Covid-19 Sentry

Contents

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

From Preprints

• Music for hedonia and eudaimonia during pandemic social isolation -
  The pandemic spread of the novel coronavirus and associated COVID-19 disease in 2020 prompted governments around the world to pursue strict containment protocols to minimize contagion risk. Although restrictions were interpreted more strictly in some countries than in others, widespread social isolation resulted on an unseen scale, leading to severe negative mental health consequences such as loss of hope, increased anxiety, stress, depressive symptoms, and sleep disturbance. During this time, while governments were battling the health crisis, musical engagement provided key, individualized coping strategies for laypeople. This was first demonstrated anecdotally in captivating balcony music videos from Italy and Spain and later substantiated in large scale, multi-country survey studies. This chapter reviews the emerging research literature on music listening and making during pandemic lockdown to establish how music became a compensatory source of hedonic pleasure and how it satisfied the need for eudaimonic meaning in life during socially and psychologically impoverished times.
  🖺 Full Text HTML: Music for hedonia and eudaimonia during pandemic social isolation
• Discovery of highly potent pancoronavirus fusion inhibitors that also effectively inhibit COVID-19 variants from the UK and South Africa -
  We report the discovery of a series of benzoic acid-based inhibitors that show highly potent pancoronavirus activity. Some compounds also show complete inhibition of CPE (IC100) at 1.25 M against an authentic SARS-CoV-2 (US_WA-1/2020). Furthermore, the most active inhibitors also potently inhibited variants initially identified in the UK and South Africa. We confirmed that one of the potent inhibitors binds to the prefusion spike protein trimer of SARS- CoV-2 by SPR. Besides, we showed that they inhibit virus-mediated cell-cell fusion. The ADME data show druglike characteristics, and in vivo PK in rats demonstrated excellent half-life (t[1/2]) of 11.3 h, mean resident time (MRT) of 14.2 h, and orally bioavailable. Despite the presence of ene-rhodamine moiety, we conclusively demonstrated that these inhibitors target the viral spike protein and are not promiscuous or colloidal aggregators. We expect the lead inhibitors to pave the way for further development to preclinical and clinical candidates.
  🖺 Full Text HTML: Discovery of highly potent pancoronavirus fusion inhibitors that also effectively inhibit COVID-19 variants from the UK and South Africa
• Optimization of single dose VSV-based COVID-19 vaccination in hamsters -
  The ongoing COVID-19 pandemic has resulted in global effects on human health, economic stability, and social norms. The emergence of viral variants raises concerns about the efficacy of existing vaccines and highlights the continued need the for the development of efficient, fast-acting, and cost-effective vaccines. Here, we demonstrate the immunogenicity and protective efficacy of two vesicular stomatitis virus (VSV)-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV). Intranasally vaccinated hamsters showed an early CD8+ T cell response in the lungs and a greater antigen-specific IgG response, while intramuscularly vaccinated hamsters had an early CD4+ T cell and NK cell response. Intranasal vaccination resulted in protection within 10 days with hamsters not showing clinical signs of pneumonia when challenged with three different SARS-CoV-2 variants. This data demonstrates that VSV-based vaccines are viable single-dose, fast- acting vaccine candidates that are protective from COVID-19.
  🖺 Full Text HTML: Optimization of single dose VSV-based COVID-19 vaccination in hamsters
• Schema Playground: A tool for authoring, extending, and using metadata schemas to improve FAIRness of biomedical data -
  Background: Biomedical researchers are strongly encouraged to make their research outputs more Findable, Accessible, Interoperable, and Reusable (FAIR). While many biomedical research outputs are more readily accessible through open data efforts, finding relevant outputs remains a significant challenge. Schema.org is a metadata vocabulary standardization project that enables web content creators to make their content more FAIR. Leveraging schema.org could benefit biomedical research resource providers, but it can be challenging to apply schema.org standards to biomedical research outputs. We created an online browser-based tool that empowers researchers and repository developers to utilize schema.org or other biomedical schema projects. Results: Our browser-based tool includes features which can help address many of the barriers towards schema.org-compliance such as: The ability to easily browse for relevant schema.org classes, the ability to extend and customize a class to be more suitable for biomedical research outputs, the ability to create data validation to ensure adherence of a research output to a customized class, and the ability to register a custom class to our schema registry enabling others to search and re-use it. We demonstrate the use of our tool with the creation of the Outbreak.info schema–a large multi-class schema for harmonizing various COVID-19 related resources. Conclusions: We have created a browser-based tool to empower biomedical research resource providers to leverage schema.org classes to make their research outputs more FAIR.
  🖺 Full Text HTML: Schema Playground: A tool for authoring, extending, and using metadata schemas to improve FAIRness of biomedical data
• Effectiveness of COVID-19 Vaccines Against SARS-CoV-2 Infection During a Delta Variant Epidemic Surge in Multnomah County, Oregon, July 2021 -

  Background: Coronavirus disease 2019 (COVID-19) vaccines have been shown to be highly effective in preventing SARS-CoV-2 infection within controlled trials and real-world vaccine effectiveness (VE) studies. Recent reports have estimated reduced VE with the emergence and dissemination of the B.1.617.2 variant (Delta variant). During July 2021, Multnomah County experienced an epidemic expansion coinciding with increased Delta variant prevalence. We assess COVID-19 VE during this time. Methods: A test-negative design (TND) matched case-control analysis was performed to estimate the effectiveness of vaccination against SARS-CoV-2 infection during July 2021. Cases included a random sample of individuals that tested positive for SARS-CoV-2 and were reported by electronic laboratory report, were >15 years of age, and had no prior known SARS-CoV-2 infections. Controls were age and postal code matched individuals that tested negative for SARS-CoV-2 during July 2021. Immunization status was assessed using the Oregon ALERT Immunization Information system (ALERT IIS). Results: 500 case-control pairs were matched (n=1000). Overall effectiveness of any completed COVID-19 immunization was 73% (95% Confidence Interval [CI] 49-86%) and 74% (95% CI 65-85%) for mRNA immunizations and 72% (95% CI 47-85%) for individuals that had started but not completed mRNA immunizations. Conclusions: Our findings estimate high, yet reduced, VE during Delta variant dissemination. These results highlight the importance of COVID-19 immunizations for reducing SARS-CoV-2 infection while juxtaposing the need for additional non- pharmaceutical interventions. Importantly, the reduced VE identified here may predict future reductions in vaccine performance in the context of ongoing viral genetic drift.

  🖺 Full Text HTML: Effectiveness of COVID-19 Vaccines Against SARS-CoV-2 Infection During a Delta Variant Epidemic Surge in Multnomah County, Oregon, July 2021
• Mathematical modeling and adequate environmental sampling plans are essential for the public health assessment of COVID-19 pandemics: development of a monitoring indicator for SARS-CoV-2 in wastewater -

  Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low- income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in WWTPs has been proposed as an alternative tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator WWI that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater. This method has been successfully applied in the context of Obepine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th

2020. On August 26th, 2021, 168 WWTPs were monitored twice a week in the metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement or even a credible alternative to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.
      🖺 Full Text HTML: Mathematical modeling and adequate environmental sampling plans are essential for the public health assessment of COVID-19 pandemics: development of a monitoring indicator for SARS-CoV-2 in wastewater

• Immune response elicited from heterologous SARS-CoV-2 vaccination: Sinovac (CoronaVac) followed by AstraZeneca (Vaxzevria) -

  Limited COVID-19 vaccines in many countries have delayed mass-immunization. Although individuals fully vaccinated with Vaxzevria (AstraZeneca) have higher antibody levels than those with CoronaVac (Sinovac), heterologous prime-boost with CoronaVac-Vaxzevria yielded comparable antibody levels to two-dose Vaxzevria. Combination use of different available vaccines may be warranted in Thailand, which faces limited vaccine choice and supply.

  🖺 Full Text HTML: Immune response elicited from heterologous SARS-CoV-2 vaccination: Sinovac (CoronaVac) followed by AstraZeneca (Vaxzevria)
• Sars-Cov-2 antibody titer 3 months post-vaccination is affected by age, gender, smoking and vitamin D. -

  Context Vaccination against Sars-Cov-2 is in full swing during COVID-19 pandemic. One of the efficient methods to evaluate response to vaccination is the assessment of humoral immunity by measuring Sars-Cov-2 antibody titer. Identification of factors that affect the humoral response is important so as to ameliorate the responses to vaccination or identify vulnerable groups that may need vaccination boosters. Objective We investigated the effect of anthropometric parameters (age, BMI), smoking, diabetes, statin use hypertension and levels of 25(OH)D and DHEAS to the Sars-Cov-2 antibody titer. Methods In this longitudinal observational cohort study 712 subjects were tested for Sars- Cov-2 antibodies 3 months after the second dose of BNT162b2 vaccine. Multiple linear regression analysis was performed to identify which factors are associated with the antibody titer. Results We identified age to be negatively associated with antibody titer (p=0.0073) and male sex (p=0.0008). However, interaction of age and gender was significant (p<0.0001) highlighting the finding that only after the age of 40 years men had lower antibody levels than women. DHEAS, an aging marker, was not associated with the antibody titer. Smoking was also associated with low antibody titer (p=0.0008) while overweight or obese subjects did not have different antibody response compared to normal weight individuals. Although diabetic and hypertensive subjects trended towards lower antibody titer, this association was not statistically significant. Replete vitamin D levels were associated with higher antibody titers (p=0.00422). Conclusions Age, male sex and smoking negatively affects antibody titer while 25(OH)D is associated with increased Sars- Cov-2 antibody titers.

  🖺 Full Text HTML: Sars-Cov-2 antibody titer 3 months post-vaccination is affected by age, gender, smoking and vitamin D.
• Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression -

  SARS-CoV-2 infection causes a wide spectrum of disease severity. Immune changes associated with severe disease include pro-inflammatory cytokine production and expansion of immature myeloid populations. The relative importance of the immunological changes in driving progression to severe disease remain poorly understood. We aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19. We sought to use tests available in an on-site diagnostic hospital laboratory to identify an immunological signature for severe disease development which could be detected prior to peak severity thereby allowing initiation of therapeutic interventions. We used univariate and multivariate analysis, including unbiased machine learning, to investigate the relationships between clinical and demographic characteristics, inflammatory markers, and leukocyte immunophenotypes with progression to severe disease in 108 patients and to rank these in importance. A combination of four features (elevated levels of interleukin-6 and C-reactive protein, coupled with reduced monocyte HLA-DR expression and reduced neutrophil CD10 expression), were strongly predictive of severe disease with an average prediction score of 0.925.

  🖺 Full Text HTML: Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression
• Wildlife in Cameroon harbor diverse coronaviruses including many isolates closely related to human coronavirus 229E -
  Zoonotic spillover of animal viruses into human populations is a continuous and increasing public health risk. SARS-CoV-2 highlights the global impact emergence events can have. Considering the history and diversity of coronaviruses (CoVs), especially in bats, SARS-CoV-2 will likely not be the last to spillover from animals into human populations. We sampled and tested wildlife in the central African country Cameroon to determine which CoVs are circulating and how they relate to previously detected human and animal CoVs. We collected animal and ecological data at sampling locations and used family-level consensus PCR combined with amplicon sequencing for virus detection. Between 2003 and 2018, samples were collected from 6,580 animals of several different orders. CoV RNA was detected in 175 bats, a civet, and a shrew. The CoV RNAs detected in the bats represented 17 different genetic clusters, coinciding with alpha (n=8) and beta (n=9) CoVs. Sequences resembling human CoV-229E (HCoV-229E) were found in 40 Hipposideridae bats. Phylogenetic analyses place the human derived HCoV-229E isolates closest to those from camels in terms of the S and N genes, but closest to isolates from bats for the E, M, and RdRp genes. The CoV RNA positivity rate in bats varied significantly (p<0.001) between the wet (8.2%) and dry season (4.5%). Most sampled species accordingly had a wet season high and dry season low, while for some the opposite was found. Eight of the suspected CoV species of which we detected RNA appear to be entirely novel CoV species, which suggests that CoV diversity in African wildlife is still rather poorly understood. The detection of multiple different variants of HCoV-229E-like viruses supports the bat reservoir hypothesis for this virus, with the phylogenetic results casting some doubt on camels as an intermediate host. The findings also support the previously proposed influence of ecological factors on CoV circulation, indicating a high level of underlying complexity to the viral ecology. These results indicate the importance of investing in surveillance activities among wild animals to detect all potential threats as well as sentinel surveillance among exposed humans to determine emerging threats.
  🖺 Full Text HTML: Wildlife in Cameroon harbor diverse coronaviruses including many isolates closely related to human coronavirus 229E
• SARS-CoV-2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an infectious disease characterized by strong induction of inflammatory cytokines, progressive lung inflammation and potentially multi-organ dysfunction. It remains unclear whether SARS-CoV-2 is sensed by pattern recognition receptors (PRRs) leading to immune activation. Several studies suggest that the Spike (S) protein of SARS-CoV-2 might interact with Toll-like receptor 4 (TLR4) and thereby activate immunity. Here we have investigated the role of TLR4 in SARS-CoV-2 infection and immunity. Neither exposure of isolated S protein, SARS-CoV-2 pseudovirus nor a primary SARS-CoV-2 isolate induced TLR4 activation in a TLR4-expressing cell line. Human monocyte-derived dendritic cells (DCs) express TLR4 but not ACE2, and DCs were not infected by a primary SARS-CoV-2 isolate. Notably, neither S protein nor the primary SARS- CoV-2 isolate induced DC maturation or cytokines, indicating that both S protein and SARS-CoV-2 virus particles do not trigger extracellular TLRs, including TLR4. Ectopic expression of ACE2 in DCs led to efficient infection by SARS-CoV-2. Strikingly, infection of ACE2-positive DCs induced type I IFN and cytokine responses, which was inhibited by antibodies against ACE2. These data strongly suggest that not extracellular TLRs but intracellular viral sensors are key players in sensing SARS-CoV-2. These data imply that SARS-CoV-2 escapes direct sensing by TLRs, which might underlie the lack of efficient immunity to SARS-CoV-2 early during infection.
  🖺 Full Text HTML: SARS-CoV-2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs
• Characterization of SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 on cell entry, host range, and sensitivity to convalescent plasma and ACE2 decoy receptor -
  Recently, highly transmissible SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 were identified in India with mutations within the spike proteins. The spike protein of Kappa contains four mutations E154K, L452R, E484Q and P681R, and Delta contains L452R, T478K and P681R, while B.1.618 spike harbors mutations {Delta}145-146 and E484K. However, it remains unknown whether these variants have altered in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies as well asNentry inhibitors. In this study, we found that Kappa, Delta or B.1.618 spike uses human ACE2 with no or slightly increased efficiency, while gains a significantly increased binding affinity with mouse, marmoset and koala ACE2 orthologs, which exhibits limited binding with WT spike. Furthermore, the P618R mutation leads to enhanced spike cleavage, which could facilitate viral entry. In addition, Kappa, Delta and B.1.618 exhibits a reduced sensitivity to neutralization by convalescent sera owning to the mutation of E484Q, T478K, {Delta}145-146 or E484K, but remains sensitive to entry inhibitors-ACE2-lg decoy receptor. Collectively, our study revealed that enhanced human and mouse ACE2 receptor engagement, increased spike cleavage and reduced sensitivity to neutralization antibodies of Kappa, Delta and B.1.618 may contribute to the rapid spread of these variants and expanded host range. Furthermore, our result also highlighted that ACE2-lg could be developed as broad-spectrum antiviral strategy against SARS-CoV-2 variants.
  🖺 Full Text HTML: Characterization of SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 on cell entry, host range, and sensitivity to convalescent plasma and ACE2 decoy receptor
• The impact of mental health and substance use issues on COVID-19 vaccine readiness: a cross sectional community- based survey in Ontario, Canada -

  Background: COVID-19 vaccines have been approved for use in Canada since December 2020. However, data about factors associated with vaccine hesitancy and the impact of mental health and/or substance use (MHSU) issues on vaccine uptake are currently not available. The goal of this study was to explore factors, particularly MHSU factors, that impact COVID-19 vaccination intentions in Ontario, Canada. Methods: A community-based cross-sectional survey with recruitment based on age, gender, and geographical location (to ensure a representative population of Ontario), was conducted in February 2021. Multinomial logistic regression was used to test the relationship between COVID-19 vaccination status and plans and sociodemographic background, social support, anxiety about contracting COVID-19, and MHSU concerns. Results: Of the total sample of 2528 respondents, 1932 (76.4%) were vaccine ready, 381 (15.1%) were hesitant, and 181 (7.1%) were resistant. Significant independent predictors of vaccine hesitancy compared with vaccine readiness included younger age (OR=2.11, 95%CI=1.62-2.74), female gender (OR=1.36, 95%CI=1.06-1.74), Black ethnicity (OR=2.11, 95%CI=1.19-3.75), lower education (OR=1.69, 95%CI=1.30-2.20), lower SES status (OR=.88, 95%CI=.84-.93), lower anxiety about self or someone close contracting COVID-19 (OR=2.06, 95%CI=1.50-2.82), and lower depression score (OR=.90, 95%CI=.82-.98). Significant independent predictors of vaccine resistance compared with readiness included younger age (OR=1.72, 95%CI=1.19-2.50), female gender (OR=1.57, 95%CI=1.10-2.24), being married (OR=1.50, 95%CI=1.04-2.16), lower SES (OR=.80, 95%CI=.74-.86), lower satisfaction with social support (OR=.78, 95%CI=.70-.88), lower anxiety about contracting COVID-19 (OR=7.51, 95%CI=5.18-10.91), and lower depression score (OR=.85, 95%CI=.76-.96). Interpretation: COVID-19 vaccination intention is affected by sociodemographic factors, anxiety about contracting COVID-19, and select mental health issues.

  🖺 Full Text HTML: The impact of mental health and substance use issues on COVID-19 vaccine readiness: a cross sectional community-based survey in Ontario, Canada
• Strengthening public COVID-19 response with private facilities in Kisumu, Kenya -

  INTRODUCTION: SARS-CoV-2 testing is one of the options to combat COVID-19 in Kenya. In the first COVID-19 year there was limited tapping of the private sector9s potential to scale up testing in Kenya. In April 2020, we initiated a unique public-private partnership (PPP) project in Kisumu County connecting the private sector to centralized testing supported by the ministry of health (MoH), COVID-Dx, to accelerate the local response to COVID-19. Within COVID-Dx, we aimed to demonstrate this PPP9s performance as a replicable model for effective public-private collaboration in responding to the COVID-19 pandemic in similar settings. METHODS: KEMRI, Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities collaborated in COVID-Dx. COVID-Dx was implemented from June 01, 2020, to March 31, 2021, in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the MoH COVID-19 case definition. Samples were tested at the central laboratory in KEMRI via SARS-CoV-2 RT-PCR. Healthcare workers in participating facilities collected data using the digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboard to all relevant stakeholders. We did descriptive statistical analyses using Stata 16 to inform project processes. RESULTS: Nine facilities participated in the project. A total of 4,324 PCR tests for SARS-CoV-2 were done, with 425 positives. We noted differences in positivity rates between the facilities. Healthcare workers were the largest group tested in the project, 1009, representing 43% of the Kisumu healthcare workforce. CONCLUSION: COVID-Dx can serve as a model for PPPs scale-up testing, especially LMICs, and digitizing the MoH case report form improved reporting efficiency, demonstrating that digital is the way forward. The COVID-Dx PPP has led to another collaboration with Kisumu County aimed towards extending the COVID-Dx model to other counties.

• The pH Dependence of Niclosamide Solubility, Dissolution, and Morphology Motivates Potentially Universal Mucin- Penetrating Nasal and Throat Sprays for COVID19, its Contagious Variants, and Other Respiratory Viral Infections -
  Motivation: With the coronavirus pandemic still raging, prophylactic nasal and early treatment throat sprays could help prevent infection and reduce viral load. Niclosamide has the potential to treat a broad range of viral infections if local bioavailability is optimized as mucin penetrating solutions as opposed to more traditional microparticle based sprays that cannot penetrate the mucin. Experimental: pH dependence of supernatant concentrations and dissolution rates of niclosamide were measured in buffered solutions by Nanodrop UV Vis spectroscopy for niclosamide from different suppliers, as precipitated material, and as cosolvates. Data was compared to predictions from Henderson Hasselbalch and precipitation pH models. Optimal microscopy was used to observe the morphologies of precipitated and converted niclosamide. Results: Supernatant concentrations of niclosamide increased with increasing pH, from 1.77uM at pH 3.66 to 30uM at pH 8, and more rapidly from 90uM at pH8.5 to 300uM at pH 9.1, reaching 641uM at pH 9.5. Logarithmic rates for dissolution increased by 3x for pHs 8.62 to 9.44. However, when precipitated from supersaturated solution, niclosamide equilibrated to much lower final supernatant concentrations, reflective of more stable polymorphs at each pH that were also apparent for niclosamide from other suppliers and cosolvates. Conclusions: Given the activity of niclosamide against COVID19, its more contagious variants, and other respiratory viral infections, these niclosamide solutions, that put the virus in lockdown, could represent universal prophylactic nasal and early treatment throat sprays. As solutions they would be the simplest and potentially most effective formulations from both an efficacy standpoint as well as manufacturing and distribution, with no cold chain. They now just need testing.
  🖺 Full Text HTML: The pH Dependence of Niclosamide Solubility, Dissolution, and Morphology Motivates Potentially Universal Mucin-Penetrating Nasal and Throat Sprays for COVID19, its Contagious Variants, and Other Respiratory Viral Infections

From Clinical Trials

• High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition:   Covid19
  Interventions:   Drug: High doses of intravenous vitamin C;   Drug: Dextrose 500 mL
  Sponsor:   Hugo Galindo
  Not yet recruiting

• Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition:   COVID-19 Vaccination
  Intervention:   Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
  Sponsors:   VA Office of Research and Development;   VA Bedford Healthcare System
  Not yet recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage 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, APPLIED SCIENCE AND TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• Andrographis Paniculata vs Boesenbergia Rotunda vs Control in Asymptomatic COVID-19 - Condition:   Covid19
  Interventions:   Drug: Andrographis Paniculata;   Drug: Boesenbergia;   Other: Standard supportive treatment
  Sponsors:   Mahidol University;   Ministry of Health, Thailand
  Not yet recruiting

• Enhancing COVID Rehabilitation With Technology - Condition:   Covid19
  Interventions:   Behavioral: NexJ Connected Wellness;   Other: Usual Care
  Sponsors:   University of Ottawa;   Canadian Institutes of Health Research (CIHR);   Ottawa Hospital Research Institute
  Not yet recruiting

• Treatment of Covid-19 With a Herbal Compound, Xagrotin - Condition:   Covid19
  Intervention:   Combination Product: Xagrotin
  Sponsors:  
  Biomad AS;   Directorate of health of Sulaimani, Iraq -KRG
  Completed

• Evaluation of Clinical and Antibody Response to Covid-19 Vaccination Strategy in TBRI, Egypt - Condition:   Covid19
  Intervention:   Biological: Astrazenica vaccine
  Sponsor:  
  Samia Hassan El-Shishtawy
  Recruiting

• Evaluation of Safety and Immunogenicity of a Novel Vaccine for Prevention of Covid-19 in Adults Previously Immunized - Condition:   Covid19
  Intervention:   Biological: A vaccine composed of a recombinant S1 antigen
  Sponsors:   Hospital do Coracao;   Farmacore Biotecnologia Ltda
  Withdrawn

• Comparison of Detection of SARS-CoV2 (COVID-19) Between Nasopharyngeal Swab Specimens and Those Obtained by Salivary Sputum - Condition:   Covid19
  Intervention:   Diagnostic Test: Salivary test for COVID19
  Sponsor:   Centre Hospitalier de Cayenne
  Active, not recruiting

• Menstrual Blood Stem Cells in Severe Covid-19 - Conditions:   Covid19;   Cytokine Storm
  Interventions:   Biological: Allogeneic human menstrual blood stem cells secretome;   Other: Intravenous saline injection
  Sponsors:   Avicenna Research Institute;   Tehran University of Medical Sciences
  Completed

• Public Health Emergency: SOLIDARITY TRIAL Philippines - Condition:   Covid19
  Interventions:   Drug: Remdesivir;   Drug: Hydroxychloroquine;   Drug: Lopinavir / Ritonavir;   Drug: Interferon beta-1a;   Drug: Acalabrutinib
  Sponsor:  
  University of the Philippines
  Active, not recruiting

• Tazemetostat for the Treatment of Moderate to Severe COVID-19 Infection - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   Cytokine Release Syndrome
  Intervention:   Drug: Tazemetostat
  Sponsor:   Ciprian Gheorghe
  Not yet recruiting

• Sexual Functions and Covid-19 - Conditions:   Covid19;   Sexual Behavior
  Intervention:   Behavioral: Women sexual dysfunctions were screened using Female Sexual Functioning Index (FSFI)
  Sponsor:  
  Gaziosmanpasa Research and Education Hospital
  Completed

• Evaluation of the Safety and Immunogenicity of SII Vaccine Constructs Based on the SARS-CoV-2 Variant in Adults - Condition:   Covid19
  Interventions:   Biological: SII B.1.351;   Biological: SII Bivalent;   Biological: SII B.1.617.2
  Sponsor:   Novavax
  Not yet recruiting

• Effect of Vojta Therapy on Covid-19 Respiratory Disease - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Other: Respiratory physiotherapy
  Sponsors:   NUMEN Foundation;   Hospital de Emergencias Enfermera Isabel Zendal de Madrid
  Not yet recruiting

From PubMed

• Development of ACE2 autoantibodies after SARS-CoV-2 infection - CONCLUSIONS: Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of…

• Ethacridine inhibits SARS-CoV-2 by inactivating viral particles - The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC50 ~ 0.08 μM). Ethacridine was identified via high-throughput screening of an FDA- approved drug library in living cells using a fluorescence assay. Plaque assays, RT-PCR and immunofluorescence imaging at various stages of viral infection demonstrate that the main mode of action of ethacridine is through inactivation of viral particles,…

• Correction to: HD5 and LL-37 Inhibit SARS-CoV and SARS-CoV-2 Binding to Human ACE2 by Molecular Simulation - No abstract

• SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: An in-silico proof-of-principle of proteomics-based drug repurposing - Severe COVID-19 is reflected by significant changes in urine peptides. Based on this observation, a clinical test predicting COVID-19 severity, CoV50, was developed and registered as in vitro diagnostic in Germany. We have hypothesized that molecular changes displayed by CoV50, likely reflective of endothelial damage, may be reversed by specific drugs. Such an impact by a drug could indicate potential benefits in the context of COVID-19. To test this hypothesis, urinary peptide data from…

• Engineering of 2D nanomaterials to trap and kill SARS-CoV-2: a new insight from multi-microsecond atomistic simulations - In late 2019, coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Spike protein is one of the surface proteins of SARS-CoV-2 that is essential for its infectious function. Therefore, it received lots of attention for the preparation of antiviral drugs, vaccines, and diagnostic tools. In the current study, we use computational methods of chemistry and biology to study the interaction between spike protein and its receptor in the body,…

• COVID-19 in Patients with Atopic Dermatitis Treated with Dupilumab: Three Cases and a Literature Review - There are limited clinical data on the impact of the SARS-CoV2 infection on patients with dermatological conditions treated with biologics. Dupilumab is a recombinant human IgG(4) human monoclonal antibody that inhibits IL4 and IL13 signaling, and is used for moderate-severe atopic dermatitis treatment. We present three patients with atopic dermatitis (AD) treated with dupilumab who contracted COVID-19. In all patients, the infection had a mild course, and only in one, as documented by SCORAD,…

• Patchy signals: capturing women’s voices in mobile phone surveys of rural India - Phone surveys are a rapid and cost-effective way to collect primary data for research, monitoring and evaluation purposes. But for these data to be precise, reliable and unbiased, women’s perspectives must be accurately represented. Throughout 2020, we conducted seven household surveys in rural India to understand households’ experiences of the COVID-19 pandemic and contemporaneous relief programmes. Given social distancing protocols, we conducted these surveys over the phone, using household…

• Synthesis of novel calcium channel blockers with ACE2 inhibition and dual antihypertensive/anti-inflammatory effects: A possible therapeutic tool for COVID-19 - Hypertension has been recognized as one of the most frequent comorbidities and risk factors for the seriousness and adverse consequences in COVID-19 patients. 3,4-dihydropyrimidin-2(1H) ones have attracted researchers to be synthesized via Beginilli reaction and evaluate their antihypertensive activities as bioisosteres of nifedipine a well-known calcium channel blocker. In this study, we report synthesis of some bioisosteres of pyrimidines as novel CCBs with potential ACE2 inhibitory effect as…

• In-silico immunoinformatic analysis of SARS-CoV-2 virus for the development of putative vaccine construct - COVID-19 (CoronaVirus disease 2019) is caused by the SARS-CoV-2 virus (severe acute respiratory syndrome corona virus 2). SARS-CoV-2 virus is highly contagious and affects the human respiratory tract resulting in symptoms such as high fever, body ache, cough, dysfunctions of tastebuds and smelling sense of body. The objective of the present study involves immunoinformatic analysis to predict COVID-19 protein for vaccine construct based on the genomic information SARS-CoV-2 virus. At present, as…

• Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection - SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral…

• Participation of nitrogen oxide and its metabolites in the genesis of hyperimmune inflammation in COVID-19 - Despite the success in the tactics of treating COVID-19, there are many unexplored issues related to the development and progression of the process in the lungs, brain, and other organs, as well as the role of individual elements, in particular, nitric oxide (NO), and in the pathogenesis of organ damage. Based on the analyzed literature data, we considered a possible pathophysiological mechanism of action of NO and its derivatives in COVID-19. It can be noted that hyperimmune systemic…

• Discovery of novel inhibitors of SARS-CoV-2 main protease - Corona Virus Disease 2019 (COVID-19), referred to as ‘New Coronary Pneumonia’, is a type of acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. M^(pro) is one of the main targets for treating COVID-19. The current research on M^(pro) mainly focuses on the repurposing of old drugs, and there are only a few novel ligands that inhibit M^(pro). In this research, we used computational free energy calculation to screen a compound library…

• Funeral Processes During the COVID-19 Pandemic: Perceptions Among Islamic Religious Leaders in Indonesia - Controversies surrounding the handling of corpses have been amplified during the present COVID-19 pandemic. According to Indonesian scholars, certain perspectives driving these controversies inhibit the implementation of health protocols issued by the government. This study comprehensively explores the diverse perceptions and responses of religious leaders regarding COVID-19 funeral management. Participants comprised six scholars from major Islamic religious organizations, two community leaders,…

• Electrochemical and Mechanistic Study of Oxidative Degradation of Favipiravir by Electrogenerated Superoxide through Proton-Coupled Electron Transfer - Electrochemical analyses aided by density functional theory calculations were used to investigate the oxidative degradation of pyrazine antiviral drugs, 3-hydroxypyrazine-2-carboxamide (T-1105) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (favipiravir, T-705), by the electrogenerated superoxide radical anion (O(2) ^(•-)). T-1105 and T-705 are antiviral RNA nucleobase analogues that selectively inhibit the RNA-dependent RNA polymerase. They are expected as a drug candidate against various viral…

• Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data - CONCLUSION: Predicting these potential drug-drug interactions, particularly related to CYP3A4, P-gp and the human Ether- à-go-go-Related Gene proteins, could be used in clinical settings for screening and management of drug-drug interactions for delivering safer chemotherapeutic tuberculosis and COVID-19 care. The current study provides an initial propulsion for further well-designed pharmacokinetic-pharmacodynamic-based drug-drug interaction studies.

From Patent Search

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• SARS-COV-2 BINDING PROTEINS - - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

• 一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link

• 一种联合检测IgG、IgM和中和抗体的试纸条及其制备方法、试剂盒 - 本申请涉及生物医学检测技术领域，具体涉及一种联合检测IgG、IgM和中和抗体的试纸条及其制备方法、试剂盒。所述试纸条包括第一检测部和第二检测部，均包括有底板以及设置在底板上并依次连接的样品垫、结合垫、检测垫和吸水垫；所述第一检测部的结合垫上包被有胶体金标记的N抗原和S抗原，所述第一检测部的检测垫上设有第一检测线和第二检测线；所述第二检测部的样品垫上包被有ACE2，所述第二检测部的结合垫上包被有胶体金标记的S‑RBD抗原，所述第二检测部的检测垫上设置有第三检测线。本申请能实现现场高准确度快检，检测人员只需要使用一个试纸条就可以准确测定机体中IgG、IgM和中和抗体。 - link

• Deep Learning Based System For Detection of Covid-19 Disease of Patient At Infection Risk. - - link