Human saliva contains a plethora of proteins whose presence and concentration can be monitored for diagnosis and progression of disease. Saliva has been extensively probed for the diagnosis of several systemic and infectious diseases because of the ease with which it can be collected. However, amylase, the most abundant protein found in saliva can obscure the detection of low-abundance proteins by MALDI-ToF MS (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) and diminish the diagnostic utility of this specimen type. In the present study, we used a device to deplete salivary amylase from water-gargle samples through affinity adsorption. After depletion, profiling of the saliva proteome was performed by MALDI-ToF MS on gargle samples from subjects whose COVID-19 (coronavirus disease 2019) status was confirmed by NP (nasopharyngeal) swab RT-qPCR (reverse transcription polymerase chain reaction). Amylase depletion led to the enhancement of signal intensities of various peaks as well as the detection of previously unobserved peaks in the MALDI-ToF spectra. The overall specificity and sensitivity after amylase depletion was 100% and 85.17% respectively for detecting COVID-19. Our simple, rapid and inexpensive technique to deplete salivary amylase can be used to unmask spectral diversity in saliva by MALDI-ToF MS, reveal low-abundant proteins and aid in the establishment of novel biomarkers for diseases.
Abstract: Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial showing lower mortality by warming afebrile sepsis patients in the intensive care unit. The objective of this prospective single-site randomized controlled trial was to determine if core warming improves respiratory physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean BMI 34.5 (±5.9) kg/m2 with COVID-19 requiring mechanical ventilation were enrolled from September 2020 through February 2022. Patients were randomized 1:1 to standard-of-care or to receive core warming for 72 hours via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The maximum target temperature was 39.8 °C. A total of 10 patients received usual care and 9 patients received esophageal core warming. After 72 hours of warming, PaO2/FiO2 ratios were 197 (±32) and 134 (±13.4), Cycle Thresholds were 30.8 (±6.4) and 31.4 (±3.2), ICU mortality was 40% and 44%, 30-day mortality was 30% and 22%, and mean 30-day ventilator-free days were 11.9 (±12.6) and 6.8 (±10.2) for standard-of-care and warmed patients, respectively (p=NS). This pilot study suggests that core warming of patients with COVID-19 undergoing mechanical ventilation is feasible and appears safe. Optimizing time to achieve febrile-range temperature may require a multimodal temperature management strategy to further evaluate effects on outcome.
Introduction: Development of drug prescription skills poses critical challenges in medical education. This study determined the effects of simulated interviews on the improvement of drug prescription skills among medical students in 2020. Methodology: This was a quantitative, cross-sectional, analytical, quasi-experimental study of simulated interviews for improving rational drug prescription skills in medical students. Baseline, pre-, and post-intervention assessments of prescription skills were performed using an expert-validated instrument constructed from the WHO Good Prescribing Guide. Three simulated interviews with different simulated patients were conducted in two groups: in-person in the first batch and remotely in the second batch due to mandatory social distancing during the Covid-19 pandemics. Friedman, Dunn-Bonferroni, and Wilcoxon tests were used, considering a significance of level p<.05 and standardized mean difference (Hedges g); data were analyzed using Excel 2016 and SPSS 28. Results: Fifty-four students completed the required assessments; in-person 28 and remotely 26. The total score for pharmacological prescription skills increased significantly from pre- to post-intervention measurements, from 12.72 +/- 2.94 to 15.44 +/- 2.50, respectively (p<.0001) (g: 0.996), and the increase from baseline to post-intervention scores for drug prescription knowledge was 5.39 +/- 3.67, 11.28 +/- 3.50, respectively (p <.01). Discussion: Our results suggest that the implementation of pre-briefing and debriefing strategies in remote and in-person clinical interviews with simulated patients significantly improved drug prescription skills and pharmacological knowledge among medical students. The logical sequence of the WHO Guide for Good Prescribing may have facilitated debriefing, knowledge acquisition, and transfer to various clinical contexts.
Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred related to difficulties with: 1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and 2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by 1) adding additional study sites, 2) increasing the frequency of meetings with site coordinators and 3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.
Intranasal sprays containing Bacillus species are being researched for treating viral respiratory tract infections. The aim of this study was to assess the relationship between the nasal carriage of Bacillus and COVID-19 severity. This was a cross-sectional study that collected nasopharyngeal samples from adults 18 years and above visiting two COVID-19 testing centers in Lagos, Nigeria between September 2020 and September 2021. Bacillus species were cultured from the respiratory samples and confirmed using molecular methods. The dependent variable was COVID-19 status classified as negative, asymptomatic, mild, or severe. The independent variable was the nasal carriage of Bacillus species. Multinomial regression analysis was done to determine the association between nasal carriage of Bacillus and COVID-19 severity after adjusting for age, sex, and co-morbidity status. About 388 participants were included in the study with a mean (standard deviation) age of 40.05 (13.563) years. The majority (61.1%) of the participants were male, 100 (25.8%) had severe COVID-19, 130 (33.5%) had pre-existing comorbidity, and 76 (19.6%) had Bacillus cultured from their nasopharyngeal specimen. Bacillus species presence was significantly associated with higher odds of severe COVID-19 compared to having a negative COVID-19 status. However, the presence of Bacillus species was significantly associated with lower odds of severe COVID-19 compared to having a mild COVID-19 status. The study suggests that nasal carriage of Bacillus species may substantially impact the clinical course of COVID-19. This study supports the exploration of Bacillus species in the prevention and management of viral respiratory tract infections.
Background: Besides major employment disruptions, the COVID-19 pandemic has generated policy responses with specific mechanisms to protect workers9 health. In Belgium, most of these policies were negotiated at national and cross-sectorial level but implemented at company level with company-based collective negotiation playing a key role. This study examines the relationship between trade union representatives9 perception of social dialogue quality and change in workers9 physical and mental health in such a context. Methods: Union representatives were surveyed throughout Belgium between August and December 2021 through an online questionnaire (N=469). We asked about the way they perceived workers9 physical and mental health within their companies and explain variations with the self-perceived change in quality of social dialogue as an exposure. We use a modified Poisson regression for binary outcomes on four stratified models that additively account for no control, company characteristics, pre-pandemic self-reported health and COVID-19-related measures. Weights are generated to ensure sector representativeness. Results: 30.1% of the sample reported a worsening social dialogue quality during the pandemic. Relative Risks (RR) of poor physical and mental health when social dialogue has worsened are respectively 1.49 [95%CI:1.03; 2.15] and 1.38 [95%CI= 1.09;1.74] when controlling for company characteristics and pre-pandemic health. Adding pandemic-related measures reduces the risk of both poor mental [RR=1.25; 95%CI: 0.84; 1.87] and physical health [RR=1.18; 95%CI:0.94;1.49]. Conclusions: Although based on self-reported variables, the study shows an association between poor social dialogue quality and poor physical and mental health during the COVID-19 pandemic that must be explored further in post-pandemic context.
Background: Evidence from population-based studies on the impact of post COVID-19 condition (PCC) on ability to work is limited but critical due to its high prevalence among individuals of working-age. Objective: To evaluate the association between PCC, work ability, and occupational changes. Design: Population-based, longitudinal cohort. Setting: General population, Canton of Zurich, Switzerland. Participants: 672 adults of working-age with SARS-CoV-2 infection. Measurements: Current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), as well as PCC-related occupational changes at one year after infection. Results: There was very strong evidence that current work ability scores were 0.62 (95% confidence interval (CI) 0.30 to 0.95) points lower among those with PCC compared to those without. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (odds ratio (OR) 0.30, 95% CI 0.20 to 0.46) and mental (OR 0.40, 0.27 to 0.62) demands among those with PCC compared to those without. Higher age and history of psychiatric diagnosis were associated with a more substantial reduction in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce and 43% of those with PCC-related occupational changes reporting financial difficulties as a result. Limitations: Selection, use of self-reported outcome measures, and limited generalizability to individuals with most severe COVID-19 or following vaccination. Conclusions: These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity. Primary Funding Source: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland. Study Registration: ISRCTN14990068.
COVID-19 affects a variety of organs and systems of the body including the central nervous system. Recent research has shown that COVID-19 survivors often experience neurological and psychological complications that can last for months after infection. We conducted a large internet study using online tests to analyze the effects of SARS-CoV-2 infection, COVID-19 severity, and vaccination on health, intelligence, memory, and information processing precision and speed in a cohort of 4,446 subjects. We found that both SARS-CoV-2 infection and COVID-19 severity were associated with negative impacts on patients9 health. Furthermore, we observed a negative association between COVID-19 severity and cognitive performance. Younger participants had a higher likelihood of SARS-CoV-2 contraction, while the elderly had a higher likelihood of severe COVID-19 and vaccination. The association between age and COVID-19 severity was primarily mediated by older participants9 impaired long-term health. Vaccination was positively associated with intelligence and the precision of information processing. However, the positive association between vaccination and intelligence was likely mediated by achieved education, which was itself strongly associated with the likelihood of being vaccinated.
During the COVID-19 pandemic, concerns were raised that face covering use may elicit risk compensation; a false sense of security resulting in reduced adherence to other protective behaviours such as physical distancing. This systematic review aimed to investigate the effect of face covering use on adherence to other COVID-19 related protective behaviours. Medline, Embase, PsychInfo, EmCare, medRxiv preprints, Research Square and WHO COVID-19 Research Database were searched. All primary research studies published from 1 January 2020 to 17th May 2022 which investigated the effect of face covering use on adherence to other protective behaviours in public settings during the COVID-19 pandemic were included. Papers were selected and screened in accordance with the PRISMA framework. Backwards and forwards citation searches of included papers were also conducted on 16th September 2022, with eligible papers published between 1st January 2020 and that date being included. A quality appraisal including risk of bias was assessed using the Academy of Nutrition and Dietetics’ Quality Criteria Checklist. This review is registered on PROSPERO, number CRD42022331961. 47 papers were included, with quality ranging from low to high. These papers investigated the effects of face covering use and face covering policies on adherence to six categories of behaviour: physical distancing; mobility; face-touching; hand hygiene; close contacts; and generalised protective behaviour. Results reveal no consistent evidence for or against risk compensation, with findings varying according to behaviour and across study types. There is a suggestion that face covering use might reduce face-touching and face covering mandates might increase mobility, though the lack of robust evidence means these are tentative claims. Evidence on the other protective behaviours is largely inconsistent, and therefore confident conclusions cannot be made in these areas. Any policy decisions related to face coverings must consider the inconsistencies and caveats in this evidence base.
Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 ) - Condition: COVID-19
Interventions: Drug: Standard of Care + Quinine Sulfate; Drug: Standard of Care
Sponsors: Universitas Padjadjaran; National Research and Innovation Agency of Indonesia; Prodia Diacro Laboratories P.T.
Recruiting
Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19 - Condition: Long COVID-19 Syndrome
Intervention: Biological: MSC-derived exosomes
Sponsors: Huazhong University of Science and Technology; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.
Recruiting
Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19 - Condition: Omicron Variant of COVID-19
Intervention: Drug: Nirmatrelvir/Ritonavir
Sponsor: Xiangao Jiang
Completed
A Nasal Treatment for COVID-19 - Condition: COVID-19
Interventions: Drug: Optate; Drug: Placebo
Sponsor: Indiana University
Not yet recruiting
A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 - Condition: COVID-19
Interventions: Biological: mRNA-1283.222; Biological: mRNA-1273.222
Sponsor: ModernaTX, Inc.
Recruiting
To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae - Condition: COVID-19
Interventions: Biological: Meplazumab for injection; Other: Normal saline
Sponsor: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Recruiting
Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19 - Condition: COVID-19
Interventions: Device: RD-X19; Device: Sham
Sponsor: EmitBio Inc.
Recruiting
Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities - Condition: COVID-19
Interventions: Drug: Ropeginterferon alfa-2b; Procedure: SOC
Sponsor: National Taiwan University Hospital
Not yet recruiting
Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes. - Condition: COVID-19
Interventions: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation
Active, not recruiting
Postoperative Sugammadex After COVID-19 - Conditions: General Anesthesia; COVID-19
Interventions: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg
Sponsor: Korea University Ansan Hospital
Not yet recruiting
A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19
Interventions: Drug: Azeliragon; Drug: Placebo
Sponsor: Salim S. Hayek
Recruiting
Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants - Condition: COVID19 Testing
Interventions: Behavioral: FABI tailored COVID-19 testing pamphlet; Behavioral: Standard COVID-19 home-based test kit
Sponsors: Texas Woman’s University; National Institutes of Health (NIH)
Not yet recruiting
Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual
Sponsor: Universität Duisburg-Essen
Not yet recruiting
A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized. - Condition: SARS-CoV-2 Infection
Interventions: Drug: PF-07817883; Drug: Placebo
Sponsor: Pfizer
Not yet recruiting
Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors - Condition: Post Acute COVID-19 Syndrome
Intervention: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)
Sponsor: Azienda Socio Sanitaria Territoriale di Lecco
Recruiting
Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding - RPS3, a universal core component of the 40S ribosomal subunit, interacts with mRNA at the entry channel. Whether RPS3 mRNA-binding contributes to specific mRNA translation and ribosome specialization in mammalian cells is unknown. Here we mutated RPS3 mRNA-contacting residues R116, R146 and K148 and report their impact on cellular and viral translation. R116D weakened cap-proximal initiation and promoted leaky scanning, while R146D had the opposite effect. Additionally, R146D and K148D displayed…
Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors - Among the various genes and proteins encoded by all coronaviruses, one particularly “druggable” or relatively easy-to-drug target is the coronavirus Main Protease (3CLproor Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small-molecule antiviral would effectively stop the ability of the virus to replicate,…
Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration - CONCLUSIONS: Esculin inhibits β(2) integrin-dependent neutrophil migration and chemotaxis, blocks the cytoskeletal remodeling process required for neutrophil recruitment, thereby contributing to its protective effect against ALI. This study demonstrates the new therapeutic potential of esculin as a novel lead compound.
FDA approved drugs with antiviral activity against SARS-CoV-2: From structure-based repurposing to host-specific mechanisms - The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and…
4’-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses - Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4’-Fluorouridine (4’-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza…
Detection of pre-existing neutralizing antibodies against Ad26 in HIV-1-infected individuals not responding to the Ad26.COV2.S vaccine - CONCLUSION: Ad26.COV2.S vaccination showed a high failure rate in HIV-1-infected patients. Pre-existing immunity against Ad26 could be an important contributor to poor vaccine efficacy in a subgroup of patients.
Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 and type 1 diabetes - Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory…
Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region - One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new coumarin derivative C30 that binds to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical…
Human Surfactant Protein A Alleviates SARS-CoV-2 Infectivity in Human Lung Epithelial Cells - SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity. The interactions…
Role of C-Reactive Protein in Kidney Diseases - BACKGROUND: C-reactive protein (CRP) is an acute-phase protein and has been found to be a risk factor for acute kidney injury (AKI) and chronic kidney diseases (CKD). However, the role and mechanisms of CRP in AKI and CKD remain largely unclear.
An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha) - Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000 years. It is a rich reservoir of pharmaceutically bioactive constituents known as withanolides (a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton). Most of the biological activities of W….
Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV - Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV….
SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors - Virus entry into animal cells is initiated by attachment to target macromolecules located on host cells. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trimeric spike glycoprotein targets host angiotensin converting enzyme 2 to gain cellular access. The SARS-CoV-2 glycoprotein contains a neurotoxin-like region that has sequence similarities to the rabies virus and the human immunodeficiency virus glycoproteins, as well as to snake neurotoxins, which interact with nicotinic…
Pathological angiogenesis: mechanisms and therapeutic strategies - In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and…
A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases - AbstractSARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analog, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for…