Covid-19 Sentry

Contents

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

From Preprints

• When Private Optimism meets Public Despair: Dissociable effects on behavior and well-being -
  When faced with a threat, peoples’ estimate of risk guides their response. When danger is to the self as well as to others two estimates are generated: the risk to oneself and the risk to others. As these estimates likely differ, it is unclear how exactly they drive a response. To answer this question, we studied a large representative sample of Americans facing the COVID-19 pandemic at two time points (N1=1145, N2=683). We discover a paradoxical duality: a tendency to be optimistic about one’s own risk of infection (private optimism) while at the same time to be pessimistic about the risk to others (public pessimism). These two estimates were found to be differentially related to affect and choice. First, private optimism, but not public pessimism, was associated with people’s positive feelings. The association between private optimism and positive affect was mediated by people’s sense of agency over their future. However, negative affect was related to both private risk perception and public risk perception. Second, people predominantly engaged in protective behaviors based on their estimated risk to the population rather than to themselves. This suggests that people were predominantly engaging in protective behaviors for the benefit of others. The findings are important for understanding how people’s beliefs about their own future and that of others are related to protective behaviors and well-being.
  🖺 Full Text HTML: When Private Optimism meets Public Despair: Dissociable effects on behavior and well-being
• Stillbirths in Germany: On the rise, but no additional increases during the first COVID-19 lockdown -
  Abstract Background A growing body of studies on the indirect effect of the COVID-19 pandemic on stillbirths shows mixed and context-dependent evidence, even within high-income countries. We examined possible changes in the stillbirth rate in Germany during the first COVID-19 lockdown. Methods We used population-level data on live and stillbirths occurring between January 1995 and July 2020 and applied negative binomial regression to estimate the yearly and monthly stillbirth rate in this period. We compared the actual stillbirth rate to the expected figure for the first seven months of 2020, based on prediction intervals derived from the detected time trend. Findings We detected a steady increase in stillbirths in Germany since 2013, which was preceded by a declining (1995-2004), and then plateauing (2005-2012) stillbirth rate. The stillbirth rate for January 2020 through July 2020 (4·148) was slightly lower than the stillbirth rate in the same period in 2019 (4·242). Furthermore, all monthly stillbirth rates during the first half of 2020 lie inside the 95% prediction interval of expected stillbirth rates for this period. Thus, stillbirths in Germany have neither increased nor decreased during the country’s first COVID-19 lockdown period. Interpretation In contrast to other European countries, stillbirth rates have been on the rise in Germany in the last decade. However, stillbirth rates during the first seven months of 2020 were not higher than expected. Our results suggest that stillbirth rates have neither increased nor decreased during the first-wave COVID-19 lockdown in this high-income setting. Further studies on the causes of the increasing stillbirth trend in Germany are needed, however. Funding statement No external funding was received for this research.
  🖺 Full Text HTML: Stillbirths in Germany: On the rise, but no additional increases during the first COVID-19 lockdown
• The company you keep: How network disciplinary diversity enhances the productivity of researchers -
  The Covid-19 pandemic has affected most organizations’ working environment and productivity. Organizations have had to make provision for staff to operate remotely following the implementation of lockdown regulations around the world, because the pandemic has led to restrictions on movement and the temporary closure of workplace premises. The purpose of this paper is to gain a deeper understanding of the effect of this transition on the productivity of work during the pandemic, by studying a distributed network of research who collaborate remotely. We examine how the productivity of researchers is affected by the distributed collaborative networks in which they are embedded. Our goal is to understand the effects of brokerage and closure on the researchers’ publication rate, which is interpreted as an indicator of their productivity. We analyze researchers’ communication networks, focusing on structural holes and diversity, and we take into account the personal qualities of the focal researcher such as seniority. We find that disciplinary diversity among researchers’ peers’ increases the researchers’ productivity, lending support to the brokerage argument. In addition, we find support for two statistical interaction effects. First, structural holes moderate diversity so that researchers with diverse networks are more productive when their networks also have a less redundant structure. Diversity and structural holes, when combined, further researchers’ productivity. Second, seniority moderates diversity; so that senior researchers are more productive than junior researchers in less diverse networks. In more diverse networks, junior researchers perform as well as senior researchers. Social capital and human capital are complementary. We conclude that the benefits of diversity on researchers’ productivity are contingent on the personal qualities of the researchers and on network structure. The brokerage / closure debate needs a more nuanced understanding of causal relationships.
  🖺 Full Text HTML: The company you keep: How network disciplinary diversity enhances the productivity of researchers
• Potent antibody immunity to SARS-CoV-2 variants elicited by a third dose of inactivated vaccine -
  SARS-CoV-2 variants are still prevalent worldwide and continue to pose a challenge to the effectiveness of current vaccines. It remains unknown whether a third dose of inactivated vaccine elicits immune potential against SARS-CoV-2 variants. Here, we showed a significant decline in plasma neutralization against SARS-CoV-2 at seven months after a second dose of the inactivated vaccine in a large-scale cohort. However, we also found that a third vaccination with an inactivated vaccine largely increased plasma neutralization against variants including Beta, Delta, and Lambda. More importantly, the high-affinity anti-RBD memory B cells were also generated by the third vaccination, suggesting a more potent and longer protection. These findings highlighted the importance and effectiveness of a third dose of inactivated vaccine in conferring higher protection against the emerging variants in populations.
  🖺 Full Text HTML: Potent antibody immunity to SARS-CoV-2 variants elicited by a third dose of inactivated vaccine
• LRRC15 suppresses SARS-CoV-2 infection and controls collagen production -
  Although ACE2 is the primary receptor for SARS-CoV-2 infection, a systematic assessment of factors controlling SARS-CoV-2 host interactions has not been described. Here we used whole genome CRISPR activation to identify host factors controlling SARS-CoV-2 Spike binding. The top hit was a Toll-like receptor-related cell surface receptor called leucine-rich repeat-containing protein 15 (LRRC15). LRRC15 expression was sufficient to promote SARS-CoV-2 Spike binding where it forms a cell surface complex with LRRC15 but does not support infection. Instead, LRRC15 functioned as a negative receptor suppressing both pseudotyped and live SARS-CoV-2 infection. LRRC15 is expressed in collagen-producing lung myofibroblasts where it can sequester virus and reduce infection in trans. Mechanistically LRRC15 is regulated by TGF-{beta}, where moderate LRRC15 expression drives collagen production but high levels suppress it, revealing a novel lung fibrosis feedback circuit. Overall, LRRC15 is a master regulator of SARS-CoV-2, suppressing infection and controlling collagen production associated with “long-haul” COVID-19.
  🖺 Full Text HTML: LRRC15 suppresses SARS-CoV-2 infection and controls collagen production
• Global Behaviors, Perceptions, and the Emergence of Social Norms at the Onset of the COVID-19 Pandemic -
  We conducted a large-scale survey covering 58 countries and over 100,000 respondents between late March and early April 2020 to study beliefs and attitudes towards citizens’ and governments’ responses at the onset of the COVID-19 pandemic. Most respondents reported holding normative beliefs in support of COVID-19 containment measures, as well as high rates of adherence to these measures. They also believed that their government and their country’s citizens were not doing enough and underestimated the degree to which others in their country supported strong behavioral and policy responses to the pandemic. Normative beliefs were strongly associated with adherence, as well as beliefs about others’ and the government’s response. Lockdowns were associated with greater optimism about others’ and the government’s response, and improvements in measures of perceived mental well-being; these effects tended to be larger for those with stronger normative beliefs. Our findings highlight how social norms can arise quickly and effectively to support cooperation at a global scale.
  🖺 Full Text HTML: Global Behaviors, Perceptions, and the Emergence of Social Norms at the Onset of the COVID-19 Pandemic
• Design of D-amino acids SARS-CoV-2 Main protease inhibitors using the cationic peptide from rattlesnake venom as a scaffold -
  The C30 Endopeptidase (3C-like protease; 3CLpro) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and is hence a promising drug target. Molecules isolated from animals, insects, plants or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low M range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo, probably targeting the viral protease 3CLpro.
  🖺 Full Text HTML: Design of D-amino acids SARS-CoV-2 Main protease inhibitors using the cationic peptide from rattlesnake venom as a scaffold
• A novel histone deacetylase inhibitor-based approach to eliminate microglia and retain astrocyte properties in glial cell culture. -
  The close association between astrocytes and microglia causes great difficulties to distinguish their individual roles in innate immune responses in central nervous system. Current chemical-based methods to eliminate microglia in glial cell culture introduce various molecular and functional alterations to astrocytes. Here, we describe a novel two- step approach to achieve a complete elimination of microglia without affecting the biological properties of co-cultured astrocytes by temporal treatment of histone deacetylase inhibitor trichostatin A (TSA). We verify TSA as a potent inducer for microglial-specific cell death, which also causes comprehensive gene expression changes in astrocytes. However, withdrawal of TSA not only ensures no microglia repopulation, but also restores all the gene expression changes in terms of astrocyte functions, including neurotrophic factors, glutamate and potassium transporters, and reactive astrocyte subtypes. By contrast, withdrawal of PLX5622, the commonly used colony-stimulating factor 1 receptor inhibitor neither prevents microglia repopulation nor restores the gene expression changes mentioned above. Using this method, we are able to discriminate differential roles of microglia and astrocytes in the induced expression of antiviral and pro- inflammatory cytokines upon various pathological stimuli including the spike protein of SARS-CoV-2. This simple and efficient method can be customized for the understanding of microglia-astrocyte interaction and the development of epigenetic therapies that target over-activated microglia in neuroinflammation-related diseases.
  🖺 Full Text HTML: A novel histone deacetylase inhibitor-based approach to eliminate microglia and retain astrocyte properties in glial cell culture.
• The P681H mutation in the Spike glycoprotein confers Type I interferon resistance in the SARS-CoV-2 alpha (B.1.1.7) variant -
  Variants of concern (VOCs) of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) threaten the global response to the COVID-19 pandemic. The alpha (B.1.1.7) variant appeared in the UK became dominant in Europe and North America in early 2021. The Spike glycoprotein of alpha has acquired a number mutations including the P681H mutation in the polybasic cleavage site that has been suggested to enhance Spike cleavage. Here, we show that the alpha Spike protein confers a level of resistance to the effects of interferon-{beta} (IFN{beta}) in lung epithelial cells. This correlates with resistance to restriction mediated by interferon-induced transmembrane protein-2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is necessary for comparative resistance to IFN{beta} in a molecularly cloned SARS-CoV-2 encoding alpha Spike. Overall, we suggest that in addition to adaptive immune escape, mutations associated with VOCs also confer replication advantage through adaptation to resist innate immunity.
  🖺 Full Text HTML: The P681H mutation in the Spike glycoprotein confers Type I interferon resistance in the SARS-CoV-2 alpha (B.1.1.7) variant
• Characterization of the humoral immune response to BNT162b2 in elderly residents of long-term care facilities five to seven months after vaccination -

  The elderly residing in long-term care facilities (LTCFs) are a group at high risk for COVID-19. Hence, monitoring of the vaccine-based immunity has a pivotal role in identifying strategies to provide optimal protection in this population. We examined the immune response to the mRNA vaccine BNT162b2 against COVID-19 five to seven months after completing a two-dose regimen. We determined significantly lower anti-SARS-CoV-2 antibody titers in 298 SARS-CoV-2 naive residents who were at least 75 years of age (mean 51.60 BAU/ml) (median age 87 years, range 75 to 101 years) when compared to health care workers (HCWs) aged 18 to 70 years (mean 156.99 BAU/ml, p < 0.001). Of the SARS-CoV-2 naive residents, 29 had detectable neutralizing antibodies against the Delta variant (9.5%), and 14 of those (48.3%) only had a borderline titer of 1:10. Of 114 HCWs, 36 (31.6%) had detectable neutralizing antibodies. In a group of 14 elderly residents who had had a PCR-confirmed breakthrough infection, the mean antibody titer was significantly higher than in the other two groups (3199.65 BAU/mL) (p < 0.001), and 12 (85.7%) had detectable neutralizing antibodies against the Delta variant. Our data demonstrate that 90.5% of elderly residents of LTCFs had no detectable neutralization-competent antibodies against the dominant Delta variant five to seven months after vaccination, and that neutralizing antibody titers were restored following a break-through infection. Our results suggest that both residents and health care workers in LTCFs would benefit from a booster vaccine six months after completing the two-dose schedule or earlier.

  🖺 Full Text HTML: Characterization of the humoral immune response to BNT162b2 in elderly residents of long-term care facilities five to seven months after vaccination
• Unexposed populations and potential COVID-19 burden in European countries -

  We estimate the potential remaining COVID-19 burden in 19 European countries by estimating the proportion of each country9s population that has acquired immunity to severe disease through infection or vaccination. Our results suggest that many European countries could still face a substantial burden of hospitalisations and deaths, particularly those with lower vaccine coverage, less historical transmission, and/or older populations. Continued non-pharmaceutical interventions and efforts to achieve high vaccine coverage are required in these countries to limit severe COVID-19 outcomes.

  🖺 Full Text HTML: Unexposed populations and potential COVID-19 burden in European countries
• Viral kinetic modeling and clinical trial simulation predicts disruption of respiratory disease trials by non- pharmaceutical COVID-19 interventions -

  Clinical research in infectious respiratory diseases has been profoundly affected by non-pharmaceutical interventions (NPIs) against COVID-19. On top of trial delays or even discontinuation which have been observed in all disease areas, NPIs altered transmission pattern of many seasonal respiratory viruses which followed regular patterns for decades before the pandemic. Clinical trial design based on pre-pandemic historical data therefore needs to be put in question. In this article, we show how knowledge-based mathematical modeling can be used to address this issue. We set up an epidemiological model of respiratory tract infection (RTI) sensitive to a time dependent between-host transmission rate and coupled this model to a mechanistic description of viral RTI episodes in an individual patient. By reducing the transmission rate when the lockdown was introduced in the United Kingdom in March 2020, we were able to reproduce the perturbed 2020 RTI disease burden data. Using this setup, we simulated several NPIs scenarios of various strength (none, mild, medium, strong) and conducted placebo-controlled in silico clinical trials in pediatric patients with recurrent RTIs (RRTI) quantifying annual RTI rate distributions. In interventional arms, virtual patients aged 1-5 years received the bacterial lysate OM-85 (approved in several countries for the prevention of pediatric RRTIs) through a pro-type I immunomodulation mechanism of action described by a physiologically based pharmacokinetics and pharmacodynamics approach (PBPK/PD). Our predictions showed that sample size estimates based on the ratio of RTI rates (or the post-hoc power of fixed sample size trials) are not majorly impacted under NPIs which are less severe (none, mild and medium NPIs) than a strict lockdown (strong NPI). However, NPIs show a stronger impact on metrics more relevant for assessing the clinical relevance of the effect such as absolute benefit. This dichotomy shows the risk that successful trials (even with their primary endpoints being met) still get challenged in risk benefit assessment during the review of market authorization. Furthermore, we found that a mild NPI scenario already affected the time to recruit significantly when sticking to eligibility criteria complying with historical data. In summary, our model predictions can help rationalize and forecast post-COVID-19 trial feasibility. They advocate for gauging absolute and relative benefit metrics as well as clinical relevance for assessing efficacy hypotheses in trial design and they question eligibility criteria misaligned with the actual disease burden.

  🖺 Full Text HTML: Viral kinetic modeling and clinical trial simulation predicts disruption of respiratory disease trials by non-pharmaceutical COVID-19 interventions
• ChAdOx1 n-COV-19 Vaccine Side Effects Among Health Care Workers in Trinidad and Tobago -

  Background: The pharmaceutical firms have been lauded for the swift development, trial, approval, and rollout of various Covid-19 vaccines. However, a key issue in the vaccination campaign relates to vaccine hesitancy due to concerns on Covid-19 vaccines safety. Method: A retrospective longitudinal study was carried out via a telephone validated questionnaire among Health Care Workers in Trinidad and Tobago. The questionnaire domains included demographic data, medical and COVID-19 related anamneses, and local and systemic side effects 48 hours after receiving the first dose of the vaccine and 48 hours after receiving the second dose of the vaccine. Results: The questionnaire was administered to a sample of 687 healthcare workers (Male = 275; Female = 412). The results indicated that the incidence of reported fever, body pain, chills, nausea, myalgia, headache, malaise, fatigue and other systemic symptoms declined significantly 48 hours after administration of the second dose compared to the first dose. The Chi-square test and multiple logistics regression results were consistent in demonstrating that younger vaccine recipients were more likely to report fever, body pain, chills, nausea, myalgia, headache, fatigue and other symptoms compared to older vaccine recipients. The multiple logistics regression indicate that female vaccine recipients had greater odds of reporting headache, fatigue, discomfort and less likely to report no symptoms compared to male vaccine recipients, 48 hours after receiving both doses. Conclusions: The findings indicate that on average, vaccine recipients reported fewer number of local and systemic side effects within 48 hours after receiving the second dose compared to 48 hours after receiving the first dose. The findings have implications on public health policy efforts to lower vaccine hesitancy.

  🖺 Full Text HTML: ChAdOx1 n-COV-19 Vaccine Side Effects Among Health Care Workers in Trinidad and Tobago
• Genomic landscape of SARS-CoV-2 pandemic in Brazil suggests an external P.1 variant origin -

  Brazil was the epicenter of worldwide pandemics at the peak of its second wave. The genomic/proteomic perspective of the COVID-19 pandemic in Brazil can bring new light to understand the global pandemics behavior. In this study, we track SARS-CoV-2 molecular information in Brazil using real-time bioinformatics and data science strategies to provide a comparative and evolutive panorama of the lineages in the country. SWeeP vectors represented the Brazilian and worldwide genomic/proteomic data from GISAID between 02/2020-08/2021. Clusters were analyzed and compared with PANGO lineages. Hierarchical clustering provided phylogenetic and evolutionary analysis of the lineages, and we tracked the P.1 (Gamma) variant origin. The genomic diversity based on Chao9s estimation allowed us to compare richness and coverage among Brazilian states and other representative countries. We found that epidemics in Brazil occurred in two distinct moments, with different genetic profiles. The P.1 lineages emerged in the second wave, which was more aggressive. We could not trace the origin of P.1 from the variants present in Brazil in 2020. Instead, we found evidence pointing to its external source and a possible recombinant event that may relate P.1 to the B.1.1.28 variant subset. We discussed the potential application of the pipeline for emerging variants detection and the stability of the PANGO terminology over time. The diversity analysis showed that the low coverage and unbalanced sequencing among states in Brazil could have allowed the silenty entry and dissemination of P.1 and other dangerous variants. This comparative and evolutionary analysis may help to understand the development and the consequences of the entry of variants of concern (VOC).

  🖺 Full Text HTML: Genomic landscape of SARS-CoV-2 pandemic in Brazil suggests an external P.1 variant origin
• Phase 2 dose-ranging study of the virologic efficacy and safety of the combination COVID-19 antibodies casirivimab and imdevimab in the outpatient setting -

  Background: The monoclonal antibody combination casirivimab and imdevimab (REGEN-COV®) reduced viral load, hospitalisation, or death when administered 1:1 as an intravenous (IV) dose ≥1200 mg in a phase 3 COVID-19 outpatient study. Availability of subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. Methods: This is a double-blind, placebo-controlled study of SARS-CoV-2-infected outpatients who were asymptomatic, or symptomatic but without risk factors for severe COVID-19. Patients were randomised to single IV dose (517 patients) of REGEN-COV 300, 600, 1200 or 2400 mg or placebo; or a single SC dose (286 patients) of REGEN-COV 600 or 1200 mg or placebo. The primary endpoint was time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative to SARS-CoV-2 at baseline. Findings: All REGEN-COV treatments showed significant (p<0.001 versus pooled placebo) virologic reduction through day 7. Least-squares mean differences in TWACB viral load for the treatments versus placebo ranged from –0·56 to –0.71 log₁₀ copies/mL. Each REGEN-COV treatment showed significant (p<0.001 versus pooled placebo) and similar virologic reduction through day 7. There were no safety concerns, dose-related safety findings, grade ≥2 infusion related/hypersensitivity reactions, grade ≥3 injection-site reactions, nor fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. Interpretation: In asymptomatic and low-risk symptomatic SARS-CoV-2-infected outpatients seronegative for antibodies against SARS-CoV-2 at baseline, REGEN-COV significantly and comparably reduced viral load at all IV and SC doses.

  🖺 Full Text HTML: Phase 2 dose-ranging study of the virologic efficacy and safety of the combination COVID-19 antibodies casirivimab and imdevimab in the outpatient setting

From Clinical Trials

• BREATHE: Virtual Self-management for Long COVID-19 - Condition:   COVID-19
  Intervention:   Other: BREATHE
  Sponsor:  
  University of Calgary
  Not yet recruiting

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

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

• Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan - Condition:   COVID-19
  Intervention:   Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG)
  Sponsors:   The Allergy and Asthma Institute, Pakistan;   University of Edinburgh
  Recruiting

• Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell) - Condition:   COVID-19
  Intervention:   Biological: Experimental Group
  Sponsor:  
  Sinovac Biotech Co., Ltd
  Not yet recruiting

• A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 DNA Vaccine;   Biological: Matching placebo
  Sponsors:   The University of Hong Kong;   Immuno Cure 3 Limited
  Not yet recruiting

• Homeopathic Treatment of Post-acute COVID-19 Syndrome - Condition:   Post-acute Covid-19 Syndrome
  Interventions:   Drug: Homeopathic Medication;   Other: Placebo
  Sponsors:   Southwest College of Naturopathic Medicine;   Samueli Institute for Information Biology
  Recruiting

• Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo - Conditions:   COVID-19 Vaccine Knowledge;   COVID-19 Vaccine Beliefs
  Interventions:  
  Behavioral: COVID-19 Vaccine IVR Training;   Behavioral: Control Condition
  Sponsors:   Stanford University;   Viamo
  Not yet recruiting

• A Clinical Trial to Evaluate the Efficacy of RUTI® to Reduce the Severity of SARS-CoV-2 Infection (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: RUTI® vaccine;   Biological: Placebo
  Sponsors:   RUTI Immunotherapeutics S.L.;   Archivel Farma S.L.
  Not yet recruiting

• Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Vaccine (IN-B009) in Healthy Adults (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: IN-B009 (Low-dose);   Biological: IN-B009 (High- dose)
  Sponsor:   HK inno.N Corporation
  Recruiting

• Lot-to-lot Consistency of an Inactivated SARS-CoV-2 Vaccine Between Different Workshops in Healthy Children Aged 3-17 Years - Condition:   COVID-19
  Interventions:   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 1
  Sponsor:   Sinovac Biotech Co., Ltd
  Recruiting

• The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19 - Condition:   2019 Novel Coronavirus
  Interventions:   Drug: HCQ01;   Other: standard of care (SOC) for COVID-19
  Sponsors:   Ministry of Health Jordan;   King Hussein Cancer Center;   ACDIMA Biocenter;   Amman Pharmaceutical Industries;   Sana Pharmaceutical Industry
  Not yet recruiting

• The Effect Of Music On Compliance Of Patients İn COVİD-19 Intensive Care Unit With CPAP Device - Conditions:   COVID-19;   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Device: Listening to music with a bluetooth headset to patients receiving CPAP support
  Sponsors:   SÜMEYYE BİLGİLİ;   Ataturk University
  Recruiting

• Ad26.COV2.S as a Heterologous Booster in Adults After Single- or Two-Dose of Inactivated COVID-19 Vaccine - Condition:   SARS-CoV-2 Infection
  Interventions:   Biological: Full dose of Ad26.COV2.;   Biological: Half dose of Ad26.COV2.
  Sponsors:   Mahidol University;   National Vaccine Institute, Thailand;   International Vaccine Institute;   Janssen Pharmaceuticals
  Not yet recruiting

• Evaluation of Immunogenicity, Safety and Antibody Persistence of COVID-19 Booster Vaccine (Produced in Wuhan) in Patients With Hypertension and/or Diabetes - Condition:   COVID-19 Pneumonia
  Interventions:   Biological: Covid-19 vaccine (0-1-4 schedule);   Biological: Covid-19 vaccine (0-1-6 schedule)
  Sponsors:   China National Biotec Group Company Limited;   Guizhou Center for Disease Control and Prevention;   Hunan Center for Disease Control and Prevention;   Fujian Center for Disease Control and Prevention;   Wuhan Institute of Biological Products Co., Ltd
  Not yet recruiting

From PubMed

• High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS - Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6…

• Network Meta-analysis on the Changes of Amyloid Precursor Protein Expression Following SARS-CoV-2 Infection - SARS-CoV-2 infection begins with the attachment of its spike (S) protein to angiotensin-converting enzyme-2 (ACE2) followed by complex host immune responses with cardiovascular and neurological implications. Our meta-analyses used QIAGEN Ingenuity Pathway Analysis (IPA) and Knowledge Base (QKB) to investigate how the expression of amyloid precursor protein (APP) was modulated by attachment of SARS-CoV-2 S protein in the brain microvascular endothelial cells (BMVECs) and during COVID-19 in…

• A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling - Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic…

• Natural biflavones are potent inhibitors against SARS-CoV-2 papain-like protease - Papain-like protease (PL^(pro)) is a key enzyme encoded by SARS-CoV-2 that is essential for viral replication and immune evasion. Significant suppression of viral spread and promotion of antiviral immunity can be achieved by inhibition of PL^(pro), revealing an inspiring strategy for COVID-19 treatment. This study aimed to discover PL^(pro) inhibitors by investigating the national compound library of traditional Chinese medicines (NCLTCMs), a phytochemical library comprising over 9000…

• A natural product compound inhibits coronaviral replication in vitro by binding to the conserved Nsp9 SARS-CoV-2 protein - The Nsp9 replicase is a conserved coronaviral protein that acts as an essential accessory component of the multi-subunit viral replication/transcription complex. Nsp9 is the predominant substrate for the essential nucleotidylation activity of Nsp12. Compounds specifically interfering with this viral activity would facilitate its study. Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin,…

• Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm - Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS- CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a…

• Antiviral drugs suppress infection of 2019-nCoV spike pseudotyped virus by interacting with ACE2 protein - The outbreak of coronavirus disease 2019 (COVID-19) has induced a large number of deaths worldwide. Angiotensin- converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019-nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID-19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019-nCoV infection….

• Literature Overview of the IL-17 Inhibition from Psoriasis to COVID-19 - The COVID-19 pandemic has posed a serious problem for drug anti-viral efficacy in combatting the cytokine storm triggered by SARS-CoV-2. From dermato-epidemiological studies conducted on psoriatic and other rheumatological patients, IL-17 inhibitors seem to attenuate or even prevent the cytokine storm and thus ICU referral. Furthermore, both in-vivo and in-vitro experiments suggest that IL-17 plays a key role in SARS-CoV-2 infection progression. Due to this evidence, we decided to summarize the…

• Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2 - Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (K(d) = 100-200 μM) of gangliosides for the RBD are similar to another…

• Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19 - Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. The exact mechanisms of COVID-19 associated hypercoagulopathy, however, remain elusive. Recently, we observed that platelets (PLTs) from patients with severe COVID-19 infection express high levels of procoagulant markers, which were found to be associated with increased risk for thrombosis. In the current study, we investigated the time course as well as the mechanisms leading to procoagulant PLTs in…

• Broad antiviral and anti-inflammatory activity of Qingwenjiere mixture against SARS-CoV-2 and other human coronavirus infections - CONCLUSIONS: QJM has broad antiviral and anti-inflammatory activity against both common and newly emerged HCoVs possibly by inhibiting the activation of key components in NF-κB/MAPKs signaling pathway. QJM also has a prevention effect against HCoV infections and inhibits the host receptor required for virus entry. These results indicate that QJM may have the therapeutic potential in the treatment of diseases caused by a broad range of HCoVs.

• Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis - In addition to uncontrolled diabetes and the excess use of corticosteroids, it is believed that other factors may be responsible for the recent spurt of COVID-19 associated mucormycosis (CAM). In the present paper it is argued that COVID-19 increases the susceptibility of the patients to mucormycosis by augmenting the virulence factors of the mucor species, where deficient synthesis of melatonin plays a key role. Melatonin is synthesized from tryptophan via the serotonin pathway and melatonin…

• A pilot open-label study of aldose reductase inhibition with AT-001 (caficrestat) in patients hospitalized for COVID-19 infection: Results from a registry-based matched-control analysis - CONCLUSIONS: In hospitalized patients with COVID-19 and co-morbid diabetes mellitus and heart disease, treatment with AT-001 was safe and well tolerated. Exposure to AT-001 was associated with a trend of reduced mortality and shortened LOS. While the observed trend did not reach statistical significance, the present study provides the rationale for investigating potential benefit of AT-001 in COVID 19 affected patients in future studies.

• Antibody-mediated procoagulant platelet formation in COVID-19 is AKT dependent - CONCLUSIONS: Our study shows that pAKT/AKT signaling pathway is associated with the formation of procoagulant platelets in severe COVID-19 patients without integrin GPIIb/IIIa engagement. The inhibition of PI3K/AKT phosphorylation might represent a promising strategy to reduce the risk for thrombosis in patients with severe COVID-19.

• Transparent Polymeric Formulations Effective against SARS-CoV-2 Infection - The main route of the transmission of the SARS-CoV-2 virus is through airborne small aerosol particles containing viable virus as well as through droplets transmitted between people within close proximity. Transmission via contaminated surfaces has also been recognized as an important route for the spread of SARS-CoV-2 coronavirus. Among a variety of antimicrobial agents currently in use, polymers represent a class of biocides that have become increasingly important as an alternative to existing…

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

• 扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link

• 多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - link