecus, may be at high risk. Given that lemurs are endemic to Madagascar and among the primates at highest risk of extinction globally, further understanding of the potential threat of COVID-19 to their health should be a conservation priority. All feasible actions should be taken to limit their exposure to SARS-CoV-2.
  🖺 Full Text HTML: Variation in predicted COVID-19 risk among lemurs and lorises
• Molecular dynamics simulation study of effects of key mutations in SARS-CoV-2 on protein structures -
  SARS-CoV-2 has been spreading rapidly since 2019 and has produced large-scale mutations in the genomes. Differences in gene sequences may lead to changes in protein structure and traits, which would have a great impact on the epidemiological characteristics. In this study, we selected the key mutations of SARS-CoV-2, including D614G and A222V of S protein and Q57H of ORF3a protein, to conduct molecular dynamics simulation and analysis on the structures of the mutant proteins. The results suggested that D614G improved the stability of S protein, while A222V enhanced the ability of protein to react with the outside environment. Q57H enhanced the structural flexibility of ORF3a protein. Our findings could complete the mechanistic link between genotype--phenotype--epidemiological characteristics in the study of SARS-CoV-2. We also found no significant changes in the antigenicity of S protein, ORF3a protein and their mutants, which provides reference for vaccine development and application.
  🖺 Full Text HTML: Molecular dynamics simulation study of effects of key mutations in SARS-CoV-2 on protein structures
• Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2 -
  Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, we predict that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds nucleoside triphosphates at its proposed active site. Additionally, using molecular docking we have predicted the binding of three widely used kinase inhibitors and five well characterized anti-microbial compounds at the NiRAN domain active site along with their drug-likeliness as well as DFT properties. For the first time ever, using basic biochemical tools, this study shows the presence of a kinase like activity exhibited by the SARS-CoV-2 RdRp. Interestingly, the proposed kinase inhibitors and a few of the predicted nucleotidyl transferase inhibitors significantly inhibited the aforementioned enzymatic activity. In line with the current global COVID-19 pandemic urgency and the emergence of newer strains with significantly higher infectivity, this study provides a new anti-SARS-CoV-2 drug target and potential lead compounds for drug repurposing against SARS-CoV-2.
  🖺 Full Text HTML: Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2
• A high-throughput radioactivity-based assay for screening SARS-CoV-2 nsp10-nsp16 complex -
  Frequent outbreaks of novel coronaviruses (CoVs), highlighted by the current SARS-CoV-2 pandemic, necessitate the development of therapeutics that could be easily and effectively administered world-wide. The conserved mRNA-capping process enables CoVs to evade their host immune system and is a target for antiviral development. Nonstructural protein (nsp) 16 in complex with nsp10 catalyzes the final step of coronaviral mRNA-capping through its 2'-O-methylation activity. Like other methyltransferases, SARS-CoV-2 nsp10-nsp16 complex is druggable. However, the availability of an optimized assay for high-throughput screening (HTS) is an unmet need. Here, we report the development of a radioactivity-based assay for methyltransferase activity of nsp10-nsp16 complex in a 384-well format, and kinetic characterization, and optimization of the assay for HTS (Z'-factor: 0.83). Considering the high conservation of nsp16 across known CoV species, the potential inhibitors targeting SARS-CoV-2 nsp10-nsp16 complex may also be effective against other emerging pathogenic CoVs.
  🖺 Full Text HTML: A high-throughput radioactivity-based assay for screening SARS-CoV-2 nsp10-nsp16 complex
• Multi-specific DARPin(R) therapeutics demonstrate very high potency against mutated SARS-CoV-2 variants in vitro -
  The SARS-CoV-2 virus responsible for the COVID-19 pandemic has so far infected more than 100 million people globally, and continues to undergo genomic evolution. Emerging SARS-CoV-2 variants show increased infectivity and may lead to resistance against immune responses of previously immunized individuals or existing therapeutics, especially antibody-based therapies. Several monoclonal antibody therapeutics authorized for emergency use or in development start to lose potency against various SARS-CoV-2 variants. Cocktails of two different monoclonal antibodies constitute a promising approach to protect against such variants as long as both antibodies are potent, but come with increased development complexity and therefore cost. As an alternative, we developed two multi-specific DARPin(R) therapeutics, each combining three independent DARPin(R) domains binding the SARS-CoV-2 spike protein in one molecule, to potently neutralize the virus and overcome virus escape. Here, we show in a panel of in vitro studies that both multi-specific DARPin(R) therapeutics, ensovibep (MP0420) and MP0423, are highly potent against the new circulating SARS-CoV-2 variants B.1.1.7 (UK variant) and B.1.351 (South African variant) and the most frequent emerging mutations in the spike protein. Additionally, viral passaging experiments show potent protection by ensovibep and MP0423 against development of escape mutations. Furthermore, we demonstrate that the cooperative binding of the individual modules in a multi-specific DARPin(R) antiviral is key for potent virus inhibition and protection from escape variants. These results, combined with the relatively small size and high production yields of DARPin(R) molecules, suggests ensovibep and MP0423 as superior alternatives to monoclonal antibody cocktails for global supply and demonstrate the strength of the DARPin(R) platform for achieving potent and lasting virus inhibition for SARS-CoV-2 and possibly other viruses.
  🖺 Full Text HTML: Multi-specific DARPin(R) therapeutics demonstrate very high potency against mutated SARS-CoV-2 variants in vitro
• Impact of the B.1.1.7 variant on neutralizing monoclonal antibodies recognizing diverse epitopes on SARS-CoV-2 Spike -
  The interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the ACE2 receptor on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, the N-terminal domain (NTD) and S2 subunits of Spike. To fully understand how these mutations affect the antigenicity of Spike, we have isolated and characterized neutralizing antibodies targeting epitopes beyond the already identified RBD epitopes. Using recombinant Spike as a sorting bait, we isolated >100 Spike-reactive monoclonal antibodies from SARS-CoV-2 infected individuals. {approx}45% showed neutralizing activity of which {approx}20% were NTD-specific. None of the S2-specific antibodies showed neutralizing activity. Competition ELISA revealed that NTD-specific mAbs formed two distinct groups: the first group was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Importantly, mutations present in B.1.1.7 Spike frequently conferred resistance to neutralization by the NTD-specific neutralizing antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes need to be considered when investigating antigenic drift in emerging variants.
  🖺 Full Text HTML: Impact of the B.1.1.7 variant on neutralizing monoclonal antibodies recognizing diverse epitopes on SARS-CoV-2 Spike

From Clinical Trials

• Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

• Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition:   Covid19
  Interventions:   Drug: Placebo;   Drug: Fluvoxamine
  Sponsor:   SigmaDrugs Research Ltd.
  Recruiting

• TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition:   Covid19
  Intervention:   Drug: Tocilizumab
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• Convalescent Plasma in the Treatment of Covid-19 - Condition:   Covid19
  Interventions:   Biological: Convalescent plasma from COVID-19 donors;   Biological: Placebo
  Sponsors:   Helsinki University Central Hospital;   Finnish Red Cross
  Recruiting

• A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19 - Condition:   Severe COVID-19
  Interventions:   Drug: VB-201 + Standard of care;   Drug: Standard of care
  Sponsor:   Vascular Biogenics Ltd. operating as VBL Therapeutics
  Recruiting

• Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition:   Covid-19
  Intervention:   Other: ivermectin impregnated mask
  Sponsor:   South Valley University
  Recruiting

• An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition:   Covid19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Doxycycline Tablets;   Drug: Placebo
  Sponsor:   Max Health, Subsero Health
  Recruiting

• COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition:   Covid19
  Interventions:   Biological: Omalizumab;   Other: Placebo
  Sponsor:   McGill University Health Centre/Research Institute of the McGill University Health Centre
  Not yet recruiting

• CPI-006 Plus Standard of Care Versus Placebo Plus Standard of Care in Mild to Moderately Symptomatic Hospitalized Covid-19 Patients - Condition:   Covid-19
  Interventions:   Drug: CPI-006 2 mg/kg + SOC;   Drug: CPI-006 1 mg/kg + SOC;   Drug: Placebo + SOC
  Sponsor:   Corvus Pharmaceuticals, Inc.
  Recruiting

• Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Biological: Placebo
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   West China Hospital
  Not yet recruiting

• Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Ivermectin
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition:   Covid-19
  Interventions:   Drug: Famotidine;   Drug: Placebo
  Sponsors:   Northwell Health;   Cold Spring Harbor Laboratory
  Recruiting

• Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 - Conditions:   Severe Acute Respiratory Syndrome Coronavirus 2;   COVID-19
  Interventions:   Drug: SNG001;   Drug: Placebo
  Sponsor:   Synairgen Research Ltd.
  Recruiting

From PubMed

• Complement inhibition initiated recovery of a severe myasthenic crisis with COVID-19 - We report on a patient with refractory Myasthenia gravis with acetylcholine receptor antibodies with two prior myasthenic crises suffering from COVID-19 with rapid evolving weakness and respiratory failure. Respiratory failure developed and prolonged mechanical ventilation was necessary. After plasmapheresis, residual, severe generalized and bulbar weakness persisted. Complement inhibition with eculizumab was, therefore, introduced and lead to rapid recovery. In refractory myasthenic crisis...

• Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study - A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness...

• Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity - Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the...

• Analogue discovery of safer alternatives to HCQ and CQ drugs for SAR-CoV-2 by computational design - COVID-19 outbreak poses a severe health emergency to the global community. Due to availability of limited data, the selection of an effective treatment is a challenge. Hydroxychloroquine (HCQ), a chloroquine (CQ) derivative administered for malaria and autoimmune diseases, has been shown to be effective against both Severe Acute Respiratory Syndrome (SARS-CoV-1) and SARS-CoV-2. Apart from the known adverse effects of these drugs, recently the use of CQ and HCQ as a potential treatment for...

• Repurposing of Tetracyclines for COVID-19 Neurological and Neuropsychiatric Manifestations: A Valid Option to Control SARS-CoV-2-Associated Neuroinflammation? - The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not...

• SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4 - Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in...

• Prediction of Single Point Mutations in Human Coronavirus and Their Effects on Binding to 9-O-Acetylated Sialic Acid and Hidroxychloroquine - Due to the current spreading of the new disease CoViD-19, the World Health Organization formally declared a world pandemic on March 11, 2020. The present trends indicate that the pandemic will have an enormous clinical and economic impact on population health. Infections are initiated by the transmembrane spike (S) glycoproteins of human coronavirus (hCoV) binding to host receptors. Ongoing research and therapeutic product development are of vital importance for the successful treatment of...

• Graphene Sheets with Defined Dual Functionalities for the Strong SARS-CoV-2 Interactions - Search of new strategies for the inhibition of respiratory viruses is one of the urgent health challenges worldwide, as most of the current therapeutic agents and treatments are inefficient. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic and has taken lives of approximately two million people to date. Even though various vaccines are currently under development, virus, and especially its spike glycoprotein can mutate, which highlights a need for a...

• Computational and Experimental Studies Reveal That Thymoquinone Blocks the Entry of Coronaviruses Into In Vitro Cells - CONCLUSION: Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.

• SARS-CoV-2 recruits a haem metabolite to evade antibody immunity - The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune...

• Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection - The interferon response is a potent antiviral defense mechanism, but its effectiveness depends on its timing relative to viral replication. Here, we report viral replication and host response kinetics in patients at the start of SARS-CoV-2 infection and explore the impact of these kinetics experimentally. In both longitudinal patient nasopharyngeal samples and airway epithelial organoids, we found that SARS-CoV-2 initially replicated exponentially with a doubling time of ∼6hr, and induced...

• Genome-scale metabolic modeling reveals SARS-CoV-2-induced host metabolic reprogramming and identifies metabolic antiviral targets - Tremendous progress has been made to control the COVID-19 pandemic, including the development and approval of vaccines as well as the drug remdesivir, which inhibits the SARS-CoV-2 virus that causes COVID-19. However, remdesivir confers only mild benefits to a subset of patients, and additional effective therapeutic options are needed. Drug repurposing and drug combinations may represent practical strategies to address these urgent unmet medical needs. Viruses, including coronaviruses, are known...

• Aurintricarboxylic acid and its metal ion complexes in comparative virtual screening versus Lopinavir and Hydroxychloroquine in fighting COVID-19 pandemic: synthesis and characterization - The salt of Aurintricarboxylic acid (ATA) was utilized in this study to synthesize new alkaline earth metal ion complexes. The analytical results proposed the isolation of mononuclear (Sr^(+2)&Ba(+2)) and binuclear complexes (Mg^(+2)&Ca(+2)). These complexes were analyzed by available analytical and spectral techniques. The tetrahedral geometry was suggested for all complexes (SP³) through bidentate binding mode of ligand with each central atom. UV-Vis spectra reveal the influence of L→M...

• Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors - The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses. We report a substantive body of structural, biochemical, and virus replication studies that...

• Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity - The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory...

From Patent Search

• SARS-CoV-2 antibodies - - link

• SARS-CoV-2 antibodies - - link

• A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link

• TREATMENT OF COVID-19 WITH REBAMIPIDE - - link

• METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link

• A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link

• Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -

  Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.

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• 一种医用可佩戴式防护口鼻的微型气幕系统 - 本发明公开了一种医用可佩戴式防护口鼻的微型气幕系统，包括框柱，框柱一侧开凿有气幕送风口和呼吸用送风口，气幕送风口和呼吸用送风口内分别连接有软管一和软管二，框柱内开凿有水平条缝和垂直条缝，水平条缝与垂直条缝均与气幕送风口相连通，框柱靠近水平条缝的一侧贯穿开凿有出风口，出风口内设有滤网，出风口贯穿框柱的一端连接有高效过滤器，滤网与高效过滤器之间连接有吸气泵，框柱靠近出风口的一侧连接有电池和开关。本发明通过提出一种在口腔处应用洁净空气幕阻挡气溶胶传播的可佩戴装置，可以在口腔类相关诊疗过程，保护医生和周围人的健康，避免引起可能引发的呼吸道疾病交叉感染。 - link

• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• Vorrichtung umfassend einen Schutzschirm und einen Filter zum Herausfiltern von Viren aus einem Schall erzeugenden Luftstrom -

  Vorrichtung (10) umfassend einen Schutzschirm (12) und einen Filter (14) zum Herausfiltern von Viren (16) aus einem Schall erzeugenden Luftstrom (18), der von einem Musiker (20) beim Musizieren mit einem Musikinstrument oder beim Singen erzeugt wird, wobei der Schutzschirm (12) zur Verringerung des Risikos einer Infektion mit den Viren (16) dafür vorgesehen ist, wenigstens einen Teil der mit dem Luftstrom transportierten Viren (16) aufzufangen, der Schutzschirm (12) eine erste Seite (22) und eine zweite Seite (24) aufweist, die voneinander abgewandt sind, und der Schutzschirm (12) wenigstens einen sich von der ersten (22) bis zu der zweiten Seite (24) erstreckenden Durchlass (26) aufweist, wobei dieser Durchlass (26) zum Durchströmen mit wenigstens einem Teil des beim Musizieren erzeugten Luftstroms (18) vorgesehen ist und der Filter (14) zum Herausfiltern von Viren (16) aus dem Luftstrom (18) in dem Durchlass (26) des Schutzschirms (12) angeordnet ist.

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