Covid-19 Sentry

Contents

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

From Preprints

• Modeling reactive attention among congressional witnesses during the COVID-19 pandemic -
  Although often considered dichotomous drivers of congressional agenda activity, indicators and focusing events may exist on a continuum if indicators are capable of culminating in a singular event that focuses attention. Identifying this culmination point could help explain how anticipatory, indicator-driven threats such as COVID-19 can dominate policy agendas in a manner similar to a focusing event. This paper investigates whether the culmination point can be identified by quantifying anticipatory and reactive attention of congressional committee witnesses towards an indicator- driven threat. The findings demonstrate that peaks in congressional witness numbers during the COVID-19 pandemic coincided with a transition from anticipatory to reactive attention, which was associated with rapid increases in unemployment. This demonstrates that a transition from anticipatory to reactive attention could mark the culmination point of an indicator-driven event such as COVID-19, and explain how and why some indicators are capable of focusing attention, but others are not.
  🖺 Full Text HTML: Modeling reactive attention among congressional witnesses during the COVID-19 pandemic
• The effects of non-pharmaceutical interventions on COVID-19-related mortality: A generalized synthetic control approach across 169 countries -
  Background: Most governments have introduced various non-pharmaceutical interventions (NPIs) in response to the pandemic outbreak of Coronavirus disease (COVID-19) since early 2020. While NPIs aim at avoiding fatalities related to COVID-19, the previous literature on their efficacy has focused on infections and on data of the first half of 2020. Still, findings of early NPI studies may be subject to underreporting and missing timeliness of reporting of cases. Moreover, the low variation in treatment timing during the first wave makes identification of robust treatment effects difficult. Methods: To circumvent problems of reporting and treatment variation, we analyse data on daily confirmed COVID-19-related deaths per capita from Our World in Data, and on 10 different NPIs from the Oxford COVID-19 Government Response Tracker for 169 countries from 1st July 2020 to 31st May 2021. To identify the causal effects of introducing NPIs on COVID-19-related confirmed fatalities per capita, we apply the generalized synthetic control (GSC) method to each NPI, while controlling for the remaining NPIs, weather conditions, vaccinations, and NPI-residualized COVID-19 cases. Findings: We do not find substantial and consistent mitigating effects of any NPI under investigation on COVID-19-related deaths per capita. We see a tentative change in the trend of COVID-19-related deaths around 30 days after workplace closing, public transport closing, and stay at home rules have been implemented, but none of them exerts a statistically significant effect. Interpretation: The study enhances the literature on the effectivity of NPIs with respect to the time frame, the number of countries, and the analytical approach. The results provide further guidance to judge the proportionality of NPIs.
  🖺 Full Text HTML: The effects of non-pharmaceutical interventions on COVID-19-related mortality: A generalized synthetic control approach across 169 countries
• SARS-CoV-2 variants of concern Alpha, Beta, Gamma and Delta have extended ACE2 receptor host-ranges -
  Following the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these, Alpha and Delta, subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.
  🖺 Full Text HTML: SARS-CoV-2 variants of concern Alpha, Beta, Gamma and Delta have extended ACE2 receptor host-ranges
• A modified porous silicon microparticle promotes mucosal delivery of SARS-CoV-2 antigen and induction of potent and durable systemic and mucosal T helper 1 skewed protective immunity -
  Development of optimal SARS-CoV-2 vaccines to induce potent, long-lasting immunity and provide cross-reactive protection against emerging variants remains a high priority. Here, we report that a modified porous silicon microparticle (mPSM)-adjuvanted SARS-CoV-2 receptor-binding domain (RBD) vaccine activated dendritic cells and generated more potent and durable SARS-CoV-2-specific systemic humoral and type 1 helper T (Th) cell-mediated immune responses than alum-formulated RBD following parenteral vaccination, and protected mice from SARS-CoV-2 and Beta variant infection. mPSM facilitated the uptake of SARS-CoV-2 RBD antigens by nasal and airway epithelial cells. Parenteral and intranasal prime and boost vaccinations with mPSM-RBD elicited potent systemic and lung resident memory T and B cells and SARS-CoV-2 specific IgA responses, and markedly diminished viral loads and inflammation in the lung following SARS- CoV-2 Delta variant infection. Our results suggest that mPSM can serve as potent adjuvant for SARS-CoV-2 subunit vaccine which is effective for systemic and mucosal vaccination.
  🖺 Full Text HTML: A modified porous silicon microparticle promotes mucosal delivery of SARS-CoV-2 antigen and induction of potent and durable systemic and mucosal T helper 1 skewed protective immunity
• Stabilization of the SARS-CoV-2 Receptor Binding Domain by Protein Core Redesign and Deep Mutational Scanning -
  Stabilizing antigenic proteins as vaccine immunogens or diagnostic reagents is a stringent case of protein engineering and design as the exterior surface must maintain recognition by receptor(s) and antigen specific antibodies at multiple distinct epitopes. This is a challenge, as stability-enhancing mutations must be focused on the protein core, whereas successful computational stabilization algorithms typically select mutations at solvent-facing positions. In this study we report the stabilization of SARS-CoV-2 Wuhan Hu-1 Spike receptor binding domain (S RBD) using a combination of deep mutational scanning and computational design, including the FuncLib algorithm. Our most successful design encodes I358F, Y365W, T430I, and I513L RBD mutations, maintains recognition by the receptor ACE2 and a panel of different anti-RBD monoclonal antibodies, is between 1-2{degrees}C more thermally stable than the original RBD using a thermal shift assay, and is less proteolytically sensitive to chymotrypsin and thermolysin than the original RBD. Our approach could be applied to the computational stabilization of a wide range of proteins without requiring detailed knowledge of active sites or binding epitopes, particularly powerful for cases when there are multiple or unknown binding sites.
  🖺 Full Text HTML: Stabilization of the SARS-CoV-2 Receptor Binding Domain by Protein Core Redesign and Deep Mutational Scanning
• Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19 -
  COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by brain inflammation, triggered by the virus infecting the central nervous system of COVID-19 patients, however we still don’t fully understand the mechanisms for these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides and discovered that they do rapidly self-assemble into amyloid. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID, especially those symptoms which are novel to long COVID in contrast to other post-viral syndromes.
  🖺 Full Text HTML: Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19
• Uptake of Covid-19 preventive measures among 10 immigrant ethnic groups in Norway -

  Background: A pessimistic view of the impact of Covid-19 on immigrants has generated an interest in exploring the role of socio-economic and cultural factors on excess infection, hospitalization and death among immigrants. Nowhere in the world is such interest more palpable than in Western countries, including Norway. An expanding amount of literature has demonstrated that preexisting socio-economic inequalities have affected Covid-19 control programs through a disruption of immigrants uptake to preventive measures. Nonetheless, until very recently, no qualitative research has been conducted to address the impact of socio-economic and socio-cultural factors on immigrants uptake on preventive measures of Covid-19 in Norway. Methods: An interview-based qualitative study consisting of 88 participants (49 women and 39 men) from 10 immigrant ethnic groups were carried out. Participants were recruited through purposive sampling and snowballing. In-depth interviews were held through telephone or online for those who have experience in the use of zoom or teams. Data were analyzed using thematic analysis Results: We found that participants attitudes toward the pandemic in general, and more specifically their adherence to preventive measures, have increased over time. However, the number of barriers that hinder immigrants from adhering to preventive measures were identified and classified more broadly into three main subthemes: 1) socio-economic barriers; 2) socio-cultural barriers, and 3) other barriers. Socio-economic barriers include overcrowded households, working in first-line jobs, education and language. Socio-cultural barriers include collectivist culture, religious fatalism and risk perception toward the pandemic. Conclusion: To reduce the health inequality that arises from overcrowded housing, there is a need for a long-term strategy to help improve the housing situation of low-income immigrant families that live in overcrowded households. In addition, increasing health literacy and more generally, the integration of immigrants, may also reduce the effect of socio-cultural factors on an immigrant9s uptake of preventive measures.

  🖺 Full Text HTML: Uptake of Covid-19 preventive measures among 10 immigrant ethnic groups in Norway
• SARS-CoV-2 within-host and in-vitro genomic variability and sub-genomic RNA levels indicate differences in viral expression between clinical and in-vitro cohorts. -

  Background: Low frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomic RNA (sgRNA) expression and its impact on genomic diversity and infection outcome remain poorly understood. This study aims to investigate and quantify iSNVs and sgRNA expression in single and longitudinally sampled cohorts over the course of mild and severe SARS-CoV-2 infection benchmarked against an in-vitro infection model. Methods: Two clinical cohorts of SARS-CoV-2 positive cases in New South Wales, Australia collected between March 2020 and August 2021 were sequenced. Longitudinal samples from cases hospitalised due to SARS-CoV-2 infection (severe) were analysed and compared with cases that presented with SARS-CoV-2 symptoms but were not hospitalised (mild). SARS-CoV-2 genomic diversity profiles were also examined from daily sampling of culture experiments for three SARS-CoV-2 variants (Lineage A, B.1.351, and B.1.617.2) cultured in VeroE6 C1008 cells (n = 33). Results: ISNVs were detected in 83% (19/23) of the mild cohort cases and 100% (16/16) of the severe cohort cases. SNP profiles remained relatively fixed over time, with an average of 1.66 SNPs gained or lost and an average of 4.2 and 5.9 low frequency variants per patient were detected in severe and mild infection, respectively. SgRNA was detected in 100% (25/25) of the mild genomes and 92% (24/26) of the severe genomes. Total sgRNA expressed across all genes in the mild cohort was significantly higher than that of the severe cohort. Significantly higher expression levels were detected in the spike and the nucleocapsid genes. There was significantly less sgRNA detected in the culture cohort than the clinical. Discussion and Conclusions: The positions and frequencies of iSNVs in the severe and mild infection cohorts were dynamic overtime, highlighting the importance of continual monitoring, particularly during community outbreaks where multiple SARS-Cov-2 variants may co- circulate. SgRNA levels can vary across patients and the overall level of sgRNA reads compared to genomic RNA can be less than 1%. The relative contribution of sgRNA to the severity of illness warrants further investigation given the level of variation between genomes. Further monitoring of sgRNAs will improve the understanding of SARS-CoV-2 evolution and the effectiveness of therapeutic and public health containment measures during the pandemic.

  🖺 Full Text HTML: SARS-CoV-2 within-host and in-vitro genomic variability and sub-genomic RNA levels indicate differences in viral expression between clinical and in-vitro cohorts.
• Severe COVID-19 induces molecular signatures of aging in the human brain -

  Coronavirus disease 2019 (COVID-19) is predominantly an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and remains a significant threat to public health. COVID-19 is accompanied by neurological symptoms and cognitive decline, but the molecular mechanisms underlying this effect remain unclear. As aging induces distinct molecular signatures in the brain associated with cognitive decline in healthy populations, we hypothesized that COVID-19 may induce molecular signatures of aging. Here, we performed whole transcriptomic analysis of human frontal cortex, a critical area for cognitive function, in 12 COVID-19 cases and age- and sex-matched uninfected controls. COVID-19 induces profound changes in gene expression, despite the absence of detectable virus in brain tissue. Pathway analysis shows downregulation of genes involved in synaptic function and cognition and upregulation of genes involved in immune processes. Comparison with five independent transcriptomic datasets of aging human frontal cortex reveals striking similarities between aged individuals and severe COVID-19 patients. Critically, individuals below 65 years of age exhibit profound transcriptomic changes not observed among older individuals in our patient cohort. Our data indicate that severe COVID-19 induces molecular signatures of aging in the human brain and emphasize the value of neurological follow-up in recovered individuals.

  🖺 Full Text HTML: Severe COVID-19 induces molecular signatures of aging in the human brain
• A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors -

  The number of occupants in a space influences the risk of far-field airborne transmission of the SARS-CoV-2 virus because the likelihood of having infectious and susceptible people both scale with the number of occupants. Mass- balance and dose-response models determine far-field transmission risks for an individual person and a population of people after sub-dividing a large reference space into 10 identical comparator spaces. For a single infected person when the per capita ventilation rate is preserved, the dose received by an individual person in the comparator space is 10-times higher because the equivalent ventilation rate per infected person is lower. However, accounting for population dispersion, such as the community infection rate, the probability of an infected person being present and uncertainty in their viral load, shows the probability of transmission increases with occupancy. Also, far-field transmission is likely to be a rare event that requires a set of Goldilocks conditions that are just right, when mitigation measures have limited effect. Therefore, resilient buildings should deliver the equivalent ventilation rate required by standards and increase the space volume per person, but also require reductions in the viral loads and the infection rate of the wider population.

  🖺 Full Text HTML: A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors
• Recurring Spatiotemporal Patterns of COVID-19 in the United States -

  We analyzed the waxing and waning patterns (9surges9) of reported SARS-CoV-2 cases from January 1, 2020 through Oct 31, 2021 in all states and provinces (n = 93) in the USA, Mexico, and Canada, and across all counties (N =

3142. in the USA. A correlation matrix of the 576 x 576 daily case incidence rates in the 50 US states generates a distinctive 9checkerboard9 pattern showing that the epidemic has consisted of seven distinct internally coherent spatiotemporal wave patterns, four in the first year of the epidemic, and three thus far in the second year. Geoclustering of state case rate trajectories reveals three dominant co-varying spatial clusters of similar case rate trajectories, in the northeastern, southeastern and central/western regions of the USA. The spatiotemporal patterns of epidemic year 1 have thus far been repeated (p<.001) in epidemic year 2. The 9checkerboard9 pattern of the correlation matrix of case trajectories can be closely simulated as three sets of interacting sine waves with annual frequencies of 1:1:2 major cycles per year, corresponding to the northeastern, central/western, and southeastern state clusters. Case incidence patterns in Mexico and Canada have been similar to nearby regions in the southern US and the northern US, respectively. Time lapse videos allow visualization of the wave patterns. These highly structured geographical and temporal patterns, coupled with emerging evidence of annual repetition of these same patterns, show that SARS-CoV-2 case rates are driven at least in part by predictable seasonal factors.
      🖺 Full Text HTML: Recurring Spatiotemporal Patterns of COVID-19 in the United States

• Reinfection with SARS-CoV-2: outcome, risk factors and vaccine efficacy in a Scottish cohort -

  Background – The objective of this study was to investigate how protection against COVID-19 conferred by previous infection is modified by vaccination. Methods – In a cohort of all 152655 individuals in Scotland alive at 90 days after a positive test for SARS-CoV-2 (confirmed by cycle threshold < 30, or two tests) followed till 22 September 2021, rate ratios for reinfection were estimated with calendar time or tests as timescale. Findings – Rates of detected and hospitalised reinfection with COVID-19 while unvaccinated were respectively 6.8 (95% CI 6.4 to 7.2) and 0.18 (95% CI 0.12 to 0.25) per 1000 person-months. These rates were respectively 68% and 74% lower than in a matched cohort of individuals who had not previously tested positive. Efficacy of two doses of vaccine in those with previous infection was estimated as as 84% (95 percent CI 81% to 86%) against detected reinfection and 71% (95 percent CI 29% to 88%) against hospitalised or fatal reinfection. The rate of detected reinfection after two doses of vaccine was 1.35 (95% CI 1.02 to 1.78) times higher in those vaccinated before first infection than in those unvaccinated at first infection. Interpretation – The combination of natural infection and vaccination provides maximal protection against new infection with SARS-CoV-2: prior vaccination does not impair this protection.

  🖺 Full Text HTML: Reinfection with SARS-CoV-2: outcome, risk factors and vaccine efficacy in a Scottish cohort
• Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals -

  The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) break through infection- or vaccine-induced immunity is not well understood. Here, we analyze 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity.

  🖺 Full Text HTML: Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
• Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales -

  Importance: The long-term effects of COVID-19 on the incidence of vascular diseases are unclear. Objective: To quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease. Design: Cohort study based on population-wide linked electronic health records, with follow up from January 1st to December 7th 2020. Setting and participants: Adults registered with an NHS general practice in England or Wales and alive on January 1st 2020. Exposures: Time since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis. Main outcomes and measures: Primary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications. Results: Among 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non- hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses. Conclusions and Relevance: High rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID-19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.

  🖺 Full Text HTML: Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales
• A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes -

  We describe the results of the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE). In sex-disaggregated genome-wide studies of COVID-19 hospitalization, we found two known loci associated among males (SLC6A20-LZTFL1 and IFNAR2), and a novel one among females (TLE1). Meta-analyses with independent studies revealed two novel associations (AQP3 and ARHGAP33) and replicated ELF5. A genetic risk score predicted COVID-19 severity, especially among younger males. We found less SNP-heritability and larger heritability differences by age (<60/≥60 years) among males than females. Inbreeding depression was associated with COVID-19 hospitalization and severity, and the effect was stronger among older males.

  🖺 Full Text HTML: A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes

From Clinical Trials

• Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: RO7496998;   Drug: Placebo
  Sponsor:  
  Hoffmann-La Roche
  Suspended

• Mesenchymal Stem Cell Secretome In Severe Cases of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Injection of secretome - mesenchymal stem cell;   Other: Placebo;   Drug: Standard treatment of Covid-19
  Sponsor:   Indonesia University
  Completed

• Allogenic UCMSCs as Adjuvant Therapy for Severe COVID-19 Patients - Condition:   Covid 19
  Interventions:   Biological: Normoxic Allogenic UCMSC;   Other: Normal saline solution
  Sponsors:   Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia;   Dr. Moewardi General Hospital, Surakarta, Indonesia;   Dr. Sardjito General Hospital, Yogyakarta, Indonesia;   Dr. Hasan Sadikin General Hospital, Bandung, Indonesia;   PT Bifarma Adiluhung
  Recruiting

• Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Mild-to-Moderate COVID-19: A Phase II Clinical Trial - Condition:   COVID-19
  Intervention:   Drug: ExoFlo
  Sponsor:   Direct Biologics, LLC
  Recruiting

• Physical Fitness in Young Healthy Adults After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Other: Physical Activity Level;   Other: Evaluation of knee extension and elbow flexion muscle strength;   Other: Evaluation of functional strength of trunk muscles;   Other: Muscle Endurance;   Other: Flexibility;   Other: Balance;   Other: Fatigue
  Sponsor:  
  Baskent University
  Enrolling by invitation

• The South Proxa-Rescue AndroCoV Trial Against COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Proxalutamide;   Drug: Placebo
  Sponsors:   Corpometria Institute;   Hospital da Brigada Militar de Porto Alegre, Porto Alegre, Brazil;   Hospital Arcanjo Sao Miguel, Gramado, Brazil;   Hospital Unimed Chapeco, Chapeco, Brazil
  Completed

• Vitamin D Supplementation and Clinical Improvement in COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: Vitamin D3 10000 IU;   Dietary Supplement: Vitamin D3 1000 IU
  Sponsor:   Bumi Herman
  Completed

• Feasibility Pilot Clinical Trial of Omega-3 Supplement vs. Placebo for Post Covid-19 Recovery Among Health Care Workers - Condition:   COVID-19
  Interventions:   Drug: Omega-3 (EPA+DHA);   Drug: Placebo
  Sponsor:   Hackensack Meridian Health
  Not yet recruiting

• Adding Colchicine to Tocilizumab in Patients With Severe COVID-19 Pneumonia. - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Colchicine
  Sponsor:  
  Hamad Medical Corporation
  Recruiting

• Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Candesartan Cilexetil;   Drug: Repagermanium;   Drug: Candesartan Placebo;   Drug: Repagermanium Placebo
  Sponsors:  
  University of Sydney;   The George Institute for Global Health, India
  Not yet recruiting

• Partnerships to Address COVID-19 Inequities - Condition:   COVID-19
  Interventions:   Behavioral: Crowdsourced campaign package;   Behavioral: Standard information
  Sponsor:   Duke University
  Not yet recruiting

• Study to Evaluate the inHaled Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) On the Protective-Efficacy in Adults (SeiHOPE) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (adenovirus type 5 vector) for Inhalation (Ad5-nCoV-IH);   Biological: Placebo
  Sponsors:   CanSino Biologics Inc.;   Beijing Institute of Biotechnology
  Not yet recruiting

• Pharmacokinetics, Pharmacodynamics, and Safety of Single-dose Sotrovimab in High-risk Pediatric Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Sotrovimab
  Sponsors:  
  GlaxoSmithKline;   Vir Biotechnology, Inc.
  Not yet recruiting

• PREVENT-COVID-19: A Q-Griffithsin Intranasal Spray - Condition:   COVID-19 Prevention
  Interventions:   Drug: Q-Griffithsin;   Other: Placebo
  Sponsors:   Kenneth Palmer;   United States Department of Defense
  Recruiting

• Nutritional Supplementation of Vitamin D, Quercetin and Curcumin With Standard of Care for Managing Mild Early Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Standard of care;   Dietary Supplement: Investigational treatment
  Sponsor:   King Edward Medical University
  Recruiting

From PubMed

• Discovery of Zafirlukast as a novel SARS-CoV-2 helicase inhibitor using in silico modelling and a FRET-based assay - The coronavirus helicase is an essential enzyme required for viral replication/transcription pathways. Structural studies revealed a sulphate moiety that interacts with key residues within the nucleotide-binding site of the helicase. Compounds with a sulphoxide or a sulphone moiety could interfere with these interactions and consequently inhibit the enzyme. The molecular operating environment (MOE) was used to dock 189 sulphoxide and sulphone-containing FDA-approved compounds to the…

• Minimizing errors in RT-PCR detection and quantification of SARS-CoV-2 RNA for wastewater surveillance - Wastewater surveillance for pathogens using reverse transcription-polymerase chain reaction (RT-PCR) is an effective and resource-efficient tool for gathering community-level public health information, including the incidence of coronavirus disease-19 (COVID-19). Surveillance of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in wastewater can potentially provide an early warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and…

• Stapled Peptides Targeting SARS-CoV-2 Spike Protein HR1 Inhibit the Fusion of Virus to Its Cell Receptor - The pandemic of acute respiratory disease in 2019 caused by highly pathogenic and infectious SARS-CoV-2 has seriously endangered human public safety. The 6-HB (HR1-HR2 complex) formation occurring in the process of spike protein-mediated membrane fusion could serve as a conserved and potential target for the design of fusion inhibitors. Based on the HR2 domain of 6-HB, we designed and synthesized 32 stapled peptides using an all-hydrocarbon peptide stapling strategy. Owing to the improved…

• Site-Specific Labeling of Endogenous Proteins Using CoLDR Chemistry - Chemical modifications of native proteins can affect their stability, activity, interactions, localization, and more. However, there are few nongenetic methods for the installation of chemical modifications at a specific protein site in cells. Here we report a covalent ligand directed release (CoLDR) site-specific labeling strategy, which enables the installation of a variety of functional tags on a target protein while releasing the directing ligand. Using this approach, we were able to label…

• Computational hunting of natural active compounds as an alternative for Remdesivir to target RNA-dependent polymerase - The hunt for potential lead/drug molecules from different resources, especially from natural resources, for possible treatment of COVID-19 is ongoing. Several compounds have already been identified, but only a few are good enough to show potential against the virus. Among the identified druggable target proteins of SARS-CoV-2, this study focuses on non- structural RNA-dependent RNA polymerase protein (RdRp), a well-known enzyme for both viral genome replication and viral mRNA synthesis, and is…

• Evaluation of Humoral Immune Response after SARS-CoV-2 Vaccination Using Two Binding Antibody Assays and a Neutralizing Antibody Assay - Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and administered to mitigate the coronavirus disease 2019 (COVID-19) pandemic. We assessed the humoral response of BNT162b2 and ChAdOx1 nCoV-19 using Siemens SARS-CoV-2 IgG (sCOVG; cutoff of ≥1.0 U/ml), Abbott SARS-CoV-2 IgG II Quant (CoV-2 IgG II; cutoff of ≥50.0 AU/ml), and GenScript cPASS SARS-CoV-2 neutralization antibody detection kits (cPASS; cutoff of ≥30% inhibition). We collected…

• Glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein - The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19, uses its spike (S) glycoprotein anchored in the viral membrane to enter host cells. The S glycoprotein is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by co-expression of SARS-CoV-2 S, M, E…

• The N-terminal Region of Middle East Respiratory Syndrome Coronavirus Accessory Protein 8b is Essential for Enhanced Virulence of an Attenuated Murine Coronavirus - Middle East respiratory syndrome coronavirus (MERS-CoV) is a beta coronavirus that emerged in 2012, causing severe pneumonia and renal failure. MERS-CoV encodes five accessory proteins. Some of them have been shown to interfere with host antiviral immune response. However, the roles of protein 8b in innate immunity and viral virulence was rarely studied. Here, we introduced individual MERS-CoV accessory protein genes into the genome of an attenuated murine coronavirus (Mouse hepatitis virus,…

• Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients’ medical, epidemiological…

• Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2 - Inhibitors of Bromodomain and Extra-terminal domain (BET) proteins are possible anti-SARS-CoV-2 prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here, we show that BET proteins should not be inactivated therapeutically as they are critical antiviral factors at the post-entry level. Knockouts of BRD3 or BRD4 in cells overexpressing ACE2 exacerbate SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during…

• Multimodal Identification by Transcriptomics and Multiscale Bioassays of Active Components in Xuanfeibaidu Formula to Suppress Macrophage-Mediated Immune Response - Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances….

• Tea and coffee polyphenols and their biological properties based on the latest in vitro investigations - Tea and coffee contain numerous polyphenolic compounds that exhibit health-promoting properties for humans, including antioxidant and neuroprotective properties, and can also take part in the treatment of covid-19 and improve fertility. This review, presents the activity of polyphenols found in different types of tea and coffee and describes the effects of tea fermentation and coffee roasting on their polyphenol composition and antioxidant properties. Polyphenol oxidase activity is reduced in…

• SARS-CoV-2 receptor binding domain radio-probe: a non-invasive approach for angiotensin-converting enzyme 2 mapping in mice - The spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) of human respiratory epithelial cells, which leads to infection. Furthermore, low-dose radiation has been found to reduce inflammation and aid the curing of COVID-19. The receptor binding domain (RBD), a recombinant spike protein with a His tag at the C-terminus, binds to ACE2 in human body. We thus constructed a radioiodinated RBD as a molecule-targeted probe to non-invasively explore ACE2 expression in vivo,…

• ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury - Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS- CoV-2-infected hamsters, leading…

• Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity - The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (M^(pro), also called 3CLpro) that cut the viral precursor polyproteins and is a major target for antiviral drug design. Here, we showed that heparin interacts with the M^(pro) of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the M^(pro) protein with dissociation constants K(D) of 16.66 and 31.60 μM at 25 and 35 °C, respectively. From thermodynamic…

From Patent Search

• A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link

• A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link

• PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - link

• Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients. - - link

• ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - link

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• Secured Health monitoring system using cloud computing - As used in public health surveillance, the invention generally relates to remote health monitoring systems with cloud computing. This is particularly relevant about a multi-user remote health monitoring system that can detect and gather data from healthcare professionals on the ground and systems in laboratories and hospitals to help the public health sector. It is possible to utilize the system for tracking, monitoring, and collecting patient data and for querying and collecting more information on the health of the people. - link

• Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法 - 本发明在野生型Bst DNA聚合酶序列上进行了Ser358Asp、Thr480Asn、Asp533Glu、Ala539Gly几个点位的突变，然后将进行点突变后的Bst DNA聚合酶的292‑305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL，在突变后Bst DNA聚合酶序列的C端融合了一个DNA结合蛋白，在突变后Bst DNA聚合酶序列的N端融合了一个HP47多肽序列（SEQ ID No.17），在HP47多肽序列前面融合了一个CL7‑SUMO‑Tag，得到一种具有高活性和热稳定性的Bst DNA聚合酶重组突变体Super‑Bst（SEQ ID No.16）。Super‑Bst在热稳定性、特异性、链置换能力、延伸能力和逆转录酶活性上得到了显著地提升，能够耐受高盐和各类抑制剂，且可以通过原核表达和亲和纯化大量获得。本发明还公开了其编码DNA，以及一种超快磁珠LAMP检测方法。 - link

• 一种新型冠状病毒及其德尔塔突变株检测试剂盒及其检测方法 - 本发明提供了一种新型冠状病毒及其德尔塔突变株检测试剂盒及其检测方法，属于分子生物学检测技术领域。本发明重新设计了一系列引物探针组，增加检测靶点，从而有效区分新型冠状病毒野生型和德尔塔突变株。可用于体外定性检测新型冠状病毒或德尔塔突变株感染的肺炎疑似病例、疑似聚集性病例患者、其他需要进行新型冠状病毒感染诊断或鉴别诊断者的鼻咽拭子、痰液等样本中的新型冠状病毒基因。 - link