Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children -

  It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic human coronavirus (HCoV) infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Blood samples were collected from study participants annually in February-April. Respiratory samples were collected from participants that met testing criteria. Blood samples collected in were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-year-old children were tested for endemic HCoV antibodies. Respiratory samples were tested for each of the endemic HCoVs from 2011-2016 and for SARS-CoV-2 from 2020-2021 via rt-PCR. By April 2021, 854 (49%) cohort participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic HCoV infections from 2011-2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic HCoV infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.

  🖺 Full Text HTML: SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children
• Unraveling the Enzymatic Mechanism of the SARS-CoV-2 RNA-Dependent-RNA-Polymerase. An Unusual Active Site Leading to High Replication Rates. -
  Viral infection relies on the hijacking of cellular machineries to enforce the reproduc- tion of the infecting virus and its subsequent diffusion. In this context the replication of the viral genome is a key step performed by specific enzymes, i.e. polymerases. The replication of SARS-CoV-2, the causative agent of the COVID-19 pandemics, is based on the duplication of its RNA genome, an action performed by the viral RNA- dependent-RNA polymerase. In this contribution, for the first time and by using two- dimensional enhanced sampling quantum mechanics/ molecular mechanics, we have determined the chemical mechanisms leading to the inclusion of a nucleotide in the nascent viral RNA strand. We prove the high efficiency of the polymerase, which low- ers the activation free energy to less than 10 kcal/mol. Furthermore, the SARS-CoV-2 polymerase active site is slightly different from those found usually found in other similar enzymes, and particularly it lacks the possibility to enforce a proton shuttle via a nearby histidine. Our simulations show that this absence is partially compensate by lysine, whose proton assist the reaction opening up an alternative, but highly efficient, reactive channel. Our results present the first mechanistic resolution of SARS-CoV-2 genome replication and shed light on unusual enzymatic reactivity paving the way for future rational design of antivirals targeting emerging RNA viruses.
  🖺 Full Text HTML: Unraveling the Enzymatic Mechanism of the SARS-CoV-2 RNA-Dependent-RNA-Polymerase. An Unusual Active Site Leading to High Replication Rates.
• Is mandatory vaccination in population over 60 adequate to control the COVID-19 pandemic in E.U.? -

  Vaccine hesitancy, which potentially leads to refusal or delayed acceptance of COVID-19 vaccines, is considered a key driver for the increasing death toll from the pandemic in the E.U.. European Commission and several member states governments are either planning or have already directly or indirectly announced mandatory vaccination for individuals aged over 60, the group repeatedly proved to be the most vulnerable. In this paper, an assessment of this strategy benefits is attempted. This is done by examining the reduction of Standard Expected Years of Life Lost (SEYLL) per person of the EU population over 60 as a function of their vaccination percentage. Publicly available data and some first results of the second iteration of the SHARE COVID-19 survey conducted during the summer of 2021 on acceptance of COVID-19 vaccines are used as input.

  🖺 Full Text HTML: Is mandatory vaccination in population over 60 adequate to control the COVID-19 pandemic in E.U.?
• 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 SARS-CoV-2 because the likelihood of having infectious and susceptible people both correlate with the number of occupants. This paper explores the relationship between occupancy and the probability of infection, and how this affects an individual person and a population of people. 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, 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 when the per capita ventilation rate is preserved. However, accounting for population dispersion, such as the community prevalence of the virus, the probability of an infected person being present and uncertainty in their viral load, shows the transmission probability increases with occupancy and the reference space has a higher transmission risk. Also, far-field transmission is likely to be a rare event that requires a high emission rate, and there are a set of Goldilocks conditions that are just right when ventilation is effective at mitigating against transmission. These conditions depend on the viral load, because when they are very high or low, ventilation has little effect on transmission risk. Nevertheless, resilient buildings should deliver the equivalent ventilation rate required by standards as minimum.

  🖺 Full Text HTML: A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS- CoV-2 indoors
• COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism -
  Background: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection. Objectives: To determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. Methods: hACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP. Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone. Results: hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone. Conclusions: Our observations have important implications for long-term public health, given the number of people that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of PD also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination.
  🖺 Full Text HTML: COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism
• Development and optimisation of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: evaluation of 5676 phase 1 passed structures -
  Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging-based SARS-CoV-2 infection assay was developed in VeroE6-eGFP cells and was used to screen a library of 5676 compounds that passed phase 1 clinical trials. Eight candidates (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) with in vitro anti-SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines were identified. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment.
  🖺 Full Text HTML: Development and optimisation of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: evaluation of 5676 phase 1 passed structures
• Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: a randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU) -

  Background: After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. Methods: In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n=192) or SoC only (n=195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: Intention to treat (ITT) based on randomisation; Per protocol (PP), excluding patients not treated according to randomisation; and As treated (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. Results: Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P=0.063); PP 40.7% RRR, 9.6% ARR (P=0.017); AT 43.2% RRR, 10.8% ARR (P=0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. Conclusions: In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

  🖺 Full Text HTML: Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: a randomized, controlled, open- label, parallel group trial (DOXPREVENT.ICU)
• COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme -

  Laboratory tests for the accurate and rapid identification of SARS-CoV-2 variants can potentially guide the treatment of COVID-19 patients and inform infection control and public health surveillance efforts. Here we present the development and validation of a rapid COVID-19 variant DETECTR assay incorporating loop-mediated isothermal amplification (LAMP) followed by CRISPR-Cas12 based identification of single nucleotide polymorphism (SNP) mutations in the SARS-CoV-2 spike (S) gene. This assay targets the L452R, E484K/Q/A, and N501Y mutations that are associated with nearly all circulating viral lineages and identifies the two circulating variants of concern, Delta and Omicron. In a comparison of three different Cas12 enzymes, only the newly identified enzyme CasDx1 was able to accurately identify all targeted SNP mutations. An analysis pipeline for CRISPR-based SNP identification from 139 clinical samples yielded an overall SNP concordance of 98% and agreement with SARS-CoV-2 lineage classification of 138/139 compared to viral whole- genome sequencing. We also showed that detection of the single E484A mutation was necessary and sufficient to accurately identify Omicron from other major circulating variants in patient samples. These findings demonstrate the utility of CRISPR-based DETECTR as a faster and simpler diagnostic than sequencing for SARS-CoV-2 variant identification in clinical and public health laboratories.

  🖺 Full Text HTML: COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme
• Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine -
  In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Initial studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529. We report here the rapid development of a replicating RNA vaccine expressing the B.1.1.529 spike and show that this B.1.1.529-targeted vaccine is immunogenic in mice and hamsters. Interestingly, we found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529- targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine.
  🖺 Full Text HTML: Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine
• How consistent are smartphone application preferences? A longitudinal study of mobile application repertoires using behavioral data -
  Smartphones afford users the ability to select their own mobile application repertoires through the installation of various applications. We report a quantitative descriptive study of the types of applications that people commonly use, the amount of time they spend with these applications, the application combinations that they construct, the consistency of these combinations over time, and the differences in these outcomes by demographic characteristics. Using a longitudinal dataset collected from a U.S. adult sample during the COVID-19 pandemic, the study leverages behavioral data collected via data donations to identify key application adoption patterns and shows that peoples’ mobile application repertoires are concentrated around a set of popular applications that is relatively consistent over time. However, within this set there is considerable diversity between individuals and applications, suggesting that quantifying smartphone usage with a single metric— ‘screentime’ —is unlikely to capture the full extent of media that users engage with.
  🖺 Full Text HTML: How consistent are smartphone application preferences? A longitudinal study of mobile application repertoires using behavioral data
• A mixed methods analysis of participation in social contact surveys -

  Background Social contact survey data forms a core component of modern epidemic models: however, there has been little assessment of the potential biases in such data. Methods We conducted focus groups with university students who had (n=13) and had not (n=14) completed a social contact survey during the COVID-19 pandemic. Qualitative findings were explored quantitatively by analysing participation data. Results The opportunity to contribute to COVID-19 research, to be heard and feel useful were frequently reported motivators for participating in the contact survey. Reductions in survey engagement following lifting of COVID-19 restrictions may have occurred because the research was perceived to be less critical and/ or because the participants were busier and had more contacts. Having a high number of contacts to report, uncertainty around how to report each contact, and concerns around confidentiality were identified as factors leading to inaccurate reporting. Focus groups participants thought that financial incentives or provision of study results would encourage participation. Conclusions Incentives could improve engagement with social contact surveys. Qualitative research can inform the format, timing, and wording of surveys to optimise completion and accuracy.

  🖺 Full Text HTML: A mixed methods analysis of participation in social contact surveys
• Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics -

  The Covid-19 pandemic outbreak was followed by a huge amount of modelling studies in order to rapidly gain insights to implement the best public health policies. Most of these compartmental models involved ordinary differential equations (ODEs) systems. Such a formalism implicitly assumes that the time spent in each compartment does not depend on the time already spent in it, which is at odds with the clinical data. To overcome this `memoryless99 issue, a widely used solution is to increase and chain the number of compartments of a unique reality (e.g. have infected individual move between several compartments). This allows for greater heterogeneity and thus be closer to the observed situation, but also tends to make the whole model more difficult to apprehend and parameterize. We develop a non- Markovian alternative formalism based on partial differential equations (PDEs) instead of ODEs, which, by construction, provides a memory structure for each compartment thereby allowing us to limit the number of compartments. We apply our model to the French 2021 SARS-CoV-2 epidemic and, while accounting for vaccine-induced and natural immunity, we analyse and determine the major components that contributed to the Covid-19 hospital admissions. The results indicate that the observed vaccination rate alone is not enough to control the epidemic, and a global sensitivity analysis highlights a huge uncertainty attributable to the age-structured contact matrix. Our study shows the flexibility and robustness of PDE formalism to capture national COVID-19 dynamics and opens perspectives to study medium or long-term scenarios involving immune waning or virus evolution.

  🖺 Full Text HTML: Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics
• The evolutionary functions of imagination and fiction and how they may contribute to psychological wellbeing during a pandemic -
  The COVID-19 pandemic caused widespread social disruption and lockdowns, with negative consequences for psychological wellbeing worldwide. We argue that mental simulation, through the cognitive capacity of imagination and its instigator fiction, may have substantial positive contributions to psychological wellbeing during the pandemic. We review relevant research on the evolutionary functions of simulation through imagination and fiction, and propose that simulation is a tool to support (i) planning and future thought, (ii) coping and emotion regulation, (iii) bonding and social needs, and (iv) identity and worldviews. We suggest that these functions can contribute to coping during the pandemic. We also address the dark side of simulation, whereby excessive simulation may have negative effects such as rumination. In light of previous research and the negative psychological effects of COVID-19 disruptions and lockdowns, we suggest that there is much scope for future research on this topic, including whether simulations offered by imaginative activity could be useful and inexpensive mental health tools.
  🖺 Full Text HTML: The evolutionary functions of imagination and fiction and how they may contribute to psychological wellbeing during a pandemic
• Use caution when applying behavioural science to policy -
  Social and behavioural scientists have attempted to speak to the COVID-19 crisis. But is behavioural research on COVID-19 suitable for making policy decisions? We offer a taxonomy that lets our science advance in Evidence Readiness Levels to be suitable for policy. We caution practitioners to take extreme care translating our findings to applications.
  🖺 Full Text HTML: Use caution when applying behavioural science to policy
• A network perspective on real-life threat, anxiety, and avoidance -
  Anxiety, approach and avoidance motivation crucially influence mental and physical health, especially when environments are stressful. The interplay between anxiety and behavioral motivation is modulated by multiple individual factors. This proof of concept study applies graph-theoretical network analysis to explore complex associations between self-reported trait anxiety, approach and avoidance motivation, situational anxiety, stress symptoms, perceived threat, perceived positive consequences of approach, and self-reported avoidance behavior in real-life threat situations. 541 participants (218 patients, 323 community) completed an online survey assessing these factors in response to the COVID-19 pandemic. The resulting cross-sectional psychological network revealed a complex pattern with multiple positive (e.g., between trait anxiety, avoidance motivation, and avoidance behavior) and negative associations (e.g., between approach and avoidance motivation). The patient and community subsample networks did not differ significantly, however, descriptive differences may inform future research.
  🖺 Full Text HTML: A network perspective on real-life threat, anxiety, and avoidance

From Clinical Trials

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of MVC-COV1901 or MVC-COV1901(Beta) Against COVID-19 - Condition:   COVID-19 Vaccine
  Interventions:   Biological: MVC-COV1901(Beta);   Biological: MVC- COV1901
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Exercise Fatigue Parameters and Endothelial Function in Pediatric Patients With a History of COVID-19 Infection or MIS-C - Conditions:   COVID-19;   MIS-C Associated With COVID-19
  Interventions:  
  Device: Cardiopulmonary exercise test (CPET);   Device: Peripheral Arterial Tonography (PAT) using the EndoPAT™ device;   Diagnostic Test: Endothelin
  Sponsors:   Rambam Health Care Campus;   The Baruch Padeh Medical Center, Poriya
  Recruiting

• Evaluate the Efficacy and Safety of TF0023 in Treatments for COVID-19 in Hospitalized Adults - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: TF0023
  Sponsor:  
  Techfields Inc
  Not yet recruiting

• Short Daily Versus Conventional Hemodialysis for COVID-19 Patients - Condition:   COVID-19
  Intervention:   Other: Short daily dialysis
  Sponsor:  
  Shahid Beheshti University of Medical Sciences
  Completed

• Non-inferiority Trial on Monoclonal Antibodies in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Bamlanivimab Etesevimab;   Drug: Sotrovimab;   Drug: Casirivimab-Imdevimab
  Sponsors:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine
  Recruiting

• Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Ingavirin®, 90 mg capsules;   Drug: Placebo
  Sponsor:   Valenta Pharm JSC
  Recruiting

• Availability and Advice on Test Uptake During the COVID-19 Pandemic: a Vignette Study. - Condition:   COVID-19
  Interventions:   Behavioral: Customised testing advice;   Behavioral: Regular testing advice;   Behavioral: LFT available;   Behavioral: No LFT available
  Sponsor:  
  National Institute for Public Health and the Environment (RIVM)
  Completed

• Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: Quantitative PCR SARS-CoV-2;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: Screening Blood tests;   Diagnostic Test: Electrocardiogram;   Other: NEWS-2 score;   Other: WHO score;   Other: Physical examination;   Other: COVID-19-Related Symptoms assessment
  Sponsor:   Code Pharma
  Recruiting

• Exercise in Adults With Post-Acute Sequelae of SARS-CoV-2 (COVID-19) Infection Study - Condition:   COVID-19
  Intervention:   Other: Exercise Prescription
  Sponsor:  
  Baylor Research Institute
  Not yet recruiting

• Safety and Immunogenicity Study of EgyVax Vaccine Candidate for Prophylaxis of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: EgyVax Vaccine Candidate;   Drug: Placebo
  Sponsors:   Eva Pharma;   Veterinary Serum & Vaccine Research Institute (VSVRI), Egypt;   The Supreme Council of University Hospitals, Egypt;   Ministry of Higher Education and Scientific Research, Egypt
  Not yet recruiting

• To Evaluate Safety & Immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 for COVID-19 in Healthy Adults Received 2 Doses of BNT162b2 - Condition:   Covid19
  Interventions:   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: Matching placebo
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• Treatment of Non-Severe COVID-19 Outpatients With Xagrotin, Phase 3 - Condition:   Sars-cov-2
  Interventions:   Drug: Xagrotin;   Drug: Green tea
  Sponsor:  
  Biomad AS
  Not yet recruiting

• Phase 2b Booster Vaccination (TURKOVAC) Against COVID-19 - Conditions:   COVID-19;   Sars-CoV-2 Infection
  Interventions:   Biological: TURKOVAC-Dollvet;   Biological: TURKOVAC-Koçak
  Sponsor:   Health Institutes of Turkey
  Recruiting

• Efficacy of Synchronous and Asynchronous Telerehabilitation in COVID-19 Discharges - Conditions:   COVID-19;   Telerehabilitation
  Interventions:  
  Other: Synchronous telerehabilitation programme;   Other: Asynchronous telerehabilitation programme
  Sponsors:   Bitlis Eren University;   Marmara University
  Recruiting

• Intranasal Heparin Treatment to Reduce Transmission Among Household Contacts of COVID 19 Positive Adults and Children - Condition:   COVID-19
  Interventions:   Drug: unfractionated heparin;   Drug: 0.9%sodium chloride
  Sponsors:   Murdoch Childrens Research Institute;   University of Melbourne;   Northern Hospital, Australia;   Monash University;   The Peter Doherty Institute for Infection and Immunity;   St Vincent’s Hospital Melbourne
  Not yet recruiting

From PubMed

• Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability - Immunization with SARS-CoV-2 spike elicits diverse antibodies, but can any of these neutralize broadly? Here, we report the isolation and characterization of antibody WS6, from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, MERS-CoV, and hCoV- OC43. The crystal…

• Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail - The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-CoV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the cilgavimab (AZD1061) mAb. Here, we show that this residue substitution remodels the ACE2-binding site allosterically, thereby dampening receptor recognition severely and altering the epitopes recognized by these three mAbs. Although vaccine-elicited neutralizing antibody titers are decreased similarly against the E406…

• Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 - COVID 19 is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; SC2) which has caused a world-wide pandemic with striking morbidity and mortality. Evaluation of early SC2 strains suggested limited viral genetic diversity. However, genetic and epidemiologic investigations in the interim have revealed impressive genetic variability. Many of these viral variants are now defined as variants of concern (VOC) based on genetic alterations in their spike (S) and other…

• Hantavirus Induced Kidney Disease - Hantavirus induced hemorrhagic fever with renal syndrome (HFRS) is an emerging viral zoonosis affecting up to 200,000 humans annually worldwide. This review article is focused on recent advances in the mechanism, epidemiology, diagnosis, and treatment of hantavirus induced HFRS. The importance of interactions between viral and host factors in the design of therapeutic strategies is discussed. Hantavirus induced HFRS is characterized by thrombocytopenia and proteinuria of varying severities. The…

• Circulating Microparticles in the Pathogenesis and Early Anticoagulation of Thrombosis in COVID-19 With Kidney Injury - As more is learned about the pathophysiological mechanisms of COVID-19, systemic thrombosis has been recognized as being associated with more severe clinical manifestations, mortality and sequelae. As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury, with coagulation abnormalities the main cause of impaired function. However, the mechanism of renal thrombosis and the process leading to kidney injury are unclear. Microparticles (MPs) are membrane bubbles…

• Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection - CONCLUSION: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

• Association of Complement C3 with Clinical Deterioration Among Hospitalized Patients with COVID-19 - CONCLUSION: Low complement C3 levels are associated with a higher risk for clinical worsening among inpatients with COVID-19. The serum C3 levels may contribute to the identification of patient populations that could benefit from therapeutic complement inhibition.

• Telacebec (Q203): Is there a novel effective and safe anti-tuberculosis drug on the horizon? - High prevalence and stronger emergency of various forms of drug-resistant tuberculosis (DR-TB), including the multidrug- resistant (MDR-TB) as well as extensively drug-resistant (XDR-TB) ones, caused by variously resistant Mycobacterium tuberculosis pathogens, make first-line anti-tuberculosis (anti-TB) agents therapeutically more and more ineffective. Therefore, there is an imperative to develop novel highly efficient (synthetic) agents against both drug-sensitive-TB and DR-TB. The exploration…

• Development of targeted nanoparticles loaded with antiviral drugs for SARS-CoV-2 inhibition - Recently, a novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised global concerns, being the etiological agent of the current pandemic infectious coronavirus disease 2019 (COVID-19). Specific prophylactic treatments like vaccines, have been authorized for use by regulatory bodies in multiple countries, however there is an urgent need to identify new, safe, and targeted therapeutics as post-exposure therapy for COVID-19. Among a plethora of potential…

• Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications - CONCLUSION: Keeping in mind that the natural alternatives are in the priority for the management and prevention of the COVID-19, the present review may help to develop an alternative approach for the management of COVID-19 viral infection and post-COVID complications from a mechanistic point of view.

• Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged 65 years: a phase 2, randomised, open-label study - BACKGROUND: Concomitant seasonal influenza vaccination with a COVID-19 vaccine booster could help to minimise potential disruption to the seasonal influenza vaccination campaign and maximise protection against both diseases among individuals at risk of severe disease and hospitalisation. This study aimed to assess the safety and immunogenicity of concomitant administration of high-dose quadrivalent influenza vaccine (QIV-HD) and a mRNA-1273 vaccine booster dose in older adults.

• Absence of association between host genetic mutations in the ORAI1 gene and COVID-19 fatality - The calcium ion channel ORAI1 has emerged as a promising therapeutic target for the Coronavirus Disease 19 (COVID-19)-associated pneumonia, and a pharmacological inhibitor of ORAI1 has now reached clinical trials for severe COVID-19 pneumonia. Whether ORAI1 itself is associated with an increased risk for severe COVID-19 presentation is still unknown. Here, we employed genetic association analysis to investigate the potential association of host genetic polymorphisms of ORAI1 with the risk of…

• Nanocurcumin Potently Inhibits SARS-CoV-2 Spike Protein-Induced Cytokine Storm by Deactivation of MAPK/NF-kappaB Signaling in Epithelial Cells - Interleukin-mediated deep cytokine storm, an aggressive inflammatory response to SARS-CoV-2 virus infection in COVID-19 patients, is correlated directly with lung injury, multi-organ failure, and poor prognosis of severe COVID-19 patients. Curcumin (CUR), a phenolic antioxidant compound obtained from turmeric (Curcuma longa L.), is well-known for its strong anti-inflammatory activity. However, its in vivo efficacy is constrained due to poor bioavailability. Herein, we report that…

• Glucosinolates and their hydrolysis products as potential nutraceuticals to combat cytokine storm in SARS-COV-2 - CONCLUSION: Accordingly, these compounds can be helpful in combating the cytokine storm associated with COVID-19.

• Protective Effects of Exercise Become Especially Important for the Aging Immune System in The Covid-19 Era - Aging is a complex, multietiological process and a major risk factor for most non-genetic, chronic diseases including geriatric syndromes that negatively affect healthspan and longevity. In the scenario of “healthy or good aging”, especially during the COVID-19 era, the proper implementation of exercise as “adjuvant” or “polypill” to improve disease-related symptoms and comorbidities in the general population is a top priority. However, there is still a gap concerning studies analyzing influence…

From Patent Search

• IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link

• ANTIMICROBIAL SANITIZING FORMULATION - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - link

• A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - link

• RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - link

• REDUCING AND STOPPING OXYGEN WASTAGE IN HOSPITAL - In an aspect, the present invention discloses a system (200) for prevention and reduction of oxygen wastage from oxygen mask (202). The system (200) includes the oxygen mask (202) having straps; a tension sensor (204), the tension sensor being sensitive towards tension produced in the straps as the oxygen gets leakage through sides of the mask (202); a processor configured in alignment with the tension sensor (204); and a buzzer (206) in alignment with processor. - link

• 编码SARS-COV-2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

• SARS-COV-2病毒B.1.617.2突变株DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒B.1.617.2突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• A METHOD TO REVEAL MOTIF PATTERNS OF COVID-19 USING MULTIPLE SEQUENCE ALIGNMENT - This present invention consists of different levels of computation and work in a pipeline manner i.e., input of one will be output of another and it is sequential process. Input data given in form of nucleotide sequence (DNA) of different COVID-19 patients (1). Using these nucleotide sequence perform mutation if possible and arrange them in a sequential order (2). Arrange number of nucleotide sequences of different patients in row wise and also compute number of characters in each row. (3). Compute frequency of occurrence of character in column wise and create a matrix having 4 rows and maximum sequence length will be the column size (4). Find the character like A, T, C, and G which one has maximum score and similarly find for each column to produce a final sequence (5). - link