Covid-19 Sentry

Contents

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

From Preprints

• ROLE OF DEEP LEARNING STRATEGIES IN DETECTING COVID-19 PNEUMONIA -
  In this chapter, we will describe the various deep learning strategies used in detecting COVID-19 pneumonia with the help of different models.
  🖺 Full Text HTML: ROLE OF DEEP LEARNING STRATEGIES IN DETECTING COVID-19 PNEUMONIA
• Vaccination shapes evolutionary trajectories of SARS-CoV-2 -
  The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by previous infections or vaccinations. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain these results from a fitness model with intrinsic and antigenic fitness components. To infer model parameters, we combine time-resolved sequence data, epidemiological records, and cross-neutralisation assays. This model accurately captures the large-scale evolutionary dynamics of SARS-CoV-2 in multiple geographical regions. In particular, it quantifies how recent vaccinations and infections affect the speed of frequency shifts between viral variants.Our results show that timely neutralisation data can be harvested to identify hotspots of antigenic selection and to predict the impact of vaccination on viral evolution.
  🖺 Full Text HTML: Vaccination shapes evolutionary trajectories of SARS-CoV-2
• Who believes in conspiracy theories? A meta-analysis on personality correlates -
  Conspiracy theories are ubiquitous (e.g., 9/11, COVID-19) and can have negative consequences (e.g., prejudice). Thus, there is an increasing need for evidence-based recommendations (e.g. possible target groups) with respect to interventions and prevention measures. Present Bayesian three-level meta-analysis (686 correlations, 127 independent samples) includes a synthesis of the extant literature with respect to 12 personality correlates and their relationship with conspiracy beliefs. On average, people who believe in pseudoscience, suffer from paranoia or schizotypy, are narcissistic or religious/spiritual and have relatively low cognitive ability, are more likely to believe in conspiracy theories. Heterogeneity was partially explained by the examined moderators and no strong evidence for publication bias was found. Implications for developing tailored interventions are discussed in the article.
  🖺 Full Text HTML: Who believes in conspiracy theories? A meta-analysis on personality correlates
• A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex -
  We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease.
  🖺 Full Text HTML: A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex
• The First Geographic Identification by Country of Sustainable Mutations of SARS-COV-2 Sequence Samples: Worldwide Natural Selection Trends -
  The high mutation rates of RNA viruses, coupled with short generation times and large population sizes, allow viruses to evolve rapidly and adapt to the host environment. The rapidity of viral mutation also causes problems in developing successful vaccines and antiviral drugs. With the spread of SARS-CoV-2 worldwide, thousands of mutations have been identified, some of which have relatively high incidences, but their potential impacts on virus characteristics remain unknown. The present study analyzed mutation patterns, SARS-CoV-2 AASs retrieved from the GISAID database containing 10,500,000 samples. Python 3.8.0 programming language was utilized to pre-process FASTA data, align to the reference sequence, and analyze the sequences. Upon completion, all mutations discovered were categorized based on geographical regions and dates. The most stable mutations were found in nsp1(8% S135R), nsp12(99.3% P323L), nsp16 (1.2% R216C), envelope (30.6% T9I), spike (97.6% D614G), and Orf8 (3.5% S24L), and were identified in the United States on April 3, 2020, and England, Gibraltar, and, New Zealand, on January 1, 2020, respectively. The study of mutations is the key to improving understanding of the function of the SARS-CoV-2, and recent information on mutations helps provide strategic planning for the prevention and treatment of this disease. Viral mutation studies could improve the development of vaccines, antiviral drugs, and diagnostic assays designed with high accuracy, specifically useful during pandemics. This knowledge helps to be one step ahead of new emergence variants.
  🖺 Full Text HTML: The First Geographic Identification by Country of Sustainable Mutations of SARS-COV-2 Sequence Samples: Worldwide Natural Selection Trends
• Determinants of healthcare employee preference to continue teleworking after the COVID-19 pandemic: a cross-sectional study using hierarchical regression -

  Employee post-pandemic telework preference is an important consideration for navigating post-pandemic work arrangements and can inform organizational planning and workforce management. A cross-sectional survey of employees (n=400, participation rate =36.4%) of a regional health authority who teleworked during the COVID-19 pandemic was conducted. The most common post-pandemic telework preference was all the time (52%) followed by over half but not all the time (32%) and less than half the time or not at all (16%). Using hierarchical multinomial logistic regression models and less than half the time or not at all as the reference outcome, being a provider of direct patient care and productivity while teleworking were strong determinants of post-pandemic telework preference while two or more weekly teleconference hours, work-life balance and having one or more people over five years of age in the home while teleworking were moderate determinants.

  🖺 Full Text HTML: Determinants of healthcare employee preference to continue teleworking after the COVID-19 pandemic: a cross-sectional study using hierarchical regression
• COVID-associated pulmonary aspergillosis in immunocompetent patients -
  Purpose: The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to Aspergillus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. Methods: We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. Results: The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Conclusions: Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.
  🖺 Full Text HTML: COVID-associated pulmonary aspergillosis in immunocompetent patients
• Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection -
  The COVID-19 pandemic is a serious global health threat mainly due to the surging cases along with new variants of COVID-19. Though global vaccinations have indeed some effects on the virus spread, its longevity is still unknown. Therefore an orally administrable anti-viral agent against SARS-CoV-2 would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we repurposed niclosamide (NIC), an FDA approved anthelmintic drug in to MgO, which was further coated with hydroxyl propyl methyl cellulose (HPMC) to get the de-sired product called NIC-MgO-HPMC, which has improved anti-SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of NIC-MgO-HPMC on SARS-CoV-2 replication leads to the prevention of inflammation as well as lung injury. These data strongly support that repurposed NIC-MgO-HPMC could be highly beneficial for controlling the ongoing pandemic thereby achieving an endemic phase.
  🖺 Full Text HTML: Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection
• Discovering host protein interactions specific for SARS-CoV-2 RNA genome -
  SARS-CoV-2 is a positive single-stranded RNA virus that interacts with proteins of infected cells at different stages of its life cycle. These interactions are necessary for the host to recognize and block the replication of the virus. Yet, if cells fail to block SARS-CoV-2, host proteins are recruited to translate, transcribe and replicate the genetic material of the virus. To identify the host proteins that bind to SARS-CoV-2 RNA, we adopted the RNA-Protein Interaction Detection coupled to Mass Spectrometry (RaPID-MS) technology, which allows the purification and identification by MS-based proteomics of the proteins associated with a specific RNA of interest expressed in mammalian cells. We specifically investigated proteins associated with the 5’ and 3’ end regions of SARS-CoV-2 RNA. As associations might involve non-physical protein-RNA interactions, we defined a set of reliable protein-RNA interactions by exploiting the predictive power of the catRAPID algorithm that assesses the direct binding potential of proteins to a given RNA region. Among these specific SARS-CoV-2 RNA end interactors, we identified the pseudouridine synthase PUS7 that binds to both 5’ and 3’ ends of viral RNA, which harbor the canonical consensus sequence modified by PUS7. We corroborated our results through SARS-CoV-2 RNA analysis by nanopore direct RNA sequencing. Indeed, these PUS7 consensus regions were found highly modified on viral RNAs, as demonstrated by ionic current features that are significantly different compared to the unmodified in vitro transcribed RNA. Overall, our data map the specific host protein interactions of SARS-CoV-2 RNA and point to a role for cellular pseudouridine synthases and the post-transcriptional pseudouridine modifications in the viral life cycle.
  🖺 Full Text HTML: Discovering host protein interactions specific for SARS-CoV-2 RNA genome
• Monovalent and trivalent VSV-based COVID-19 vaccines elicit potent neutralizing antibodies and immunodominant CD8+ T cells against diverse SARS-CoV-2 variants -
  Recombinant vesicular stomatitis virus (rVSV) vaccines expressing Spike proteins of Wuhan, Beta and/or Delta variants of SARS-CoV-2 were generated and tested for induction of antibody and T cell immune responses in mice. rVSV-Wuhan and rVSV-Delta vaccines and a rVSV-Trivalent (mixed rVSV-Wuhan, -Beta, -Delta) vaccine elicited potent neutralizing antibodies (nAbs) against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) viruses. Prime-boost vaccination with rVSV-Beta was less effective in this capacity. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with rVSV-Trivalent vaccine consistently effective in inducing nAbs against all the SARS-CoV-2 variants tested. All vaccines, including rVSV-Beta, elicited a spike-specific immunodominant CD8+ T cell response. Collectively, rVSV vaccines targeting SARS-CoV-2 variants of concern may be considered in the global fight against COVID-19.
  🖺 Full Text HTML: Monovalent and trivalent VSV-based COVID-19 vaccines elicit potent neutralizing antibodies and immunodominant CD8+ T cells against diverse SARS-CoV-2 variants
• Adjusting non-pharmaceutical interventions based on hospital bed capacity using a multi-operator differential evolution -

  Without vaccines and medicine, non-pharmaceutical interventions (NPIs) such as social distancing, have been the main strategy in controlling the spread of COVID-19. Strict social distancing policies may lead to heavy economic losses, while relaxed social distancing policies can threaten public health systems. We formulate an optimization problem that minimizes the stringency of NPIs during the prevaccination and vaccination phases and guarantees that cases requiring hospitalization will not exceed the number of available hospital beds. The approach utilizes an SEIQR model that separates mild from severe cases and includes a parameter μ that quantifies NPIs. Payoff constraints ensure that daily cases are decreasing at the end of the prevaccination phase and cases are minimal at the end of the vaccination phase. Using the penalty method, the constrained minimization is transformed into a non-convex, multi-modal unconstrained optimization problem, which is solved using a metaheuristic algorithm called the improved multi-operator differential evolution. We apply the framework to determine optimal social distancing strategies in the Republic of Korea given different amounts and types of antiviral drugs. The model considers variants, booster shots, and waning of immunity. The optimal μ values show that fast administration of vaccines is as important as using highly effective vaccines. The initial number of infections and daily imported cases should be kept minimum especially if the severe bed capacity is low. In Korea, a gradual easing of NPIs without exceeding the severe bed capacity is possible if there are at least seven million antiviral drugs and the effectiveness of the drug in reducing disease severity is at least 86%. Model parameters can be adapted to a specific region or country, or other infectious disease. The framework can also be used as a decision support tool in planning practical and economic policies, especially in countries with limited healthcare resources.

  🖺 Full Text HTML: Adjusting non-pharmaceutical interventions based on hospital bed capacity using a multi-operator differential evolution
• Impact of SARS-Cov-2 on Clinical Trial Unit Staff: The EPIC Observational Study -

  Introduction Clinical Trials Units (CTUs) are a key component of delivering non-commercial and commercial clinical research globally. Within the UK, CTUs are seen as a specialist and independent entity available to all researchers requiring support to setup, conduct and deliver clinical trials. Therefore, an involvement of a CTU is highly recommended by national regulators and positively accepted by funders, especially for drug and/or medical device and/or complex intervention trials. Aim: This study aims to determine the challenges associated with the management of Covid-19 research managed via the CTU workforce, including the challenges associated with quality assurance, trial setup and data management. Additionally, this study will explore the by stander effect on trial staff by way of evaluating the mental and physical health impact. Methods/ Design: This is a mixed methods study. An online novel questionnaire survey study will be conducted among the UK CTU workforce. Quantitative data will be collected using the Qualtrics XM platform. We aim to recruit up to 1,500 CTU staff across the UK workforce. A subgroup sample will be randomly invited to take part in semi-structured interviews. Therefore, this survey will generate both quantitative and qualitative data inclusive of demographic data. Results: The findings will inform current initiatives and identify key themes for prioritising in further research to develop robust approaches to support CTU staff, including the development of a start-re-start framework for CTUs for any future pandemics relevant to developing and delivering communicable diseases and non-communicable diseases-based research. Strengths/Limitations: The validation of the EPIC impact questionnaire used qualitative and quantitative methods which is a strength of the study. However, the study has a single timepoint to obtain data with the secondary outcome measures to be completed at two timepoints as this is an exploratory study attempting to obtain a wider data pool.

  🖺 Full Text HTML: Impact of SARS-Cov-2 on Clinical Trial Unit Staff: The EPIC Observational Study
• 90K/LGALS3BP Expression is Upregulated in COVID-19 but Does Not Restrict SARS-CoV-2 Infection -

  Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients. 90K protein serum levels were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties.

  🖺 Full Text HTML: 90K/LGALS3BP Expression is Upregulated in COVID-19 but Does Not Restrict SARS-CoV-2 Infection
• Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant -

  Background Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision- making. Methods The current cross-sectional, population-based study, conducted in April 2022 in the Valencian Community (VC), recruited 935 participants of all ages. Anti-SARS-CoV-2-Receptor Binding Domain-RBD- total antibodies and anti-Nucleocapsid (N)- IgGs were measured by electrochemiluminescence assays. To account for past SARS-CoV-2 infection the VC microbiology registry (RedMiVa) was interrogated. Quantitation of neutralizing antibodies (NtAb) against the ancestral and Omicron BA.1 and BA.2 (sub)variants by an S-pseudotyped neutralization assay and for enumeration of SARS-CoV-2-S specific-IFNgamma;-producing CD4+ and CD8+ T cells by Intracellular Cytokine Staining assay was performed in a subset of participants (n=100 and 137, respectively). Findings The weighted cumulative incidence was 51.9% (95% CI, 48.7-55.1), and was inversely related to age. Anti-RBD total antibodies were detected in 906/931 (97.3%) participants, those vaccinated and SARS-CoV-2-experienced (VAC-ex;=442) displaying higher levels (P<0.001) than vaccinated/naive (VAC-n;(n=472) and non-vaccinated/experienced (UNVAC-ex; n(n=63). Antibody levels correlated inversely with the time elapsed since receipt of last vaccine dose in VAC-n (Rho, -0.52; 95% CI, -0.59 to -0.45; P<0.001) but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75% and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively, while in 97%, 84% and 40%, against Omicron BA.2. SARS-CoV-2-S-reactive IFNgamma; T cells were detected in 73%, 75%, and 64% for VAC-ex, VAC-n, UNVAC-ex, respectively. Interpretation By April 2022 around half of the VC population had been infected with SARS-CoV-2 and due to extensive vaccination display hybrid immunity. The large percentage of participants with detectable functional antibody and T-cell responses against SARS-CoV-2, which may be cross-reactive to some extent, points towards lower expected severity than in previous waves.

  🖺 Full Text HTML: Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant
• Adaptive sentinel testing in workplace for COVID-19 pandemic -

  Testing and isolation of infectious employees is one of the critical strategies to make the workplace safe during the pandemic for many organizations. Adaptive testing frequency reduces cost while keeping the pandemic under control at the workplace. However, most models aimed at estimating test frequencies were structured for municipalities or large organizations such as university campuses of highly mobile individuals. By contrast, the workplace exhibits distinct characteristics: employee positivity rate may be different from the local community because of rigorous protective measures at workplace, or self-selection of co-workers with common behavioral tendencies for adherence to pandemic mitigation guidelines. Moreover, dual exposure to COVID19 occurs at work and at home that complicates transmission modeling, as does transmission tracing at the workplace. Hence, we developed a bi-modal SEIR model and R-shiny tool that ac-counts for these differentiating factors to adaptively estimate the testing frequency for workplace. Our tool uses easily measurable parameters: community incidence rate, risks of acquiring infection from community and workplace, workforce size, and sensitivity of testing. Our model is best suited for moderate-sized organizations with low internal transmission rates, no-outward facing employees whose position demands frequent in-person interactions with the public, and low to medium population positivity rates. Simulations revealed that employee behavior in adherence to protective measures at work and in their community, and the onsite workforce size have large effects on testing frequency. Reducing workplace transmission rate through workplace mitigation protocols and higher sensitivity of the test deployed, though to a lesser extent. Furthermore, our simulations showed that sentinel testing leads to only a marginal increase in the number of infections even for high community incidence rates, suggesting that this may be a cost-effective approach in future pandemics. We used our model to accurately guide the testing regimen for three campuses of The Jackson Laboratory.

  🖺 Full Text HTML: Adaptive sentinel testing in workplace for COVID-19 pandemic

From Clinical Trials

• Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition:   COVID-19
  Intervention:   Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
  Sponsor:   Central Hospital, Nancy, France
  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

• Beta-glucans for Hospitalised Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MC 3x3;   Drug: Placebo
  Sponsors:   Concentra Educacion e Investigación Biomédica;   Wohlstand Pharmaceutical
  Not yet recruiting

• A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition:   COVID-19
  Intervention:   Drug: Molnupiravir 200 mg
  Sponsors:   University of Witwatersrand, South Africa;   Bill and Melinda Gates Foundation
  Not yet 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

• 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

• Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsor:   WestVac Biopharma Co., Ltd.
  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

• Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: mRNA COVID-19 vaccine (Moderna);   Biological: Viral Vector COVID-19 vaccine (AstraZeneca)
  Sponsor:   WestVac Biopharma Co., Ltd.
  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

From PubMed

• Recent Progress in the Development of Opaganib for the Treatment of Covid-19 - The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the…

• A computational evaluation of FDA medicines’ ability to inhibit hypoxia-inducible factor prolyl hydroxylase-2 (PHD-2) for acute respiratory distress syndrome - COVID-19 infection is associated with a significant fatality rate in individuals suffering from severe acute respiratory distress syndrome (ARDS). Among the several possibilities, inhibition of hypoxia-inducible factor prolyl hydroxylase-2 or prolyl hydroxylase domain-containing protein 2 (PHD2) in a hypoxia-independent way is a prospective therapeutic target for the treatment of ARDS. Vadadustat, Roxadustat, Daprodustat, Desidustat, and Enarudustat are the available clinical trial inhibitors….

• Targeting the Conserved Sequence of the Substrate for the Proteinase of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2) Using Nano-Networks: Efficacy, Stability, and No Cytotoxicity - Herein, we designed a nano peptide that contains three important motifs for targeting the chemotrypsin-like cysteine protease (3CL^(pro)) which is the enzyme responsible for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication. The novel nano peptide contains the Nap Phe-Phe motif that is responsible for peptide self-assembly, an octapeptide (Ser-Ala-Val-Leu-Gln-Ser-Gly-Phe) motif where the enzyme recognizes the substrate and induces enzyme sensitivity, and a tetrapeptide…

• Inhibiting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants: Targeting the Spike and Envelope Proteins Using Nanomaterial Like Peptides - Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant death, economic crisis, and the world to almost completely shut down. This present study focused on targeting the novel SARS-CoV-2 envelope protein, which has not been frequently mutating, and the S protein with a much larger peptide capable of inhibiting virus-mammalian cell attraction. In doing so, molecular dynamics software was used here to model six peptides…

• Complement C3 activation in the ICU: Disease and therapy as Bonnie and Clyde - Patients in the intensive care unit (ICU) often straddle the divide between life and death. Understanding the complex underlying pathomechanisms relevant to such situations may help intensivists select broadly acting treatment options that can improve the outcome for these patients. As one of the most important defense mechanisms of the innate immune system, the complement system plays a crucial role in a diverse spectrum of diseases that can necessitate ICU admission. Among others, myocardial…

• Application of emetine in SARS-CoV-2 treatment: regulation of p38 MAPK signaling pathway for preventing emetine-induced cardiac complications - Emetine is one of the most highly potent anti-SARS-CoV-2 agents ever identified. In addition to having strong anti-SARS-CoV-2 activities, emetine has other valuable therapeutic effects such as strong anti-inflammatory and anti-arterial pulmonary hypertension (APH) properties, which are suitable for the treatment of COVID-19. Its proper concomitant therapeutic effect has led researchers to test this compound in clinical trials to combat COVID-19. However, due to the risks of cardiac…

• The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint - The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to…

• Molnupiravir for the treatment of COVID-19 - Molnupiravir (MK-4482, EIDD-2801) is a promising broad-spectrum experimental antiviral developed by Merck & Co. It is a nucleoside analogue prodrug that undergoes rapid conversion into nucleoside triphosphate (NTP) by intracellular metabolic processes. NTP inhibits viral polymerase by acting as an alternative substrate. Molnupiravir was initially developed to treat influenza and Venezuelan equine encephalitis virus (VEEV) infection as it exerts its antiviral activity by inhibiting RNA-dependent…

• COVID-19 vaccine hesitancy in Africa: a scoping review - CONCLUSIONS: Our review demonstrated the contextualized and multifaceted reasons inhibiting or encouraging vaccine uptake in African countries. This evidence is key to operationalizing interventions based on facts as opposed to assumptions. Our paper provided important considerations for addressing the challenge of COVID-19 vaccine hesitancy and blunting the impact of the pandemic in Africa.

• A narrative review on yoga: a potential intervention for augmenting immunomodulation and mental health in COVID-19 - CONCLUSION AND RELEVANCE: This review paves the path for further research on yoga as a potential intervention for enhancing innate immunity and mental health and thus its role in prevention and adjunctive treatment in COVID-19.

• In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding - Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find…

• Drug repurposing based on a quantum-inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 - The COVID-19 pandemic has accelerated the need to identify new antiviral therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir, the first antiviral against SARS-CoV-2 approved for human use, using a quantum-inspired device. We modelled Remdesivir and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum…

• Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response - Translation of SARS-CoV-2-encoded mRNAs by the host ribosomes is essential for its propagation. Following infection, the early expressed viral protein NSP1 binds the ribosome, represses translation, and induces mRNA degradation, while the host elicits an anti-viral response. The mechanisms enabling viral mRNAs to escape this multifaceted repression remain obscure. Here we show that expression of NSP1 leads to destabilization of multi-exon cellular mRNAs, while intron-less transcripts, such as…

• Iron and iron-related proteins in COVID-19 - COVID-19 can cause detrimental effects on health. Vaccines have helped in reducing disease severity and transmission but their long-term effects on health and effectiveness against future viral variants remain unknown. COVID-19 pathogenesis involves alteration in iron homeostasis. Thus, a contextual understanding of iron-related parameters would be very valuable for disease prognosis and therapeutics.Accordingly, we reviewed the status of iron and iron-related proteins in COVID-19….

• Evaluation of apigenin-based biflavonoid derivatives as potential therapeutic agents against viral protease (3CLpro) of SARS-CoV-2 via molecular docking, molecular dynamics and quantum mechanics studies - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic COVID-19 disease that affects human respiratory function. Despite the scientific progression made in the development of the vaccine, there is an urgent need for the discovery of antiviral drugs for better performance at different stages of SARS-CoV-2 reproduction. The main protease (Mpro or 3CLpro) plays a pivotal role in the life cycle of the virus, making it an attractive target for the…

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