Covid-19 Sentry

Contents

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

From Preprints

• Being cut off from social identity resources has shaped loneliness during the COVID-19 pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom -
  Loneliness can develop as a result of the identity transitions accompanying older adulthood, particularly if individuals become less mobile and able to participate in social groups. During the COVID-19 pandemic, medically vulnerable older adults were placed under particularly stringent social isolation conditions. This study aimed to explore how the pandemic elicited processes of loneliness and social identity transitions for this group. We used a qualitative longitudinal interview approach and a theoretically guided thematic analysis to explore loneliness and identity change at three timepoints amongst medically vulnerable older adults during the pandemic (N=9, Mage=78.7). Due to their vulnerable status, participants experienced “Threatened Social Contact”, which was exacerbated dramatically during the COVID-19 isolation measures. This created a paucity of psychological resources to manage “Being Categorised as a Vulnerable Older Adult”, left individuals with a “Restriction in Ability to Gain or Maintain Identities”, and resulted in “Undermining of Reciprocal Support” and “Wellbeing hindered by Loneliness-Related Fears”. In sum, the pandemic recovery effort will require facilitating positive ageing identities to counteract the vulnerabilities exacerbated by the pandemic.
  🖺 Full Text HTML: Being cut off from social identity resources has shaped loneliness during the COVID-19 pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom
• People’s Republic of China Legal Update: Supreme People’s Court’s Guiding Opinion on Refund Requests Relating to Unauthorised Online Video Gaming Transactions Paid for by Minors (Published 15 May 2020) -
  The Supreme People’s Court (SPC) of the People’s Republic of China (PRC) promulgated its Guiding Opinion on Several Issues Concerning the Lawful and Proper Handling of Civil Cases Involving the Novel Coronavirus Pneumonia (COVID-19) Epidemic No. 2 (hereinafter, the ‘Guiding Opinion’) on 15 May 2020. Paragraph 9 of the Guiding Opinion declares that: ‘If a person with “limited capacity for civil conduct,” without the consent of their guardian, engages with paid online video games [e.g., purchases a video game software or makes in-game purchases through microtransactions], or “donates” to content creators or makes other similar payments on livestreaming platforms, to such a sum which is “incompatible with their age and intellectual abilities,” the courts shall support claims from their guardians demanding refund from the internet service providers [e.g., the game company or the livestreaming platform] for such payments.’
  🖺 Full Text HTML: People’s Republic of China Legal Update: Supreme People’s Court’s Guiding Opinion on Refund Requests Relating to Unauthorised Online Video Gaming Transactions Paid for by Minors (Published 15 May 2020)
• A systematic literature review of individual-level psychological and behavioral responses to the health information of COVID-19 from social media and legacy media -

  Covid-19 has been recognized as a terrifying global health threat since its detection, with far-reaching consequences that are unprecedented in the modern era. Since the outbreak of the pandemic, social media and legacy media have collectively delivered health information related to COVID-19 to the public as a catalyst to community perception of risk. However, the existing literature exhibits different viewpoints toward the role of social media and legacy media in disseminating health information of COVID-19. In this regard, this article conducted a systematic literature review to provide an overview of the current state of research concerning individuals-level psychological and behavioral response to COVID-19 related information from different sources, as well as presents the challenges and future research directions.

  🖺 Full Text HTML: A systematic literature review of individual-level psychological and behavioral responses to the health information of COVID-19 from social media and legacy media
• Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up? -
  Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials. Some of the most notable benefits include such properties as anti-pathogenic, antioxidant, anti- inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The use of medicinal mushrooms (MMs) as extracts in nutraceuticals and other health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.
  🖺 Full Text HTML: Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up?
• mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection in a prospective community cohort, rural Wisconsin, November 2020-December 2021 -

  Reduced COVID-19 vaccine effectiveness (VE) has been observed with increasing predominance of the Delta variant. In a prospective rural community cohort of 1265 participants, VE against symptomatic and asymptomatic SARS-CoV-2 infection was 56% for mRNA COVID-19 vaccines.

  🖺 Full Text HTML: mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection in a prospective community cohort, rural Wisconsin, November 2020-December 2021
• The impact of environmental mycobiomes on geographic variation in COVID-19 mortality -

  Mortality rates during the COVID-19 pandemic have varied by orders of magnitude across communities in the United States. Individual, socioeconomic, and environmental factors have been linked to health outcomes of COVID-19. It is now widely appreciated that the environmental microbiome, composed of microbial communities associated with soil, water, atmosphere, and the built environment, impacts immune system development and susceptibility to immune-mediated disease. The human microbiome has been linked to individual COVID-19 disease outcomes, but there are limited data on the influence of the environmental microbiome on geographic variation in COVID-19 across populations. To fill this knowledge gap, we used taxonomic profiles of fungal communities associated with 1,135 homes in 494 counties from across the United States in a machine learning analysis to predict COVID-19 Infection Fatality Ratios (the number of deaths caused by COVID-19 per 1000 SARS-CoV-2 infections; 9IFR9). Here we show that exposure to increased fungal diversity, and in particular indoor exposure to outdoor fungi, is associated with reduced SARS-CoV-2 IFR. Further, we identify seven fungal genera that are the predominant drivers of this protective signal and may play a role in suppressing COVID-19 mortality. This relationship is strongest in counties where human populations have remained stable over at least the previous decade, consistent with the importance of early-life microbial exposures. We also assessed the explanatory power of 754 other environmental and socioeconomic factors, and found that indoor-outdoor fungal beta-diversity is amongst the strongest predictors of county-level IFR, on par with the most important known COVID-19 risk factors, including age. We anticipate that our study will be a starting point for further integration of environmental mycobiome data with population health information, providing an important missing link in our capacity to identify vulnerable populations. Ultimately, our identification of specific genera predicted to be protective against COVID-19 mortality may point toward novel, proactive therapeutic approaches to infectious disease.

  🖺 Full Text HTML: The impact of environmental mycobiomes on geographic variation in COVID-19 mortality
• Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY -

  Background While the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of individuals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk. Methods With the approval of NHS England we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated individuals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough. Results As of 01st November 2021, a total of 15,436,455 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: ​​107-179). From within this population, a total of 577245 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was ​​98.02 (95% CI 97.9-98.15). There were 16,120 COVID-19-related hospital admissions, 1,100 COVID-19 critical care admission patients and 3,925 COVID-19-related deaths; corresponding incidence rates of 2.72 (95% C 2.7-2.74), 0.19 (95% C 0.18-0.19) and 0.66 (95% C 0.65-0.67), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes and those over 80 years of age. Comorbidities with the highest rates of breakthrough COVID-19 included chronic kidney disease, dialysis, transplant, haematological malignancy, and immunocompromised. Conclusion The majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the continued increase in numbers of positive SARS-CoV-2 tests are concerning. As numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying individuals at higher risk, are therefore required.

  🖺 Full Text HTML: Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY
• Simulation of the omicron variant of SARS-CoV-2 shows broad antibody escape, weakened ACE2 binding, and modest increase in furin binding -
  The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is significant reduction of antibody binding strength corresponding to escape, the omicron spike pays a cost in terms of weaker receptor binding. The furin cleavage domain is the same or weaker binding than the alpha variant, suggesting less viral load and disease intensity than the extant delta variant.
  🖺 Full Text HTML: Simulation of the omicron variant of SARS-CoV-2 shows broad antibody escape, weakened ACE2 binding, and modest increase in furin binding
• SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet pro-coagulant activity -
  Background: Thrombosis of the lung micro-vasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting this activity. As TMEM16F plays an important role in the stimulation of the pro-coagulant activity of platelets, and considering that platelet abnormalities are common in COVID-19 patients, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Methods: We produced SARS-CoV-2 Spike or VSV-G protein-pseudotyped virions, or generated cells expressing Spike on their plasma membrane, and tested their effects on platelet adhesion (fluorescence), aggregation (absorbance), exposure of phosphatidylserine (flow cytometry for annexin V binding), calcium flux (flow cytometry for fluo-4 AM), and clot formation and retraction. These experiments were also conducted in the presence of the TMEM16F activity inhibitors Niclosamide and Clofazimine. Results: Here we show that exposure to SARS-CoV-2 Spike promotes platelet activation, adhesion and spreading, both when present on the envelope of virions or upon expression on the plasma membrane of cells. Spike was effective both as a sole agonist or by enhancing the effect of known platelet activators, such as collagen and collagen-related peptide. In particular, Spike exerted a noticeable effect on the procoagulant phenotype of platelets, by enhancing calcium flux, phosphatidylserine externalisation, and thrombin generation. Eventually, this resulted in a striking increase in thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine almost abolished this Spike-induced pro-coagulant response. Conclusions: Together, these findings provide a pathogenic mechanism to explain thrombosis associated to COVID-19 lung disease, by which Spike present in SARS-CoV-2 virions or exposed on the surface of infected cells, leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing drugs targeting this protein, such as Niclosamide, for COVID-19 therapy.
  🖺 Full Text HTML: SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet pro-coagulant activity
• Compared with SARS-CoV2 wild type’s spike protein, the SARS-CoV2 omicron’s receptor binding motif has adopted a more SARS-CoV1 and/or bat/civet-like structure. -
  Our study focuses on free energy calculations of SARS-Cov2 spike protein receptor binding motives (RBMs) from wild type and variants-of-concern with particular emphasis on currently emerging SARS- CoV2 omicron variants of concern (VOC). Our computational free energy analysis underlines the occurrence of positive selection processes that specify omicron host adaption and bring changes on the molecular level into context with clinically relevant observations. Our free energy calculations studies regarding the interaction of omicron’s RBM with human ACE2 shows weaker binding to ACE2 than alpha’s, delta’s, or wild type’s RBM. Thus, less virus is predicted to be generated in time per infected cell. Our mutant analyses predict with focus on omicron variants a reduced spike-protein binding to ACE2–receptor protein possibly enhancing viral fitness / transmissibility and resulting in a delayed induction of danger signals as trade-off. Finally, more virus is produced but less per cell accompanied with delayed Covid-19 immunogenicity and pathogenicity. Regarding the latter, more virus is assumed to be required to initiate inflammatory immune responses.
  🖺 Full Text HTML: Compared with SARS-CoV2 wild type’s spike protein, the SARS-CoV2 omicron’s receptor binding motif has adopted a more SARS-CoV1 and/or bat/civet-like structure.
• Development and Characterization of Recombinant Vesicular Stomatitis Virus (rVSV)-based Bivalent Vaccine Against COVID-19 Delta Variant and Influenza Virus -
  COVID-19 and influenza are both highly contagious respiratory diseases with a wide range of severe symptoms and cause great disease burdens globally. It has become very urgent and important to develop a bivalent vaccine that is able to target these two infectious diseases simultaneously. In this study, we generated three attenuated replicating recombinant VSV (rVSV) vaccine candidates. These rVSV-based vaccines co-express SARS-CoV-2 Delta variant spike protein (SP) or the receptor binding domain (RBD) and four copies of the highly conserved M2 ectodomain (M2e) of influenza A fused with the Ebola glycoprotein DC-targeting/activation domain. Animal studies have shown that immunization with these bivalent rVSV vaccines induced efficient but variable levels of humoral and cell-mediated immune responses against both SARS-CoV-2 and influenza M2e protein. Significantly, our vaccine candidates induced production of high levels of neutralizing antibodies that protected cells against SARS-CoV-2 Delta and other SP-pseudovirus infections in culture. Furthermore, vaccination with the bivalent VSV vaccine via either intramuscular or intranasal route efficiently protected mice from the lethal challenge of H1N1 and H3N2 influenza viruses and significantly reduced viral load in the lungs. These studies provide convincing evidence for the high efficacy of this bivalent vaccine to prevent influenza replication and initiate robust immune responses against SARS-CoV-2 Delta variants. Further investigation of its efficacy to protect against SARS-CoV-2 Delta variants will provide substantial evidence for new avenues to control two contagious respiratory infections, COVID-19 and influenza.
  🖺 Full Text HTML: Development and Characterization of Recombinant Vesicular Stomatitis Virus (rVSV)-based Bivalent Vaccine Against COVID-19 Delta Variant and Influenza Virus
• Computational analysis of the effect of SARS-CoV-2 variant Omicron Spike protein mutations on dynamics, ACE2 binding and propensity for immune escape -
  The recently reported Omicron (B.1.1.529) SARS-CoV-2 variant has a large number of mutations in the Spike (S) protein compared to previous variants. Here we evaluate the potential effect of Omicron S mutations on S protein dynamics and ACE2 binding as contributing factors to infectivity as well as propensity for immune escape. We define a consensus set of mutations from 77 sequences assigned as Omicron in GISAID as of November 25. We create structural models of the Omicron S protein in the open and closed states, as part of a complex with ACE2 and for each of 77 complexes of S bound to different antibodies with known structures. We have previously utilized Dynamical Signatures (DS) and the Vibrational Entropy Score (VDS) to evaluate the propensity of S variants to favour the open state. Here, we introduce the Binding Influence Score (BIS) to evaluate the influence of mutations on binding affinity based on the net gain or loss of interactions within the protein-protein interface. BIS shows excellent correlation with experimental data (Pearson correlation coefficient of 0.87) on individual mutations in the ACE2 interface for the Alpha, Beta, Gamma, Delta and Omicron variants combined. On the one hand, the DS of Omicron highly favours a more rigid open state and a more flexible closed state with the largest VDS of all variants to date, suggesting a large increase in the chances to interact with ACE2. On the other hand, the BIS shows that apart from N501Y, all other mutations in the interface reduce ACE2 binding affinity. VDS and BIS show opposing effects on the overall effectiveness of Omicron mutations to promote binding to ACE2 and therefore initiate infection. To evaluate the propensity for immune escape we calculated the net change of favourable and unfavourable interactions within each S-antibody interface. The net change of interactions shows a positive score (a net increase of favourable interactions and decrease of unfavourable ones) for 41 out of 77 antibodies, a nil score for 15 and a negative score for 21 antibodies. Therefore, in only 28% of S-antibody complexes (21/77) we predict some level of immune escape due to a weakening of the interactions with Omicron S. Considering that most antibody epitopes and the mutations are within the S-ACE2 interface our results suggest that mutations within the RBD of Omicron may give rise to only partial immune escape, which comes at the expense of reduced ACE2 binding affinity. However, this reduced ACE2 affinity appears to have been offset by increasing the occupancy of the open state of the Spike protein.
  🖺 Full Text HTML: Computational analysis of the effect of SARS-CoV-2 variant Omicron Spike protein mutations on dynamics, ACE2 binding and propensity for immune escape
• Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization -
  The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa. It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development, and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.

• Investigating the prevalence of anxiety and depression during the first COVID-19 lockdown in the UK: systematic review and meta-analyses -
  Background: The COVID-19 pandemic has had a significant impact on mental health. Specifically, the stringent lockdown restrictions have heightened anxiety and depression. Therefore, monitoring and supporting the mental health of the population during these unprecedented times is an immediate priority. Methods: In this systematic review and meta- analyses, articles that explored the prevalence of anxiety and depression during the first COVID-19 lockdown in the UK were included. We searched the databases Embase, Medline (PubMed), Web of Science, and PsycINFO for cross-sectional studies. We conducted meta-analyses of prevalence rates using a random-effects model, and the heterogeneity of studies was examined using the I^2 index. Results: Fourteen studies involving 46,158 participants were included in the review. The studies use clinical cut-off scores on anxiety and depression measures to define cases. While the prevalence of anxiety was 31.00% (95% CI = 26.00 to 35.00), the prevalence of depression was 32.00% (95% CI = 29.00 to 35.00). The prevalence of anxiety pre-pandemic was 4.65%, indicating a 26.35% increase. Whereas the prevalence of depression pre-pandemic was 4.12%, indicating a 27.88% increase. Moreover, participants experienced a slightly greater prevalence of depression than anxiety by 1.00%. Conclusions: To conclude, the first COVID-19 lockdown in the UK increased the prevalence of anxiety and depression amongst the general population, compared to pre-pandemic data. Hence, it is vital that policymakers and mental health services maximise their efforts to monitor mental health and provide interventions to support those in need.
  🖺 Full Text HTML: Investigating the prevalence of anxiety and depression during the first COVID-19 lockdown in the UK: systematic review and meta-analyses
• Risk of hospitalization and mortality after breakthrough SARS-CoV-2 infection by vaccine type and previous SARS- CoV-2 infection utilizing medical claims data -

  We compare the risks of hospitalization (n=1121) and mortality (n=138) in a cohort of 17,881 breakthrough SARS-CoV-2 infections for the Pfizer, Moderna and Janssen vaccines for those with and without SARS-CoV-2 infections prior to vaccination. Cox regression analysis results in a lower hazard ratio for breakthroughs receiving the Moderna vaccine, but a significantly higher hazard ratio for breakthroughs receiving the Janssen vaccine, as compared to breakthroughs who got the Pfizer vaccine. Further, the risk of hospitalization (P<0.001) and death (P<0.05) were lower among breakthroughs who had a SARS-CoV-2 infection prior to vaccination, independent of age, sex, comorbidities, and vaccine type.

  🖺 Full Text HTML: Risk of hospitalization and mortality after breakthrough SARS-CoV-2 infection by vaccine type and previous SARS-CoV-2 infection utilizing medical claims data

From Clinical Trials

• Trial to Evaluate Nitazoxanide for Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Drug: Placebo;   Dietary Supplement: Vitamin Super-B Complex
  Sponsor:   Romark Laboratories L.C.
  Not yet recruiting

• Trial to Evaluate Nitazoxanide for Treatment of Mild or Moderate COVID-19 in Subjects at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Dietary Supplement: Vitamin Super-B Complex;   Drug: Placebo;   Other: Standard of Care
  Sponsor:  
  Romark Laboratories L.C.
  Not yet recruiting

• A Double-blind Randomized Controlled Trial of Ivermectin With Favipiravir in Mild-to-moderate COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Other: Placebo
  Sponsors:   Mahidol University;   Prince of Songkla University
  Not yet recruiting

• Australian Phase 2/3b Study to Assess Effectiveness of a Protein-based Covid-19 Vaccine (Spikogen) - Condition:   COVID-19
  Intervention:   Biological: Spikogen/Covax-19
  Sponsors:  
  Vaxine Pty Ltd;   Australian Respiratory and Sleep Medicine Institute;   Cinnagen
  Not yet recruiting

• Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC] - Condition:   COVID-19
  Interventions:   Biological: Homologous mRNA booster vaccine;   Biological: Heterologous mRNA booster vaccine;   Biological: Non-mRNA booster vaccine A;   Biological: Non- mRNA booster vaccine B;   Biological: Non-mRNA booster vaccine C
  Sponsors:   Tan Tock Seng Hospital;   A*Star;   Duke-NUS Graduate Medical School;   KK Women’s and Children’s Hospital
  Recruiting

• Study of GRT-R910 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Boost Vaccine in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: GRT-R910 booster 113 days after prime;   Biological: GRT-R910 booster 28 days after prime
  Sponsor:   Gritstone Oncology, Inc.
  Recruiting

• Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial - Condition:   COVID-19
  Interventions:   Biological: Adrecizumab (HAM 8101);   Drug: Placebo
  Sponsor:   Universitätsklinikum Hamburg-Eppendorf
  Not yet recruiting

• Immunogenicity Study of the Covid-19 (Recombinante) Vaccine With a 4 or 8 Week Interval Between the First Doses. - Condition:   COVID-19
  Intervention:   Biological: Covid-19 (recombinante) vaccine
  Sponsor:   The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  Active, not recruiting

• A Study to Evaluate Efficacy and Safety of the Combination of SCTA01 & SCTA01C in Outpatients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SCTA01 and SCTA01C;   Drug: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Study of Immunogenicity Equivalence of a Homologous Third Dose of Covid-19 (Recombinante) Vaccine - Condition:   COVID-19
  Intervention:   Biological: Covid -19 (recombinante) vaccine
  Sponsor:   The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  Recruiting

• Study to Evaluate the Safety and Efficacy of a Monoclonal Antibody Cocktail for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ADM03820;   Other: Placebo
  Sponsors:  
  Ology Bioservices;   Enabling Biotechnologies (EB)
  Not yet recruiting

• Efficacy,Immunogenicity and Safety of COVID-19 Vaccine , Inactivated Booster Dose in Adults Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: Medium-dosage COVID-19 Vaccine,Inactivated;   Biological: High-dosage COVID-19 Vaccine,Inactivated;   Biological: Placebo-comparator group
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Communities Fighting COVID-19! - Condition:   Covid19
  Interventions:   Other: COVID-19 Testing Home-based (Aim 1);   Other: COVID-19 Testing Mobile (Aim 1);   Other: COVID-19 Testing Mobile Approach 1 (Aim 2);   Other: COVID-19 Testing Mobile Approach 2 (Aim 2)
  Sponsors:   San Diego State University;   National Cancer Institute (NCI)
  Recruiting

• Clinical Trial for Oral Formula of Vanillin and Wheat Germ Oil for Treatment of Mild and Moderate COVID-19 Viral Disease - Condition:   Mild-to-moderate COVID-19
  Intervention:   Drug: Oral Capsule
  Sponsors:  
  Alexandria University;   Assoc. Prof. Ayman Baeis;   Dr. Noha Alaa Eldine Hassan Hamdy;   Ph. Hanya Hesham Sweilam
  Recruiting

• Oral Neutralizing Antibody Booster for Post-vaccinated People With COVID19 Vaccine - Condition:   COVID-19 Pandemic
  Intervention:   Dietary Supplement: Bacillus subtilis spore extract
  Sponsors:   DreamTec Research Limited;   Hong Kong Metropolitan University;   DreamTec Cytokine Limited
  Recruiting

From PubMed

• QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CL(pro) Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches - Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS),…

• In silico screening, SAR and kinetic studies of naturally occurring flavonoids against SARS CoV-2 main protease - The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) pandemic has become a global challenge based on its replication within the host cells that relies on non-structural proteins, protease (M^(pro)). Flavonoids, an important class of naturally occurring compounds with medicinal importance, are frequently available within fruits and vegetables. Herein, we report the in silico studies on naturally occurring flavonoids consisting of molecular docking studies and evaluation of theoretical…

• Antiviral peptides against the main protease of SARS-CoV-2: A molecular docking and dynamics study - The recent coronavirus outbreak has changed the world’s economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the…

• Development of superior antibodies against the S-protein of SARS-Cov-2 using macrocyclic epitopes - One of the proven methods to prevent and inhibit viral infections is to use antibodies to block the initial Receptor Binding Domain (RBD) of SARS-CoV-2 S protein and avoid its binding with the host cells. Thus, developing these RBD- targeting antibodies would be a promising approach for treating the SARS-CoV-2 infectious disease and stop virus replication. Macrocyclic epitopes constitute closer mimics of the receptor’s actual topology and, as such, are expected to be superior epitopes for…

• TRIPS waiver of COVID-19 vaccines: Impact on pharmaceutical industry and what it means to developing countries - The WTO was formed in 1995 and since then countries have abide by Trade Related Aspects of Intellectual Property Rights (TRIPS). The agreement provides for comprehensive plan for patenting and protection including those of medical supply units including vaccines and diagnosis. Recently developing countries such as India and South Africa have demanded TRIPS waiver for access to vaccines for all the developing countries The TRIPS waiver demanded, would apply to vaccines, diagnosis, and treatment…

• The second wave of COVID-19 results in outbreak of mucormycosis: diabetes and immunological perspective - CONCLUSIONS: Hyperglycaemia impairs the motility of phagocytes and also decreases the oxidative and non-oxidative mechanism of killing the causative pathogen. Chronic hyperglycemia also leads to the formation of advanced glycation end-products (AGE), which leads to cross-linking between key proteins of inflammation and connective tissue such as collagen which makes tissue susceptible to immunological dysregulation. The receptor for AGE (RAGE) is expressed on various inflammatory cells including…

• Apolipoprotein E4 as a Novel Treatment Target for Alzheimer’s Disease - The importance of Alzheime’s Disease (AD) research has never been greater from a worldwide perspective with the disease becoming increasingly prevalent with life expectancy on the rise. One emerging factor that has presented as a serious risk that still requires more research and understanding is the role and effects of Apolipoprotein E4 (ApoE4). When present, individuals are three times more likely to develop AD in their lifetime. This is due to ApoE4’s ability to not only increase amyloid beta…

• Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation - Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such as hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to DMVs formed during autophagy, but lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 and 2 in the ER is important for DMV biogenesis in viral replication and autophagy. Using DMVs in HCV-replicating…

• Vitamin C inhibits Angiotensin-Converting Enzyme-2 in Isolated Rat Aortic Ring - CONCLUSION: This investigation provides valuable experimental proof of the efficacy of ascorbic acid (Vitamin C) on inhibiting ex vivo vascular angiotensin-converting enzyme II, which is known among the pharmacological targets of anti- Covid-19 drugs.

• Discovery of potent inhibitors for M(pro) enzyme of SARS-COV2 by multi-stage in-silico screening of Alkannin/shikonin - Novel coronavirus disease, a serious challenge for the healthcare system, has diverted all the researchers toward the exploration of potential targets, compounds or vaccines for the management of this disease. M^(pro) enzyme was found to be crucial for replication of this virus which makes this enzyme an attractive drug target for SARS-CoV-2. Diverse pharmacological profile of Alkannin/shikonin (A/S) derivatives build up curiosity to study their antiviral profile. Therefore, current study…

• Antigenic characterization of influenza and SARS-CoV-2 viruses - Antigenic characterization of emerging and re-emerging viruses is necessary for the prevention of and response to outbreaks, evaluation of infection mechanisms, understanding of virus evolution, and selection of strains for vaccine development. Primary analytic methods, including enzyme-linked immunosorbent/lectin assays, hemagglutination inhibition, neuraminidase inhibition, micro-neutralization assays, and antigenic cartography, have been widely used in the field of influenza research. These…

• Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene - The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the…

• High-Throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain - Macrodomains are a class of conserved ADP-ribosylhydrolases expressed by viruses of pandemic concern, including coronaviruses and alphaviruses. Viral macrodomains are critical for replication and virus-induced pathogenesis; therefore, these enzymes are a promising target for antiviral therapy. However, no potent or selective viral macrodomain inhibitors currently exist, in part due to the lack of a high-throughput assay for this class of enzymes. Here we developed a high-throughput…

• Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial - COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by -89%….

• Structural modification of antineoplastic drug carmofur designed to the inhibition of SARS-CoV-2 main protease: A theoretical investigation - A coherent account of the reaction mechanistic details, structural modifications, and inhibition potentials of antineoplastic drug carmofur and its modified analogs to inhibition of SARS-CoV-2 main protease (M^(pro)) is reported. The survey is performed by integrating the density functional based tight binding (DFTB3) with density functional theory (DFT) calculations. The inhibition process commences with nucleophilic attack from the sulfur atom on the carbonyl group, yielding a C-S bond…

From Patent Search

• METHODS OF TREATING SARS-COV-2 INFECTION - - link

• REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link

• P2P 네트워크를 이용한 내장된 화상회의 시스템 - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - link

• 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

• 靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗 - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - link

• 跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途 - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - 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