Covid-19 Sentry

Contents

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

From Preprints

• Phenotypic grouping of Catheter-Associated Escherichia coli from COVID-19 isolation wards using Hierarchical clustering in Surabaya -

  Introduction Moderate to critical COVID-19 patients may be indicated for urinary catheter use due to risk of immobility and ventilator or oxygen use. In intensive care units, 18-81.7% of all patients use urinary catheter. Almost all patients with urinary catheter suffered from bacteriuria in 30 catheter-days. Hospital associated isolate tracing is mainly performed using complex molecular tests that is not vastly available. This study aims to trace catheter associated urinary tract infection (CAUTI) isolates using common hierarchical clustering method that is vastly available Methods This is a descriptive study presenting collection of Escherichia coli culture data performed by dr. Soetomo Public Hospital microbiology laboratory from 26 March 2020- 31 March 2021. Hierarchical clustering were performed using statistical software using Ward s clustering method. Results There are 36 E.coli associated with CAUTI. Isolate biochemistry profile and minimum inhibitory concentrations profiles were clustered into 3 clades for each profile. A total of 9 cluster combinations were found. Cluster ID 1 was melibiose fermenters, Cluster ID 2 was non-Arginine utilizer, and Cluster ID-3 was Arginine utilizer. Cluster MIC A consist of third generation Cephalosporin resistant isolates, Cluster MIC C was multi-susceptible isolates. Chi-square test between cluster ID and MIC showed no significant differences between number of isolates per group (X2, p = .430, CI = 95%). Conclusion CAUTI associated E.coli is divided into 9 clusters. This indicates no cluster dominates the isolates, thus CAUTI is not caused by hospital transmission but normal flora carried by the admitted patient.

  🖺 Full Text HTML: Phenotypic grouping of Catheter-Associated Escherichia coli from COVID-19 isolation wards using Hierarchical clustering in Surabaya
• High connectivity and human movement limits the impact of travel time on infectious disease transmission -

  The speed of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic highlights the importance of understanding how infections are transmitted in a highly connected world. Prior to vaccination, changes in human mobility patterns were used as non-pharmaceutical interventions to eliminate or suppress viral transmission. The rapid spread of respiratory viruses, various intervention approaches, and the global dissemination of SARS-CoV-2 underscore the necessity for epidemiological models that incorporate mobility to comprehend the spread of the virus. Here, we introduce a metapopulation susceptible exposed infectious recovered (SEIR) model parameterised with human movement data from 340 cities in China. Our model replicates the early case trajectory in the COVID-19 pandemic. We then use machine learning algorithms to determine which network properties best predict spread between cities and find travel time to be most important, followed by the human movement Weighted Personalised PageRank. However, we show that travel time is most influential locally, after which the high connectivity between cities reduces the impact of travel time between individual cities on transmission speed. Additionally, we demonstrate that only significantly reduced movement substantially impacts infection spread times throughout the network.

  🖺 Full Text HTML: High connectivity and human movement limits the impact of travel time on infectious disease transmission
• Integrating Mental Health and Psycho-Social Support (MHPSS) into infectious disease outbreak and epidemic response: an umbrella review and operational framework -

  Introduction Infectious disease outbreaks have a substantial impact on people9s psychosocial well-being. Yet, mental health and psychosocial support (MHPSS) interventions are not systemically integrated into outbreak and epidemic response. Our review aims to synthesise evidence on the effectiveness of MHPSS interventions in outbreaks and propose a framework for systematically integrating MHPSS into outbreak response. Methods We conducted an umbrella review in accordance with the Joanna Briggs Institute (JBI) methodology for umbrella reviews. Results We identified 23 systematic literature reviews, 6 of which involved meta-analysis, and only 30% (n=7) were of high quality. Most of the available literature was produced during COVID-19 and focused on clinical case management and medical staff well-being, with scarce evidence on the well-being of other outbreak responders and MHPSS in other outbreak response pillars. Conclusion Despite the low quality of the majority of the existing evidence, MHPSS interventions have the potential to improve the psychological well-being of those affected by and those responding to outbreaks. They also can improve the outcomes of the outbreak response activities such as contact tracing, infection prevention and control, and clinical case management. Our proposed framework would facilitate integrating MHPSS into outbreak response and hence mitigate the mental health impact of outbreaks. Review registration PROSPERO CRD42022297138.

  🖺 Full Text HTML: Integrating Mental Health and Psycho-Social Support (MHPSS) into infectious disease outbreak and epidemic response: an umbrella review and operational framework
• The Impact of Post Embryo Transfer SARS-CoV-2 Infection on Pregnancy in In Vitro Fertilization: A Prospective Cohort Study -

  Abstract Importance: Limited knowledge exists on the effects of SARS-CoV-2 infection after embryo transfer, despite an increasing number of studies exploring the impact of previous SARS-CoV-2 infection on IVF outcomes. Objective: This prospective cohort study aimed to assess the influence of SARS-CoV-2 infection at various time stages after embryo transfer on pregnancy outcomes in patients undergoing conventional in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI) treatment. Design: The study was conducted at a single public IVF center in China. Setting This was a population-based prospective cohort study. Participants: Female patients aged 20 to 39 years, with a body mass index (BMI) between 18 and 30 kg/m2, undergoing IVF/ICSI treatment, were enrolled from September 2022 to December 2022, with follow-up until March 2023. Exposure: The pregnancy outcome of patients was compared between those SARS-CoV-2-infected after embryo transfer and those noninfected during the follow-up period. Main Outcomes and Measures: The pregnancy outcomes included biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. Results: A total of 857 female patients undergoing IVF/ICSI treatment were included in the analysis. We observed the incidence of SARS-CoV-2 infection within 10 weeks after embryo transfer. The biochemical pregnancy rate and implantation rate were lower in the infected group than the uninfected group (58.1% vs 65.9%; 36.6% vs 44.0%, respectively), but no statistically significant. Although, the clinical pregnancy rate was significant lower in the infection group when compared with the uninfected group (49.1%vs 58.2%, p < 0.05), after adjustment for confounders, this increased risk was no longer significant between the two groups (adjusted OR, 0.736, 95% CI, 0.518-1.046). With continued follow-up, a slightly higher risk of early miscarriage in the infected group compared to the uninfected group (9.3% vs 8.8%), but it was not significant (adjusted OR, 0.907, 95% CI, 0.414-1.986). Conclusions and Relevance: The study9s findings suggested that SARS-CoV-2 infection within 10 weeks after embryo transfer may have not significantly affect pregnancy outcomes. This evidence allays concerns and provides valuable insights for assisted reproduction practices.

  🖺 Full Text HTML: The Impact of Post Embryo Transfer SARS-CoV-2 Infection on Pregnancy in In Vitro Fertilization: A Prospective Cohort Study
• Mask exposure during COVID-19 changes emotional face processing -
  Faces are one of the key ways that we obtain social information about others. They allow people to identify individuals, understand conversational cues, and make judgements about other’s mental states. When the COVID-19 pandemic hit the United States, widespread mask-wearing practices were implemented, causing a shift in the way Americans typically interact. This introduction of masks into social exchanges posed a potential challenge – how would people make these important inferences about others when a large source of information was no longer available? We conducted two studies that investigated the impact of mask exposure on emotion perception. In particular, we measured how participants used facial landmarks (visual cues) and the expressed valence and arousal (affective cues), to make similarity judgements about pairs of emotion faces. Study 1 found that participants with higher levels of mask exposure used cues from the eyes to a greater extent when judging emotion similarity than participants with less mask exposure. Study 2 measured participants’ emotion perception in both April and September 2020 – before and after widespread mask adoption – in the same group of participants to examine changes in the use of facial cues over time. Results revealed an overall increase in the use of visual cues from April to September. Further, as mask exposure increased, people with the most social interaction showed the largest increase in the use of visual facial cues. These results provide evidence that a shift has occurred in how people process faces such that the more people are interacting with others that are wearing masks, the more they have learned to focus on visual cues from the eye area of the face.
  🖺 Full Text HTML: Mask exposure during COVID-19 changes emotional face processing
• Scoring epidemiological forecasts on transformed scales -

  Forecast evaluation is essential for the development of predictive epidemic models and can inform their use for public health decision-making. Common scores to evaluate epidemiological forecasts are the Continuous Ranked Probability Score (CRPS) and the Weighted Interval Score (WIS), which can be seen as measures of the absolute distance between the forecast distribution and the observation. However, applying these scores directly to predicted and observed incidence counts may not be the most appropriate due to the exponential nature of epidemic processes and the varying magnitudes of observed values across space and time. In this paper, we argue that transforming counts before applying scores such as the CRPS or WIS can effectively mitigate these difficulties and yield epidemiologically meaningful and easily interpretable results. Using the CRPS on log-transformed values as an example, we list three attractive properties: Firstly, it can be interpreted as a probabilistic version of a relative error. Secondly, it reflects how well models predicted the time-varying epidemic growth rate. And lastly, using arguments on variance-stabilizing transformations, it can be shown that under the assumption of a quadratic mean-variance relationship, the logarithmic transformation leads to expected CRPS values which are independent of the order of magnitude of the predicted quantity. Applying a transformation of log(x + 1) to data and forecasts from the European COVID-19 Forecast Hub, we find that it changes model rankings regardless of stratification by forecast date, location or target types. Situations in which models missed the beginning of upward swings are more strongly emphasised while failing to predict a downturn following a peak is less severely penalised when scoring transformed forecasts as opposed to untransformed ones. We conclude that appropriate transformations, of which the natural logarithm is only one particularly attractive option, should be considered when assessing the performance of different models in the context of infectious disease incidence.

  🖺 Full Text HTML: Scoring epidemiological forecasts on transformed scales
• Prolonged exposure to lung-derived cytokines is associated with inflammatory activation of microglia in patients with COVID-19 -
  Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors of pneumonia from any cause have an elevated risk of dementia. Dysfunction in microglia, the primary immune cell in the brain, has been linked to cognitive impairment in murine models of dementia and in humans. Here, we report a transcriptional response in human microglia collected from patients who died following COVID-19 suggestive of their activation by TNF- and other circulating pro-inflammatory cytokines. Consistent with these findings, the levels of 55 alveolar and plasma cytokines were elevated in a cohort of 341 patients with respiratory failure, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. While peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, cumulative cytokine exposure was higher in patients with COVID-19. Corticosteroid treatment, which has been shown to be beneficial in patients with COVID-19, was associated with lower levels of CXCL10, CCL8, and CCL2 - molecules that sustain inflammatory circuits between alveolar macrophages harboring SARS-CoV-2 and activated T cells. These findings suggest that corticosteroids may break this cycle and decrease systemic exposure to lung-derived cytokines and inflammatory activation of microglia in patients with COVID-19.
  🖺 Full Text HTML: Prolonged exposure to lung-derived cytokines is associated with inflammatory activation of microglia in patients with COVID-19
• New design strategies for ultra-specific CRISPR-Cas13a-based RNA-diagnostic tools with single-nucleotide mismatch sensitivity -
  The pressing need for clinical diagnostics has required the development of novel nucleic acid-based detection technologies that are sensitive, fast, and inexpensive, and that can be deployed at point-of-care. Recently, the RNA-guided ribonuclease CRISPR-Cas13 has been successfully harnessed for such purposes. However, developing assays for detection of genetic variability, for example single-nucleotide polymorphisms, is still challenging and previously described design strategies are not always generalizable. Here, we expanded our characterization of LbuCas13a RNA-detection specificity by performing a combination of experimental RNA mismatch tolerance profiling, molecular dynamics simulations, protein, and crRNA engineering. We found certain positions in the crRNA-target-RNA duplex that are particularly sensitive to mismatches and establish the effect of RNA concentration in mismatch tolerance. Additionally, we determined that shortening the crRNA spacer or modifying the direct repeat of the crRNA leads to stricter specificities. Furthermore, we harnessed our understanding of LbuCas13a allosteric activation pathways through molecular dynamics and structure-guided engineering to develop novel Cas13a variants that display increased sensitivities to single-nucleotide mismatches. We deployed these Cas13a variants and crRNA design strategies to achieve superior discrimination of SARS-CoV-2 strains compared to wild-type LbuCas13a. Together, our work provides new design criteria and new Cas13a variants for easier-to-implement Cas13-based diagnostics.
  🖺 Full Text HTML: New design strategies for ultra-specific CRISPR-Cas13a-based RNA-diagnostic tools with single-nucleotide mismatch sensitivity
• Butyrate Protects against SARS-CoV-2-induced Tissue Damage in Golden Hamsters. -
  Butyrate, produced by gut microbe during dietary fiber fermentation, plays anti-inflammatory and antioxidant effects in chronic inflammation diseases, yet it remains to be explored whether butyrate has protective effects against viral infections. Here, we demonstrated that butyrate alleviated tissue injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected golden hamsters with supplementation of butyrate before and during the infection. Butyrate-treated hamsters showed augmentation of type I interferon (IFN) response and activation of endothelial cells without exaggerated inflammation. In addition, butyrate regulated redox homeostasis by enhancing the activity of superoxide dismutase (SOD) to inhibit excessive apoptotic cell death. Therefore, butyrate exhibited an effective prevention against SARS-CoV-2 by upregulating antiviral immune responses and promoting cell survival.
  🖺 Full Text HTML: Butyrate Protects against SARS-CoV-2-induced Tissue Damage in Golden Hamsters.
• Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells -
  SARS-CoV-2 is able to re-structure chromatin organization and alters the epigenomic landscape of the host genome, though the mechanisms that produce such changes are still poorly understood. Here, we investigate with polymer physics chromatin reorganization of the host genome, in space and time upon SARS-CoV-2 viral infection. We show that re-structuring of A/B compartments is well explained by a remodulation of intra-compartment homotypic affinities, which leads to the weakening of A-A interactions and enhances A-B mixing. At TAD level, re-arrangements are physically described by a general reduction of the loop extrusion activity coupled with an alteration of chromatin phase-separation properties, resulting in more intermingling between different TADs and spread in space of TADs themselves. In addition, the architecture of loci relevant to the antiviral interferon (IFN) response, such as DDX58 or IFIT, results more variable within the 3D single-molecule population of the infected model, suggesting that viral infection leads to a loss of chromatin structural specificity. Analysis of time trajectories of pairwise gene-enhancer and higher-order contacts reveals that such variability derives from a more fluctuating dynamics in infected case, suggesting that SARS-CoV-2 alters gene regulation by impacting the stability of the contact network in time. Overall, our study provides the first polymer-physics based 4D reconstruction of SARS-CoV-2 infected genome with mechanistic insights on the consequent gene misregulation.
  🖺 Full Text HTML: Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
• A nine-year investigation of industry payments to emergency physicians in the United States between 2013 and 2021 -

  Objectives To examine the characteristics and trends in the industry payments to emergency physicians since the inception of the Open Payments Database in 2013 and the COVID-19 pandemic in 2020. Methods Using the Open Payments Database between August 2013 and December 2021, this population based cohort study examined all research and general payments made by the healthcare industry to emergency physicians registered in the National Plan and Provider Enumeration System in the United States. We performed descriptive analyses on payment data and generalized estimating equations for payment trends. Results Among 50,483 active emergency physicians, 28,678 (56.8%) accepted a total of $457,640,796.73 payments from the healthcare industry between 2013 and 2021. 56.6% and 1.3% of all emergency physicians received general and research payments, respectively. 20.8% ($94.98 million) of overall industry payments were general payments. Median general and research payments per-physician (interquartile range) were $133.21 ($44.78-$355.77) and $62,842.97 ($10,320.00-$273,285.28), respectively. The top 1% of emergency physicians received 86.2% of overall general payments, respectively. The number of physicians receiving general payments decreased by 2.9% (95% CI: -3.2 to -2.5, p<0.001) annually between 2014 and 2019 and 47.8% (95% CI: -49.8 to -45.6, p<0.001) in 2020. Although there were no significant changes in research payments before the COVID-19 pandemic, the research payments significantly increased by 69.4% (95% CI: 28.9 to 122.7, p<0.001) in 2021 compared to those in 2020. Conclusions The majority of emergency physicians accepted general payments from the healthcare industry, but the number of emergency physicians accepting general payments significantly decreased since the inception of the Open Payments Database.

  🖺 Full Text HTML: A nine-year investigation of industry payments to emergency physicians in the United States between 2013 and 2021
• Industry payments to anesthesiologists in the United States between 2014 and 2022 -

  Background: Financial relationships between physicians and the healthcare industry could be beneficial to improve patient care, but could lead to conflicts of interest. However, there was no study specifically evaluating the extent of financial relationships between anesthesiologists and the healthcare industry in the United States. Methods Using the Open Payments Database between 2014 and 2022, this longitudinal cross-sectional study examined the size, prevalence and trends of general (non-research) payments made by the healthcare industry to all anesthesiologists in the United States. Results: Over the nine-year period, 67.0% of all anesthesiologists received general payments totaling $272.0 million over nine years, while 21.0% to 35.3% of anesthesiologists received one or more general payments each year. Median annual general payments to anesthesiologists ranged from $57 to $115. The top 1%, 5%, and 10% of anesthesiologists received 73.4%, 90.3%, and 94.8% of all general payments, respectively. There were no constant yearly trends in the total amounts and per-anesthesiologist general payments between 2014 and 2019, but significant declines occurred in 2020, likely due to the COVID-19 pandemic. Pain medicine physicians received the highest median general payments of $4,426 in nine-year combined total amounts, followed by addiction medicine ($431), critical care medicine ($277), and general anesthesiology ($256). Conclusion: This study reveals significant financial relationships between the healthcare industry and anesthesiologists, with a disproportionate concentration of payments among a minority of anesthesiologists. While no clear trends in payments were evident before the pandemic, there was a substantial reduction during the COVID-19 outbreak.

  🖺 Full Text HTML: Industry payments to anesthesiologists in the United States between 2014 and 2022
• Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents -

  Key to understanding COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Sex- and age-specific immune differences have a wide impact on outcomes from infections and immunisations. Typically, adult females make stronger immune responses and have better disease outcomes but suffer more adverse events following vaccination and are more prone to autoimmune disease. To understand better the mechanisms underlying these differences in vaccine responses, we studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n=34, ages 12-16), an age group previously shown to make significantly greater immune responses to the same vaccine compared to young adults. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine, which has been shown to induce stronger immune responses in adult females. Blood samples from 34 adolescents taken pre- and post-vaccination with COVID-19 and influenza vaccines were assayed for SARS-CoV-2-specific IgG and neutralising antibodies, and cellular immunity specific for SARS-CoV-2 and endemic betacoronaviruses. IgG targeting influenza lineages contained in the influenza vaccine was also assessed. As previously demonstrated, total IgG responses to SARS-CoV-2 Spike antigens were significantly higher among vaccinated adolescents compared to adults (aged 32-52) who received the BNT162b2 vaccine (comparing infection-naive, 49,696 vs 33,339; p=0.03; comparing SARS-CoV-2 previously-infected, 743,691 vs 269,985; p<0.0001) by MSD v-plex assay. However, unexpectedly, antibody responses to BNT162b2 and the live-attenuated influenza vaccine were not higher among female adolescents compared to males; among infection-naive adolescents, antibody responses to BNT162b2 were higher in males than females (62,270 vs 36,951 p=0.008). No sex difference was identified in vaccinated adults. These unexpected findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends, and providing new insights into what might be protective following COVID-19 vaccination.

  🖺 Full Text HTML: Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents
• WEIRD or not: A Cross-Cultural Behavioral Economic Assessment of Demand for HIV and COVID-19 Vaccines -

  Background: Despite empirical evidence supporting vaccine effectiveness, vaccine hesitancy continues to thrive. Demand as a behavioral economic process provides useful indices for evaluating vaccine acceptance likelihood in individuals and groups. Using this framework, our study investigates the dynamics governing vaccine acceptance in two culturally dissimilar countries. Methods: Hypothetical purchase tasks (HPTs) assessed how Nigerian and US participants varied vaccine acceptance as a function of hospitalization risks due to vaccination (N = 109). Aggregate and individual demand indices (Q0 and Pmax) were computed with nonlinear regressions. Secondary analyses were conducted using repeated measures ANOVAs with vaccine type (COVID-19 and HIV) as the within-subject factor; country, age, and socioeconomic status as between-subjects factors; demand indices served as dependent variables. Results: Demand indices varied significantly as a function of vaccine type (F(1, 57) = 17.609, p < .001, ηp2 = .236). Demand for HIV vaccines was higher relative to COVID-19 vaccines. Interactions between vaccine type and country of origin (F(1, 56) = 4.001, p = .05, ηp2 = .067) were also significant with demand for HIV vaccines among Nigerian respondents higher than that of COVID-19 vaccines. This was reversed for US participants. Interactions between vaccine type, country of origin and age were also significant (F(2, 51) = 3.506, p < .05, ηp2 = .121). Conclusions: These findings provide evidence that vaccine type can influence demand. The relationship between demand and vaccine type also varies as a function of country of origin and age. Significance, limitations, and future directions are also discussed.

  🖺 Full Text HTML: WEIRD or not: A Cross-Cultural Behavioral Economic Assessment of Demand for HIV and COVID-19 Vaccines
• Fight or Flight: Emergency Healthcare Workers Willingness to Work during Crises and Disasters: A cross-sectional multicentre study in the Netherlands -

  Objective: Expanding staff levels is a strategy for hospitals to increase surge capacity. This study aimed to evaluate whether emergency healthcare workers (HCWs) are willing to work (WTW) during a crises or disaster and which working conditions would influence their decision. Methods: HCWs of emergency departments (ED) and intensive care units (ICU) of five Dutch hospitals were surveyed about elevens disaster scenarios. For each scenario, HCWs were asked about their WTW and which conditions would influence their decision. Knowledge and perceived risk and danger was assessed per scenario. Results: 306/630 HCWs completed the survey. An influenza epidemic, SARS-CoV-2 pandemic and natural disaster were associated with highest WTW rates (69.0%, 63.7% and 53.3% respectively). WTW was lowest in nuclear incident (4.6%) and dirty bomb (3.3%) scenarios. WTW was higher in physicians than in nurses. Male ED HCWS, single HCWs and childless HCWs were more often WTW. Personal protective equipment (PPE) and safety of HCWs family were the most important working conditions. Perceived knowledge scored lowest in dirty bomb, biological and nuclear incident scenarios. These scenarios rated highest with regards to perceived danger. Conclusions: WTW depended on disaster type, profession and working department. Provision of PPE and safety of HCWs family were found to be predominant working conditions.

  🖺 Full Text HTML: Fight or Flight: Emergency Healthcare Workers Willingness to Work during Crises and Disasters: A cross-sectional multicentre study in the Netherlands

From Clinical Trials

• 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

• Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3) - Condition:   COVID-19
  Interventions:   Drug: theophylline;   Drug: Placebo
  Sponsor:   Washington University School of Medicine
  Recruiting

• Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition:   COVID-19
  Intervention:   Procedure: Lymph node aspiration / Blood sampling
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Recruiting

• COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults - Condition:   Covid19
  Interventions:   Biological: MVA-SARS-2-S;   Other: Placebo
  Sponsors:   Universitätsklinikum Hamburg-Eppendorf;   German Center for Infection Research;   Philipps University Marburg Medical Center;   Ludwig-Maximilians - University of Munich;   University Hospital Tuebingen;   CTC-NORTH
  Withdrawn

• Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome - Conditions:   Fatigue;   Post-Acute COVID-19 Syndrome
  Intervention:   Procedure: Immunoadsorption vs. sham immunoadsorption
  Sponsor:   Hannover Medical School
  Not yet recruiting

• Non-ventilated Prone Positioning in the COVID-19 Population - Conditions:   COVID-19;   Proning;   Oxygenation;   Length of Stay
  Interventions:   Other: Proning group;   Other: Control group
  Sponsor:   Baylor St. Luke’s Medical Center
  Completed

• 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

• Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS). - Conditions:   Post-Acute COVID-19 Syndrome;   Cognitive Impairment;   Neurological Complication
  Intervention:   Drug: VIX001
  Sponsor:   Neobiosis, LLC
  Not yet recruiting

• A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition:   SARS-CoV-2
  Interventions:   Biological: CV0701 Bivalent High dose;   Biological: CV0701 Bivalent Medium dose;   Biological: CV0701 Bivalent Low dose;   Biological: CV0601 Monovalent High dose;   Biological: Control vaccine
  Sponsors:   GlaxoSmithKline;   CureVac
  Not yet recruiting

• PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition:   SARS-CoV-2
  Interventions:   Drug: Upamostat;   Drug: Placebo (PO)
  Sponsors:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited
  Not yet recruiting

• A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression - Conditions:   COVID 19 Disease;   Mild to Moderate COVID 19 Disease;   SARS-CoV-2;   Infectious Disease;   Severe Acute Respiratory Syndrome Coronavirus 2
  Interventions:   Drug: Tafenoquine Oral Tablet;   Drug: Placebo
  Sponsor:   60P Australia Pty Ltd
  Not yet recruiting

• Impact of COVID-19 on Sinus Augmentation Surgery - Condition:   Bone Loss
  Interventions:   Procedure: Sinus lift in patients with positive COVID-19 history;   Procedure: Sinus lift with negative COVID-19 history
  Sponsor:   Cairo University
  Completed

• Expressive Interviewing Agents to Support Health-Related Behavior Change - Condition:   Mental Stress
  Intervention:   Other: Expressive Interviewing
  Sponsors:   University of Michigan;   University of Texas at Austin
  Completed

• Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine Coadministered With Two Attenuated Vaccines - Conditions:   SARS-CoV-2 Infection;   Varicella;   Measles;   Mumps;   Rubella
  Interventions:   Biological: Inactivated SARS-CoV-2 vaccine coadministered with vricella vaccine;   Biological: Inactivated SARS-CoV-2 vaccine coadministered with MMR;   Biological: Inactivated SARS-CoV-2 vaccine administered alone
  Sponsors:   Shanghai Municipal Center for Disease Control and Prevention;   China National Biotec Group Company Limited
  Not yet recruiting

• Impact of Breathing Exercises and Meditation on Improving Quality of Life in Glaucoma Patients - Conditions:   Glaucoma;   Depression;   Anxiety;   Quality of Life;   Sleep Disorder
  Intervention:   Behavioral: Breathing Exercises followed by Meditation
  Sponsor:   Lawson Health Research Institute
  Not yet recruiting

From PubMed

• PARP14 is a writer, reader and eraser of mono-ADP-ribosylation - PARP14/BAL2 is a large multidomain enzyme involved in signaling pathways with relevance to cancer, inflammation, and infection. Inhibition of its mono-ADP-ribosylating PARP homology domain and its three ADP-ribosyl binding macro domains has been regarded as a potential means of therapeutic intervention. Macrodomains-2 and -3 are known to stably bind to ADP-ribosylated target proteins; but the function of macrodomain-1 has remained somewhat elusive. Here, we used biochemical assays of…

• Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques - Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous…

• Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile; in silico and in virto assessments with structure-activity relationship - The proteolytic enzyme 3 C-like protease (3Clpro or M^(pro)) is considered the most important target for SARS-CoV-2 which could be attributed to its crucial role in viral maturation and/or replication. Besides, natural phytoconstituents from plant origin are always promising lead compounds in the drug discovery area. Herein, the previously isolated and identified seven compounds from Jasminum humile (J. humile) were examined in vitro and in silico against the SARS-CoV-2 M^(pro). First, the Vero…

• Structural Transitions of Papain-like Cysteine Proteases: Implications for Sensor Development - The significant role of papain-like cysteine proteases, including papain, cathepsin L and SARS-CoV-2 PLpro, in biomedicine and biotechnology makes them interesting model systems for sensor development. These enzymes have a free thiol group that is suitable for many sensor designs including strong binding to gold nanoparticles or low-molecular-weight inhibitors. Focusing on the importance of the preservation of native protein structure for inhibitor-binding and molecular-imprinting, which has…

• SARS-CoV-2 NSP1 induces mRNA cleavages on the ribosome - In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to the mRNA entry channel of the ribosome and, together with the 5’-untranslated region (UTR) of the viral mRNAs, allows the evasion of that inhibition. Here, we show that NSP1 mediates endonucleolytic cleavages of both host and viral mRNAs in the 5’UTR, but with different cleavage patterns. The first pattern is observed in host mRNAs with cleavages…

• Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors - Emerging variants of concern of SARS-CoV-2 can significantly reduce the prophylactic and therapeutic efficacy of vaccines and neutralizing antibodies due to mutations in the viral genome. Targeting cell host factors required for infection provides a complementary strategy to overcome this problem since the host genome is less susceptible to variation during the life span of infection. The enzymatic activities of the endosomal PIKfyve phosphoinositide kinase and the serine protease TMPRSS2 are…

• Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease - Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by…

• Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial - CONCLUSION: In patients with COVID-19 and in need of ventilatory support, the use of cyproheptadine plus usual care, compared with usual care alone, did not increase the number of ventilatory support-free days in 28 days.

• Potential pharmacokinetic interactions with concurrent use of herbal medicines and a ritonavir-boosted COVID-19 protease inhibitor in low and middle-income countries - The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, nirmatrelvir/ritonavir (Paxlovid™) fixed-dose combination is recommended by the World Health Organization for treatment of COVID-19. The ritonavir component is an inhibitor of cytochrome P450 (CYP) 3A, which is used in this combination to achieve needed…

• Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation - The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly…

• Computational analysis of spike protein of SARS-CoV-2 (Omicron variant) for development of peptide-based therapeutics and diagnostics - In the last few years, the worldwide population has suffered from the SARS-CoV-2 pandemic. The WHO dashboard indicated that around 504,079,039 people were infected and 6,204,155 died from COVID-19 caused by different variants of SARS-CoV-2. Recently, a new variant of SARS-CoV-2 (B.1.1.529) was reported by South Africa known as Omicron. The high transmissibility rate and resistance towards available anti-SARS-CoV-2 drugs/vaccines/monoclonal antibodies, make Omicron a variant of concern. Because…

• A case of T-cell-Epstein-Barr virus-haemophagocytic lymphohistiocytosis and sustained remission following ruxolitinib therapy - CONCLUSION: EBV viraemia requires adequate treatment to control EBV-associated HLH as rituximab may be insufficient, and corticosteroid resistance can result in continued EBV infection in CD8^(+) T cells. This entity is known as T-cell-EBV-HLH. Ruxolitinib is a novel treatment strategy in this specific context and has several advantages, including inhibition of corticosteroid resistance to promote apoptosis of EBV-infected T cells.

• Neuroimaging findings in adolescent gaming disorder: a systematic review - CONCLUSIONS: A number of key brain regions are affected in adolescent gaming disorder. These findings can help clinicians understand adolescent presentations with gaming disorder from a neurobiological perspective. Future studies should focus on forming a robust neurobiological and clinical framework for adolescent gaming disorder.

• A high-throughput screening system for SARS-CoV-2 entry inhibition, syncytia formation and cell toxicity - CONCLUSION: A BSL-2 compatible assay system that is equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effects on syncytia. Studies using clinical isolates of SARS-CoV-2 are warranted to confirm the antiviral potency of the leads and the utility of the screening system.

• Rapid genetic screening with high quality factor metasurfaces - Genetic analysis methods are foundational to advancing personalized medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) rely on sample amplification and can suffer from inhibition. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with nucleic acid fragments….

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