Covid-19 Sentry

Contents

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

From Preprints

• Whole genome sequencing of SARS-CoV-2 links wastewater RNA to individual cases in catchments. -
  After a limited first wave of community transmission in March 2020, Western Australia has remained largely free of COVID-19, with cases restricted to hotel quarantine, commercial vessels, and small, infrequent community clusters. Despite so few cases, whole genome sequencing (WGS) of SARS-CoV-2 from wastewater of large municipal treatments plants yielded genomic coverage up to 98% with sufficient depth to link wastewater to the WGS sequences of active cases in the catchment at the time. WGS analysis of wastewater contemporaneous with clinical cases can also be used to rule out transmission between cases in different catchments, when their SARS-CoV-2 genomes differ. These findings reveal a greater potential of wastewater WGS to inform outbreak control and disease surveillance than previously recognized.
  🖺 Full Text HTML: Whole genome sequencing of SARS-CoV-2 links wastewater RNA to individual cases in catchments.
• Systematic review of interventions to promote the performance of physical distancing behaviours during pandemics/epidemics of infectious diseases spread via aerosols or droplets -
  Objectives Physical distancing, that is keeping 1-2m apart when co-located, can prevent cases of droplet or aerosol transmitted infectious diseases such as SARS-COV2. During the COVID-19 pandemic, distancing was a recommendation or a requirement in many countries. This systematic review aimed to determine which interventions and behaviour change techniques (BCTs) are effective in promoting adherence to distancing and through which potential mechanisms of action (MOAs). Methods Six databases were searched. The review included studies that were (a) conducted on humans, (b) reported physical distancing interventions, (c) included any comparator (e.g., pre-intervention versus post-intervention; randomised controlled trial) and (d) reported actual distancing or predictors of distancing behaviour. Risk of bias was assessed using the Mixed Methods Appraisal Tool. BCTs and potential MoAs were identified in each intervention. Results Six moderate or high quality papers indicated that distancing interventions could successfully change MoAs and behaviour. Successful BCTs (MoAs) included feedback on behaviour (e.g., motivation); information about health consequences, salience of health consequences (e.g., beliefs about consequences), demonstration (e.g., beliefs about capabilities) and restructuring the physical environment (e.g., environmental context and resources). The most promising interventions were proximity buzzers, directional systems and posters with loss-framed messages that demonstrated the behaviours. Conclusions The evidence indicates several BCTs and potential MoAs that should be targeted in interventions and highlights the gaps that should be focused on in future research.
  🖺 Full Text HTML: Systematic review of interventions to promote the performance of physical distancing behaviours during pandemics/epidemics of infectious diseases spread via aerosols or droplets
• The humanized nanobody RBD-1-2G tolerates the spike N501Y mutation to neutralize SARS-CoV-2 -
  Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS- BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.
  🖺 Full Text HTML: The humanized nanobody RBD-1-2G tolerates the spike N501Y mutation to neutralize SARS-CoV-2
• Characterization of raloxifene as potential pharmacological agent against SARS-CoV-2 and its variants -
  The new coronavirus that emerged, called SARS-CoV-2, is the causative agent of the COVID-19 pandemic. The identification of potential drug candidates that can rapidly enter clinical trials for the prevention and treatment of COVID-19 is an urgent need, despite the recent introduction of several new vaccines for the prevention and protection of this infectious disease which in many cases becomes severe. Drug repurposing (DR), a process for studying existing pharmaceutical products for new therapeutic indications, represents one of the most effective potential strategies employed to increase the success rate in the development of new drug therapies. We identified raloxifene, a known Selective Estrogen Receptor modulator (SERM), as a potential pharmacological agent for the treatment of COVID-19 patients. Following a virtual screening campaign on the most relevant viral protein targets, in this work we report the results of the first pharmacological characterization of raloxifene in relevant cellular models of COVID-19 infection. The results obtained on all the most common viral variants originating in Europe, United Kingdom, Brazil, South Africa and India, currently in circulation, are also reported, confirming the efficacy of raloxifene and, consequently, the relevance of the proposed approach. Taken together, all the information gathered supports the clinical development of raloxifene and confirms that the drug can be proposed as a viable new option to fight the pandemic in at least some patient populations. The results obtained so far have paved the way for a first clinical study to test the safety and efficacy of raloxifene, just concluded in patients with COVID-19 paucisymptomatic.
  🖺 Full Text HTML: Characterization of raloxifene as potential pharmacological agent against SARS-CoV-2 and its variants
• SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes -
  Coronaviruses belong to a well-known family of enveloped RNA viruses and are the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS- CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome and lead to death. Unfortunately, COVID-19 has already caused more than 4.4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV-2. Here we show that, besides infecting hamsters astrocytes, SARS-CoV-2 induces changes in protein expression and metabolic pathways involved in carbon metabolism, glycolysis, mitochondrial respiration, and synaptic transmission. Interestingly, many of the differentially expressed proteins are concurrent with proteins that correlate with neurological diseases, such as Parkinsons’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration. Further metabolomics analysis confirmed the consumption of many metabolites, including glucose, pyruvate, glutamine, and alpha ketoglutarate. Interestingly, we observed that glutamine was significantly reduced in infected cultures, and the blockade of mitochondrial glutaminolysis significantly reduced viral replication and pro-inflammatory response. SARS-CoV-2 was confirmed in vivo as hippocampus, cortex, and olfactory bulb of intranasally infected hamsters were positive for viral genome several days post-infection. Altogether, our data reveals important changes in overall protein expression, mostly of those related to carbon metabolism and energy generation, causing an imbalance in important metabolic molecules and neurotransmitters. This may suggest that some of the neurological features observed during COVID-19, as memory and cognitive impairment, may rely on altered energetic profile of brain cells, as well as an unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.
  🖺 Full Text HTML: SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes
• Inactivation of SARS Coronavirus 2 and COVID-19 patient samples for contemporary immunology and metabolomics studies -
  In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China spurring the Coronavirus Disease-19 (COVID-19) pandemic that has resulted in over 219 million confirmed cases and nearly 4.6 million deaths worldwide. Intensive research efforts ensued to constrain SARS-CoV-2 and reduce COVID-19 disease burden. Due to the severity of this disease, the US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) recommend that manipulation of active viral cultures of SARS-CoV-2 and respiratory secretions from COVID-19 patients be performed in biosafety level 3 (BSL3) containment laboratories. Therefore, it is imperative to develop viral inactivation procedures that permit samples to be transferred and manipulated at lower containment levels (i.e., BSL2), and maintain the fidelity of downstream assays to expedite the development of medical countermeasures (MCMs). We demonstrate optimal conditions for complete viral inactivation following fixation of infected cells with paraformaldehyde solution or other commonly-used branded reagents for flow cytometry, UVC inactivation in sera and respiratory secretions for protein and antibody detection assays, heat inactivation following cDNA amplification of single-cell emulsions for droplet-based single-cell mRNA sequencing applications, and extraction with an organic solvent for metabolomic studies. Thus, we provide a suite of protocols for viral inactivation of SARS-CoV-2 and COVID-19 patient samples for downstream contemporary immunology assays that facilitate sample transfer to BSL2, providing a conceptual framework for rapid initiation of high-fidelity research as the COVID-19 pandemic continues.
  🖺 Full Text HTML: Inactivation of SARS Coronavirus 2 and COVID-19 patient samples for contemporary immunology and metabolomics studies
• Human coronaviruses disassemble processing bodies -
  The Coronaviridae are a family of viruses with large RNA genomes. Seven coronaviruses (CoVs) have been shown to infect humans, including the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). The host response to CoV infection is complex and regulated, in part, by intracellular antiviral signaling pathways triggered in infected cells. Pathogenic CoVs can hijack these antiviral responses, reshaping the production of interferons and proinflammatory cytokines. Processing bodies (PBs) are membraneless ribonucleoprotein granules that mediate decay or translational suppression of cellular mRNAs; this is particularly relevant for proinflammatory cytokine mRNA which normally reside in PBs and are repressed. PBs or their components are believed to play important direct-acting antiviral roles, providing a compelling reason for their frequent disassembly by many viruses. Prior to this report, no information was known about how human CoVs impact PBs. Here, we show that three human CoVs, SARS-CoV-2 and the common cold CoVs, OC43 and 229E, induce PB loss. Moreover, we screened a SARS-CoV-2 gene library and identified that expression of the viral nucleocapsid (N) protein from SARS-CoV-2 was sufficient to mediate PB disassembly. N protein mediated PB loss correlated with elevated transcript levels of selected proinflammatory cytokines that would normally be repressed in PBs. Ectopic expression of the N proteins from four other human coronaviruses (OC43, MERS, 229E and NL63) did not cause PB disassembly, suggesting that this feature is unique to SARS-CoV-2 N protein. These data indicate that SARS-CoV-2 disassembles PBs during infection. As an unintended side effect, the disassembly of PBs may enhance levels of proinflammatory cytokine mRNAs which normally reside in PBs, thereby reshaping the subsequent immune response.
  🖺 Full Text HTML: Human coronaviruses disassemble processing bodies
• Therapy of depression by the method of behavioral activation -
  The dramatic consequences of several new waves of COVID-19 infection have had a devastating effect on people’s personal lives and the economic situation of the country, which has led to the formation of depressive moods in people of different ages. Behavioral activation is one of the most effective methods to reduce and prevent depression, which is discussed in detail in this article.
  🖺 Full Text HTML: Therapy of depression by the method of behavioral activation
• Some aspects of cognitive-behavioral therapy treatment of anxiety -
  With massive spread of COVID-19 infection, people often experience anxiety symptoms and increased levels of anxiety. When conducting telephone, online or face-to-face therapy and counseling with clients, it is essential that the psychologist-consultant possesses methods and techniques for reducing and preventing anxiety symptoms that he or she will offer clients and alleviate their difficult emotional state. The article presents strategies for treating anxiety symptoms with cognitive-behavioral therapy methods.
  🖺 Full Text HTML: Some aspects of cognitive-behavioral therapy treatment of anxiety
• A New Infodemiological Approach Through Google Trends: Longitudinal Analysis of COVID-19 Scientific and Infodemic Names in Italy -
  COVID-19 has been classified by the scientific community as the worst pandemic in human history. The damage caused by the new disease was direct (e.g., deaths) and indirect (e.g., closure of economic activities). Within the latter category, we find infodemic phenomena such as the adoption of generic and stigmatizing names used to identify COVID-19 and the related novel coronavirus 2019 variants. These monikers have fostered the spread of health disinformation and misinformation, and fomented racism and segregation towards the Chinese population. In this regard, we present a comprehensive infodemiological picture of Italy from the epidemic outbreak in December 2019 until September 2021. In particular, we propose a new procedure to examine in detail the web interest of users in scientific and infodemic monikers linked to the identification of COVID-19. To do this, we exploited the online tool Google Trends. Our findings reveal the widespread use of multiple COVID-19-related names not considered in the previous literature, as well as a persistent trend in the adoption of stigmatizing and misleading terms. Inappropriate names for cataloging novel coronavirus 2019 variants of concern have even been adopted by national health agencies. Furthermore, we also showed that early denominations influenced user behavior for a long time and were difficult to replace. For these reasons, we suggest that the assignments of scientific names to new diseases are more timely and advise against mass media and international health authorities using terms linked to the geographical origin of the novel coronavirus 2019 variants.
  🖺 Full Text HTML: A New Infodemiological Approach Through Google Trends: Longitudinal Analysis of COVID-19 Scientific and Infodemic Names in Italy
• PermaPhosSer: autonomous synthesis of functional, permanently phosphorylated proteins -
  Installing stable, functional mimics of phosphorylated amino acids into proteins offers a powerful strategy to study protein regulation. Previously, a genetic code expansion (GCE) system was developed to translationally install non-hydrolyzable phosphoserine (nhpSer), with the {gamma}-oxygen replaced with carbon, but it has seen limited usage. Here, we achieve a 40-fold improvement in this system by engineering into Escherichia coli a biosynthetic pathway that produces nhpSer from the central metabolite phosphoenolpyruvate. Using this “PermaPhosSer” system – an autonomous 21-amino acid E. coli expression system for incorporating nhpSer into target proteins – we show that nhpSer faithfully mimics the effects of phosphoserine in three stringent test cases: promoting 14-3-3/client complexation, disrupting 14-3-3 dimers, and activating GSK3-{beta} phosphorylation of the SARS-CoV-2 nucleocapsid protein. This facile access to nhpSer containing proteins should allow nhpSer to replace Asp and Glu as the go-to pSer phosphomimetic for proteins produced in E. coli.
  🖺 Full Text HTML: PermaPhosSer: autonomous synthesis of functional, permanently phosphorylated proteins
• Nanoviricides Platform Technology based NV-387 polymer Protects Remdesivir from Plasma-Mediated Catabolism in vitro:Importance of its increased lifetime for in vivo action -
  As of today seven coronaviruses were identified to infect humans, out of which only 4 of them belongs to beta family of coronavirus, like HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV. SARS family of viruses were known to cause severe respiratory disease in humans. SARS-CoV-2 infection causes pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for Covid-19 therapy by FDA. However its efficacy is limited in vivo due to its low stability in presence of Plasma.
  🖺 Full Text HTML: Nanoviricides Platform Technology based NV-387 polymer Protects Remdesivir from Plasma-Mediated Catabolism in vitro:Importance of its increased lifetime for in vivo action
• Generation time of the Alpha and Delta SARS-CoV-2 variants -

  Background: In May 2021, the Delta SARS-CoV-2 variant became dominant in the UK. This variant is associated with increased transmissibility compared to the Alpha variant that was previously dominant. To understand ongoing transmission and interventions, a key question is whether the Delta variant generation time (the time between infections in infector-infectee pairs) is typically shorter-i.e., transmissions are happening more quickly-or whether infected individuals simply generate more infections. Methods: We analysed transmission data from a UK Health Security Agency household study. By fitting a mathematical transmission model to the data, we estimated the generation times for the Alpha and Delta variants. Results: The mean intrinsic generation time (the generation time if there had been a constant supply of susceptibles throughout infection) was shorter for the Delta variant (4.6 days, 95% CrI 4.0-5.4 days) than the Alpha variant (5.5 days, 95% CrI 4.6-6.4 days), although within uncertainty ranges. However, there was a larger difference in the realised mean household generation time between the Delta (3.2 days, 95% CrI 2.4-4.2 days) and Alpha (4.5 days, 95% CrI 3.7-5.4 days) variants. This is because higher transmissibility led to faster susceptible depletion in households, in addition to the reduced intrinsic generation time. Conclusions: The Delta variant transmits more quickly than previously circulating variants. This has implications for interventions such as contact tracing, testing and isolation, which are less effective if the virus is transmitted quickly. Epidemiological models of interventions should be updated to include the shorter generation time of the Delta variant.

  🖺 Full Text HTML: Generation time of the Alpha and Delta SARS-CoV-2 variants
• Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in China: a nationwide case- control study -

  OBJECTIVE To formally compare the clinical course of Coronavirus disease 2019 (COVID-19) in pregnant women with their nonpregnant counterparts. METHODS Clinical data of pregnant women with confirmed COVID-19 in the designated hospitals of mainland China were retrieved up to April 12, 2020 through an epidemic reporting system maintained at the National Health Commission of the People9s Republic China. Each pregnant patient was randomly matched to a nonpregnant woman with confirmed COVID-19 in the same hospital as control, then their clinical courses were formally compared. RESULTS 138 pregnant women had been identified as confirmed COVID-19 cases. Among them, 17 severe cases and 1 maternal death were recorded, which was less than their nonpregnant peers (23 severe cases and 3 death). 57.2% had been infected with SARS-CoV-2 during the third trimester, including 13 severe cases and 1 maternal death. 7.3% of pregnant patients had diarrhea and 3.6% had nausea or vomiting, compared with related proportion as 15.2% (OR: 0.38, 95%CI: 0.15, 0.96) and 10.1% (OR: 0.25, 95%CI: 0.07, 0.89) in nonpregnant patients. Pregnant patients infected with SARS-CoV-2 in early pregnancy presented similar laboratory tests with their nonpregnant peers, however, with pregnancy progresses, increased inflammation, coagulation and hepatic injury markers happened more and more frequently (p<0.001) in pregnant patients. CONCLUSIONS Being pregnant did not represent a risk for severe condition when compared with their nonpregnant peers. Patients infected with SARS-CoV-2 in early pregnancy were even at lower risk of severe illness than those infected in late pregnancy.

  🖺 Full Text HTML: Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in China: a nationwide case-control study
• Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: a descriptive cohort study among 1.1 million vaccinated people in Hong Kong -

  Background Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals.

  Methods This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users (≥16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution.

  Results This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10–1.94).

  Conclusions Autoimmune conditions requiring hospital care are rare following mRNA and inactivated virus COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events.

  Funding: Research Grant from the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01).

  🖺 Full Text HTML: Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: a descriptive cohort study among 1.1 million vaccinated people in Hong Kong

From Clinical Trials

• Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care - Condition:   COVID-19
  Intervention:   Drug: Apixaban
  Sponsors:  
  Scotmann Pharmaceuticals;   Rawalpindi Medical College
  Not yet recruiting

• Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition:   Covid19
  Intervention:   Device: Inspiratory muscle training
  Sponsor:  
  Universidade Federal do Rio Grande do Norte
  Recruiting

• COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition:   COVID-19
  Intervention:   Drug: casirivimab+imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca);   Biological: CoronaVac (Sinovac Biotech);   Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   Instituto Fernandes Figueira
  Not yet recruiting

• Tocilizumab Versus Baricitinib in Patients With Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tocilizumab;   Drug: Baricitinib
  Sponsor:   University Hospital of Patras
  Recruiting

• The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients (Phase3) - Condition:   COVID-19
  Interventions:   Drug: Pyramax;   Drug: Placebo
  Sponsor:  
  Shin Poong Pharmaceutical Co. Ltd.
  Recruiting

• Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition:   COVID-19
  Intervention:   Diagnostic Test: diaphragm ultrasonography
  Sponsor:   University Hospital, Limoges
  Not yet recruiting

• JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: JINZHEN Granules for Oral Solution;   Drug: Placebo
  Sponsor:   Lianyungang Kanion Group, Ltd.
  Not yet recruiting

• Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition:   COVID-19
  Intervention:   Device: Chatbot
  Sponsor:   Sun Yat- sen University
  Recruiting

• Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID - Condition:   COVID-19
  Interventions:   Dietary Supplement: Probiotics;   Dietary Supplement: Placebo
  Sponsors:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions
  Not yet recruiting

• Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial - Condition:   COVID-19
  Interventions:   Behavioral: Self-Benefit/Social Norm;   Behavioral: Self- Benefit/No Social Norm;   Behavioral: Other Benefit/Social Norm;   Behavioral: Other Benefit/No Social Norm
  Sponsors:   University of Pennsylvania;   Pennsylvania Department of Health
  Completed

• Efficacy, Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• Cardiovascular Assessment in Patient Recovered From COVID-19 and Recovery of Autonomic Nervous System in Association With the Severity of the Disease - Condition:   COVID-19
  Intervention:   Other: Non invasive cardiovascular monitoring with CNAP device of arterial pressure, ECG and respiratory activity
  Sponsor:   IRCCS Policlinico S. Donato
  Recruiting

• Safety and Efficacy of KOVIR (TD0068) in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR (TD0068) oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Vietstar Biomedical Research
  Recruiting

From PubMed

• SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy - Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened…

• Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry - Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures effective against SARS-CoV-2 variants and future spillovers of other sarbecoviruses. Here we describe the isolation and characterization of a human monoclonal antibody, designated S2K146, broadly neutralizing viruses belonging to all three sarbecovirus clades known to utilize ACE2 as entry receptor and protecting therapeutically against SARS-CoV-2 beta challenge in hamsters. Structural and…

• Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? - Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism…

• COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2 - Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients’ susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin’s expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues…

• Receptor-binding domain of SARS-CoV-2 spike protein efficiently inhibits SARS-CoV-2 infection and attachment to mouse lung - COVID-19, caused by a novel coronavirus, SARS-CoV-2, poses a serious global threat. It was first reported in 2019 in China and has now dramatically spread across the world. It is crucial to develop therapeutics to mitigate severe disease and viral spread. The receptor-binding domains (RBDs) in the spike protein of SARS-CoV and MERS-CoV have shown anti- viral activity in previous reports suggesting that this domain has high potential for development as therapeutics. To evaluate the potential…

• Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies - SARS coronavirus 2 (SARS-CoV-2) has spread rapidly around the world and continues to have a massive global health effect, contributing to an infectious respiratory illness called coronavirus infection-19 (COVID-19). TMPRSS2 is an emerging molecular target that plays a role in the early stages of SARS-CoV-2 infection; hence, inhibiting its activity might be a target for COVID-19. This study aims to use many computational approaches to provide compounds that could be optimized into clinical…

• Transparent Air Filters with Active Thermal Sterilization - The worldwide proliferation of COVID-19 poses the urgent need for sterilizable and transparent air filters to inhibit virus transmission while retaining ease of communication. Here, we introduce copper nanowires to fabricate transparent and self-sterilizable air filters. Copper nanowire air filter (CNAF) allowed visible light penetration, thereby can exhibit facial expressions, helpful for better communication. CNAF effectively captured particulate matter (PM) by mechanical and electrostatic…

• Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy - Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc…

• Current treatment strategies for COVID-19 (Review) - The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo…

• Niclosamide for Covid-19: bridging the gap - CONCLUSIONS: NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

• A review on protective roles and potential mechanisms of metformin in diabetic patients diagnosed with COVID-19 - The novel coronavirus disease 2019 (COVID-19), is currently the leading threat to public health and a huge challenge to the healthcare systems across the globe and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity, a state of chronic inflammation, and diabetes mellitus are risk factors for severe SARS-CoV-2. Metformin is one of the most commonly used antidiabetic medications that displayed immunomodulatory activity through AMP-activated protein kinase. Metformin has…

• SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated…

• Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue - The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that…

• Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19 - COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to…

• Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort - No abstract

From Patent Search

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

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

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 广谱抗冠状病毒和流感病毒及口腔致病菌复合IgY及其制剂 - 本发明提供一种广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂。本发明提供制备广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂的方法。广谱抗冠状病毒IgY和广谱抗流感病毒IgY可结合保守的抗原表位，达到广谱中和效果，解决新冠病毒和流感病毒变异的问题。本发明将广谱抗新冠病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体制成系列制剂，包括牙膏和口含片以及潄口水和其它日用品、口鼻喷雾剂、消毒剂、洗手液、粉剂、片剂、糖果、滴鼻剂、滴眼剂、口服剂、胶囊剂，应用于防治新冠和流感以及口腔疾病的药物、消毒产品、保健品和医疗器械中。 - link

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 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