Covid-19 Sentry

Contents

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

From Preprints

• The Usage of Mindsponge Theory for Explaining the Protective Behavior Against COVID-19 in The Early Stage of Pandemic -
  The COVID-19 pandemic has caught the public’s attention globally, especially in the early stage of the pandemic in China. COVID-19 was perceived as a big threat to human health and well-being. Acquiring more initial information about COVID-19 has made people perceive a higher threat and presented a higher demand for related information. People’s initial information acquisition may be important in their behavioral responses. The high demand for COVID-19-related information has led Pang et al. [1] to investigate 4,605 Chinese regarding their perceived threat and information-processing strategies in pandemic situations. Findings showed that the high demand for COVID-19-related information has made respondents more likely to seek and process information, subsequently motivating their protective behavior. The perceived threat could positively affect protective behavior but failed to predict the experiential assessment. Information-seeking behavior and experiential assessment significantly influence protective behavior. Information-seeking behavior facilitated analytical assessment and decreased experiential assessment, thus predicting people’s protective behavior [1].
  🖺 Full Text HTML: The Usage of Mindsponge Theory for Explaining the Protective Behavior Against COVID-19 in The Early Stage of Pandemic
• Socio-demographic determinants of COVID-19 vaccine uptake in Ontario: Exploring differences across the Health Region model -

  The COVID-19 pandemic continues to be a worldwide public health concern. Although vaccines against this disease were rapidly developed, vaccination uptake has not been equal across all the segments of the population. In particular, it has been shown that there have been differences in vaccine uptake across different segments of the population. However, there are also differences in vaccination across geographical areas, which might be important to consider in the development of future public health vaccination policies. In this study, we examined the relationship between vaccination status (having received the first dose of a COVID-19 vaccine), and different socio-economic and geographical factors. Our results show that between October of 2021 and January of 2022, individuals from underrepresented communities were three times less likely to be vaccinated than White/Caucasian individuals across the province of Ontario in Canada, and that in some cases, within these groups, individuals in low-income brackets had significantly higher odds of vaccination when compared to their peers in high income brackets. Finally, we identified significantly lower odds of vaccination in the Central, East and West Health Regions of Ontario within certain underrepresented groups. This study shows that there is an ongoing need to better understand and address differences in vaccination uptake across diverse segments of the population of Ontario that the pandemic has largely impacted.

  🖺 Full Text HTML: Socio-demographic determinants of COVID-19 vaccine uptake in Ontario: Exploring differences across the Health Region model
• Genetic Variant rs1205 is Associated with COVID-19 Outcomes: The Strong Heart Study and Strong Heart Family Study. -

  Background: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. Methodology/Principal Findings: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Chi-square tests, logistic regression and generalized linear mixed models (implemented in SOLAR) were used in analysis. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 39 untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p=0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. Conclusion: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.

  🖺 Full Text HTML: Genetic Variant rs1205 is Associated with COVID-19 Outcomes: The Strong Heart Study and Strong Heart Family Study.
• Estimating epidemic dynamics with genomic and time series data -

  Accurately estimating the prevalence and transmissibility of an infectious disease is a critical part of genetic infectious disease epidemiology. However, generating accurate estimates of these quantities, informed by both time series and sequencing data, is challenging. Birth-death processes and coalescent-based models are popular methods for modelling the transmission of infectious diseases, but they struggle with estimating the prevalence of infection. We extended our approximation of the likelihood for a point process of viral genomes and time series of case counts so it can estimate historical prevalence, and we implemented this in a BEAST2 package called Timtam. In a simulation study the approximation recovered the parameters from simulated data, even when we aggregated the point process data into a time series of daily case counts. To demonstrate how Timtam can be applied to real datasets, we estimated the reproduction number and the prevalence of infection through time during the SARS-CoV-2 outbreak onboard the Diamond Princess using a time series of confirmed cases and sequence data. We found a greater prevalence than previously estimated and comment on how differences in the algorithms used could explain this.

  🖺 Full Text HTML: Estimating epidemic dynamics with genomic and time series data
• GRAPHENE FIELD EFFECT BIOSENSOR FOR CONCURRENT AND SPECIFIC DETECTION OF SARS-COV-2 AND INFLUENZA -

  The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology, based on liquid-gated graphene field-effect transistors, for rapid and ultraprecise detection and differentiation of influenza and SARS-CoV-2 surface protein. Most distinctively, our device consists of 4 onboard graphene field-effect electrolyte-gated transistors arranged in a quadruple architecture, where each quarter is functionalized individually (with either antibodies or chemically passivated control) but measured collectively. Our sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at ~50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, which is 5-fold lower than the values reported previously on a similar platform. Unlike the classic Real-Time Polymerase Chain Reaction (RT-PCR) test, which has a turnaround time of a few hours, our technology presents an ultrafast response time of ~10 seconds even in complex media such as saliva. Thus, we have developed a multi-analyte, highly sensitive, and fault-tolerant technology for rapid diagnostic of contemporary, emerging, and future pandemics.

  🖺 Full Text HTML: GRAPHENE FIELD EFFECT BIOSENSOR FOR CONCURRENT AND SPECIFIC DETECTION OF SARS-COV-2 AND INFLUENZA
• Prediction of Daily New COVID-19 Cases - Difficulties and Possible Solutions -

  Epidemiological compartmental models, such as SEIR (Susceptible, Exposed, Infectious, and Recovered) models, have been generally used in analyzing epidemiological data and forecasting the trajectory of transmission of infectious diseases such as COVID-19. Experience shows that accurately forecasting the trajectory of COVID-19 transmission curve is a big challenge to researchers in the field of epidemiological modeling. Multiple factors (such as social distancing, vaccinations, public health interventions, and new COVID-19 variants) can affect the trajectory of COVID-19 transmission. In the past years, we used a new compartmental model, l-i SEIR model, to analyze the COVID-19 transmission trend in the United States. The letters l and i are two parameters in the model representing the average time length of the latent period and the average time length of infectious period. The l-i SEIR model takes into account of the temporal heterogeneity of infected individuals and thus improves the accuracy in forecasting the trajectory of transmission of infectious diseases. This paper describes how these multiple factors mentioned above could significantly change COVID-19 transmission trends, why accurately forecasting COVID-19 transmission trend is difficult, what the strategies we have used to improve the forecast outcome, and some of successful examples that we have obtained.

  🖺 Full Text HTML: Prediction of Daily New COVID-19 Cases - Difficulties and Possible Solutions
• Equivalent Binding Of Sera From Omicron And Delta Period To Future Omicron Subvariants. -

  Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. Binding of sera to spike protein of future variants in the context of heterogeneous exposure, has not been studied. We tested archival sera (delta and omicron period) stratified by anti-spike levels for reactivity to omicron subvariant (BA.1, BA.2, BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike. Antibody reactivity to wild-type (CLIA) and subvariants (ELISA) spike were similar between periods (p>0.05). Both High S group and Low S group of delta and omicron periods were closely related to future subvariants by Antigenic Cartography. Anti-spike antibodies to wild type (S1/S2 and Trimeric S) clustered with subvariant-binding antibodies. Low S group interspersed between High S group on hierarchical clustering. Hybrid immunity caused by cumulative virus exposure in delta or omicron periods caused equivalent binding to future variants. Low S antibody group demonstrating similar binding is a prominent finding.

  🖺 Full Text HTML: Equivalent Binding Of Sera From Omicron And Delta Period To Future Omicron Subvariants.
• What Risk Factors to Cause Long COVID and Its Impact on Patient Survival Outcomes when Combined with the Effect from Organ Transplantation in the Acute COVID -

  Background Coronavirus disease 2019 (COVID-19) in solid organ transplant (SOT) patients is associated with more severe outcomes than non-immunosuppressed hosts. However, exactly which risk factors cause Long COVID in acute COVID cases remains unknown. More importantly, the impact of Long COVID on patient survival remains understudied, especially when examined alongside the effect of SOT. Methods All patients have been identified with acute COVID in the National COVID Collaborative Cohort registry from July 1, 2020, to June 30, 2022. We compared patient demographics in Long COVID vs. those without Long COVID based on descriptive statistics. Multivariable logistics regressions were used to determine the factors related to the likelihood of developing Long COVID from a case of acute COVID. Multi-variables Cox regression was used to determine the time-to-event outcome of patient survival with Long COVID. Results This study reviewed data from a cohort of 6,416,500 acute COVID patients. Of that group, 31,744 (0.5%) patients developed Long COVID from ICD diagnosis. The mean (q1, q3) age was 39 (22, 57) years old, and 55% of patients were female. From this cohort, a total of 31,744 (1%) developed Long COVID and 43,565 (1%) had SOT, with a total of 698 SOT patients identified with Long COVID. Mean age of those with Long COVID was 52 (39, 64) years old and 64% of patients were female. Most of the SOT patients were kidney transplant recipients. From the Cox regression analysis of patient survival, there were many significant factors related to patient survival (death), with elderly SOT patients having a much higher hazard ratio of 27.8 (26.3, 29.4). Conclusion This study has identified the important risk factors that are more likely to cause Long COVID in an acute COVID cohort. We investigated hazard ratios of patient survival based on multivariable Cox models, which found that Long COVID had a more direct impact on survival in elderly patients and those with SOT.

  🖺 Full Text HTML: What Risk Factors to Cause Long COVID and Its Impact on Patient Survival Outcomes when Combined with the Effect from Organ Transplantation in the Acute COVID
• Crowdsourcing Temporal Transcriptomic Coronavirus Host Infection Data: resources, guide, and novel insights. -
  The emergence of SARS-CoV-2 reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of COVID-19 during the pandemic. This study coupled existing transcriptomic data from SARS-CoV-1 lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g., CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA Damage Response and Repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients that died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens. The data from this study is available in an interactive portal (http://18.222.95.219:8047).
  🖺 Full Text HTML: Crowdsourcing Temporal Transcriptomic Coronavirus Host Infection Data: resources, guide, and novel insights.
• Virtual Social Interaction and Loneliness Among Emerging Adults Amid the COVID-19 Pandemic -
  Many social activities moved online during the global COVID-19 pandemic, yet research investigating whether virtual social interactions facilitate social connectedness has been inconclusive. In this study, participants completed online questionnaires assessing objective social isolation, loneliness, mental health, and virtual social interactions. There was clear evidence for worsening mental health among emerging adults during the COVID-19 pandemic characterized by large increases in depressive symptoms (mean increase = 8.35, 95% CI [6.97, 9.73], t(118) = 118, p < .001), and large decrements in happiness (mean decrease = -0.71, 95% CI [-0.84, -0.57], t(118) = 10.09, p < .001) and social satisfaction (mean decrease = -0.81, 95% CI [-1.00,-0.62], t(115) = 8.28, p < .001) post-pandemic onset. In line with expectations, those living in larger households amid the pandemic reported lower levels of loneliness and higher levels of happiness. A negative association was found between household size (an index of objective social isolation) and loneliness, b = -3.01, t(79) = 2.60, p = .011, 95% CI [-5.32, -0.71], and a positive association was found between household size and happiness, b = 22.86, t(75) = 3.30, p = .001, 95% CI [9.06, 36.65]. However, contrary to expectations, there was no association between loneliness and frequency of virtual social interactions. There was also no association between frequency of virtual social interactions and either happiness or depression. More research investigating social connectedness in the context of virtual social interactions is warranted.
  🖺 Full Text HTML: Virtual Social Interaction and Loneliness Among Emerging Adults Amid the COVID-19 Pandemic
• Post-COVID symptoms in the absence of organic deficit - Lessons from diseases we know -
  Given the increasing number of patients suffering severe physical symptoms after SARS-CoV-2 infection for which there is no conclusive organic explanation, it is important to remember a phenomenon well known in medicine: the authenticity and significance of symptoms does not necessarily depend on organic impairment. Rather, the same symptoms and their intensity can occur when structure is intact, but body signals are misinterpreted and incorrectly processed in the brain. For breathlessness, fatigue and dizziness there are already established experimental paradigms to measure such dysfunctions in the absence of organic impairment. Here, we describe these paradigms and explain how they could help to better understand persistent and debilitating symptoms after COVID-19.
  🖺 Full Text HTML: Post-COVID symptoms in the absence of organic deficit - Lessons from diseases we know
• Online Asynchronous Learning English for Specific Purposes Terminology -
  The pandemic and military actions in the country triggered our study in considering the challenges Ukrainian higher education faces referring asynchronous learning. We assume that the challenges are threefold – namely – psychological, technical (availability of means for providing asynchronous communication and technological (scientifically grounded methods of quality asynchronous learning). In our study the focus is on the methods of asynchronous learning specialized terminology. The background of the research was the study of the literature concerning benefits and limitations of asynchronous learning and implementing online courses into the learning process. The purpose of this research was to prove the effectiveness of asynchronous learning specialized vocabulary with the help of the Moodle-based course. The aim was achieved by fulfilling the following tasks: literary review to study the benefits and limitations of asynchronous and synchronous learning for finding the most suitable mode of communication for the Ukrainian students, to design a Moodle-based course, to verify it in the experimental learning. The experiment was conducted in 2020 in the time of Covid-19 pandemic at the National Technical University of Ukraine, Igor Sikorsky Kyiv Polytechnic Institute, and involved seventy students of the Power Engineering Department. The research purpose of both the article and the experiment was to assess the effectiveness of the developed online simulator which included audio recordings of native English specialists’ communication, interdisciplinary and industry-specific terminology, training tasks, and instructional guidelines. The outcome of the research proves the efficiency of applying an online simulator in the development of students’ professional competence in terms of adequate using interdisciplinary and industry-specific terminology.
  🖺 Full Text HTML: Online Asynchronous Learning English for Specific Purposes Terminology
• The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022 -
  The COVID-19 pandemic changed the way people lived, worked, and studied around the world, with direct consequences for domestic energy use. This study assesses the impact of COVID-19 lockdowns in the first two years of the pandemic on household electricity and gas use in England and Wales. Using data for 508 (electricity) and 326 (gas) homes, elastic net regression, neural network and extreme gradient boosting predictive models were trained and tested on pre-pandemic data. The most accurate model for each household was used to create counterfactuals (predictions in the absence of COVID-19) against which observed pandemic energy use was compared. Median monthly model error (CV(RMSE)) was 3.86% (electricity) and 3.19% (gas) and bias (NMBE) was 0.21% (electricity) and -0.10% (gas). Our analysis showed that on average (electricity; gas) consumption increased by (7.8%; 5.7%) in year 1 of the pandemic and by (2.2%; 0.2%) in year 2. The greatest increases were in the winter lockdown (January – March 2021) by 11.6% and 9.0% for electricity and gas, respectively. At the start of 2022 electricity use remained 2.0% higher while gas use was around 1.9% lower than predicted. Households with children showed the greatest increase in electricity consumption during lockdowns, followed by those with adults in work. Wealthier households increased their electricity consumption by more than the less wealthy and continued to use more than predicted throughout the two-year period while the less wealthy returned to pre-pandemic or lower consumption from summer 2021. Low dwelling efficiency was associated with a greater increase in energy consumption during the pandemic. Additionally, this study shows the value of different machine learning techniques for counterfactual modelling at the individual-dwelling level, and our approach can be used to robustly estimate the impact of other events and interventions.
  🖺 Full Text HTML: The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022
• Human-Network Regions as Effective Geographic Units for Disease Mitigation -
  Susceptibility to infectious diseases such as COVID-19 depends on how those diseases spread, and many studies have examined the decrease in COVID-19 spread due to reduction in travel. However, less is known about how much functional geographic regions, which capture natural movements and social interactions, limit the spread of COVID-19. To determine boundaries between functional regions, we apply community-detection algorithms to large networks of mobility and social-media connections to construct geographic regions that reflect natural human movement and relationships at the county level in the continental United States. We measure COVID-19 case counts, case rates, and case-rate variations across adjacent counties and examine how often COVID-19 crosses the boundaries of these functional regions. We find that regions that we construct using GPS-trace networks and especially commute networks have the lowest COVID-19 case rates along the boundaries, so these regions may reflect natural partitions in COVID-19 transmission. Conversely, regions that we construct from geolocated Facebook friendships and Twitter connections yield less effective partitions. Our analysis reveals that regions that are derived from movement flows are more appropriate geographic units than states for making policy decisions about opening areas for activity, assessing vulnerability of populations, and allocating resources. Our insights are also relevant for policy decisions and public messaging in future emergency situations.
  🖺 Full Text HTML: Human-Network Regions as Effective Geographic Units for Disease Mitigation
• Within-host evolution of SARS-CoV-2: how often are mutations transmitted? -
  Despite a relatively low mutation rate, the large number of SARS-CoV-2 infections has allowed for substantial genetic change, leading to a multitude of emerging variants. Using a recently determined mutation rate (per site replication), as well as parameter estimates for within-host SARS-CoV-2 infection, we apply a stochastic transmission-bottleneck model to describe the survival probability of de novo SARS-CoV-2 mutations. For narrow bottlenecks, we find mutations affecting per-target-cell attachment rate (with phenotypes associated with fusogenicity and ACE2 binding), have similar transmission probabilities to mutations affecting viral load clearance (with phenotypes associated with humoral evasion). We further find that mutations affecting the eclipse rate (with phenotypes associated with reorganization of cellular metabolic processes and synthesis of viral budding precursor material) are highly favoured relative to all other traits examined. We find mutations leading to reduced removal rates of infected cells (with phenotypes associated with innate immune evasion) have limited transmission advantage relative to mutations leading to humoral evasion. Predicted transmission probabilities, however, for mutations affecting innate immune evasion are more consistent with the range of clinically-estimated household transmission probabilities for de novo mutations. This result suggests that although mutations affecting humoral evasion are more easily transmitted when they occur, mutations affecting innate immune evasion may occur more readily. We examine our predictions in the context of a number of previously characterized mutations in circulating strains of SARS-CoV-2. Our work offers both a null model for SARS-CoV-2 substitution rates and predicts which aspects of viral life history are most likely to successfully evolve, despite low mutation rates and repeated transmission bottlenecks.
  🖺 Full Text HTML: Within-host evolution of SARS-CoV-2: how often are mutations transmitted?

From Clinical Trials

• A Phase 2/3 Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose of Previously Vaccinated Participants. - Condition:   COVID-19
  Interventions:   Biological: XBB.1.5 Vaccine (Booster);   Biological: XBB.1.5 Vaccine (single dose)
  Sponsor:   Novavax
  Not yet recruiting

• Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)
  Sponsor:   Asfendiyarov Kazakh National Medical University
  Not yet recruiting

• Effects of Exercise Training on Patients With Long COVID-19 - Condition:   Long COVID-19
  Intervention:   Behavioral: Exercise training
  Sponsor:   Guangdong Provincial People’s Hospital
  Recruiting

• EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition:   Post-COVID-19 Syndrome
  Intervention:   Behavioral: rehacom
  Sponsor:   Cairo University
  Enrolling by invitation

• Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly - Conditions:   Vaccination; Infection;   COVID-19
  Intervention:   Biological: Comirnaty
  Sponsor:   Radboud University Medical Center
  Not yet recruiting

• A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition:   COVID-19
  Interventions:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo
  Sponsor:   GlaxoSmithKline
  Not yet recruiting

• Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
  Sponsor:   Novavax
  Not yet recruiting

• Hyperbaric on Pulmonary Functions in Post Covid -19 Patients. - Condition:   Post COVID-19 Patients
  Interventions:   Device: hyperbaric oxygen therapy;   Device: breathing exercise;   Drug: medical treatment
  Sponsor:   Cairo University
  Completed

• Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome - Conditions:   Post-Acute COVID-19 Syndrome;   Fatigue
  Interventions:   Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome;   Other: Attention Control
  Sponsor:   University of Maryland, Baltimore
  Not yet recruiting

• A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions:   SARS CoV 2 Infection;   Influenza, Human
  Interventions:   Biological: BIMERVAX;   Biological: SIIV
  Sponsor:   Hipra Scientific, S.L.U
  Not yet recruiting

• HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions:   COVID-19;   Delirium;   Critical Illness
  Interventions:   Combination Product: Active HD-tDCS;   Combination Product: Sham HD-tDCS
  Sponsors:   Suellen Andrade;   City University of New York
  Completed

• RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions:   Long COVID-19;   Long COVID
  Interventions:   Drug: Paxlovid 25 day dosing;   Drug: Paxlovid 15 day dosing;   Drug: Control
  Sponsor:   Kanecia Obie Zimmerman
  Enrolling by invitation

• RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

• Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition:   Post Acute Sequelae Covid-19 Hyposmia
  Interventions:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge
  Sponsor:   Duke University
  Not yet recruiting

• RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

From PubMed

• TGF-β uncouples glycolysis and inflammation in macrophages and controls survival during sepsis - Changes in metabolism of macrophages are required to sustain macrophage activation in response to different stimuli. We showed that the cytokine TGF-β (transforming growth factor-β) regulates glycolysis in macrophages independently of inflammatory cytokine production and affects survival in mouse models of sepsis. During macrophage activation, TGF-β increased the expression and activity of the glycolytic enzyme PFKL (phosphofructokinase-1 liver type) and promoted glycolysis but suppressed the…

• Escape from senescence: molecular basis and therapeutic ramifications - Cellular senescence constitutes a stress response mechanism in reaction to a plethora of stimuli. Senescent cells exhibit cell-cycle arrest and altered function. While cell-cycle withdrawal has been perceived as permanent, recent evidence in cancer research introduced the so-called escape-from-senescence concept. In particular, under certain conditions, senescent cells may resume proliferation, acquiring highly aggressive features. As such, they have been associated with tumour relapse,…

• Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial - BACKGROUND: Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma-BioNTech; mRNA vaccine).

• Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2 - The Coronavirus envelope (E) protein is a small structural protein with ion channel activity that plays an important role in virus assembly, budding, immunopathogenesis and disease severity. The viroporin E is also located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we evaluated in vitro antiviral activity, mechanism of action and in vivo efficacy of BIT225 for the treatment of SARS-CoV-2 infection. BIT225 showed…

• The Role of the Tyrosine-Based Sorting Signals of the ORF3a Protein of SARS-CoV-2 on Intracellular Trafficking, Autophagy, and Apoptosis - The open reading frame 3a (ORF3a) is an accessory transmembrane protein that is important to the pathogenicity of SARS-CoV-2. The cytoplasmic domain of ORF3a has three canonical tyrosine-based sorting signals (YxxΦ; where x is any amino acid and Φ is a hydrophobic amino acid with a bulky -R group). They have been implicated in the trafficking of membrane proteins to the cell plasma membrane and to intracellular organelles. Previous studies have indicated that mutation of the ^(160) YSNV ^(163)…

• Discovery of Hybrid Thiouracil-Coumarin Conjugates as Potential Novel Anti-SARS-CoV-2 Agents Targeting the Virus’s Polymerase “RdRp” as a Confirmed Interacting Biomolecule - The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin…

• Transfer and biotransformation of the COVID-19 prodrug molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-placenta barrier - BACKGROUND: Molnupiravir is an orally bioavailable prodrug of the nucleoside analogue β-D-N4-hydroxycytidine (NHC) and is used to treat coronavirus disease 2019 (COVID-19). However, the pharmacokinetics and transplacental transfer of molnupiravir in pregnant women are still not well understood. In the present study, we investigated the hypothesis that molnupiravir and NHC cross the blood-placenta barrier into the fetus.

• Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19 - PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in…

• SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters - ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with…

• Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds - CONCLUSION: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo…

• Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic - The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, and…

• Inhibition by components of Glycyrrhiza uralensis of 3CLpro and HCoV-OC43 proliferation - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N,…

• An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen - The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains 3 linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was…

• Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…

• Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…

From Patent Search