Covid-19 Sentry

Contents

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

From Preprints

• VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis -
  The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via non-integrative and safe nucleoside-modified mRNA encapsulated into lipid-nanoparticles (mRNA-LNP) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and reversion of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals novel therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.
  🖺 Full Text HTML: VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis
• Growth Hormone Accelerates Recovery From Acetaminophen-Induced Murine Liver Injury -
  Background and Aims: Acetaminophen (APAP) overdose is the leading cause of acute liver failure, with one available treatment, N-acetyl cysteine (NAC). Yet, NAC effectiveness diminishes about ten hours after APAP overdose, urging for therapeutic alternatives. This study addresses this need by deciphering a mechanism of sexual dimorphism in APAP-induced liver injury, and leveraging it to accelerate liver recovery via growth hormone (GH) treatment. GH secretory patterns, pulsatile in males and near-continuous in females, determine the sex bias in many liver metabolic functions. Here, we aim to establish GH as a novel therapy to treat APAP hepatotoxicity. Approach and Results: Our results demonstrate sex-dependent APAP toxicity, with females showing reduced liver cell death and faster recovery than males. Single-cell RNA sequencing analyses reveal that female hepatocytes have significantly greater levels of GH receptor expression and GH pathway activation compared to males. In harnessing this female-specific advantage, we demonstrate that a single injection of recombinant human GH protein accelerates liver recovery, promotes survival in males following sub-lethal dose of APAP, and is superior to standard-of-care NAC. Alternatively, slow-release delivery of human GH via the safe non-integrative lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP), a technology validated by widely used COVID-19 vaccines, rescues males from APAP-induced death that otherwise occurred in control mRNA-LNP-treated mice. Conclusions: Our study demonstrates a sexually dimorphic liver repair advantage in females following APAP overdose, leveraged by establishing GH as an alternative treatment, delivered either as recombinant protein or mRNA-LNP, to potentially prevent liver failure and liver transplant in APAP-overdosed patients.
  🖺 Full Text HTML: Growth Hormone Accelerates Recovery From Acetaminophen-Induced Murine Liver Injury
• A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity -
  An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 and 8 ({triangleup}3678) was previously reported to protect hamsters from SARS-CoV-2 infection and transmission. Here we report that a single-dose intranasal vaccination of {triangleup}3678 protects K18-hACE2 mice from wild-type or variant SARS-CoV-2 challenge. Compared with wild-type virus infection, the {triangleup}3678 vaccination induces equivalent or higher levels of lung and systemic T cell, B cell, IgA, and IgG responses. The results suggest {triangleup}3678 as an attractive mucosal vaccine candidate to boost pulmonary immunity against SARS-CoV-2.
  🖺 Full Text HTML: A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity
• Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection -
  SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel amino acid mutations in the spike protein alone. While most studies focus on the impact of receptor binding domain changes, mutations in the C-terminal of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replication in vitro and less disease in vivo. Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Together, the data show that N679K is a loss-of-function mutation reducing overall spike levels during omicron infection, which may have important implications for disease severity, immunity, and vaccine efficacy.
  🖺 Full Text HTML: Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection
• A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo -
  Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the therapeutic potential of Mac1 inhibition, we generated recombinant viruses and replicons encoding catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site. While substitution to alanine (N40A) reduced activity by ~10-fold, mutations to aspartic acid (N40D) reduced the catalytic activity by ~100-fold relative to wildtype activity. Importantly, the N40A mutation rendered Mac1 unstable in vitro and lowered expression levels in bacterial and mammalian cells. When incorporated into SARS-CoV-2 molecular clones, the N40D mutant only modestly affected viral fitness in immortalized cell lines, but reduced viral replication in human airway organoids by 10-fold. In mice, N40D replicated at >1000-fold lower levels while inducing a robust interferon response, and all infected animals survived infection with the mutant, but not the wildtype virus. Our data validate SARS-CoV-2 NSP3 Mac1 domain as a critical viral pathogenesis factor and a reasonable target to develop antivirals, while emphasizing the importance of amino acid identity in viral mutagenesis studies and underscoring the limitations of solely relying on in vitro viral replication studies for target validation.
  🖺 Full Text HTML: A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo
• A national audit of pancreatic enzyme prescribing in pancreatic cancer from 2015 to 2023 in England using OpenSAFELY-TPP -

  Objectives: Cancer treatments were variably disrupted during the COVID-19 pandemic. UK guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. The aim was to investigate the impact of COVID-19 on PERT prescribing to people with unresectable pancreatic cancer and to investigate the national and regional rates from January 2015 to January 2023. Data sources: With the approval of NHS England, we conducted this study using 24 million electronic healthcare records of people within the OpenSAFELY-TPP research platform. There were 22,860 people diagnosed with pancreatic cancer in the study cohort. We visualised the trends over time and modelled the effect of COVID-19 with the interrupted time series analysis. Conclusions: In contrast to many other treatments, prescribing of PERT was not affected during the pandemic. Overall, since 2015, the rates increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in early 2023. There was substantial regional variation with the highest rates of 50% to 60% in West Midlands. Implications for Nursing Practice: In pancreatic cancer, if PERT is prescribed, it is usually initiated in hospitals by clinical nurse specialists and continued after discharge by primary care. At just under 50% in early 2023, the rates were still below the recommended 100% standard. More research is needed to understand barriers to prescribing of PERT and geographic variation to improve quality of care. Prior work relied on manual audits. With OpenSAFELY, we developed an automated audit allowing for regular updates.

  🖺 Full Text HTML: A national audit of pancreatic enzyme prescribing in pancreatic cancer from 2015 to 2023 in England using OpenSAFELY-TPP
• Mental Health, Substance Use, and the Importance of Religion during the COVID-19 Pandemic -

  COVID-19 has impacted all areas of life, with lasting effects on physical, mental, and societal health. Specifically, COVID and related losses have exacerbated prolonged grief responses and mental disorders including depression and anxiety. These mental health concerns are associated with increased detrimental coping strategies including substance use. In this study, we analyzed secondary data from the National Survey on Drug Use and Health (NSDUH) collected during the COVID-19 pandemic. Our results showed a positive association between serious psychological distress and marijuana use, while frequent religious service attendance acted as a moderator in this relationship. Individuals involved in communal religious activity were less likely to use marijuana. This study highlights the impact of religion and faith in bringing hope and purpose during periods of loss, coping with stress, grief, mental health challenges, and substance use.

  🖺 Full Text HTML: Mental Health, Substance Use, and the Importance of Religion during the COVID-19 Pandemic
• A compartmental Mathematical model of COVID-19 intervention scenarios for Mumbai -

  A new mathematical method with an outstanding potential to predict the incidence of COVID-19 diseases has been proposed. The model proposed is an improvement to the SEIR model. In order to improve the basic understanding of disease spread and outcomes, four compartments included presymptomatic, asymptomatic, quarantine hospitalized and hospitalized. We have studied COVID-19 cases in the city of Mumbai. We first gather clinical details and fit it on death cases using the Lavenberg-Marquardt model to approximate the various parameters. The model uses logistic regression to calculate the basic reproduction number over time and the case fatality rate based on the age-category scenario of the city of Mumbai. Two types of case fatality rate are calculated by the model: one is CFR daily, and the other is total CFR. The total case fatality rate is 4.2, which is almost the same as the actual scenario. The proposed model predicts the approximate time when the disease is at its worst and the approximate time when death cases barely arise and determines how many hospital beds in the peak days of infection would be expected. The proposed model outperforms the classic ARX, SARIMAX and the ARIMA model. And It also outperforms the deep learning models LSTM and Seq2Seq model. To validate results, RMSE, MAPE and R squared matrices are used and are represented using Taylor diagrams graphically.

  🖺 Full Text HTML: A compartmental Mathematical model of COVID-19 intervention scenarios for Mumbai
• The beneficial role of Candida intermedia and Saccharomyces boulardii yeasts on the immune response of mice vaccinated with a SARS-CoV-2 experimental vaccine -
  Non-Saccharomyces yeasts emerge as possible new probiotics with a beneficial effect equal to or greater than the reference probiotic yeast, Saccharomyces boulardii. In this work, we evaluated the immunomodulation effect caused by Candida intermedia in mice vaccinated with inactivated SARS-CoV-2. We conducted preliminary tests using murine macrophages (RAW 264.7) stimulated with viable and heat-killed yeast cells, culture supernatant, and DNA, using qPCR to detect the mRNA transcription. Next, mice were supplemented with C. intermedia before each dose of the SARS-CoV-2 vaccine, and then antibody production was measured by ELISA. The probiotic strain S. boulardii CNCM I-745 was used as a control. We also explored the differences in fecal microbiomes between the non-supplemented and supplemented groups. Live cells of C. intermedia increased the transcription of IL-4, IL-13, and STAT3 by macrophages RAW 264.7, while heat-killed cells up-regulated TNF and Bcl6, and the culture supernatant positively impacted TLR2 transcription. Concanavalin, zymosan, and lipopolysaccharide were used to stimulate splenocytes from C. intermedia-supplemented animals, which showed increased transcription of TNF, IFN{gamma}, IL-4, Bcl6, and STAT3. Sera from these animals showed enhanced levels of anti-SARS-CoV-2 IgG, as well as IgG1 and IgM isotypes, and sIgA in fecal samples. The microbiome of the C. intermedia-supplemented group showed a higher abundance of Bacteroides spp. and Clostridium spp., impacting the Bacteroidetes/Firmicutes balance. We concluded that C. intermedia and S. boulardii could stimulate and impact the gene expression of cells important for innate immunity, influence the composition of the gastrointestinal microbiome, and primarily boost the humoral response after vaccination.
  🖺 Full Text HTML: The beneficial role of Candida intermedia and Saccharomyces boulardii yeasts on the immune response of mice vaccinated with a SARS-CoV-2 experimental vaccine
• Effect of Yoga on the Stress, Anxiety, and Depression of COVID-19-Positive Patients. A Quasi-Randomized Controlled Study. International Journal of Yoga therapy 2022 (32) -
  The spread of COVID-19 has resulted in reports of an increase in stress, anxiety, and depression across society, especially in people who have tested positive for COVID-19, which affects their mental health and well-being. This article reports a quasi-randomized controlled study conducted in the COVID wards of a hospital to examine the efficacy of add-on yoga intervention in reducing stress, anxiety, and depression in COVID-affected patients under quarantine. The peripheral capillary oxygen saturation level and heart rate of the COVID-19-affected patients were also measured. A total of 62 COVID-19-positive patients participated in the study. The participants were randomized into a control group (n = 31), which received conventional medical treatment alone, and a yoga intervention group (n = 31), which received 50 minutes of yoga intervention along with the conventional medical treatment. Standardized Hospital Anxiety and Depression Scale, Generalized Anxiety Disorder–7 Item, Patient Health Questionnaire–9, and Perceived Stress Scale were administered at the beginning and end of the quarantine period. A significant decrease in stress, anxiety, and depression was observed in the patients who undertook the add-on yoga intervention. There was also a significant decrease in anxiety in the control group, but the yoga intervention group had a larger decrease compared to the control group. Further significant improvements in oxygen saturation and heart rate levels were observed in the group of patients who were practicing yoga, but no significant improvement was observed in the control group. The findings of this study suggest that yoga intervention can be an effective add-on practice in reducing stress, anxiety, and depression levels in COVID-19 patients.
  🖺 Full Text HTML: Effect of Yoga on the Stress, Anxiety, and Depression of COVID-19-Positive Patients. A Quasi-Randomized Controlled Study. International Journal of Yoga therapy 2022 (32)
• AMYLASE DEPLETION SIGNIFICANTLY IMPROVES THE MALDI-TOF PROFILE OF SALIVA-APPLICATION TO COVID-19 DIAGNOSTICS -

  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.

  🖺 Full Text HTML: AMYLASE DEPLETION SIGNIFICANTLY IMPROVES THE MALDI-TOF PROFILE OF SALIVA-APPLICATION TO COVID-19 DIAGNOSTICS
• Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation - a pilot study -

  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.

  🖺 Full Text HTML: Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation - a pilot study
• Improvement in drug prescription skills in medical students through in-person and remote simulated interviews -

  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.

  🖺 Full Text HTML: Improvement in drug prescription skills in medical students through in-person and remote simulated interviews
• Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study -

  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.

  🖺 Full Text HTML: Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study
• Effect of nasal carriage of Bacillus species on COVID-19 severity: A cross-sectional study -

  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.

  🖺 Full Text HTML: Effect of nasal carriage of Bacillus species on COVID-19 severity: A cross-sectional study

From Clinical Trials

• 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

• 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

• Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome - Condition:   Post-COVID-19 Syndrome
  Intervention:   Dietary Supplement: PS23 heat-treated
  Sponsors:   Mackay Memorial Hospital;   Bened Biomedical Co., Ltd.
  Recruiting

From PubMed

• Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis - Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HRESIMS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3’-C-8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak…

• Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results - CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.

• Awareness raising and dealing with methanol poisoning based on effective strategies - Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are…

• Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease - The 3-chymotrypsin-like protease 3CLpro from SARS-CoV-2 is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using a HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by the…

• Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility - Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found…

• 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.

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