Covid-19 Sentry

Contents

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

From Preprints

• Mapping Transcriptomic Vector Fields of Single Cells -
  Single-cell RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires dynamical models capable of predicting cell fate and unveiling the governing regulatory mechanisms. Here, we introduce dynamo, an analytical framework that reconciles intrinsic splicing and labeling kinetics to estimate absolute RNA velocities, reconstructs continuous velocity vector fields that predict future cell fates, and finally employs differential geometry analyses to elucidate the underlying regulatory networks. We applied dynamo to a wide range of disparate biological processes including prediction of future states of differentiating hematopoietic stem cell lineages, deconvolution of glucocorticoid responses from orthogonal cell-cycle progression, characterization of regulatory networks driving zebrafish pigmentation, and identification of possible routes of resistance to SARS-CoV-2 infection. Our work thus represents an important step in going from qualitative, metaphorical conceptualizations of differentiation, as exemplified by Waddington’s epigenetic landscape, to quantitative and predictive theories.
  🖺 Full Text HTML: Mapping Transcriptomic Vector Fields of Single Cells
• An integrated rural health system baseline assessment of COVID-19 preparedness in Siaya Kenya -

  Objective: Our aim was to assess Siaya county COVID-19 preparedness at community and health facility levels and measure baseline household prevalences of fever and cough. Design: There was retrospective and prospective data collection using standard tools. We determined the prevalence of fever and cough in households. We evaluated household knowledge about COVID-19 prevention and adherence to preventive measures. We evaluated the presence of a workforce, essential infrastructure and equipment needed for COVID-19 case management, and the availability of essential maternal and child health services in health facilities. Setting: Siaya in rural Western Kenya Participants: households and health facilities in Siaya Results: We visited 19474 households and assessed 152 facilities. The prevalences of fever and cough ranged from 1.4% to 4.3% and 0.2 to 0.8% respectively ; 97% and 98% of households had not received a guest from nor travelled outside Siaya respectively; 97% knew about frequent handwashing, 66% knew about keeping distance, and 80% knew about wearing a mask; 63% washed their hands countless times; 53% remained home; and 74% used a mask when out in public. The health facility assessment showed: 93.6% were dispensaries and health centers; 90.4% had nurses; 40.5% had oxygen capacity; 13.5% had pulse oximeters; and 2 ventilators were available; 94.2% of facilities did not have COVID-19 testing kits; 94% and 91% of facilities continued to provide antenatal care and immunization services respectively. Health care worker training in COVID-19 had been planned. Conclusions: Household prevalence of fever and cough was low suggesting Siaya had not entered the active community transmission phase in June 2020. Our assessment revealed a need for training in COVID-19 case management, and a need for basic equipment and supplies including pulse oximeters and oxygen. Future interventions should address these gaps. Strengths and limitations: This study provides an example of how to successfully carry out an integrated rural health system baseline assessment of COVID-19 preparedness; an approach that would be useful for any country experiencing COVID-19 with a significant rural population. Some of our data were retrospective in nature and therefore vulnerable to multiple sources of bias including: recall bias and misclassification.

  🖺 Full Text HTML: An integrated rural health system baseline assessment of COVID-19 preparedness in Siaya Kenya
• Impact on Mental Health of students due to restriction caused by COVID-19 pandemic: Cross-sectional study -

  Abstract Background: The goal of the study was to investigate fear, depression and anxiety symptoms among students of India due to COVID-19 pandemic and its restriction. Method: The cross-sectional web-based research was conducted between mid-November and mid-December 2020 with the objective of understanding the psychological and behavioral consequences of the COVID-19 pandemic effect on students due to the constraint of forced control. The study included a) socio-demographic questions such as age, gender, degree enrolled and any member of the family infected with COVID-19, b) psychometric scales evaluating the psychological and behavioral impact caused by COVID-19 pandemic restrictions such as fear of the COVID-19 scale (FCV-19S), depression by the Brief Patient Health Questionnaire (PHQ-9) depression scale, and anxiety by the Generalized Anxiety Disorder scale (GAD-7). Results: Total number of 324 students participated in this study in which 44.4% were male and 55.6% were female. Fear of COVID-19 scale showed 68.8% student had high fear among students, 24.4% had moderate to severe depression and 51.5% had moderate to severe anxiety. The correlation between fear of COVID-19 scale (FCV-19s) and Generalized Anxiety scale (GAD-7) was found to be 0.474 and 0.492 was found between fear of COVID-19 (FCV-19s) scale and brief patient health questionnaire (PHQ-9) Conclusion: This research concludes that there is a very strong fear of COVID-19 among students, along with anxiety and depression. This study also concludes that the fear of the COVID-19 scale and the GAD-7 and PHQ-9 scales have a strong positive correlation.

  🖺 Full Text HTML: Impact on Mental Health of students due to restriction caused by COVID-19 pandemic: Cross-sectional study
• L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England -

  The Variant of Concern (VOC)-202012/01 (also known as B.1.1.7) is a rapidly growing lineage of SARS-CoV-2. In January 2021, VOC-202012/01 constituted about 80% of SARS-CoV-2 genomes sequenced in England and was present in 27 out of 29 countries that reported at least 50 viral genomes. As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. Based on GISAID data we systematically estimated growth rates of mutations acquired by the lineage to find that L18F substitution in spike initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56-1.96] in relation to the remaining VOC-202012/01 substrains. We also indicate three mutations in the receptor binding motive of spike, that arose in VOC-202012/01: E484K, F490S, S494P, and may give rise to escape mutants. Such mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine induced seroprevalence.

  🖺 Full Text HTML: L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England
• Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina -

  Several cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021. This variant has been associated with higher levels of transmissibility. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number. We found that the effective reproduction number for North Carolina and Guilford County may exceed one, indicating a return to accelerating spread of infection in April as the proportion of B1.1.7 increases. Existing non-pharmaceutical interventions will need to remain in effect through the spring.

  🖺 Full Text HTML: Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
• Linking excess mortality to Google mobility data during the COVID-19 pandemic in England and Wales -
  Following the outbreak of COVID-19, a number of non-pharmaceutical interventions have been implemented to contain the spread of the pandemic. Despite the recent reduction in the number of infections and deaths in Europe, it is still unclear to which extent these governmental actions have contained the spread of the disease and reduced mortality. In this article, we estimate the effects of reduced human mobility on excess mortality using digital mobility data at the regional level in England and Wales. Specifically, we employ the Google COVID-19 Community Mobility Reports, which offer an approximation to the changes in mobility due to different social distancing measures. Considering that changes in mobility would require some time before having an effect on mortality, we analyse the relationship between excess mortality and lagged indicators of human mobility. We find a negative association between excess mortality and time spent at home, as well as a positive association with changes in outdoor mobility, after controlling for the time trend of the pandemic and regional differences. We estimate that almost 130,000 excess deaths have been averted as a result of the increased time spent at home. In addition to addressing a key scientific question, our results have important policy implications for future pandemics and a potential second wave of COVID-19.
  🖺 Full Text HTML: Linking excess mortality to Google mobility data during the COVID-19 pandemic in England and Wales
• What drives us to be (ir)responsible for our health during the COVID-19 pandemic? The role of personality, thinking styles and conspiracy mentality -
  Abstract The study aimed to investigate the role of personality, thinking styles, and conspiracy mentality in health-related behaviors during the COVID-19 pandemic, i.e., recommended health behaviors according to COVID-19 guidelines and engagement in pseudoscientific practices related to COVID-19. Basic personality space was defined by the HEXACO model complemented by Disintegration, which represents psychotic-like experiences and behaviors reconceptualized as a personality trait. Mediation analyses conducted on a convenient sample from the general population recruited via social media and by snowballing (N=417) showed that engagement in pseudoscientific behaviors was predicted by high Disintegration. However, this relationship was entirely mediated by high experiential and low rational thinking styles. Adherence to health practices recommended by COVID-19 guidelines was predicted by high Honesty traits, while low Disintegration had both direct and indirect effects through conspiracy mentality.
  🖺 Full Text HTML: What drives us to be (ir)responsible for our health during the COVID-19 pandemic? The role of personality, thinking styles and conspiracy mentality
• Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2 -
  Coronavirus disease 2019 (COVID-19) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is a worsening global pandemic. COVID-19 has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 patients with severe respiratory damage that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (tg-mice hACE2) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected tg-mice hACE2 significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-{gamma}, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1, IL-9, IL-6, LIX/CXCL5, KC/CXCL1, MIP-2/CXCL2, MIP-1/CCL3, and G-CSF, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 patients.
  🖺 Full Text HTML: Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2
• Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway -
  A fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.
  🖺 Full Text HTML: Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway
• SARS-CoV-2 Encodes a PPxY Late Domain Motif Known to Enhance Budding and Spread in Enveloped RNA Viruses -
  The current COVID-19 (Coronavirus Disease-2019) pandemic is affecting the health and/or socioeconomic welfare of almost everyone in the world. Finding vaccines and therapeutics is therefore urgent, but elucidation of the molecular mechanisms that allow some viruses to cross host species boundaries, becoming a threat to human health, must also be given close attention. Here, analysis of all proteins of SARS-CoV-2 revealed a unique PPxY Late (L) domain motif, 25-PPAY-28, in a spike (S) protein inside a predicted hot disordered loop subject to phosphorylation and binding. PPxY motifs in enveloped RNA viruses are known to recruit Nedd4 E3 ubiquitin ligases and ultimately the ESCRT complex to enhance virus budding and release, resulting in higher viral loads, hence facilitating new infections. Interestingly, proteins of SARS-CoV-1 do not feature PPxY motifs, which could explain why SARS-CoV-2 is more contagious than SARS-CoV-1. Should an experimental assessment of this hypothesis show that the PPxY motif plays the same role in SARS-CoV-2 as it does in other enveloped RNA viruses, this motif will become a promising target for the development of novel host-oriented antiviral therapeutics for preventing S proteins from recruiting Nedd4 E3 ubiquitin ligase partners.
  🖺 Full Text HTML: SARS-CoV-2 Encodes a PPxY Late Domain Motif Known to Enhance Budding and Spread in Enveloped RNA Viruses
• The feasibility of targeted test-trace-isolate for the control of SARS-CoV-2 variants -

  The SARS-CoV-2 variant B.1.1.7 reportedly exhibits substantially higher transmission than the ancestral strain and may generate a major surge of cases before vaccines become widely available, while the P.1 and B.1.351 variants may be equally transmissible and also resist vaccines. All three variants can be sensitively detected by RT-PCR due to an otherwise rare del11288-11296 mutation in orf1ab; B.1.1.7 can also be detected using the common TaqPath kit. Testing, contact tracing, and isolation programs overwhelmed by SARS-CoV-2 could slow the spread of the new variants, which are still outnumbered by tracers in most countries. However, past failures and high rates of mistrust may lead health agencies to conclude that tracing is futile, dissuading them from redirecting existing tracers to focus on the new variants. Here we apply a branching-process model to estimate the effectiveness of implementing a variant-focused testing, contact tracing, and isolation strategy with realistic levels of performance. Our model indicates that bidirectional contact tracing can substantially slow the spread of SARS-CoV-2 variants even in regions where a large fraction of the population refuses to cooperate with contact tracers or to abide by quarantine and isolation requests.

  🖺 Full Text HTML: The feasibility of targeted test-trace-isolate for the control of SARS-CoV-2 variants
• COVID Outcome Prediction in the Emergency Department (COPE): Development and validation of a model for predicting death and need for intensive care in COVID-19 patients -

  Background and aim: COVID-19 is putting extraordinary pressure on emergency departments (EDs). To support decision making in the ED, we aimed to develop a simple and valid model for predicting mortality and need for intensive care unit (ICU) admission in suspected COVID-19 patients. Methods: For model development, we retrospectively collected data of patients who were admitted to 4 large Dutch hospitals with suspected COVID-19 between March and August 2020 (first wave of the pandemic). Based on prior literature we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. Logistic regression analyses with post-hoc uniform shrinkage was used to obtain predicted probabilities of in-hospital death and of the need for ICU admission, both within 28 days after hospital admission. We assessed model performance (Area Under the ROC curve (AUC); calibration plots) with temporal validation in patients who presented between September and December 2020 (second wave). We used multiple imputation to account for missing values. Results: The development data included 5,831 patients, of whom 629 (10.8%) died and 5,070 (86.9%) were discharged within 28 days after admission. ICU admission was fully recorded for 2,633 first wave patients in 2 hospitals, with 214 (8%) ICU admissions within 28 days. A simple model - COVID Outcome Prediction in the Emergency Department (COPE) - with age, respiratory rate, C-reactive protein, lactic dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well-calibrated and showed good discrimination in 3,252 second wave patients (AUC in 4 hospitals: 0.82 [0.78; 0.86]; 0.82 [0.74; 0.90]; 0.79 [0.70; 0.88]; 0.83 [0.79; 0.86]). COPE was also able to identify patients at high risk of needing IC in 706 second wave patients with complete information on ICU admission (AUC: 0.84 [0.78; 0.90]; 0.81 [0.66; 0.95]). The models are implemented in web-based and mobile applications. Conclusion: COPE is a simple tool that is well able to predict mortality and need for ICU admission for patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.

  🖺 Full Text HTML: COVID Outcome Prediction in the Emergency Department (COPE): Development and validation of a model for predicting death and need for intensive care in COVID-19 patients
• Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort -

  Objectives: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. Methods: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. Findings: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. Interpretation: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

  🖺 Full Text HTML: Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort
• Explaining ethnicity disparities in COVID-19 mortality: population-based, prospective cohort study -

  Ethnic disparities in COVID-19 hospitalizations and mortality have been reported but there is scant understanding of how these inequalities are embodied. The UK Biobank prospective cohort study comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on ethnic background and potential explanatory factors was captured. Study members were linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 354 deaths were ascribed to COVID-19 between 5th March and the end of follow-up on 17th September 2020. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around seven times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 7.25; 4.65, 11.33), while there was a doubling in the Asian group (1.98; 1.02, 3.84). Controlling for baseline comorbidities, socioeconomic circumstances, and lifestyle factors explained 53% of the differential in risk for Asian people (1.37; 0.68, 2.77) and 27% in Black study members (4.28; 2.67, 6.86). The residual risk in ethnic minority groups for COVID-19 deaths may be ascribed to unknown genetic factors or unmeasured phenotypes, most obviously racial discrimination.

  🖺 Full Text HTML: Explaining ethnicity disparities in COVID-19 mortality: population-based, prospective cohort study
• Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in two Kenyan referral hospitals -

  The high proportion of asymptomatic and undetected SARS-CoV-2 infections presents a challenge to tracking the progress of the pandemic and implementing control measures in Kenya. We determined the prevalence of IgG to SARS-CoV-2 in residual blood samples from mothers attending antenatal care services at 2 referral hospitals in Kenya. A total of 196 samples were analysed from Kenyatta National Hospital in Nairobi in August 2020, seroprevalence, adjusted for assay sensitivity and specificity, was 49.8% (95% CI 42.0-57.8). In Kilifi County Hospital in coastal Kenya, 419 samples were analysed between September and November 2020, seroprevalence, adjusted for assay sensitivity and specificity, increased from 1.3% (95% CI 0.03-4.8) in September to 10.9% (95% CI 6.1, 16.8) in November 2020. There has been substantial, unobserved transmission of SARS-CoV-2 in parts of Nairobi and Kilifi Counties.

  🖺 Full Text HTML: Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in two Kenyan referral hospitals

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

• Telerehabilitation in Covid-19 After Hospital Discharge - Condition:   Covid19
  Intervention:   Other: Telerehabilitation intervention
  Sponsor:   Universidad de Granada
  Not yet 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

• 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

• 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

• 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

• COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition:   Covid19
  Intervention:   Other: Specimens specific for the study
  Sponsor:   Hopital Foch
  Recruiting

• AGILE (Early Phase Platform Trial for COVID-19) - Condition:   Covid19
  Interventions:   Drug: CST-2: EIDD-2801;   Drug: CST-2: Placebo
  Sponsors:   University of Liverpool;   University of Southampton;   Liverpool School of Tropical Medicine;   Lancaster University;   Liverpool University Hospitals NHS Foundation Trust
  Recruiting

• A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Condition:   Coronavirus Disease 2019 (COVID-19)
  Interventions:   Drug: Placebo;   Drug: Prothione™ (6g)
  Sponsor:   Prothione, LLC
  Not yet recruiting

• Ivermectin Role in Covid-19 Clinical Trial - Condition:   Covid19
  Interventions:   Drug: ivermectin;   Drug: hydroxychloroquine;   Drug: Placebo
  Sponsors:   Elaraby Hospital;   Shebin-Elkom Teaching Hospital
  Completed

From PubMed

• An update review of emerging small-molecule therapeutic options for COVID-19 - The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with…

• Interaction of small molecules with the SARS-CoV-2 papain-like protease: In silico studies and in vitro validation of protease activity inhibition using an enzymatic inhibition assay - The SARS-CoV-2 virus is causing COVID-19, an ongoing pandemic, with extraordinary global health, social, and political implications. Currently, extensive research and development efforts are aimed at producing a safe and effective vaccine. In the interim, small molecules are being widely investigated for antiviral effects. With respect to viral replication, the papain-like (PL^(pro)) and main proteases (M^(pro)), are critical for processing viral replicase polypeptides. Further, the PL^(pro)…

• SARS-CoV-2 mutation 614G creates an elastase cleavage site enhancing its spread in high AAT-deficient regions - SARS-CoV-2 was first reported from China. Within three months, it evolved to 10 additional subtypes. Two evolved subtypes (A2 and A2a) carry a non-synonymous Spike protein mutation (D614G). We conducted phylodynamic analysis of over 70,000 SARS-CoV-2 coronaviruses worldwide, sequenced until July2020, and found that the mutant subtype (614G) outcompeted the pre-existing type (614D), significantly faster in Europe and North-America than in East Asia. Bioinformatically and computationally, we…

• Avelumab, a PD-L1 Inhibitor, in Combination with Hypofractionated Radiotherapy and the Abscopal Effect in Relapsed Refractory Multiple Myeloma - CONCLUSION: Avelumab in combination with radiotherapy for patients with RRMM and EMD was associated with very modest systemic clinical benefit; however, patients did benefit as usual from local radiotherapy. Furthermore, the combination was very well tolerated compared with historical RRMM treatment regimens.

• Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19 - Clinical studies have identified a cytokine storm in the third stage of disease progression in critical ill patients with coronavirus disease 2019 (COVID-19). Hence, effectively suppressing the uncontrolled immune response of the host towards the invaded viruses in a cytokine storm is a critical step to prevent the deterioration of patient conditions and decrease the rate of mortality. Therapeutic monoclonal antibodies (mAbs) are found to be effective for the management of acute respiratory…

• The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus - Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the Vini in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective. Besides,…

• Recent Advances in Systemic Therapies for Advanced Hepatocellular Carcinoma - PURPOSE OF REVIEW: This paper aims to summarize the data of recently completed and key ongoing clinical trials of systemic agents for advanced hepatocellular carcinoma (aHCC). In particular, the review focuses on ongoing checkpoint inhibitor combination trials and promising studies combining tyrosine kinase inhibitors with checkpoint inhibitors.

• Mechanistic insight into anti-COVID-19 drugs: recent trends and advancements - The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has been established now to be a deadly disease afflicting the whole world with worst consequences on healthcare, economy and day-to-day life activities. Being a communicable disease, which is highly pathogenic in humans, causing cough, throat infection, breathing problems, high fever, muscle pain, and may lead to death in some cases especially those having other comorbid conditions such as heart or kidney problems, and diabetes….

• Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides? - In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the…

• CSF3 Is a Potential Drug Target for the Treatment of COVID-19 - Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two…

• The computational intervention of macrolide antibiotics in the treatment of COVID-19 - The spike (S) glycoprotein of SARS coronavirus (SARS-CoV-2) and human Angiotensin-converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for a computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). These compounds were able to block the residues…

• COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies - CONCLUSION: COVID-19 patients often present with strong reactivity in PF4/heparin antigen tests without the presence of platelet-activating antibodies. Diagnosis of HIT requires confirmation of heparin-dependent, platelets activating antibodies to avoid overdiagnosis and overtreatment with non-heparin anticoagulants.

• Novel insights into impacts of the COVID-19 pandemic on aquatic environment of Beijing-Hangzhou Grand Canal in southern Jiangsu region - In 2020, a sudden COVID-19 pandemic unprecedentedly weakened anthropogenic activities and as results minified the pollution discharge to aquatic environment. In this study, the impacts of the COVID-19 pandemic on aquatic environment of the southern Jiangsu (SJ) segment of Beijing-Hangzhou Grand Canal (SJ-BHGC) were explored. Fluorescent component similarity and high-performance size exclusion chromatography analyses indicated that the textile printing and dyeing wastewater might be one of the…

• SARS-CoV-2: From the pathogenesis to potential anti-viral treatments - INTRODUCTION: The world is witnessing the spread of one of the members of Coronaviruses (CoVs) family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the 21st century. Considering the short time spent after its prevalence, limited information is known about the effect of the virus mechanism on different organs of the body; meanwhile the lack of specific treatment and vaccine for this virus has exposed millions of people to a big challenge.

• Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir - Remdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United…

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

• 一种新冠肺炎CT检测识别定位系统及计算设备 - 本发明涉及图像处理领域，公开了一种新冠肺炎CT检测识别定位系统及计算设备，包括图像采集单元、模块建立单元、新冠肺炎病灶识别单元和新冠肺炎病灶定位单元；图像采集单元采集待识别检测新冠肺炎的CT图像、新冠肺炎CT影像病灶分割训练数据集和新冠CT图像识别训练集；模块建立单元建立U_Net卷积神经网络模型、加入注意力机制的InceptionV3网络和目标检测模型；新冠肺炎病灶识别单元对已分割出病灶的轮廓特征图像进行识别；新冠肺炎病灶定位单元确定病灶在人体肺部的位置。本发明利用U_Net卷积神经网络模型对新冠病灶检测分割，并通过加入注意力机制的网络进行新冠肺炎识别，通过目标检测模型定位病灶在肺部的位置，识别准确率高，计算速度快。 - link

• 一种基于磁微粒化学发光的新型冠状病毒抗体检测试剂盒 - 本发明提供一种基于磁微粒化学发光的新型冠状病毒抗体检测试剂盒。所述检测试剂盒包括：链霉亲和素磁微粒、生物素标记的新型冠状病毒抗原、吖啶磺酰胺标记的二抗、样本稀释液和质控品；所述生物素标记的新型冠状病毒抗原包括重组核衣壳蛋白和重组棘突蛋白S1。将待检样本、生物素标记抗原与链霉亲和素磁微粒混合，孵育和洗涤，再加入吖啶磺酰胺标记的抗体，形成磁微粒‑链霉亲和素‑生物素‑抗原‑新型冠状病毒抗体‑二抗复合物，进而检测发光强度实现对待测样品的定性。 - 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