Covid-19 Sentry

Contents

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

From Preprints

• Computer model and code sharing practices in healthcare discrete-event simulation: a systematic scoping review -
  Objectives: Discrete-event simulation is a widely used computational method in health services and health economic studies. This systematic scoping review investigates to what extent authors share computer models, and audits if sharing adheres to best practice. Data sources: The Web of Science, Scopus, PubMed, and ACM Digital Library databases were searched between 1st January 2019 till 31st December 2022. Eligibility criteria for selecting studies: Cost-effectiveness, Health service research and methodology studies in a health context were included. Data extraction and synthesis: The data extraction and best practice audit were performed by two reviewers. We developed best practice audit criteria based on the Turing Way and other published reproducibility guides. Main outcomes and measures: We measured the proportion of literature that shared models; we report analyses by publication type, year of publication, Covid-19 application; and free and open source versus commercial software. Results: 47 (8.3%) of the 564 studies included cited a published DES computer model; rising to 9.0% in 2022. Studies were more likely to share models if they had been developed using free and open source tools. Studies rarely followed best practice when sharing computer models. Conclusions: Although still in the minority, there is evidence that healthcare DES authors are increasingly sharing their computer model artifacts. Although commercial software dominates the DES literature, free and open source software plays a crucial role in sharing. The DES community can adopt many simple best practices to improve the quality of sharing.
  🖺 Full Text HTML: Computer model and code sharing practices in healthcare discrete-event simulation: a systematic scoping review
• Direct measures of liking and intensity of taste, smell, and chemesthetic stimuli are similar between young people reporting they did or did not have COVID-19 -
  The recovery period from post-COVID-19 smell and taste dysfunctions varies substantially, lasting from a few days to over a year. We aimed to assess the impact of COVID-19 on post-COVID-19 chemosensory sensitivity in a group of young convalescents of eastern/central European ancestry. We measured subjects smell and taste capabilities with a standard testing kit, Monell Flavor Quiz (MFQ), and collected surveys on COVID-19 history. During testing, subjects rated liking and intensity of six odor samples (galaxolide, guaiacol, beta-ionone, trimethylamine, phenylethyl alcohol, 2-ethyl fenchol) and six taste samples (sucralose, sodium chloride, citric acid, phenylthiocarbamide, menthol, capsaicin) on a scale from 1 (dislike extremely, or no intensity) to 9 (like extremely, or extremely intense). There was no statistical difference in intensity ratings or liking of any sample between subjects who reported a history of COVID-19 (n = 34) and those reporting no history (n = 40), independent of presence/absence or severity of smell/taste impairments (P > 0.05). Additionally, neither vaccination status (full vaccination or no vaccination) nor time from the COVID-19 onset (2-27 months) correlated with liking or intensity. These results suggest that most young adults who had COVID-19 recovered their sense of smell and taste.
  🖺 Full Text HTML: Direct measures of liking and intensity of taste, smell, and chemesthetic stimuli are similar between young people reporting they did or did not have COVID-19
• The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection -
  To assess the role of the Omicron BA.1 Spike (S) protein in the pathogenesis of the severe acute respiratory coronavirus 2 (SARS-CoV-2), we generated recombinant viruses harboring the S D614G mutation (rWA1-D614G) and the Omicron BA.1 S gene (rWA1-Omi-S) in the backbone of the ancestral SARS-CoV-2 WA1 strain genome. The recombinant viruses were characterized in vitro and in vivo. Viral entry, cell-cell fusion, viral plaque size, and viral replication kinetics of the rWA1-Omi-S virus were markedly impaired when compared to the rWA1-D614G virus, demonstrating a lower fusogenicity and ability to spread cell-to-cell of rWA1-Omi-S. To assess the contribution of the Omicron BA.1 S protein to SARS-CoV-2 pathogenesis the pathogenicity of rWA1-D614G and rWA1-Omi-S viruses were compared using a feline model of infection. While the rWA1-D614G-inoculated cats became lethargic and showed increased body temperatures on days 2 and 3 post-infection (pi), rWA1-Omi-S-inoculated cats remained subclinical and gained weight throughout the 14-day experimental period. Animals inoculated with rWA1-D614G presented higher levels of infectious virus shedding in nasal secretions, when compared to rWA1-Omi-S-inoculated animals. In addition, tissue replication of the rWA1-Omi-S was markedly reduced compared to the rWA1-D614G, as evidenced by lower in situ viral RNA and lower viral load in tissues on days 3 and 5 pi. Histologic examination of the nasal turbinate and lungs revealed intense inflammatory infiltration in rWA1-D614G-inoculated animals, whereas rWA1-Omi-S-inoculated cats presented only mild to modest inflammation. Together, these results demonstrate that the S protein is a major virulence determinant for SARS-CoV-2 playing a major role for the attenuated phenotype of the Omicron virus.
  🖺 Full Text HTML: The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection
• LETHAL COVID-19 ASSOCIATES WITH RAAS-INDUCED INFLAMMATION FOR MULTIPLE ORGAN DAMAGE INCLUDING MEDIASTINAL LYMPH NODES -
  Lethal COVID-19 causation most often invokes classic cytokine storm and attendant excessive immune signaling. We re-visit this question using RNA sequencing in nasopharyngeal and 40 autopsy samples from both COVID-19-positive and negative individuals. In nasal swabs, the top 100 genes expressed, and significantly correlated with COVID-19 viral load, indeed include many canonical innate immune genes. However, 22 much less studied "non-canonical" genes are found and despite the absence of viral transcripts, subsets of these are upregulated in heart, lung, kidney, and liver, but not mediastinal lymph nodes. An important regulatory potential emerges for the non-canonical genes for over-activating the renin-angiotensin-activation-system (RAAS) pathway, resembling this phenomenon in hereditary angioedema (HAE) and its overlapping multiple features with lethal COVID-19 infections. Specifically, RAAS overactivation links increased fibrin deposition, leaky vessels, thrombotic tendency, and initiating the PANoptosis death pathway, as suggested in heart, lung, and especially mediastinal lymph nodes, and a tight association mitochondrial dysfunction linked to immune responses. For mediastinal lymph nodes, immunohistochemistry studies correlate showing abnormal architecture, excess fibrin and collagen deposition, and pathogenic fibroblasts. Further, our findings overlap these for COVID-19 infected hamsters, C57BL/6 and BALB/c mouse models, and importantly peripheral blood mononuclear cell (PBMC) and whole blood samples from COVID-19 patients infected with early alpha but also later COVID-19 omicron strains. We thus present cytokine storm in lethal COVID-19 disease as an interplay between upstream immune gene signaling producing downstream RAAS overactivation with resultant severe organ damage, especially compromising mediastinal lymph node function.
  🖺 Full Text HTML: LETHAL COVID-19 ASSOCIATES WITH RAAS-INDUCED INFLAMMATION FOR MULTIPLE ORGAN DAMAGE INCLUDING MEDIASTINAL LYMPH NODES
• Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster -
  It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 h), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 micrometer) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 h). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.
  🖺 Full Text HTML: Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster
• Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study -

  Objectives: To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi). Methods: We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston, MA, USA. Patients were followed from the date of 3rd vaccine dose until breakthrough COVID-19, death, or end of follow-up (18/Jan/2023). Covariates included demographics, lifestyle, comorbidities, and prior COVID-19. We used Cox proportional hazards models to estimate breakthrough COVID-19 risk by immunomodulator drug class. We used propensity score (PS) overlap-weighting to compare users of CD20i vs. TNFi. Results: We analyzed 5781 patients with RA that received 3 mRNA vaccine doses (78.8% female, mean age 64.2 years). During mean follow-up of 12.8 months, 1173 (20.2%) had breakthrough COVID_19. Use of CD20i (adjusted HR 1.74, 95%CI 1.30-2.33) and glucocorticoid monotherapy (adjusted HR 1.47, 95%CI 1.09-1.98) were each associated with breakthrough COVID-19 compared to TNFi use. In the PS overlap-weighted analysis, CD20i users also had higher breakthrough COVID-19 risk than TNFi users (HR 1.62, 95%CI 1.02-2.56). A sensitivity analysis excluding patients with cancer or interstitial lung disease yielded similar findings. Conclusions: We identified CD20i and glucocorticoid monotherapy as risk factors for breakthrough COVID-19 among patients with RA after a 3rd vaccine dose. This contemporary study highlights the real-world impact of blunted immune responses in these subgroups and the need for effective risk mitigation strategies.

  🖺 Full Text HTML: Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study
• Impact of sampling site on diagnostic test accuracy of RT-PCR in diagnosing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection since the emergence of omicron: a systematic review and meta-analysis -

  Nasopharyngeal sampling (NP) is the routine standard for SASR-CoV-2 detection using reverse transcription polymerase chain reaction (RT-PCR). In this systematic review, we assessed diagnostic test accuracy of alternative sampling sites compared to NP for RT-PCR testing of Omicron (sub)-variants. We systematically searched for studies from January 2022 until February 2023 investigating any type of respiratory sample for RT-PCR in people with suspected, known, or known absence of SARS-CoV-2 Omicron infection. Data were pooled for each comparison using the bivariate model, sensitivity and specificity was estimated with 95% confidence intervals (CIs). Risk of bias was assessed with QUADAS-2 tool, certainty of evidence with GRADE. We included three cohort-type cross-sectional studies (1,003 participants). Saliva versus NP sampling in three studies showed a sensitivity of 92% (95% CI 87% to 96%) and a specificity of 94% (95% CI 83% to 98%). AN versus NP sampling in one study showed a sensitivity of 90% (95% CI 82% to 95%) and a specificity of 99% (95% CI 95% to 100%). Certainty of evidence for sensitivity and specificity of both comparisons was low to very low. Based on the current very low‐ to low‐certainty evidence, we are uncertain about accuracy of different sampling sites for RT-PCR.

  🖺 Full Text HTML: Impact of sampling site on diagnostic test accuracy of RT-PCR in diagnosing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection since the emergence of omicron: a systematic review and meta-analysis
• Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size -

  Objective: The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign. Design: Longitudinal observational cohort and province-wide analysis. Methods: 62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022. Results: Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p>0.4). The magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike antibody response did not correlate with changes in reservoir size nor detectable pVL frequency (p>0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART. Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.

  🖺 Full Text HTML: Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size
• Establishment of regional genomic surveillance networks in lower and lower-middle income countries -
  This is a position letter that represents the stance of the members of the UNESCO-TWAS Advisory Committee on COVID-19, who come from various countries in the Global South. It addresses the disparity in SARS-CoV-2 genomic data between different countries of the global North and South. It discusses possible causes of the problem and suggests establishing regional genomic surveillance networks.
  🖺 Full Text HTML: Establishment of regional genomic surveillance networks in lower and lower-middle income countries
• Non-pharmacological interventions aimed at promoting the mental health of children and adolescents during the COVID-19 pandemic -

  Background: Interventions to promote mental health in pediatrics need to be effective, especially in crisis contexts. This systematic review proposes compile and analyze the findings of non-pharmacological interventions conducted in samples of children and adolescents during the COVID-19 pandemic, focusing on mental health. Method: The research was carried out in PsycINFO, PubMed and Web of Science databases for empirical studies, including interventions in which measures of outcome variables were collected at least twice (pre and post). The studies samples were children and adolescents up to 19 years old, and interventions were developed throughout the COVID-19 pandemic. After eligibility analyses, 16 studies were included in this review. Results: Studies used different theoretical approaches, focusing on promotion, prevention and treatment in mental health in specifics contexts. Some were delivered online, in-person, or in hybrid formats. Particularly, depression, the most frequently assessed outcome, demonstrated more favorable results within the interventions. However, due to considerable risk of bias, the analysis of results of many included studies should be performed with caution. Conclusions: Most of the interventions necessitate further validation. However, the emergence of interventions during crises, such as the COVID-19 pandemic, provides an opportunity to expand evidence-based mental health practices, paving the way for their application in other crisis situations. Given that mental health prevention and promotion practices can be integrated into the roles of all healthcare providers, possessing insight into the most suitable evidence-based interventions can elevate the quality of care delivered.

  🖺 Full Text HTML: Non-pharmacological interventions aimed at promoting the mental health of children and adolescents during the COVID-19 pandemic
• Conversations with a concern-addressing chatbot increase COVID-19 vaccination intentions among social media users in Kenya and Nigeria -
  During mass vaccination campaigns, social media platforms can facilitate the dissemination of public health information but may also contribute to vaccine hesitancy by serving as a vehicle for the spread of false and misleading information. Although talking with health professionals is an important avenue to address individuals’ concerns, one-on-one conversations with healthcare providers are challenging to scale. Can automated, personalized messaging delivered by a chatbot address individuals’ concerns and increase vaccine acceptance? To answer this question, we designed and deployed a Facebook Messenger chatbot to address questions and concerns social media users in Kenya and Nigeria had about the COVID-19 vaccine. After optimizing messaging using an adaptive experimental design on 3,905 respondents, we compare the interactive concern-addressing chatbot to a chatbot that delivers a non-interactive public service announcement (PSA), as well as to a control, no information, chatbot condition. We find that the concern-addressing chatbot increases COVID-19 vaccine intentions and willingness by 4-5% compared to the control condition, and by 3-4% compared to the PSA intervention. Among the 22,052 respondents in our evaluation sample, who at the time of the survey in early 2022 had not yet received a single COVID-19 vaccine, we observe the largest treatment effects among those most hesitant at baseline. With advertising costs as low as $0.21 per person engaged and $4.33 per person influenced, policymakers may want to consider using personalized messaging on digital platforms to quickly and cheaply reach many people to encourage compliance with public health programs during disease outbreaks.
  🖺 Full Text HTML: Conversations with a concern-addressing chatbot increase COVID-19 vaccination intentions among social media users in Kenya and Nigeria
• Unravelling Causal Associations between Population Mobility and COVID-19 Cases in Spain: a Transfer Entropy Analysis -

  Human mobility is a well-known factor in the spread of infectious diseases. During the COVID-19 pandemic, the rapid spread of the SARS-CoV-2 virus led to healthcare systems collapsing in numerous countries, such as Spain and Italy, resulting in a significant number of deaths. To avoid such disastrous outcomes in the future, it is vital to understand how population mobility is linked to the spread of infectious diseases. To assess that, we applied an information theoretic approach called transfer entropy (TE) to measure the influence of the number of infected people travelling between two localities on the future number of infected people in the destination. We first validated our approach using simulated data from a SIR epidemiological model and found that the mobility-based TE was effective in filtering out non-causal influences that could otherwise arise, thereby successfully recovering the epidemic9s spreading patterns and the mobility network topology. We then applied the mobility-based TE to analyse the COVID-19 pandemic in Spain. We identified which regions acted as the main drivers of the pandemic at different periods, both globally and locally. Our results unravelled significant epidemiological events such as the outbreak in Lleida during the Summer of 2020, caused by the influx of temporary workers. We also analysed the effects of a non-pharmaceutical intervention in Catalunya, using mobility-based TE to compare the infection dynamics with a control region. These results help clarify how human mobility influences the dynamic spread of infectious diseases and could be used to inform future non-pharmaceutical interventions.

  🖺 Full Text HTML: Unravelling Causal Associations between Population Mobility and COVID-19 Cases in Spain: a Transfer Entropy Analysis
• Bayesian workflow for time-varying transmission in stratified compartmental infectious disease transmission models -

  Compartmental models that describe infectious disease transmission across subpopulations are central for assessing the impact of non-pharmaceutical interventions, behavioral changes and seasonal effects on the spread of respiratory infections. We present a Bayesian workflow for such models, including four features: (1) an adjustment for incomplete case ascertainment, (2) an adequate sampling distribution of laboratory-confirmed cases, (3) a flexible, time-varying transmission rate, and (4) a stratification by age group. We benchmarked the performance of various implementations of two of these features (2 and 3). For the second feature, we used SARS-CoV-2 data from the canton of Geneva (Switzerland) and found that a quasi-Poisson distribution is the most suitable sampling distribution for describing the overdispersion in the observed laboratory-confirmed cases. For the third feature, we implemented three methods: Brownian motion, B-splines, and approximate Gaussian processes (aGP). We compared their performance in terms of the number of effective samples per second, and the error and sharpness in estimating the time-varying transmission rate over a selection of ordinary differential equation solvers and tuning parameters, using simulated seroprevalence and laboratory-confirmed case data. Even though all methods could recover the time-varying dynamics in the transmission rate accurately, we found that B-splines perform up to four and ten times faster than Brownian motion and aGPs, respectively. We validated the B-spline model with simulated age-stratified data. We applied this model to 2020 laboratory-confirmed SARS-CoV-2 cases and two seroprevalence studies from the canton of Geneva. This resulted in detailed estimates of the transmission rate over time and the case ascertainment. Our results illustrate the potential of the presented workflow including stratified transmission to estimate age-specific epidemiological parameters. The workflow is freely available in the R package HETTMO, and can be easily adapted and applied to other surveillance data.

  🖺 Full Text HTML: Bayesian workflow for time-varying transmission in stratified compartmental infectious disease transmission models
• Covid-19 vaccine safety in pregnancy, a nested case-control study in births from April 2021 to March 2022, England -

  Introduction: Vaccine safety in pregnancy is always of paramount importance. Current evidence of COVID-19 vaccine safety in pregnancy has been reassuring with no association found with negative maternal and neonatal outcomes. However, very few safety studies are conducted on a national level and investigate dosage, timing of vaccination as well as vaccine manufacturer. To fill this knowledge gap, we conducted a population based COVID-19 vaccine safety evaluation in England, including timing of vaccination by trimester, dosage and vaccine manufacturer received in pregnancy. Method: A matched case control study nested in a retrospective cohort where adverse maternal and neonatal pregnancy outcomes were compared across several COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for a range of demographic and health characteristics. Eligible participants were identified from the national maternity services dataset (MSDS) and records were linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching criteria differed by outcome but included participant9s age and estimated week of conception. Results: 514,013 pregnant individuals aged between 18 and 50 years were identified during the study period (births from 16th of April 2021- 31st March 2022). Receiving at least one dose of COVID-19 vaccine during pregnancy conferred lower odds of giving birth to a baby who was low birthweight (aOR=0.86, 95% CI: 0.79 - 0.93), preterm (aOR=0.89, 95% CI: 0.85 - 0.92) or who had an Apgar score less than 7 at five mins of age (aOR=0.89, 95% CI: 0.80 - 0.98). There was no association between vaccination in pregnancy and stillbirth (aOR=0.90, 95% CI: 0.76 - 1.07), neonatal death (aOR=1.27, 95% CI: 0.91 - 1.77) perinatal death (aOR=0.98, 95% CI: 0.83 - 1.16), and maternal venous thromboembolism in pregnancy (aOR=0.82, 95% CI: 0.43 - 1.56). The odds of maternal admission to intensive care unit were lower in vaccinated pregnant women (aOR=0.85, 95% CI: 0.76 - 0.95). Conclusion: COVID-19 vaccines are safe to use in pregnancy and they confer protection against SARS-CoV-2 infection which can lead to adverse outcomes for both the mother and the infant. Our findings generated important information to communicate to pregnant women and health professionals to support COVID-19 maternal vaccination programmes.

  🖺 Full Text HTML: Covid-19 vaccine safety in pregnancy, a nested case-control study in births from April 2021 to March 2022, England
• Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science -
  Biopsy is crucial in clinical medicine to obtain tissues and cells that directly reflect the pathological changes of each disease. However, the brain is an exception due to ethical and practical challenges. Nasal biopsy, which captures the olfactory neuronal epithelium, has been considered as an alternative method of obtaining neuronal cells from living patients. Multiple groups have enriched olfactory neuronal cells (ONCs) from biopsied nasal tissue. ONCs can be obtained from repeated biopsies in a longitudinal study, providing mechanistic insight associated with dynamic changes along the disease trajectory and treatment response. Nevertheless, molecular characterization of biopsied nasal cells/tissue has been insufficient. Taking advantage of recent advances in next-generation sequencing technologies at the single-cell resolution and related rich public databases, we aimed to define the neuronal characteristics, homogeneity, and utility of ONCs. We applied single-cell and bulk RNA sequencing for ONCs, analyzing and comparing the data with multiple public datasets. We observed that the molecular signatures of ONCs are similar to those of neurons, distinct from major glial cells. The signatures of ONCs resemble those of developing neurons and share features of excitatory neurons in the prefrontal and cingulate cortex. The high homogeneity of ONCs is advantageous in pharmacological, functional, and protein studies. Accordingly, we provide two proof-of-concept examples for functional and protein studies, solidifying the utility of ONCs in studying objective biomarkers and molecular mechanisms for brain disorders. The ONCs may also be useful in the studies for the olfactory epithelium impairment and the resultant mental dysfunction elicited by SARS-CoV-2.
  🖺 Full Text HTML: Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

From Clinical Trials

• Equity Evaluation of Fact Boxes - Study Protocol for a Multi-center Cluster Randomised Controlled Trial (RCT) - Conditions: COVID-19; Influenza
  Interventions: Other: Fact box
  Sponsors: Harding Center for Risk Literacy
  Not yet recruiting

• tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
  Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
  Sponsors: Universidade Federal de Pernambuco; São Paulo State University
  Recruiting

• Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19. - Conditions: COVID-19 Pneumonia
  Interventions: Other: Prone position; Other: Standard treatment
  Sponsors: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  Terminated

• ACTIVATE in Public Housing - Conditions: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy
  Interventions: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination
  Sponsors: Charles Drew University of Medicine and Science
  Not yet recruiting

• Effects of a Home-Based Exercise Intervention on Physical Function, Symptoms and Health-Related Quality of Life in Subjects With Long Covid - Conditions: Long COVID-19; Post-COVID-19 Syndrome
  Interventions: Other: home-based concurrent exercise
  Sponsors: University of Vienna
  Recruiting

• Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition) - Conditions: COVID-19
  Interventions: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers - Conditions: COVID-19
  Interventions: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile)
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Exercise Interventions in Post-acute Sequelae of Covid-19 - Conditions: COVID-19
  Interventions: Behavioral: Exercise
  Sponsors: University of Virginia
  Not yet recruiting

• Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC) - Conditions: Long Covid19; Fatigue Syndrome, Chronic
  Interventions: Dietary Supplement: Flavonoids
  Sponsors: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
  Recruiting

• The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection - Conditions: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease
  Interventions: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing)
  Sponsors: Sarang K. Yoon, DO, MOH; Westat; Novavax
  Not yet recruiting

• Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects - Conditions: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection
  Interventions: Combination Product: RQ-001; Other: Placebo
  Sponsors: Red Queen Therapeutics, Inc.; PPD
  Recruiting

• Motivational Interviewing for Vaccine Uptake in Latinx Adults - Conditions: Vaccine Hesitancy
  Interventions: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse
  Sponsors: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR)
  Not yet recruiting

• Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition. - Conditions: COVID-19
  Interventions: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 - Conditions: COVID-19, SARS-CoV-2
  Interventions: Biological: Biological: AZD3152; Biological: Biological: Placebo
  Sponsors: AstraZeneca
  Not yet recruiting

• Examining the Function of Cs4 on Post-COVID-19 Disorders - Conditions: Long COVID
  Interventions: Other: Chinese medicine nutritional supplement Cs4
  Sponsors: The University of Hong Kong
  Recruiting

From PubMed

• Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2 - Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds…

• Native SEC and Reversed-Phase LC-MS Reveal Impact of Fab Glycosylation of Anti-SARS-COV-2 Antibodies on Binding to the Receptor Binding Domain - The binding affinity of monoclonal antibodies (mAbs) for their intended therapeutic targets is often affected by chemical and post-translational modifications in the antigen binding (Fab) domains. A new two-dimensional analytical approach is described here utilizing native size exclusion chromatography (SEC) to separate populations of antibodies and bound antibody-antigen complexes for subsequent characterization of these modifications by reversed-phase (RP) liquid chromatography-mass…

• Comparative docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets - Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: β-d-N⁴-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN’s interactions with off-target proteins beyond the viral genome, suggesting that the complete…

• In Silico and In Vitro Potential of FDA-Approved Drugs for Antimalarial Drug Repurposing against Plasmodium Serine Hydroxymethyltransferases - Malaria has spread in many countries, with a 12% increase in deaths after the coronavirus disease 2019 pandemic. Malaria is one of the most concerning diseases in the Greater Mekong subregion, showing increased drug-resistant rates. Serine hydroxymethyltransferase (SHMT), a key enzyme in the deoxythymidylate synthesis pathway, has been identified as a promising antimalarial drug target due to its conserved folate binding pocket. This study used a molecular docking approach to screen 2509 US Food…

• Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides - Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a…

• Multi-effective characteristics and advantages of acupuncture in COVID-19 treatment - Coronavirus disease 2019 (COVID-19) is a major disease that threatens human life and health. Its pathogenesis is complex and still not fully clarified. The clinical treatment is mainly supportive and lacks specific treatment methods. Acupuncture treatment can inhibit immune inflammatory reactions, neuroinflammatory reactions, oxidative stress levels, and hypothalamus-pituitary-adrenal (HPA) axis activity, improve lung function, and relieve migraine, fatigue, anxiety, and depression. However,…

• In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K - SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor for viral entry, while TMPRSS2 proteolytically cleaves the S protein into S1 and S2 subunits, promoting membrane fusion. Therefore, ACE-2 and TMPRSS2 are potential drug…

• Development and evaluation of a novel chromium III-based compound for potential inhibition of emerging SARS-CoV-2 variants - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused 403 million cases of coronavirus disease (COVID-19) and resulted in more than 5.7 million deaths worldwide. Extensive research has identified several potential drug treatments for COVID-19. However, the development of new compounds or therapies is necessary to prevent the emergence of drug resistance in SARS-CoV-2. In this study, a novel compound based on hexaacetotetraaquadihydroxochromium(III)diiron(III) nitrate, which…

• Curcumin-derived carbon-dots as a potential COVID-19 antiviral drug - Even entering the third year of the COVID-19 pandemic, only a small number of COVID-19 antiviral drugs are approved. Curcumin has previously shown antiviral activity against SARS-CoV-2 nucleocapsid, but its poor bioavailability limits its clinical uses. Utilizing nanotechnology structures, curcumin-derived carbon-dots (cur-CDs) were synthesized to increase low bioavailability of curcumin. In-silico analyses were performed using molecular docking, inhibition of SARS-CoV-2 nucleocapsid C-terminal…

• Using a function-first ‘scout fragment’-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes - Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity. As a result, helicases are important targets…

• Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo - The rapid evolution of variants of SARS-CoV-2 highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His10 epitope tag. In cultured cells, mutant ACE2 competitively…

• Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease - We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including the COVID-19 pandemic caused by SARS-CoV-2. Main protease (M ^(Pro) ) is a highly conserved and essential protease that plays key roles in viral replication and pathogenesis among various CoVs, representing one of the most attractive drug targets for antiviral drug development. Traditional antiviral drug development strategies focus on the pursuit of high-affinity binding inhibitors against M ^(Pro) . However,…

• Inhibition of SARS-CoV-2 Infection in Human Airway Epithelium with a Xeno-Nucleic Acid Aptamer - CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.

• Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells - Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of…

• Paxlovid mouth likely is mediated by activation of the TAS2R1 bitter receptor by nirmatrelvir - Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has remained a public health threat since late 2019. Among the strategies rapidly developed to prevent and treat COVID-19, the antiviral medication Paxlovid (nirmatrelvir/ritonavir combination) has shown remarkable efficacy in reducing viral load and relieving clinical symptoms. Unexpectedly, a persistent bitter/bad taste, referred to as “Paxlovid mouth”, has been frequently noted….

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