Covid-19 Sentry

Contents

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

From Preprints

• The AstraZeneca affair. A litmus test of information disorder in the Italian hybrid media ecosystem -
  In this paper we seek to demonstrate how a variety of information disorder phenomena comes to be at the intersection of legacy and social media interaction. To do so, we collected more than 750.000 tweets and 30.000 news articles related to the adoption of AstraZeneca vaccine in Italy for a period of six months (1st January 2021 - 30th June 2021). Initially, using timestamps of publications and tweets, we tracked the pace of public debate. Then, using a mixed methods approach, we investigated Twitter reaction during the climax of attention toward AstraZeneca. Acting as a litmus test, our study reveals three different but intertwined information disorder phenomena: first, the vaccine debate exhibit a flat progression with few condensed peaks of attention (acceleration phenomenon); second, the two main peaks that involve both journalistic coverage and Twitter discussion generate from news of suspect deaths related to AstraZeneca (sensationalisation phenomenon); and finally, the report of suspect deaths news by mainstream media accounts on Twitter correlates with a polarized and ideological reaction of the connected publics (fragmentation phenomenon). These results highlight how a direct implication of the hybrid media ecosystem’s actual configuration could be a resistance in the formation of a public arena capable of sustaining a prolonged and effective debate, particularly with respect to controversial societal issues such as those related to the covid-19 vaccination campaign.
  🖺 Full Text HTML: The AstraZeneca affair. A litmus test of information disorder in the Italian hybrid media ecosystem
• The role of personality, conspiracy mentality, REBT irrational beliefs, and adult attachment in COVID-19 related health behaviors -
  There is evidence that different types of irrational thinking and beliefs are significant predictors of questionable and maladaptive COVID-19 related health practices. In this study, we investigated the role of two under- researched types of irrational thinking, more typical for a clinical setting: irrational beliefs defined in rational- emotive cognitive-behavior therapy (REBT) and attachment anxiety and avoidance. We investigated whether REBT irrational beliefs, attachment dimensions, and conspiracy mentality mediated the relationship between personality traits, on the one side, and COVID-19 health behaviors, on the other. We proposed that HEXACO personality traits, and especially Disintegration (proneness to psychotic-like experiences) predicted irrational thinking and beliefs, which in turn predicted higher susceptibility to questionable health practices. Structural equation modeling on a sample of 287 participants from the general population, showed that Disintegration was related to REBT irrational beliefs, attachment dimensions, and conspiracy mentality, highlighting the important effect of Disintegration on irrational thinking and beliefs. Conspiracy mentality mediated the effects of Disintegration to low adherence to recommended health behaviors - RHB , and greater use of pseudoscientific practices - PSP . Attachment anxiety mediated the relationship between high Disintegration, high Emotionality (E), and low Honesty (H), and lower adherence to RHB. REBT irrational beliefs and attachment avoidance did not mediate the relationship between personality traits and COVID-19 health behaviors.

• Hypertonic saline and aprotinin based blockage of SARS-CoV-2 specific furin site cleavage by inhibition of nasal protease activity -
  SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Cell entry of SARS-CoV-2 needs to be pre-activated by S1/S2 boundary furin motif cleavage by furin and/or relevant proteases. It is important to locally block SARS-CoV-2 S1/S2 site cleavage caused by furin and other relevant protease activity in the nasal cavity. We tested hypertonic saline and aprotinin-based blockage of SARS-CoV-2 specific furin site cleavage by furin, trypsin and nasal swab samples containing nasal proteases. Our results show that saline and aprotinin block SARS-Cov-2 specific furin site cleavage and that a saline and aprotinin combination could significantly reduce SARS-Cov-2 wild-type and P681R mutant furin site cleavage by inhibition of nasal protease activity.
  🖺 Full Text HTML: Hypertonic saline and aprotinin based blockage of SARS-CoV-2 specific furin site cleavage by inhibition of nasal protease activity
• Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection -
  While COVID-19 infection during pregnancy is common, fetal transmission is rare, suggesting that intrauterine mechanisms form an effective blockade against SARS-CoV-2. Key among these is the decidual immune environment of the placenta. We hypothesized that decidual leukocytes are altered by maternal SARS-CoV-2 infection in pregnancy and that this decidual immune resonse is shaped by the timing of infection during gestation. To address this hypothesis, we collected decidua basalis tissues at delivery from women with symptomatic COVID-19 during second (2nd Tri COVID, n=8) or third trimester (3rd Tri COVID, n=8) and SARS-CoV-2-negative controls (Control, n=8). Decidual natural killer (NK) cells, macrophages and T cells were evaluated using quantitative microscopy, and pro- and anti- inflammatory cytokine mRNA expression was evaluated using quantitative reverse transcriptase PCR (qRT-PCR). When compared with the Control group, decidual tissues from 3rd Tri COVID exhibited significantly increased macrophages, NK cells and T cells, whereas 2nd Tri COVID only had significantly increased T cells. In evaluating decidual cytokine expression, we noted that IL-6, IL-8, IL-10 and TNF- were significantly correlated with macrophage cell abundance. However, in 2nd Tri COVID tissues, there was significant downregulation of IL-6, IL-8, IL-10, and TNF-. Taken together, these results suggest innate and adaptive immune responses are present at the maternal-fetal interface in maternal SARS- CoV-2 infections late in pregnancy, and that infections earlier in pregnancy show evidence of a resolving immune response. Further studies are warranted to characterize the full scope of intrauterine immune responses in pregnancies affected by maternal COVID-19.
  🖺 Full Text HTML: Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection
• Acute SARS-CoV-2 infection in pregnancy is associated with placental ACE-2 shedding -
  Human placental tissues have variable rates of SARS-CoV-2 invasion resulting in consistently low rates of fetal transmission suggesting a unique physiologic blockade against SARS-CoV-2. Angiotensin-converting enzyme (ACE)-2, the main receptor for SARS-CoV-2, is expressed as cell surface and soluble forms regulated by a metalloprotease cleavage enzyme, ADAM17. ACE-2 is expressed in the human placenta, but the regulation of placental ACE-2 expression in relation to timing of maternal SARS-CoV-2 infection in pregnancy is not well understood. In this study, we evaluated ACE-2 expression, ADAM17 activity and serum ACE-2 abundance in a cohort of matched villous placental and maternal serum samples from Control pregnancies (SARS-CoV-2 negative, n=8) and pregnancies affected by symptomatic maternal SARS- CoV-2 infections in the 2nd trimester (2ndTri COVID, n=8) and 3rd trimester (3rdTri COVID, n=8). In 3rdTri COVID as compared to control and 2ndTri-COVID villous placental tissues ACE-2 mRNA expression was remarkably elevated, however, ACE-2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE-2 was also significantly increased in the maternal serum from 3rdTri COVID infections as compared to control and 2ndTri- COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE-2 protein may be the result of ACE-2 shedding. Overall, this work highlights the importance of ACE-2 for ongoing studies on SARS- CoV-2 responses at the maternal-fetal interface.
  🖺 Full Text HTML: Acute SARS-CoV-2 infection in pregnancy is associated with placental ACE-2 shedding
• Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2 -
  SARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein which may influence the pathogenesis of the concern SARS-CoV-2 through the development of antibody escape variants. We consider the effect of mutations in some of the epitope regions including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. P323L mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, the fluctuations in the dihedral angles in the epitope:paratope (IgG) interface increase which destabilize the interface. Such mutations may help in escaping antibody mediated immunity of the host.
  🖺 Full Text HTML: Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2
• Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity -
  The current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III), in a wide range of human cell types. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates end-to-end dimer self-assembly of these RNAs by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory siRNAs, their activity is independent of TLR7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in both cell lines and human Lung Chips that mimic organ-level lung pathophysiology. These short dsRNAs can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics at low cost.
  🖺 Full Text HTML: Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity
• Characterization of SARS-CoV-2 public CD4+ αβ T cell clonotypes through reverse epitope discovery -
  The amount of scientific data and level of public sharing produced as a consequence of the COVID-19 pandemic, as well as the speed at which these data were produced, far exceeds any previous effort against a specific disease condition. This unprecedented situation allows for development and application of new research approaches. One of the major technical hurdles in immunology is the characterization of HLA-antigen-T cell receptor (TCR) specificities. Most approaches aim to identify reactive T cells starting from known antigens using functional assays. However, the need for a reverse approach identifying the antigen specificity of orphan TCRs is increasing. Utilizing large public single-cell gene expression and TCR datasets, we identified highly public CD4+ T cell responses to SARS-CoV-2, covering >75% of the analysed population. We performed an integrative meta-analysis to deeply characterize these clonotypes by TCR sequence, gene expression, HLA-restriction, and antigen-specificity, identifying strong and public CD4+ immunodominant responses with confirmed specificity. CD4+ COVID-enriched clonotypes show T follicular helper functional features, while clonotypes depleted in SARS-CoV-2 individuals preferentially had a central memory phenotype. In total we identify more than 1200 highly public CD4+ T cell clonotypes reactive to SARS-CoV-2. TCR similarity analysis showed six prominent TCR clusters, for which we predicted both HLA-restriction and cognate SARS-CoV-2 immunodominant epitopes. To validate our predictions we used an independent cohort of TCR repertoires before and after vaccination with ChAdOx1, a replication-deficient simian adenovirus-vectored vaccine, encoding the SARS-CoV-2 spike protein. We find statistically significant enrichment of the predicted spike-reactive TCRs after vaccination with ChAdOx1, while the frequency of TCRs specific to other SARS-CoV-2 proteins remains stable. Thus, the CD4-associated TCR repertoire differentiates vaccination from natural infection. In conclusion, our study presents a novel reverse epitope discovery approach that can be used to infer HLA- and antigen-specificity of orphan TCRs in any context, such as viral infections, antitumor immune responses, or autoimmune disease.
  🖺 Full Text HTML: Characterization of SARS-CoV-2 public CD4+ αβ T cell clonotypes through reverse epitope discovery
• ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis -
  As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5. To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Collectively, these data support the hypothesis that CF condition is unfavorable for SARS-CoV-2 infection.
  🖺 Full Text HTML: ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis
• SARS-CoV-2 papain-like protease PLpro in complex with natural compounds reveal allosteric sites for antiviral drug design -
  SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to aid coronaviruses in evading the hosts innate immune responses. We established a high-throughput X-ray screening to identify inhibitors by elucidating the native PLpro structure refined to 1.42 Angstroms and performing co- crystallization utilizing a diverse library of selected natural compounds. We identified three phenolic compounds as potential inhibitors. Crystal structures of PLpro inhibitor complexes, obtained to resolutions between 1.7-1.9 Angstroms, show that all three compounds bind at the ISG15/Ub-S2 allosteric binding site, preventing the essential ISG15-PLpro molecular interactions. All compounds demonstrate clear inhibition in a deISGylation assay, two exhibit distinct antiviral activity and one inhibited a cytopathic effect in a non-cytotoxic concentration range. These results highlight the druggability of the rarely explored ISG15/Ub-S2 PLpro allosteric binding site to identify new and effective antiviral compounds. Importantly, in the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.
  🖺 Full Text HTML: SARS-CoV-2 papain-like protease PLpro in complex with natural compounds reveal allosteric sites for antiviral drug design
• COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant, and implications for vaccination -

  Background: The COVID-19 Delta pandemic wave in India surged and declined within 3 months; cases then remained low despite the continued spread of Delta elsewhere. Here we aim to estimate key epidemiological characteristics of the Delta variant based on data from India and examine the underpinnings of its dynamics. Methods: We utilize multiple datasets and model-inference methods to reconstruct COVID-19 pandemic dynamics in India during March 2020 - June 2021. We further use model estimates to retrospectively predict cases and deaths during July - mid-Oct 2021, under various vaccination and vaccine effectiveness (VE) settings to estimate the impact of vaccination and VE for non-Delta-infection recoverees. Findings: We estimate that Delta escaped immunity in 34.6% (95% CI: 0 - 64.2%) of individuals with prior wildtype infection and was 57.0% (95% CI: 37.9 - 75.6%) more infectious than wildtype SARS-CoV-2. Models assuming higher VE among those with prior non-Delta infection, particularly after the 1st dose, generated more accurate predictions than those assuming no such increases (best-performing VE setting: 90/95% vs. 30/67% baseline for the 1st/2nd dose). Counterfactual modeling indicates that high vaccination coverage for 1st vaccine-dose in India (~50% by mid-Oct 2021) combined with the boosting of VE among recoverees averted around 60% of infections during July - mid-Oct 2021. Interpretation: Non-pharmaceutical interventions, infection seasonality, and high coverage of 1-dose vaccination likely all contributed to pandemic dynamics in India during 2021. Given the shortage of COVID-19 vaccines globally and boosting of VE, for populations with high prior infection rates, prioritizing the first vaccine-dose may protect more people.

  🖺 Full Text HTML: COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant, and implications for vaccination
• COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic -
  During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals’ experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy.
  🖺 Full Text HTML: COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic
• A Flexible Statistical Framework for Estimating Excess Mortality -

  Quantifying the impact of natural disasters or epidemics is critical for guiding policy decisions and interventions. When the effects of an event are long-lasting and difficult to detect in the short term, the accumulated effects can be devastating. Mortality is one of the most reliably measured health outcomes, partly due to its unambiguous definition. As a result, excess mortality estimates are an increasingly effective approach for quantifying the effect of an event. However, the fact that indirect effects are often characterized by small, but enduring, increases in mortality rates present a statistical challenge. This is compounded by sources of variability introduced by demographic changes, secular trends, seasonal and day of the week effects, and natural variation. Here we present a model that accounts for these sources of variability and characterizes concerning increases in mortality rates with smooth functions of time that provide statistical power. The model permits discontinuities in the smooth functions to model sudden increases due to direct effects. We implement a flexible estimation approach that permits both surveillance of concerning increases in mortality rates and careful characterization of the effect of a past event. We demonstrate our tools9 utility by estimating excess mortality after hurricanes in the United States and Puerto Rico. We use Hurricane Maria as a case study to show appealing properties that are unique to our method compared to current approaches. Finally, we show the flexibility of our approach by detecting and quantifying the 2014 Chikungunya outbreak in Puerto Rico and the COVID-19 pandemic in the United States. We make our tools available through the excessmort R package available from https://cran.r-project.org/web/packages/excessmort/.

  🖺 Full Text HTML: A Flexible Statistical Framework for Estimating Excess Mortality
• Clinical Outcome of Neurological patients with COVID-19: the impact of Healthcare organization improvement between waves. -

  Abstract Objective: The aim of this study is to evaluate the differences of clinical presentations and the impact of healthcare organization on outcomes of neurological COVID-19 patients admitted during the first and second pandemic waves. Methods: In this single center cohort study, we included all patients with SARS-CoV-2 infection admitted to a Neuro-COVID Unit. Demographic, clinical and laboratory data were compared between patients admitted during the first and second waves of COVID-19 pandemic. Results: 223 patients were included, of whom 112 and 111 hospitalized during the first and second pandemic waves, respectively. Patients admitted during the second wave were younger and exhibited pulmonary COVID-19 severity, resulting in less oxygen support (n=41, 36.9% vs n=79, 70.5%, p<0.001) and lower mortality rates (14.4% vs 31.3%, p=0.004). The different healthcare strategies and early steroid treatment emerged as significant predictors of mortality independently from age, premorbid conditions and COVID-19 severity in cox regression analyses. Conclusions: Differences in healthcare strategies during the second phase of COVID-19 pandemic probably explain the differences in clinical outcomes independently of disease severity, underlying the importance of standardized early management of neurological patients with SARS-CoV-2 infection.

  🖺 Full Text HTML: Clinical Outcome of Neurological patients with COVID-19: the impact of Healthcare organization improvement between waves.
• Conspiratorial thinking during COVID-19: The roles of paranoia, delusion-proneness, and intolerance of uncertainty -
  The COVID-19 global pandemic has left many feeling a sense of profound uncertainty about their world, safety, and livelihood. Information that can help make sense of this uncertainty is offered by both official health-organizations as well as sources espousing misinformation and conspiracy theories. Individuals high in intolerance of uncertainty (IU) may be particularly impacted by the impoverished epistemic environment and may thus be more drawn to conspiratorial thinking (CT). In the present study we show that endorsement of COVID-19-specific conspiracy theories is associated with higher levels of intolerance of uncertainty as well as anxiety, delusion-proneness, and paranoid ideation. Furthermore, delusion-proneness and paranoia explained the relationship between IU and CT, and emerged as independent partial predictors of CT even when controlling for other facets of schizotypy. In contrast, anxiety did not explain the relationship between IU and CT, suggesting a stronger role of cognitive traits as opposed to affective factors. Overall, our findings highlight the importance of individual differences in IU, delusion proneness and paranoia in the development of CT in the context of the acute uncertainty of a global crisis, in which CT is more prevalent and salient. Informational intervention designs may benefit from leveraging the body of work demonstrating the efficacy of targeting IU to incite meaningful changes in thinking.
  🖺 Full Text HTML: Conspiratorial thinking during COVID-19: The roles of paranoia, delusion-proneness, and intolerance of uncertainty

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

• 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

• 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

• the Safety and Efficacy of Meplazumab in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Meplazumab for Injection;   Drug: Sterile normal saline (0.9%)
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Health Information Technology for COVID-19 Testing in Schools (SCALE-UP Counts) - Condition:   COVID-19
  Interventions:   Behavioral: Text Messaging (TM);   Behavioral: Text Messaging + Health Navigation (TM+HN)
  Sponsors:   University of Utah;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet 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

• Design of modular autoproteolytic gene switches responsive to anti-coronavirus drug candidates - The main (Mpro) and papain-like (PLpro) proteases encoded by SARS-CoV-2 are essential to process viral polyproteins into functional units, thus representing key targets for anti-viral drug development. There is a need for an efficient inhibitor screening system that can identify drug candidates in a cellular context. Here we describe modular, tunable autoproteolytic gene switches (TAGS) relying on synthetic transcription factors that self-inactivate, unless in the presence of coronavirus…

• The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered-Dose Inhaler in the Treatment of COVID-19 Patients - CONCLUSION: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

• Immunomodulatory effects of Allium Sativum L. and its constituents against viral infections and metabolic diseases - CONCLUSION: Garlic is a fundamental part of a well-balanced diet which helps maintain general good health. The reported information regarding garlic’s ability to beneficially modulate inflammation and the immune system is encouraging. Nonetheless, more efforts must be made to understand the actual medicinal properties and mechanisms of action of the compounds found in this plant to inhibit or diminish viral infections, particularly SARS-CoV-2. Based on our findings, we propose a series of…

• Potential Papain-like Protease Inhibitors against COVID-19: A Comprehensive In Silico Based Review - The entire world has been in a battle against the COVID-19 pandemic since its first appearance in December 2019. Thus researchers are desperately working to find an effective and safe therapeutic agent for its treatment. The multifunctional coronavirus enzyme papain-like protease (PLpro) is a potential target for drug discovery to combat the ongoing pandemic responsible for cleavage of the polypeptide, deISGylation, and suppression of host immune response. The present review collates the in…

• In silico evaluation of NO donor heterocyclic vasodilators as SARS-CoV-2 M(pro) protein inhibitor - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 disease has been exponentially increasing throughout the world. The mortality rate is increasing gradually as effective treatment is unavailable to date. In silico based screening for novel testable hypotheses on SARS-CoV-2 M^(pro) protein to discover the potential lead drug candidate is an emerging area along with the discovery of a vaccine. Administration of NO-releasing agents, NO inducers or the NO gas itself…

• Functional Antibodies Against SARS-CoV-2 Receptor Binding Domain Variants with Mutations N501Y or E484K in Human Milk from COVID-19-Vaccinated, -Recovered, and -Unvaccinated Women - Background: New variants are evolving in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and receptor binding domain (RBD) mutations have been associated with a higher capacity to evade neutralizing antibodies (NAbs). We aimed at determining the impact of COVID-19 vaccine and infection on human milk antibody titers and activity against the RBD mutations from SARS-CoV-2 variants of concern. Materials and Methods: Milk samples were collected from 19 COVID-19 vaccinated women, 10…

• TMPRSS2 promotes SARS-CoV-2 evasion from NCOA7-mediated restriction - Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with the vacuolar ATPase, and promotes endo-lysosomal vesicle acidification and lysosomal protease activity. Here, we used ectopic expression and gene knockout to demonstrate that NCOA7…

• A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses - The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly,…

• Discordance Between SARS-CoV-2-specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients - CONCLUSIONS: Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.

• The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses - Viral infections may cause serious human diseases. For instance, the recent appearance of the novel virus, SARS-CoV-2, causing COVID-19, has spread globally and is a serious public health concern. The consumption of healthy, proper, functional, and nutrient-rich foods has an important role in enhancing an individual’s immune system and preventing viral infections. Several polysaccharides from natural sources such as algae, bacteria, and fungi have been considered as generally recognized as safe…

• Nanomedicine for the Diagnosis and Therapy of COVID-19 - The coronavirus disease-2019 (COVID-19) pandemics caused by the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has been spreading around the world due to its high infection rate, long incubation period, as well as lack of effective diagnosis and therapy or vaccines, which is tearing global health systems apart. It is an urgent demand for point-of-care diagnosis and effective treatment to prevent the spread of COVID-19. Currently, based on the rapid development of functional…

• Siglecs Modulate Activities of Immune Cells Through Positive and Negative Regulation of ROS Generation - Reactive oxygen species (ROS) are a group of oxygen-containing highly-reactive molecules produced from oxidative metabolic processes or in response to intracellular signals like cytokines and external stimuli like pathogen attack. They regulate a range of physiological processes and are involved in innate immune responses against infectious agents. Deregulation of ROS contributes to a plethora of disease conditions. Sialic acids are carbohydrates, present on cell surfaces or soluble proteins….

• Phillyrin for COVID-19 and Influenza Co-infection: A Potential Therapeutic Strategy Targeting Host Based on Bioinformatics Analysis - Background: The risk of co-epidemic between COVID-19 and influenza is very high, so it is urgent to find a treatment strategy for the co-infection. Previous studies have shown that phillyrin can not only inhibit the replication of the two viruses, but also has a good anti-inflammatory effect, which is expected to become a candidate compound against COVID-19 and influenza. Objective: To explore the possibility of phillyrin as a candidate compound for the treatment of COVID-19 and influenza…

• beta-Carboline alkaloids induce structural plasticity and inhibition of SARS-CoV-2 nsp3 macrodomain more potently than remdesivir metabolite GS-441524: computational approach - The nsp3 macrodomain is implicated in the viral replication, pathogenesis and host immune responses through the removal of ADP-ribosylation sites during infections of coronaviruses including the SARS-CoV-2. It has ever been modulated by macromolecules including the ADP-ribose until Ni and co-workers recently reported its inhibition and plasticity enhancement unprecedentedly by remdesivir metabolite, GS-441524, creating an opportunity for investigating other biodiverse small molecules such as…

• Determination of the interaction between the receptor binding domain of 2019-nCoV spike protein, TMPRSS2, cathepsin B and cathepsin L, and glycosidic and aglycon forms of some flavonols - The novel coronavirus (COVID-19, SARS-CoV-2) is a rapidly spreading disease with a high mortality. In this research, the interactions between specific flavonols and the 2019-nCoV receptor binding domain (RBD), transmembrane protease, serine 2 (TMPRSS2), and cathepsins (CatB and CatL) were analyzed. According to the relative binding capacity index (RBCI) calculated based on the free energy of binding and calculated inhibition constants, it was determined that robinin (ROB) and gossypetin (GOS)…

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