Covid-19 Sentry

Contents

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

From Preprints

• What Are the Kids Doing? Exploring Young Children’s Activities at Home and Relations with Externally Cued Executive Function and Child Temperament -
  Time in less-structured activities is associated with children’s developing executive function, but it is unclear why. Prior research suggests less-structured time specifically benefits self-directed executive function, by allowing children to practice making choices. We tested another hypothesis: that less-structured time also benefits externally- cued executive function, which develops earlier than self-directed executive function, theorizing that less-structured time can provide children with opportunities to acquire knowledge that supports emerging control skills. Caregivers of 93 3- to 5-year-olds reported their child’s activities on a typical day at home during the COVID-19 pandemic, and children completed a widely-used cued executive function task, the Dimensional Change Card Sort. Time and variety in less-structured activities predicted successful switching on the card sort, controlling for age, family income, caregiver education, and verbal knowledge. Caregivers were more involved in less-structured versus structured activities. Children’s temperament, as rated by caregivers, predicted how they spent their time. Findings provide a more nuanced picture of how less-structured time and executive function are related, consistent with less-structured time affording opportunities for children, particularly those higher in effortful control, to acquire diverse knowledge that supports engaging control in various ways.
  🖺 Full Text HTML: What Are the Kids Doing? Exploring Young Children’s Activities at Home and Relations with Externally Cued Executive Function and Child Temperament
• Intranasal immunization with a vaccinia virus vaccine vector expressing pre-fusion stabilized SARS-CoV-2 spike fully protected mice against lethal challenge with the heavily mutated mouse-adapted SARS2-N501YMA30 strain of SARS-CoV-2 -
  The Omicron SARS-CoV-2 variant has been designated a variant of concern because its spike protein is heavily mutated. In particular, Omicron spike is mutated at 5 positions (K417, N440, E484, Q493 and N501) that have been associated with escape from neutralizing antibodies induced by either infection with or immunization against the early Washington strain of SARS-CoV-2. The mouse-adapted strain of SARS-CoV-2, SARS2-N501YMA30, contains a spike that is also heavily mutated, with mutations at 4 of the 5 positions in Omicron spike associated with neutralizing antibody escape (K417, E484, Q493 and N501). In this manuscript we show that intranasal immunization with a pre-fusion stabilized Washington strain spike, expressed from a highly attenuated, replication-competent vaccinia virus construct, NYVAC-KC, fully protected mice against disease and death from SARS2-N501YMA30. Similarly, immunization by scarification on the skin fully protected against death, but not from mild disease. This data demonstrates that Washington strain spike, when expressed from a highly attenuated, replication-competent poxvirus, administered without parenteral injection can fully protect against the heavily mutated mouse-adapted SARS2-N501YMA30.
  🖺 Full Text HTML: Intranasal immunization with a vaccinia virus vaccine vector expressing pre-fusion stabilized SARS-CoV-2 spike fully protected mice against lethal challenge with the heavily mutated mouse-adapted SARS2-N501YMA30 strain of SARS-CoV-2
• No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination -
  The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.
  🖺 Full Text HTML: No evidence of fetal defects or anti- syncytin-1 antibody induction following COVID-19 mRNA vaccination
• Production of novel Spike truncations in Chinese hamster ovary cells -
  SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields. Alternatively, Spike receptor binding domain (RBD) is commonly expressed with higher titers, though it has lower sensitivity in serological assays. Here, we improve transient Spike expression in Chinese hamster ovary (CHO) cells. We demonstrate that Spike titers increase significantly over the expression period, maximizing at 14 mg/L at day

7. In comparison, RBD titers peak at 54 mg/L at day 3. Next, we develop 8 Spike truncations (T1-T8) in pursuit of a truncation with high expression and antibody binding. The truncations T1 and T4 express at 130 mg/L and 73 mg/L, respectively, which are higher than our RBD titers. Purified proteins were evaluated for binding to antibodies raised against full-length Spike. T1 has similar sensitivity as Spike against a monoclonal antibody and even outperforms Spike for a polyclonal antibody. These results suggest T1 is a promising Spike alternative for use in various applications.
   🖺 Full Text HTML: Production of novel Spike truncations in Chinese hamster ovary cells

• A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection -
  Infection with the SARS-CoV-2 virus results in manifestation of several clinical observations from asymptomatic to multi-organ failure. Biochemically, the serious effects are due to what is described as cytokine storm. The initial infection region for COVID-19 is the nasopharyngeal/oropharyngeal region which is the site where samples are taken to examine the presence of virus. We have earlier shown that several defensin genes are down regulated in cells from this region in patients who tested positive in the RTPCR test. We have now carried out detailed proteomic analysis of the nasopharyngeal/oropharyngeal swab samples collected from normal individuals and those tested positive for SARS-CoV-2 by RTPCR, involving high throughput quantitative proteomics analysis. Several proteins like annexins, cytokines and histones were found differentially regulated in the host human cells following SARS-CoV-2 infection. Genes for these proteins were also observed to be differentially regulated when their expression was analyzed. Majority of the cytokine proteins were found to be up regulated in the infected individuals. Cell to Cell signaling interaction, Immune cell trafficking and inflammatory response pathways were found associated with the differentially regulated proteins based on network pathway analysis.
  🖺 Full Text HTML: A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection
• Characterization of the interaction between SARS-CoV-2 Membrane Protein and Proliferating Cell Nuclear Antigen (PCNA) as a Potential Therapeutic Target -
  SARS-CoV-2 is an emerging virus from the Coronaviridae family and is responsible for the ongoing COVID-19 pandemic. In this work, we explored the previously reported SARS-CoV-2 structural membrane protein (M) interaction with human Proliferating Cell Nuclear Antigen (PCNA). The M protein is responsible for maintaining virion shape, and PCNA is a marker of DNA damage which is essential for DNA replication and repair. We validated the M PCNA interaction through immunoprecipitation, immunofluorescence co-localization, and a PLA assay. In cells infected with SARS-CoV-2 or transfected with M protein, using immunofluorescence and cell fractioning, we documented a reallocation of PCNA from the nucleus to the cytoplasm and the increase of PCNA and {gamma}H2AX (another DNA damage marker) expression. We also observed an increase of PCNA and {gamma}H2AX expression in the lung of a COVID-19 patient by immunohistochemistry. In addition, the inhibition of PCNA translocation by PCNA I1 and Verdinexor led to a reduction of plaque formation in an in vitro assay. We, therefore, propose that the transport of PCNA to the cytoplasm and its association with M could be a virus strategy to manipulate cell functions and may be considered a target for COVID-19 therapy.
  🖺 Full Text HTML: Characterization of the interaction between SARS-CoV-2 Membrane Protein and Proliferating Cell Nuclear Antigen (PCNA) as a Potential Therapeutic Target
• The cellular characterisation of SARS-CoV-2 spike protein in virus-infected cells using Receptor Binding Domain- binding specific human monoclonal antibodies. -
  A human monoclonal antibody panel (PD4, PD5, PD7, SC23 and SC29) was isolated from the B cells of convalescent patients and used to examine the S protein in SARS-CoV-2-infected cells. While all five antibodies bound conformational- specific epitopes within SARS-CoV-2 Spike (S) protein, only PD5, PD7, and SC23 were able to bind to the Receptor Binding Domain (RBD). Immunofluorescence microscopy was used to examine the S protein RBD in cells infected with the Singapore isolates SARS-CoV-2/0334 and SARS-CoV-2/1302. The RBD-binders exhibited a distinct cytoplasmic staining pattern that was primarily localised within the Golgi complex and was distinct from the diffuse cytoplasmic staining pattern exhibited by the non-RBD binders (PD4 and SC29). These data indicated that the S protein adopted a conformation in the Golgi complex that enabled the RBD recognition by the RBD-binders. The RBD-binders also recognised the uncleaved S protein indicating that S protein cleavage was not required for RBD recognition. Electron microscopy indicated high levels of cell-associated virus particles, and multiple cycle virus infection using RBD-binder staining provided evidence for direct cell-to-cell transmission for both isolates. Although similar levels of RBD-binder staining was demonstrated for each isolate, the SARS-CoV-2/1302 exhibited slower rates of cell-to-cell transmission. These data suggest that a conformational change in the S protein occurs during its transit through the Golgi complex that enables RBD recognition by the RBD-binders, and suggests that these antibodies can be used to monitor S protein RBD formation during the early stages of infection.
  🖺 Full Text HTML: The cellular characterisation of SARS-CoV-2 spike protein in virus-infected cells using Receptor Binding Domain-binding specific human monoclonal antibodies.
• Metabolic dysregulation induces impaired lymphocyte memory formation during severe SARS-CoV-2 infection -
  Cellular metabolic dysregulation is a consequence of COVID-19 infection that is a key determinant of disease severity. To understand the mechanisms underlying these cellular changes, we performed high-dimensional immune cell profiling of PBMCs from COVID-19-infected patients, in combination with single cell transcriptomic analysis of COVID-19 BALFs. Hypoxia, a hallmark of COVID-19 ARDS, was found to elicit a global metabolic reprogramming in effector lymphocytes. In response to oxygen and nutrient-deprived microenvironments, these cells shift from aerobic respiration to increase their dependence on anaerobic processes including glycolysis, mitophagy, and glutaminolysis to fulfill their bioenergetic demands. We also demonstrate metabolic dysregulation of ciliated lung epithelial cells is linked to significant increase of proinflammatory cytokine secretion and upregulation of HLA class 1 machinery. Augmented HLA class-1 antigen stimulation by epithelial cells leads to cellular exhaustion of metabolically dysregulated CD8 and NK cells, impairing their memory cell differentiation. Unsupervised clustering techniques revealed multiple distinct, differentially abundant CD8 and NK memory cell states that are marked by high glycolytic flux, mitochondrial dysfunction, and cellular exhaustion, further highlighting the connection between disrupted metabolism and impaired memory cell function in COVID-19. Our findings provide novel insight on how SARS-CoV-2 infection affects host immunometabolism and anti-viral response during COVID-19.
  🖺 Full Text HTML: Metabolic dysregulation induces impaired lymphocyte memory formation during severe SARS-CoV-2 infection
• Identifying protein sites contributing to vaccine escape via statistical comparisons of short-term molecular dynamics simulations -
  The identification of viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a molecular dynamic (MD) based approach that scales well to a desktop computer with a high-end modern graphics processor and enables the user to identify protein sites that are prone to vaccine escape in a viral antigen. We first implemented our MD pipeline to employ site-wise calculation of Kullback- Leibler divergence in atom fluctuation over replicate sets of short-term MD production runs to compare influenza hemagglutinin rapid motions in the presence and absence of three well-known neutralizing antibodies. Using this simple comparative method applied to motions of viral proteins, we successfully identified in silico all previously empirically confirmed sites of escape in hemagglutinin, predetermined via selection experiments and neutralization assays. After this validation of our computational approach, we identified potential hot spot residues in the receptor binding domain (RBD) of the SARS-CoV-2 virus in the presence of COVOX-222 and S2H97 antibodies. We identified sites in the antigen- antibody interface with strong dampening of fluctuation that may indicate potential antibody escape due to single mutations. Many of these sites were found to match known sites of mutations in SARS-CoV-2 variants of concern. The determination of single sites with large effect on antigen-antibody binding interfaces is crucial to discriminating neutral variants from potential escape variants. In summary, we provide a cheap, fast, and accurate in silico method to identify and quantify potential hot spots of functional evolution in antibody binding footprints.
  🖺 Full Text HTML: Identifying protein sites contributing to vaccine escape via statistical comparisons of short-term molecular dynamics simulations
• Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies -

  Due to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS- CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat Omicron and other emerging variants of concern.

  🖺 Full Text HTML: Reduced Neutralization of SARS- CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies
• Brain Networks Associated With COVID-19 Risk: Data From 3,662 Participants -

  Background: Our behavioral traits, and subsequent actions, could affect the risk of exposure to the coronavirus disease of 2019 (COVID-19). The current study aimed to determine whether unique brain networks are associated with the COVID-19 infection risk. Methods: This research was conducted using the UK Biobank Resource. Functional magnetic resonance imaging scans in a cohort of general population (n=3,662) were used to compute the whole-brain functional connectomes. A network-informed machine learning approach was used to identify connectome and nodal fingerprints that are associated with positive COVID-19 status during the pandemic up to February 4th, 2021. Results: The predictive models successfully identified 6 fingerprints that were associated with COVID-19 positive, compared to negative status (all p values < 0.005). Overall, lower integration across the brain modules and increased segregation, as reflected by internal within module connectivity, were associated with higher infection rates. More specifically, COVID-19 positive status was associated with 1) reduced connectivity between the central executive and ventral salience, as well as between the dorsal salience and default mode networks; 2) increased internal connectivity within the default mode, ventral salience, subcortical and sensorimotor networks; and 3) increased connectivity between the ventral salience, subcortical and sensorimotor networks. Conclusion: Individuals are at increased risk of COVID-19 infections if their brain connectome is consistent with reduced connectivity in the top-down attention and executive networks, along with increased internal connectivity in the introspective and instinctive networks. These identified risk networks could be investigated as target for treatment of illnesses with impulse control deficits.

  🖺 Full Text HTML: Brain Networks Associated With COVID-19 Risk: Data From 3,662 Participants
• THE NOVEL CORONA VIRUSIN THE DYNAMICS OF THE INTERNATIONAL SYSTEM: DISRUPTIONS AND CONNECTIONS -
  As a novel actor of International Relations, SARS-CoV-2 (COVID19) has created major upshots on the evolution of the contemporary International System: In the level of International Health (the WHO and States have been in discord and continuous verbal fracas); in terms of the International Economy (the economic crisis, the recession, etc.); on the aspect of International Security (increased activity of non-state armed groups); and finally, in terms of the ambiance of international society, it creates a new competition: the Vaccine Race. This paper examines and discusses these numerous facets and impacts of COVID19 on the international society and concludes that the novel virus, far from being just “flu”, has created fundamental alterations of disruptions and connections in the international society.
  🖺 Full Text HTML: THE NOVEL CORONA VIRUSIN THE DYNAMICS OF THE INTERNATIONAL SYSTEM: DISRUPTIONS AND CONNECTIONS
• Seroprevalence of anti-SARS-CoV-2 IgG and IgA antibodies before the launch of COVID-19 vaccination in Kazakhstan. -

  Background: COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, we assessed the prevalence of anti-SARS-CoV-2 antibody-mediated immunity in a heterogeneous cohort of public university employees in Karaganda, Kazakhstan. Methods: Asymptomatic subjects (n=100) were recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used to validate the assay positivity thresholds. Results: Anti-S IgG and IgA seropositivity rates among SARS-CoV-2 PCR-negative participants (n=100) were 42% (95% CI [32.2-52.3]) and 59% (95% CI [48.8-69.0]), respectively, and 64% (95% CI [53.4-73.1]) of the cohort tested positive for at least one of the antibodies. Anti-S IgG titres correlated with virus neutralization activity, detectable in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history of COVID-19 was associated with Kazakh ethnicity and self-reported history of respiratory illness since March 2020. Conclusions: SARS-CoV-2 exposure in this cohort is ~15-fold higher compared to the reported all-time national and regional COVID-19 prevalence. Continuous serological surveillance is critical for understanding the COVID-19 transmission dynamics and should be nationally implemented to better inform the public health response in Central Asia.

  🖺 Full Text HTML: Seroprevalence of anti-SARS-CoV-2 IgG and IgA antibodies before the launch of COVID-19 vaccination in Kazakhstan.
• Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients: a randomized clinical trial compared to a national dataset observational arm -

  Importance: SARS-CoV-2 enters the nasopharynx to replicate; mechanical debridement with nasal irrigation soon after diagnosis could reduce morbidity and mortality. Objective: To determine whether initiating nasal irrigation after COVID-19 diagnosis reduces hospitalizations and death, and whether irrigant composition impacts severity. Design: Unblinded randomized clinical trial of two nasal irrigation protocols in outpatients PCR positive for SARS-CoV-2, nested in a prospective case:cohort using laboratory-confirmed cases in the CDC COVID-19 Case Surveillance dataset. Setting: Single-lab community testing facility associated with the emergency department (ED) in Augusta, GA. Participants: A consecutive sample of outpatients 55 years and older were contacted from daily COVID-19+ lab reports between September 24 and December 21 of 2020. Patients without supplemental oxygen use or cognitive barriers agreeing to same- day irrigation initiation were remotely consented. Among 826 screened, 321 were unable to be reached, 132 were ineligible, 294 refused participation, and 79 participants were enrolled. Interventions: Participants were randomly assigned adding 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240ml of isotonic nasal irrigation twice daily for 14 days. Main Outcomes and Measures: The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive. Results: Seventy-nine participants were enrolled (mean [SD] age, 64 [8] years; 36 [46%] women; 71% Non-Hispanic White). Analyzed by intention-to-treat, by day 28, COVID-19 symptoms resulted in 1/42 hospitalizations in those irrigating with alkalinization, 0/37 in the povidone-iodine group, (1.27%) and no deaths. Of nearly three million CDC cases, 9.14% were known to be hospitalized, with an additional 1.5% mortality in those without hospitalization data. The total risk of hospitalization or death (10.6%) was 8.4 times that of enrolled patients (SE=2.74; P=.006). 62 completed daily surveys (78%), averaging 1.8 irrigations/day. Eleven had irrigation complaints, and four discontinued. There were no significant differences by additive. Conclusion: SARS-CoV-2+ participants initiating nasal irrigation were over 8 times less likely to be hospitalized than the national rate.

  🖺 Full Text HTML: Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients: a randomized clinical trial compared to a national dataset observational arm
• SARS-CoV-2 Transmission and Impacts of Unvaccinated-Only Testing in Populations of Mixed Vaccination Status -

  In populations with mixed vaccination status, testing programs focused on only the unvaccinated population are being enacted to mitigate SARS-CoV-2 spread. However, it is not well understood how viral spread occurs in mixed-status populations, including the possible benefits of unvaccinated-only testing. Here, we analyze a model of SARS-CoV-2 transmission in which a variable fraction of the population is fully vaccinated and unvaccinated individuals are proactively tested for infection, while varying transmission rates, vaccine effectiveness (VE) parameters, and prior infection rates. This analysis reveals principles of viral spread in communities of mixed vaccination status, with implications for testing policies. As vaccination rates increase, the proportions of infections occurring in unvaccinated individuals and the amount of transmission driven by the unvaccinated both decrease, such that at ~65-75% vaccine coverage, most infections are vaccine breakthroughs, and at ~76-83% vaccine coverage, most community spread is driven by breakthrough infections, under baseline mRNA VE assumptions. These ranges shift lower with waning VE and higher with boosted VE. In highly vaccinated communities proactive unvaccinated-only testing had little impact on community spread. Instead, the benefits of weekly unvaccinated-only testing were restricted to regimes with high or moderate ongoing transmission due to lower vaccination rates and strongly depended on near-perfect test compliance. By evaluating a wide range of scenarios, this work finds broadly that resources devoted to routine unvaccinated-only testing could be reallocated when vaccine coverage is sufficiently high.

  🖺 Full Text HTML: SARS-CoV-2 Transmission and Impacts of Unvaccinated-Only Testing in Populations of Mixed Vaccination Status

From Clinical Trials

• Using MOST to Optimize an Intervention to Increase COVID-19 Testing for Frontline Essential Workers - Conditions:   COVID-19;   COVID-19 Testing
  Interventions:   Behavioral: Motivational interviewing

1001. counseling;   Behavioral: Text messages (TMs) and quiz questions (QQs);   Behavioral: Peer education;   Behavioral: Access to COVID testing
      Sponsor:   New York 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

• COVID-19 Administration of Single-Dose Subcutaneous Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition:   COVID-19
  Intervention:   Drug: casirivimab+imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Recruiting

• GlowTest COVID-19 Antigen Home Test Kit QRI Use Study - Condition:   Covid 19
  Intervention:   Diagnostic Test: GlowTest COVID-19 Antigen Home Test
  Sponsors:   Arion Bio;   CSSi Life Sciences
  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

• Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial - Condition:   COVID-19
  Interventions:   Drug: Recombinant nonimmunogenic staphylokinase;   Drug: Placebo
  Sponsors:   Supergene, LLC;   Russian Academy of Medical Sciences
  Not yet recruiting

• Safety and Immunogenicity of COVID-19 Vaccine, Inactivated in Healthy Population Aged From 3 to 11 Years - Condition:   COVID-19
  Intervention:   Biological: COVID-19 Vaccine,Inactivated
  Sponsor:   Sinovac Biotech Co., 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

• 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

• Usefulness of DORNASE in COVID-19 on HFNO - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: inhalations
  Sponsor:  
  University Medical Centre Ljubljana
  Not yet recruiting

• Phase Ⅱ and Ⅲ Trial of a SARS-CoV-2 Vaccine LYB001 - Condition:   COVID-19
  Interventions:   Biological: LYB001;   Biological: Placebo
  Sponsor:   Yantai Patronus Biotech Co., Ltd.
  Not yet recruiting

• Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) - Conditions:   COVID-19;   SARS-CoV-2 Acute Respiratory Disease
  Interventions:  
  Biological: COVID-19 Vaccine HIPRA;   Biological: Cominarty (Pfizer-BioNtech)
  Sponsors:  
  Hipra Scientific, S.L.U;   Laboratorios Hipra, S.A.;   National Institute of Hygiene and Epidemiology, Vietnam
  Recruiting

• Immunogenicity and Safety of a Booster Vaccination With a Recombinant Protein RBD Candidate Vaccine Against the Virus That Cause COVID-19, Know as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) in Healthy Adults Volunteers Fully Vaccinated - Conditions:   COVID-19;   SARS-CoV-2 Acute Respiratory Disease
  Interventions:  
  Biological: COVID-19 Vaccine HIPRA;   Biological: Cominarty (Pfizer-BioNtech)
  Sponsors:  
  Hipra Scientific, S.L.U;   Laboratorios Hipra, S.A.
  Recruiting

From PubMed

• Efficacy of anti-SARS-CoV-2 mRNA vaccine in systemic autoimmune disorders: induction of high avidity and neutralising anti-RBD antibodies - CONCLUSIONS: These data show that double-dose vaccination induced in patients with SARDs anti-RBD IgG and IgA antibodies in amounts not significantly different from controls, and, most interestingly, characterised by high avidity and endowed with neutralising activity.

• Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis - The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the…

• Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in inadvertently vaccinated healthy children - Twenty-seven children aged seven months to 5 years were inadvertently vaccinated with a COVID-19 vaccine, the CoronaVac (Sinovac, China), an inactivated SARS-CoV-2 vaccine, in two different cities of Sao Paulo State, Brazil. After the event, these children were monitored by local pediatricians and serum samples were collected at the first visit and 30 days after vaccination and tested for SARS-CoV-2 S1 serology with Ortho total IgG anti-S1 protein and Cpass, an ACE2 receptor binding domain…

• QSAR, molecular docking, molecular dynamics and MM-GBSA approach for identification of prospective benzotriazole- based SARS-CoV 3CL protease inhibitors - The 3CL Protease of severe acute respiratory syndrome coronavirus (SARS-CoV), responsible for viral replication, has emerged as an essential target for designing anti-coronaviral inhibitors in drug discovery. In recent years, small molecule and peptidomimetic inhibitors have been used to target the inhibition of SARS-CoV 3CL Protease. In this study, we have developed 2D and 3D Quantitative structure activity relationship (QSAR) models on 3CL protease inhibitors with good predictive capability to…

• Isolation and characterization of ACE-I inhibitory peptides from ribbonfish for a potential inhibitor of the main protease of SARS-CoV-2; an in-silico analysis - Recently, multi-functional fish peptides (FWPs) have gained a lot of attention because of their different biological activities. In the present study, three Angiotensin-I Converting Enzyme (ACE-I) inhibitory peptides [Ala-Pro-Asp-Gly (APDG), Pro-Thr-Arg (PTR), and Ala-Asp (AD)] were isolated and characterized from ribbonfish protein hydrolysate (RFPH) and described their mechanism of action on ACE activity. As per the results peptide PTR showed ≈ 2 and 2.5-fold higher enzyme inhibitory activity…

• Dataset of functional connectivity during cognitive control for an adult lifespan sample - We provide functional connectivity matrices generated during functional magnetic resonance imaging (fMRI) during different tasks of cognitive control in healthy aging adults. These data can be used to replicate the primary results from the related manuscript: Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan (Rieck et al., 2021). One-hundred-forty-four participants (ages 20-86) were scanned on a Siemens 3T MRI scanner while they were…

• Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response - CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.

• 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…

• Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer’s Disease Prevention - Serotonin reuptake inhibitors (SRIs) are safe and widely used for a variety of indications including depressive disorders, anxiety, and chronic pain. Besides inhibiting the serotonin transporter, these medications have broad- spectrum properties in many systems. Their roles have been studied in cancer, Alzheimer’s disease, and infectious processes. The COVID-19 pandemic highlighted the importance of drug repurposing of medications already in use. We conducted a narrative review of current…

• Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape - The emergence of SARS-CoV-2 variants threatens current vaccines and therapeutic antibodies and urgently demands powerful new therapeutics that can resist viral escape. We therefore generated a large nanobody repertoire to saturate the distinct and highly conserved available epitope space of SARS-CoV-2 spike, including the S1 receptor binding domain, N-terminal domain, and the S2 subunit, to identify new nanobody binding sites that may reflect novel mechanisms of viral neutralization. Structural…

• Complement inhibition: A possible therapeutic approach in the fight against Covid-19 - The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has…

• Detecting SARS-CoV-2 Orf3a and E ion channel activity in COVID-19 blood samples - CONCLUSIONS: We developed a cell-free test that can detect Orf3a/E channel activity of SARS-CoV-2 in blood samples from COVID-19-infected individuals, confirming a hypothesis that the virus spreads to the heart via blood circulation.

• Interfering viral-like particles inhibit SARS-CoV-2 replication - No abstract

• Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models - Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS- CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking…

• Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients - Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC(50) between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate…

From Patent Search

• 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

• Medizintechnische Haltevorrichtung und Haltevorrichtungs-Kit jeweils zum Halten von allgemeinmedizinischen, chirurgischen oder diagnostischen Einrichtungen oder Instrumenten sowie deren Verwendung insbesondere zur Datenerfassung -

  Medizintechnische Haltevorrichtung (10) eingerichtet zum Halten von allgemeinmedizinischen, chirurgischen oder diagnostischen Einrichtungen oder Instrumenten, insbesondere Diagnose-Einrichtungen oder -instrumenten für den Mund-/Rachenraum aus der folgenden Gruppe: Spatel (1), Abstrich-Einrichtung (2), Lichtquelle (3), Kamera (4); wobei die Haltevorrichtung (10) aufweist:

• einen Kontaktbereich (15) zum manuellen Kontaktieren der Haltevorrichtung (10) durch einen Nutzer;
• wenigstens eine mit dem Kontaktbereich (15) verbundene Haltekupplung (11, 12, 13) zum reversiblen Kuppeln, insbesondere form- und/oder kraftschlüssigen Kuppeln, der jeweiligen Einrichtung oder des Instruments; dadurch gekennzeichnet, dass der Kontaktbereich (15) eine Mindest-Längserstreckung (x15) von 20cm aufweist, wobei die wenigstens eine Haltekupplung (11, 12) an einem Längs-Ende des Kontaktbereichs (15) angeordnet ist, und wobei der Kontaktbereich

15. zumindest teilweise aus Kupfer besteht oder Kupfer als Oberflächenmaterial/-werkstoff aufweist, wobei die medizintechnische Haltevorrichtung (10) eingerichtet ist zum Kuppeln einer/der Kamera im Kontaktbereich, insbesondere bei Verwendung einer Kamera mit einem Gehäuse mit integrierter Kuppelfunktion.

• link