Covid-19 Sentry

Contents

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

From Preprints

• Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial -

  Background: The effectiveness of inhaled corticosteroids to shorten time to symptom resolution or prevent hospitalization or death among outpatients with mild-to-moderate coronavirus 2019 (Covid-19) is unclear. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged >=30 years, experiencing >=2 symptoms of acute infection for >=7 days were randomized to inhaled fluticasone furoate 200 mcg once daily for 14 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results: Of those eligible for the fluticasone arm, 656 were randomized to and received inhaled fluticasone; 621 received concurrent placebo. There was no evidence of improvement in time to recovery with fluticasone compared with placebo (hazard ratio [HR] 1.01, 95% credible interval [CrI] 0.91-1.12; posterior probability for benefit [HR>1]=0.56). Twenty-four participants (3.7%) in the fluticasone arm had urgent care or emergency department visits or were hospitalized compared with 13 (2.1%) in the pooled, concurrent placebo arm (HR 1.9, 95% CrI 0.8-3.5; posterior probability for benefit [HR<1]=0.03). Three participants in each arm were hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusions: Treatment with inhaled fluticasone furoate for 14 days did not result in improved time to recovery among outpatients with Covid-19 in the United States during the delta and omicron variant surges.

  🖺 Full Text HTML: Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial
• Old dogs can learn new tricks. Loro viejo sí aprende a hablar. Evidence from the United Kingdom and Colombia. -
  Objective: Older adults have been impacted more than most by the COVID-19 pandemic worldwide. We identify how older adults have adapted during the COVID-19 pandemic in the United Kingdom and Colombia. Method: We investigated how older people in the United Kingdom and Colombia adapted to the pandemic. The analysis will be undertaken by qualitative constructivist grounded theory. We interviewed n=29 participants in the UK and n=33 participants in Colombia. Findings: The pandemic highlighted the ability of older adults to learn new skills when faced with challenges and adversities. The results suggest that some participants found new goals, and some found pleasure in optimising existing skills and tasks. Other participants compensated for the lack of social connectivity by intensifying hobbies they already enjoy. We identified three ways in which older adults adapted: cognitive, emotional, and behavioural. However, not all participants adapted well, instead struggled to adapt. Across countries, many participants were ‘holding the tension’ and were waiting for the pandemic to end. Conclusion: Adaptation under adverse circumstances such as the COVID-19 pandemic is possible for older adults. However, many participants were ‘holding the tension’ until the health threat was over.
  🖺 Full Text HTML: Old dogs can learn new tricks. Loro viejo sí aprende a hablar. Evidence from the United Kingdom and Colombia.
• The Very Temporary Effect of Covid-19 on English Fertility -
  This note reports estimates of the impact of the Covid-19 pandemic on English fertility. It uses monthly data on the General Fertility Rate (GFR) over the period 2011-2021 to estimate dynamic models of the GFR, some of which include measures of men’s and women’s unemployment rates. The models are used to generate monthly counterfactual fertility during 2020-21 from which the impact of the pandemic is inferred. The Covid pandemic had a very short-term depressing impact on fertility. It reduced conceptions sharply during the first wave of the pandemic (April 2020), affecting fertility in January 2021, but this was fully compensated for by a higher fertility during the last 10 months of 2021. It also appears that changes in unemployment rates played little role in these pandemic-related fertility movements.
  🖺 Full Text HTML: The Very Temporary Effect of Covid-19 on English Fertility
• propeller: testing for differences in cell type proportions in single cell data -
  Motivation: Single cell RNA Sequencing (scRNA-seq) has rapidly gained popularity over the last few years for profiling the transcriptomes of thousands to millions of single cells. This technology is now be-ing used to analyse experiments with complex designs including biological replication. One question that can be asked from single cell experiments, which has been difficult to directly address with bulk RNA-seq data, is whether the cell type proportions are different between two or more experimental conditions. As well as gene expression changes, the relative depletion or enrichment of a particular cell type can be the functional consequence of disease or treatment. However, cell type proportion estimates from scRNA-seq data are variable and statistical methods that can correctly account for different sources of variability are needed to confidently identify statistically significant shifts in cell type composition be-tween experimental conditions. Results: We have developed propeller, a robust and flexible method that leverages biological replication to find statistically significant differences in cell type proportions between groups. Using simulated cell type proportions data we show that propeller performs well under a variety of scenarios. We applied propeller to test for significant changes in cell type proportions related to human heart development, age-ing and COVID-19 disease severity. Availability: The propeller method is publicly available in the open source speckle R package (https://github.com/phipsonlab/speckle). All the analysis code for the paper is available at https://github.com/phipsonlab/propeller-paper-analysis/, and the associated analysis website is available at https://phipsonlab.github.io/propeller-paper-analysis/ .
  🖺 Full Text HTML: propeller: testing for differences in cell type proportions in single cell data
• Does a Pandemic Increase Religiosity in a Secular Nation? A Longitudinal Examination -
  The COVID-19-pandemic offers a unique, if tragic, opportunity to assess the impact of a world-wide crisis on religion. Theories from various disciplines including the psychology of religion and cultural evolution suggest that crises cause higher levels of religiosity. However, such theories also predict that levels of religiosity should remain stable in the context of well-functioning governments, secular institutions and norms that might address social, epistemic, and material needs in a crisis. While the relationship between crisis and religion have been examined in countries with higher levels of religiosity, it has yet to be extensively empirically tested in countries with lower levels of religiosity. Here, on the basis of explicit causal assumptions and using Bayesian multilevel modeling, we analyze quasi-representative longitudinal data from Denmark collected over the course of the pandemic from May 2020 to March 2021. Our analysis show that self-reported religiosity did not increase as a result of the pandemic, an inference that is robust to a range of model specifications, including full Bayesian imputation of missing covariates and post-stratification. We discuss possible interpretations of this finding and argue for an emphasis on cultural context going forward in theories of crises and religion.
  🖺 Full Text HTML: Does a Pandemic Increase Religiosity in a Secular Nation? A Longitudinal Examination
• Insights from Incorporating Quantum Computing into Drug Design Workflows -
  While many quantum computing (QC) methods promise theoretical advantages over classical counterparts, quantum hardware remains limited. Exploiting near-term QC in computer-aided drug design (CADD) thus requires judicious partitioning between classical and quantum calculations. We present HypaCADD, a hybrid classical-quantum workflow for finding ligands binding to proteins, while accounting for genetic mutations. We explicitly identify modules of our drug design workflow currently amenable to replacement by QC: non-intuitively, we identify the mutation-impact predictor as the best candidate. HypaCADD thus combines classical docking and molecular dynamics with quantum machine learning (QML) to infer the impact of mutations. We present a case study with the SARS-CoV-2 protease and associated mutants. We map a classical machine-learning module onto QC, using a neural network constructed from qubit-rotation gates. We have implemented this in simulation and on two commercial quantum computers. We find that the QML models can perform on par with, if not better than, classical baselines. In summary, HypaCADD offers a successful strategy for leveraging QC for CADD.
  🖺 Full Text HTML: Insights from Incorporating Quantum Computing into Drug Design Workflows
• Comparative analysis of retracted pre-print and peer-reviewed articles on COVID-19 -

  Introduction: Due to the accelerated pace and quantum of scientific publication during the COVID-19 pandemic, a large number of articles on COVID-19 have been retracted. Pre-prints though not peer-reviewed offer the advantage of rapid dissemination of new findings. In this study, we aim to systematically compare the article characteristics, time to retraction, social media attention, citations, and reasons for retraction between retracted pre-print and peer-reviewed articles on COVID-19. Methods: We utilized the Retraction Watch database to identify retracted articles on COVID-19 published from 1st January 2020 to 10th March 2022. The articles were reviewed and metadata such as article characteristics (type, category), time to retraction, reasons for retraction, and Altmetric Attention Score (AAS) and citation count were collected. Results: We identified 40 retracted pre-prints and 143 retracted peer-reviewed articles. The median (IQR) retraction time for pre-print and peer-reviewed articles was 29 (10-81.5) days and 139 (63-202) days (p = 0.0001). Pre-prints and peer-reviewed article had median (IQR) AAS of 26.5 (4-1155) and 8 (1-38.5), respectively (p = 0.0082). The median (IQR) citation count for pre-prints and peer-reviewed articles was 3 (0-14) and 3 (0-17), respectively (p = 0.5633). The AAS and citation counts were correlated for both pre-prints (r = 0.5200, p = 0.0006) and peer-reviewed articles(r = 0.5909, p = 0.0001). The commonest reason for retraction for pre-prints and peer-reviewed articles concerns about data and results. Conclusion: The increased adoption of pre-prints results in faster identification of erroneous articles compared to the traditional peer-review process.

  🖺 Full Text HTML: Comparative analysis of retracted pre-print and peer-reviewed articles on COVID-19
• Enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants BA.4 and BA.5 -
  SARS-CoV-2 adaptation to its human host is evidenced by the emergence of new viral lineages with distinct genotypic and phenotypic characteristics, termed variants of concern (VOCs). Particular VOCs have become sequentially dominant globally (Alpha, Delta, Omicron) with each evolving independently from the ancestral Wuhan strain. Omicron is notable for its large number of Spike mutations found to promote immune escape and re-infection. Most recently, Omicron BA.4 and BA.5 subvariants have emerged with increasing levels of adaptive immune escape threatening vaccine effectiveness and increasing hospitalisations. Here, we demonstrate that the most recent Omicron variants have enhanced capacity to antagonise or evade human innate immune defenses. We find Omicron BA.4 and BA.5 replication is associated with reduced activation of epithelial innate immune responses versus earlier BA.1 and BA.2 subvariants. We also find enhanced expression of innate immune antagonist proteins Orf6 and N, similar to Alpha, suggesting common pathways of human adaptation and linking VOC dominance to improved innate immune evasion. We conclude that Omicron BA.4 and BA.5 have combined evolution of antibody escape with enhanced antagonism of human innate immunity to improve transmission and possibly reduce immune protection from severe disease.
  🖺 Full Text HTML: Enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants BA.4 and BA.5
• Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design, identification, and correlation with globally circulating viral genomes -
  Since the onset of the COVID-19 pandemic, SARS-CoV-2 has acquired numerous variations in its intracellular proteins to quickly adapt, become more infectious, and ultimately develop drug resistance by mutating certain hotspot residues. To keep the emerging variants at bay, including Omicron and subvariants, FDA has approved the antiviral nirmatrelvir for mild-to-moderate and high-risk COVID-19 cases. Like other viruses, SARS-CoV-2 could acquire mutations in its main protease (Mpro) to adapt and develop resistance against nirmatrelvir. Employing a unique high-throughput protein design technique, the hotspot residues and signatures of adaptation of Mpro having the highest probability of mutating and rendering nirmatrelvir ineffective were identified. Our results show that ~40% of the designed mutations in Mpro already exist in the globally circulating SARS-CoV-2 lineages. The work provides a first-hand explanation of the resistance mutations in Mpro and is crucial in comprehending viral adaptation, robust antiviral design, and surveillance of evolving Mpro variations.
  🖺 Full Text HTML: Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design, identification, and correlation with globally circulating viral genomes
• Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19 -

  Effective humoral immune responses require well-orchestrated cellular interactions between B and T follicular helper (Tfh) cells. Whether this interaction is impaired and associated with COVID-19 disease severity is unknown. Here, longitudinal acute and convalescent blood samples from 49 COVID-19 patients across mild to severe disease were analysed. We found that during acute infection activated and SARS-CoV-2-specific circulating Tfh (cTfh) cell frequencies expanded with increasing disease severity. The frequency of activated and SARS-CoV-2-specific cTfh cells correlated with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, isolated from severe patients induced more pronounced differentiation of autologous plasmablast and antibody production in vitro compared to cTfh cells isolated from mild patients. However, the development of virus-specific cTfh cells was delayed in patients that displayed or later developed severe disease compared to those that maintained a mild or moderate disease. This correlated with a delayed induction of high-avidity and neutralizing virus-specific antibodies. Our study therefore suggests that impaired generation of functional virus-specific cTfh cells delays the production of high-quality antibodies to combat the infection at an early stage and thereby enabling progression to more severe COVID-19 disease.

  🖺 Full Text HTML: Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19
• Missing Americans: Early Death in the United States, 1933-2021 -

  We assessed how many U.S. deaths would have been averted each year, 1933-2021, if U.S. age-specific mortality rates had equaled those of other wealthy nations. The annual number of excess deaths in the U.S. increased steadily beginning in the late 1970s, reaching 626,353 in 2019. Excess deaths surged during the COVID-19 pandemic. In 2021, there were 1,092,293 “Missing Americans” and 25 million years of life lost due to excess mortality relative to peer nations. In 2021, half of all deaths under 65 years and 91% of the increase in under-65 mortality since 2019 would have been avoided if the U.S. had the mortality rates of its peers. Black and Native Americans made up a disproportionate share of Missing Americans, although the majority were White. One-Sentence Summary: In 2021, 1.1 million U.S. deaths – including 1 in 2 deaths under age 65 years – would have been averted if the U.S. had the mortality rates of other wealthy nations.

  🖺 Full Text HTML: Missing Americans: Early Death in the United States, 1933-2021
• Quantifying the information in noisy epidemic curves -

  Reliably estimating the dynamics of transmissible diseases from noisy surveillance data is an enduring problem in modern epidemiology. Key parameters, such as the instantaneous reproduction number, Rt at time t, are often inferred from incident time series, with the aim of informing policymakers on the growth rate of outbreaks or testing hypotheses about the effectiveness of public health interventions. However, the reliability of these inferences depends critically on reporting errors and latencies innate to those time series. While studies have proposed corrections for these issues, methodology for formally assessing how these sources of noise degrade Rt estimate quality is lacking. By adapting Fisher information and experimental design theory, we develop an analytical framework to quantify the uncertainty induced by under-reporting and delays in reporting infections. This yields a novel metric, defined by the geometric means of reporting and cumulative delay probabilities, for ranking surveillance data informativeness. We apply this metric to two primary data sources for inferring Rt: epidemic case and death curves. We find that the assumption of death curves as more reliable, commonly made for acute infectious diseases such as COVID-19 and influenza, is not obvious and possibly untrue in many settings. Our framework clarifies and quantifies how actionable information about pathogen transmissibility is lost due to surveillance limitations.

  🖺 Full Text HTML: Quantifying the information in noisy epidemic curves
• Infectious disease dynamics and restrictions on social gathering size -

  Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain size. While it is generally agreed that such restrictions reduce contacts, the specific size threshold separating “allowed” from “prohibited” gatherings often does not have a clear scientific basis, which leads to dramatic differences in guidance across location and time. Building on the observation that gathering size distributions are often heavy-tailed, we develop a theoretical model of transmission during gatherings and their contribution to general disease dynamics. We find that a key, but often overlooked, determinant of the optimal threshold is the distribution of gathering sizes. Using data on pre-pandemic contact patterns from several sources as well as empirical estimates of transmission parameters for SARS-CoV-2, we apply our model to better understand the relationship between restriction threshold and reduction in cases. We find that, under reasonable transmission parameter ranges, restrictions may have to be set quite low to have any demonstrable effect on cases due to relative frequency of smaller gatherings. We compare our conceptual model with observed changes in reported contacts during lockdown in March of 2020.

  🖺 Full Text HTML: Infectious disease dynamics and restrictions on social gathering size
• Data-driven assessment of adolescents mental health during the COVID-19 pandemic -

  The measures used to contain the COVID-19 pandemic caused severe disruption to the lives of children and adolescents, compromising their mental health and wellbeing. In this study we assessed the incidence rates of psychiatric diagnoses and drugs in Israeli adolescents before and during the COVID-19 pandemic. Analysis of health records data of over 200,000 12-17 years old adolescents identified a significant increase in all mental health diagnoses and most psychiatric drugs dispensation during the COVID-19 period compared to a corresponding pre-COVID period. A gender sub-analysis revealed that most of this increase was associated with adolescent girls. Girls exhibited increases of 68% in depression, 67% in eating disorders, 42% in anxiety and 29% in stress-related diagnoses during the COVID-19 period, which are significantly higher rates than those seen in boys and in the pre-COVID period. Sector sub-analysis showed that the increase was mainly in the general Jewish sector with almost no significant increases in the Arab and ultra-orthodox sectors. Our study highlights the mental health burden of Israeli adolescents during the pandemic and suggests that careful consideration should be given to it while deciding on measures to mitigate the pandemic.

  🖺 Full Text HTML: Data-driven assessment of adolescents mental health during the COVID-19 pandemic
• Modelling, Simulations and Analysis of the First and Second COVID-19 Epidemics in Beijing -

  Modeling and simulation are important tools that can be used to control, prevent and understand an epidemic spread. This paper introduces a symptomatic-asymptomatic-recoverer-death differential equation model (SARDDE). It presents the conditions of the asymptotical stability on the disease-free equilibrium of the SARDDE. It proposes the necessary conditions of disease spreading for the SARDDE. Based on the reported data of the first and the second COVID-19 epidemics in Beijing and simulations, it determines the parameters of the SARDDE, respectively. Numerical simulations of the SARDDE describe well the outcomes of current symptomatic and asymptomatic individuals, recovered symptomatic and asymptomatic individuals, and died individuals, respectively. The numerical simulations obtain the following results. (1) The transmission rate of the symptomatic infections caused by the symptomatic individuals in the second Beijing epidemic is about two times higher than the one in the first Beijing epidemic. (2) Both symptomatic and asymptomatic individuals cause lesser asymptomatic spread than symptomatic spread. (3) The blocking rates of 89.32% and 97.48% (reaching the infection turning points) to the symptomatic infections cannot prevent the spreads of first and second COVID-19 epidemics in Beijing, respectively. (4) That on the day 28, the symptomatic infection blocking rates reached to 100% has made the second Beijing epidemics epidemic end on day 56. (5) That on the day 98, the symptomatic infection blocking rates reached to 100% has made the first Beijing epidemics epidemic end on day 140. (6) Keeping the blocking rates, recovery rates and death rates reaching the infection turning points would make the numbers of current hospitalized infected individuals reach, on day 140, 208958 individuals and 25017 individuals for the two Beijing epidemics, respectively. Virtual simulations suggest that the strict prevention and control strategies implemented by Beijing government are effective and necessary; using the data from the beginning to the days after about two weeks after the turning points can estimate well and approximately the following outcomes of the two COVID-19 academics, respectively. To avoid multiple epidemic outbreaks, a recommendation is that the authorities need to have maintained the prevention and control measures implemented, at least, 7 days after reaching the turning point until new current infection cases disappear. It is expected that the research can provide better understanding, explaining, and dominating for epidemic spreads, prevention and control measures.

  🖺 Full Text HTML: Modelling, Simulations and Analysis of the First and Second COVID-19 Epidemics in Beijing

From Clinical Trials

• A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised - Condition:   COVID-19
  Interventions:   Drug: Nirmatrelvir;   Drug: Ritonavir;   Drug: Placebo for nirmatrelvir;   Drug: Placebo for ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa. - Condition:   COVID-19
  Interventions:   Device: Abbott Panbio rapid antigen self-tests;   Other: COVIDSmart CARE! app
  Sponsors:   McGill University Health Centre/Research Institute of the McGill University Health Centre;   University of Cape Town Lung Institute
  Not yet recruiting

• Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition:   Severe COVID-19
  Interventions:   Biological: Coronavirus-2-specific T cells;   Other: standard of care (SOC)
  Sponsors:   George Papanicolaou Hospital;   General Hospital Of Thessaloniki Ippokratio
  Recruiting

• Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition:   COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Not yet recruiting

• Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition:   COVID-19
  Interventions:   Behavioral: Full Intervention;   Other: Enhanced Usual Care
  Sponsors:   Kaiser Permanente;   Patient-Centered Outcomes Research Institute;   Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
  Recruiting

• A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: PanCytoVir™ (probenecid);   Drug: Placebo
  Sponsor:   TrippBio, Inc.
  Not yet recruiting

• Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition:   Post COVID-19
  Intervention:   Drug: Montelukast Sodium Tablets
  Sponsor:   Assiut University
  Completed

• Topical Antibacterial Agents for Prevention of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Neosporin;   Other: Vaseline
  Sponsors:   Yale University;   Bill and Melinda Gates Foundation
  Not yet recruiting

• **NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Placebo;   Drug: Experimental drug
  Sponsor:   Medesis Pharma SA
  Recruiting

• Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition:   Post-COVID19 Condition
  Interventions:   Combination Product: Plasma Exchange Procedure;   Other: Sham Plasma Exchange Procedure
  Sponsors:   Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia;   IrsiCaixa;   Banc de Sang i Teixits
  Not yet recruiting

• Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions:   COVID-19;   Rehabilitation
  Interventions:   Other: Respiratory training with the use of resistance set on respiratory muscle trainer;   Other: Respiratory training without resistance set on respiratory muscle trainer
  Sponsor:   Medical University of Bialystok
  Recruiting

• Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition:   Post-acute COVID-19 Syndrome
  Intervention:   Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
  Sponsor:   VA Office of Research and Development
  Not yet recruiting

• Mineralocorticoid Use in COVID-19 Patients - Conditions:   COVID-19;   ARDS
  Intervention:   Drug: Fludrocortisone Acetate 0.1 MG
  Sponsor:   Ain Shams University
  Completed

• Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions:   COVID-19;   Dysglycemia
  Interventions:   Drug: Insulin;   Drug: Subcutaneous Insulin
  Sponsor:   Benha University
  Completed

• A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects - Condition:   COVID-19
  Intervention:   Combination Product: Delcetravir dry powder inhaler
  Sponsor:   Esfam Biotech Pty Ltd
  Not yet recruiting

From PubMed

• Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults - Introduction: Each year, a disproportionate number of the total seasonal influenza-related hospitalizations (90%) and deaths (70%) occur among adults who are >65 years old. Inflammasome activation has been shown to be important for protection against influenza infection in animal models but has not yet been demonstrated in humans. We hypothesized that age-related dysfunction (immunosenescence) of the inflammasome may be associated with poor influenza-vaccine response among older adults. Methods:…

• SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available, or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the…

• Enzyme Nanoscale Interactions with Manganese Zinc Sulfide Give Insight into Potential Antiviral Mechanisms and SARS-CoV-2 Inhibition - Recent interest in nanomedicine has skyrocketed because of mRNA vaccine lipid nanoparticles (LNPs) against COVID-19. Ironically, despite this success, the innovative nexus between nanotechnology and biochemistry, and the impact of nanoparticles on enzyme biochemical activity is poorly understood. The studies of this group on zinc nanoparticle (ZNP) compositions suggest that nanorod morphologies are preferred and that ZNP doped with manganese or iron can increase activity against model enzymes…

• Allosteric Binders of ACE2 Are Promising Anti-SARS-CoV-2 Agents - The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for acute treatment of the disease. We investigate whether compounds that bind the human angiotensin-converting enzyme 2 (ACE2) protein can decrease SARS-CoV-2 replication without impacting ACE2’s natural enzymatic function. Initial screening of a diversity library resulted in hit compounds active in an…

• Cancer vaccine strategies using self-replicating RNA viral platforms - The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity,…

• CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation - CONCLUSIONS: This study demonstrates that SARS-CoV-2-activated platelets produce EVs to enhance thromboinflammation via CLEC5A and TLR2, and highlight the importance of CLEC5A and TLR2 as therapeutic targets to reduce the risk of ARDS in COVID-19 patients.

• Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity - CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.

• Rational identification of small molecules derived from 9,10-dihydrophenanthrene as potential inhibitors of 3CL^pro enzyme for COVID-19 therapy: a computer-aided drug design approach - Small molecules such as 9,10-dihydrophenanthrene derivatives have remarkable activity toward inhibition of SARS-CoV-2 3CL^(pro) and COVID-19 proliferation, which show a strong correlation between their structures and bioactivity. Therefore, these small compounds could be suitable for clinical pharmaceutical use against COVID-19. The objective of this study was to remodel the structures of 9,10-dihydrophenanthrene derivatives to achieve a powerful biological activity against 3CL^(pro) and…

• The Pharmacological Mechanism of Xiyanping Injection for the Treatment of Novel Coronavirus Pneumonia (COVID-19): Based on Network Pharmacology Strategy - CONCLUSION: Xiyanping injection may inhibit the release of various inflammatory factors by inhibiting intracellular pathways such as MAPK and TNF. It acts on protein targets such as HSP90AA1 and plays a potential therapeutic role in COVID-19. Thus, compound III may be treated as a potential new drug for the treatment of COVID-19 and the Xiyanping injection may treat patients with COVID-19 infection.

• Comparative Computational Analysis of Dirithromycin and Azithromycin in Search for a Potent Drug against COVID-19 caused by SARS-CoV-2: Evidence from molecular docking and dynamic simulation - Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit…

• N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial…

• Neuromodulation by selective ACE2 inhibitors - Here, neuromodulatory effects of selective ACE2 inhibitors were investigated. Two different types of small molecule ligands for ACE2 inhibition were selected using chemical genetic approach, they were synthesized using developed chemical method and tested using presynaptic rat brain nerve terminals (synaptosomes). EBC-36032 (1 µM) increased in a dose-dependent manner spontaneous and stimulated ROS generation in nerve terminals that was of non-mitochondrial origin. Another inhibitor EBC-36033…

• Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease - CONCLUSIONS: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation post SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease. This article is open access and distributed under…

• Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease - The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (M^(Pro)), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with M^(Pro). The in vitro…

• Discovery of diminazene as a dual inhibitor of SARS-CoV-2 human host proteases TMPRSS2 and furin using cell-based assays - The proteases TMPRSS2 (transmembrane protease serine 2) and furin are known to play important roles in viral infectivity including systematic COVID-19 infection through priming of the spike protein of SARS-CoV-2 and related viruses. To discover small-molecules capable of inhibiting these host proteases, we established convenient and cost-effective cell-based assays employing Vero cells overexpressing TMPRSS2 and furin. A cell-based proteolytic assay for broad-spectrum protease inhibitors was…

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