Covid-19 Sentry

Contents

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

From Preprints

• Pathology and Anticatalysis treatment of exacerbated COVID-19 -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces various systemic coronavirus diseases 2019 (COVID-19). Its pathophysiologies involve 1 the angiotensin-converting enzyme 2 (ACE2) and toll-like receptor 4 (TLR4) pathway, 2 Neuropilins (NRPs) Pathway, 3 The sterile alpha motif (SAM) and histi-dine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway 4 Inflammasome ac-tivation pathways, 5 Cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) (cGAS–STING) signaling pathway, 6 Spike protein pathway, and 7 Immunological memory en-gram pathway. COVID-19 exacerbates immune-mediated diseases whose metabolisms use 1. ACE2, TLR4 in the brain, 2. SAMHD1 tetramerization and cGAS–STING-NLRP3 signaling, 3. inflammasome–spike protein–genetic activation, and 4. innate lymphoid cells (ILCs) with NRPs. Immune triad: Aspirin, Dapsone, and Dexamethasone to treat COVID-19 have worked harmoniously with modulating ILCs. Therefore, it is necessary to prescribe this triad to alleviate and block the pathologic course due to diverse and subsequent SARS-CoV-2 variants.
  🖺 Full Text HTML: Pathology and Anticatalysis treatment of exacerbated COVID-19
• Protective non-neutralizing mAbs targets conserved opsonic epitopes on SARS-CoV-2 variants -
  Antibodies play a central role in the immune defense against SARS-CoV-2. Strong evidence has shown that non-neutralizing antibodies (nnAbs) are important for anti-SARS-Cov-2 immunity through Fc-mediated effector functions. These nnAbs bind to epitopes that could be less subjected to mutations in the emerging variants. When protective, such nnAbs would constitute a more promising alternative to neutralizing mAbs (nAbs). Here, we show that six nnAbs retain binding to Omicron, while two nAbs do not. Furthermore, two of our nnAbs, which are protective in vivo, retained binding to XBB, XBB.1.5, and BQ.1.1. They appear to bind to conserved epitopes on the N-terminal and receptor binding domain (RBD), respectively. As a proof of concept, we show that these protective non-neutralizing antibodies retain potent Fc-mediated opsonic function against BQ.1.1 and XBB. We also show that the Fc-mediated function is further enhanced by expressing the antibodies in the IgG3 subclass and combining them into a dual antibody cocktail. Our work suggests that opsonizing nnAbs could be a viable strategy for anti-SARS-CoV-2 mAb therapies against current and future SARS-CoV-2 variants.
  🖺 Full Text HTML: Protective non-neutralizing mAbs targets conserved opsonic epitopes on SARS-CoV-2 variants
• Contributions of hyperactive mutations in Mpro from SARS-CoV-2 to drug resistance -
  The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistant mutations impact inhibitor binding and/or enzyme activity. The most widely used inhibitors currently used to treat SARS-CoV-2 infections, including nirmatrelvir, target the main protease (Mpro) preventing it from processing viral polyproteins into active subunits. Previous work has systematically analyzed resistance mutations in Mpro that reduce binding to inhibitors, and here we investigate mutations that affect enzyme function. Hyperactive mutations that increase Mpro activity can contribute to drug resistance both directly by requiring elevated inhibitor concentrations to reduce function to critical levels and indirectly by increasing tolerance to mutations that reduce both substrate turnover and inhibitor binding. We comprehensively assessed how all possible individual mutations in Mpro affect enzyme function using a mutational scanning approach with a FRET-based yeast readout. We identified hundreds of mutations that significantly increased Mpro activity. Hyperactive mutations occurred both proximal and distal to the active site, consistent with protein stability and/or dynamics impacting activity. Hyperactive mutations were observed three times more than mutations that reduced apparent binding to nirmatrelvir in laboratory grown viruses selected for drug resistance and were also about three times more prevalent than nirmatrelvir binding mutations in sequenced isolates from circulating SARS-CoV-2. Our findings indicate that hyperactive mutations are likely to contribute to the natural evolution of drug resistance in Mpro and provide a comprehensive list for future surveillance efforts.
  🖺 Full Text HTML: Contributions of hyperactive mutations in Mpro from SARS-CoV-2 to drug resistance
• Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease -
  We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including the COVID-19 pandemic caused by SARS-CoV-2. Main protease (MPro) is a highly conserved and essential protease that plays key roles in viral replication and pathogenesis among various CoVs, representing one of the most attractive drug targets for antiviral drug development. Traditional antiviral drug development strategies focus on the pursuit of high-affinity binding inhibitors against MPro. However, this approach often suffers from issues such as toxicity, drug resistance, and a lack of broad-spectrum efficacy. Targeted protein degradation represents a promising strategy for developing next-generation antiviral drugs to combat infectious diseases. Here we leverage the proteolysis targeting chimera (PROTAC) technology to develop a new class of small-molecule antivirals that induce the degradation of SARS-CoV-2 MPro. Our previously developed MPro inhibitors MPI8 and MPI29 were used as MPro ligands to conjugate a CRBN E3 ligand, leading to compounds that can both inhibit and degrade SARS-CoV-2 MPro. Among them, MDP2 was demonstrated to effectively reduce MPro protein levels in 293T cells (DC50 = 296 nM), relying on a time-dependent, CRBN-mediated, and proteasome-driven mechanism. Furthermore, MPD2 exhibited remarkable efficacy in diminishing MPro protein levels in SARS-CoV-2-infected A549-ACE2 cells, concurrently demonstrating potent anti-SARS-CoV-2 activity (EC50 = 492 nM). This proof-of-concept study highlights the potential of PROTAC-mediated targeted protein degradation of MPro as an innovative and promising approach for COVID-19 drug discovery.
  🖺 Full Text HTML: Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease
• The Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13 -
  In response to the emergence of COVID-19, caused by SARS-CoV-2, there has been a growing interest in understanding the functional mechanisms of the viral proteins to aid in the development of new therapeutics. Non-structural protein 13 (Nsp13) helicase is an attractive target for antivirals because it is essential for viral replication and has a low mutation rate; yet, the structural mechanisms by which this enzyme binds and hydrolyzes ATP to cause unidirectional RNA translocation remain elusive. Using Gaussian accelerated molecular dynamics (GaMD), we generated a comprehensive conformational ensemble of all substrate states along the ATP-dependent cycle. ShapeGMM clustering of the protein yields four protein conformations that describe an opening and closing of both the ATP pocket and RNA cleft. This opening and closing is achieved through a combination of conformational selection and induction along the ATP cycle. Furthermore, three protein-RNA conformations are observed that implicate motifs Ia, IV, and V as playing a pivotal role in an ATP-dependent inchworm translocation mechanism. Finally, based on a linear discriminant analysis of protein conformations, we identify L405 as a pivotal residue for the opening and closing mechanism and propose a L405D mutation as a way of testing our proposed mechanism. This research enhances our understanding of nsp13's role in viral replication and could contribute to the development of antiviral strategies.
  🖺 Full Text HTML: The Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13
• Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases. -
  Background: COVID-19 disease is characterized by a spectrum of disease phases (mild, moderate, and severe). Each disease phase is marked by changes in omics profiles with corresponding changes in the expression of features (biosignatures). However, integrative analysis of multiple omics data from different experiments across studies to investigate biosignatures at various disease phases is limited. Exploring an integrative multi-omics profile analysis through a network approach could be used to determine biosignatures associated with specific disease phases and enable the examination of the relationships between the biosignatures. Aim: To identify and characterize biosignatures underlying various COVID-19 disease phases in an integrative multi-omics data analysis. Method: We leveraged the correlation network approach to integrate transcriptomics, metabolomics, proteomics, and lipidomics data. The World Health Organization (WHO) Ordinal Scale (WOS) was used as a disease severity reference to harmonize COVID-19 patient metadata across two studies with independent data. A unified COVID-19 knowledge graph was constructed by assembling a disease-specific interactome from the literature and databases. Disease-state omics-specific graphs were constructed by integrating multi-omics data with the unified COVID-19 knowledge graph. We expanded on the network layers of multiXrank, a random walk with restart on multilayer network algorithm, to explore disease state omics-specific graphs and perform enrichment analysis. Results: Network analysis revealed the biosignatures involved in inducing chemokines and inflammatory responses as hubs in the severe and moderate disease phases. We observed more shared biosignatures between severe and moderate disease phases as compared to mild-moderate and mild-severe disease phases. We further identified both biosignatures that discriminate between the disease states and interactions between biosignatures that are either common between or associated with COVID-19 disease phases. Interestingly, cross-layer interactions between different omics profiles increased with disease severity. Conclusion: This study identified both biosignatures of different omics types enriched in disease-related pathways and their associated interactions that are either common between or unique to mild, moderate, and severe COVID-19. These biosignatures include molecular features that underlie the observed clinical heterogeneity of COVID-19 and emphasize the need for disease-phase-specific treatment strategies. In addition, the approach implemented here can be used for other diseases.
  🖺 Full Text HTML: Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases.
• Childhood Adversity and COVID-19 Outcomes: Findings from the UK Biobank -

  Objectives. To investigate the association between childhood adversity and COVID-19-related hospitalization and COVID-19-related mortality in the UK Biobank. Design. Cohort study. Setting. United Kingdom. Participants. 151,200 participants in the UK Biobank cohort who had completed the Childhood Trauma Screen, were alive at the start of the COVID-19 pandemic (01-10-2021), and were still active in the UK Biobank when hospitalization and mortality data were most recently updated (11-2021). Main outcome measures. COVID-19-related hospitalization and COVID-19-related mortality. Results. Higher self-reports of childhood adversity were related to greater likelihood of COVID-19-related hospitalization in all statistical models. In models adjusted for age, ethnicity, and sex, childhood adversity was associated with an OR of 1.228 of hospitalization (95% CI=1.155 to 1.31, Childhood Adversity z=6.51, p<0.005) and an OR of 1.25 of a COVID-19 related death (95% CI=1.11 to 1.425, Childhood Adversity z=3.53, p<0.005). Adjustment for potential confounds attenuated these associations, although associations remained statistically significant. Conclusions. Childhood adversity was significantly associated with COVID-19-related hospitalization and COVID-19-related mortality after adjusting for sociodemographic and health confounders. Further research is needed to clarify the biological and psychosocial processes underlying these associations to inform public health intervention and prevention strategies to minimize COVID-19 disparities.

  🖺 Full Text HTML: Childhood Adversity and COVID-19 Outcomes: Findings from the UK Biobank
• Comparison of immunity induced by Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic antibody responses -

  Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show that mild BT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary IgG and IgA levels against the Omicron Spike and enhanced reactivity to the ancestral Spike for the IgA isotype, which also reacted with SARS-CoV-1. Serum neutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for mucosal vaccines to emulate the enhanced mucosal and humoral immunity induced by Omicron without exposing individuals to the risks associated with SARS-CoV-2 infection.

  🖺 Full Text HTML: Comparison of immunity induced by Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic antibody responses
• Measuring and increasing rates of self-isolation in the context of infectious diseases: A systematic review with narrative synthesis -

  Background: Self-isolation was used to prevent the spread of COVID-19 and will likely be used in future infectious disease outbreaks. Method: We conducted a systematic review following PRISMA and SWiM guidelines. MEDLINE, PsycINFO, Embase, Web of Science, PsyArXiv, medRxiv, and grey literature sources were searched (1 January 2020 to 13 December 2022) using terms related to COVID-19, isolation, and adherence. Studies were included if they contained original, quantitative data of self-isolation adherence during the COVID-19 pandemic. We extracted definitions of self-isolation, measures used to quantify adherence, adherence rates, and factors associated with adherence. The review was registered on PROSPERO (CRD42022377820). Findings: We included 45 studies. Self-isolation was inconsistently defined. Only four studies did not use self-report to measure adherence. Of 41 studies using self-report measures, only one reported reliability; another gave indirect evidence for a lack of validity of the measure. Rates of adherence to self-isolation ranged from 0% to 100%. There was little evidence that self-isolation adherence was associated with socio-demographic or psychological factors. Interpretation: There was no consensus in defining, operationalising, or measuring self-isolation. Only one study presented evidence of the psychometric properties of the measure highlighting the significant risk of bias in included studies. This, and the dearth of scientifically rigorous studies evaluating the effectiveness of interventions to increase self-isolation adherence, is a fundamental gap in the literature. Funding: This study was funded by Research England Policy Support Fund 2022-23; authors were supported by the NIHR Health Protection Research Unit in Emergency Preparedness and Response.

  🖺 Full Text HTML: Measuring and increasing rates of self-isolation in the context of infectious diseases: A systematic review with narrative synthesis
• The RAPID Survey Platform: A Tool for Child and Family-Centered Systems-Minded Design -
  This article introduced how a novel survey tool - the RAPID survey platform - was conceived out of the COVID-19 pandemic as a way to document the strengths and challenges facing young children, their parents, and other adults in their lives. It is also a narrative about how this tool has subsequently evolved into an easy-to-use and effective method for eliciting community voices to be heard as a means to inform early childhood policy, practice, systems change, and science. In this article, we described the RAPID survey platform as a tool for such systematic examinations of pandemic influences on the “COVID generation” young children. We started by describing the overarching structure of RAPID. We then introduced the key design principles of this survey platform and discussed the insights gleaned from examining surveys from the RAPID national household and ECE provider workforce. Next, we shifted to describing how RAPID has evolved into a scalable tool that transcends the pandemic and documenting how local RAPID Community Voices surveys are being sought out by a growing number of communities and states in the US and elsewhere. These communities are determined to adopt data-driven approaches and leverage information on the strengths, needs, and aspirations of adults in the lives of young children to redesign or improve the existing ECD systems.
  🖺 Full Text HTML: The RAPID Survey Platform: A Tool for Child and Family-Centered Systems-Minded Design
• Decision support system to evaluate VENTilation in the Acute Respiratory Distress Syndrome -

  Rationale. The acute respiratory distress syndrome (ARDS) shows significant heterogeneity in responsiveness to changes in mechanical ventilation and lacks personalisation. Objectives. Investigate the clinical efficacy of a physiologic-based ventilatory decision support system (DSS) on ARDS patients. Methods. An international, multi-centre, randomized, open-label study enrolling patients with ARDS during the COVID-19 pandemic. The primary outcome was to detect a reduction in average driving pressure between groups. Secondary outcomes included several clinically relevant measures of respiratory physiology, ventilator free days; time from control mode to support mode; number of changes in ventilator settings per day; percentage of time in control and support mode ventilation; ventilation related and device related adverse events; and number of times the advice is followed. Measurements and Main Results. 95 patients were randomized to this study. The DSS showed was no effect in the average driving pressure between arms. Patients in the intervention arm had statistically improved oxygenation index when in support mode ventilation (-1.41, 95% CI: -2.76, -0.08; p=0.0370). Ventilatory ratio was also significantly improved in the intervention arm for patients in control mode ventilation (-0.63, 95% CI: -1.08, -0.17, p= 0.0068). The application of the DSS resulted in a significantly increased number of ventilator changes for pressure settings and respiratory frequency. Conclusions. The application of a physiological model-based decision support system for advice on mechanical ventilation in patients with COVID-19 and non-COVID-19 ARDS showed that application of about 60% of advice improved physiological state, despite no significant difference in driving pressure as a primary outcome measure.

  🖺 Full Text HTML: Decision support system to evaluate VENTilation in the Acute Respiratory Distress Syndrome
• Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination -

  Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.

  🖺 Full Text HTML: Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination
• COVID-related Excess Missed HIV Diagnoses in the United States in 2021: Follow-up to 2020 -

  Objective: COVID-19 and related disruptions led to a significant drop in HIV diagnoses in the US in 2020. Recent analyses found 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the drop in diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021. Methods: We apply modified versions of previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether the 2021 diagnosis levels of PWH infected pre-2020 are above or below the projected pre-COVID trends. We apply these analyses on stratifications based on assigned sex at birth, transmission group, geographic region, and race/ethnicity. Results: In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-19. Among Hispanic/Latino PWH and males, diagnoses returned to pre-COVID levels. White PWH, men who have sex with men, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected. Conclusions: While overall diagnoses returned to pre-COVID levels, the large diagnosis gap observed in 2020 remained unclosed at the end of 2021. Lower than expected diagnosis levels among certain populations indicates that COVID-19 related disruptions to HIV diagnosis trends were present in 2021. Although some groups showed higher-than-projected levels of diagnoses, such increases were smaller than the corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.

  🖺 Full Text HTML: COVID-related Excess Missed HIV Diagnoses in the United States in 2021: Follow-up to 2020
• The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response -

  Protection against SARS-CoV-2 wanes over time, and booster uptake has been low. This study explores the link between post-vaccination symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 363) who received two doses of either BNT162b2 or mRNA-1273, with serum nAB concentration measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater changes in skin temperature and heart rate after the second dose predicted higher nAB levels. Skin temperature had a stronger predictive relationship for 6-month than 1-month nAB level. In the context of low ongoing vaccine uptake, our findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.

  🖺 Full Text HTML: The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response
• SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
  🖺 Full Text HTML: SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

From Clinical Trials

• Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition. - Conditions: COVID-19
  Interventions: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 - Conditions: COVID-19, SARS-CoV-2
  Interventions: Biological: Biological: AZD3152; Biological: Biological: Placebo
  Sponsors: AstraZeneca
  Not yet recruiting

• Examining the Function of Cs4 on Post-COVID-19 Disorders - Conditions: Long COVID
  Interventions: Other: Chinese medicine nutritional supplement Cs4
  Sponsors: The University of Hong Kong
  Recruiting

• Amantadine Therapy for Cognitive Impairment in Long COVID - Conditions: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome
  Interventions: Drug: Amantadine
  Sponsors: Ohio State University
  Not yet recruiting

• Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia - Conditions: Parosmia
  Interventions: Procedure: Stellate Ganglion Block; Other: Placebo
  Sponsors: Lawson Health Research Institute
  Not yet recruiting

• CPAP Efficacy in Post-COVID Patients With Sleep Apnea - Conditions: COVID-19; Sleep Apnea
  Interventions: Device: Continuous positive airway pressure
  Sponsors: University of Pittsburgh
  Not yet recruiting

• Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2) - Conditions: Systemic Inflammatory Response Syndrome
  Interventions: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000
  Sponsors: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III
  Recruiting

• SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19 - Conditions: COVID-19
  Interventions: Drug: SA55 Injection; Other: Placebo for SA55 injection
  Sponsors: Sinovac Life Sciences Co., Ltd.
  Recruiting

• Mind Body Intervention for Long COVID - Conditions: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul
  Interventions: Behavioral: Mind Body Intervention #1
  Sponsors: Beth Israel Deaconess Medical Center
  Not yet recruiting

• A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Conditions: COVID-19
  Interventions: Drug: STI-1558
  Sponsors: Zhejiang ACEA Pharmaceutical Co. Ltd.
  Not yet recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Conditions: Covid19
  Interventions: Other: Placebo; Drug: Metformin
  Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
  Recruiting

• Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Conditions: COVID-19
  Interventions: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo
  Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention
  Not yet recruiting

• SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Conditions: COVID-19
  Interventions: Drug: SA55 nasal spray
  Sponsors: Sinovac Life Sciences Co., Ltd.
  Recruiting

• Tele-physiotherapy on Post-stroke Hemiplegia Patients - Conditions: Hemiplegia; Muscle Spasticity
  Interventions: Other: Conventional Physiotherapy + telephysiotherapty
  Sponsors: Universidad Católica San Antonio de Murcia; Hermanas Hospitalarias del Sagrado Corazón de Jesús; Hospital Universitario Virgen de la Arrixaca
  Completed

• Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Conditions: Post-COVID-19 Syndrome
  Interventions: Behavioral: Exercise Therapy; Behavioral: Psychotherapy
  Sponsors: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research
  Not yet recruiting

From PubMed

• Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells - New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six…

• Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome - Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms….

• Antibacterial and anti-corona virus (229E) activity of Nigella sativa oil combined with photodynamic therapy based on methylene blue in wound infection: in vitro and in vivo study - Microbial skin infections, antibiotic resistance, and poor wound healing are major problems, and new treatments are needed. Our study targeted solving this problem with Nigella sativa (NS) oil and photodynamic therapy based on methylene blue (MB-PDT). Antibacterial activity and minimum inhibitory concentration (MIC) were determined via agar well diffusion assay and broth microdilution, respectively. Transmission electron microscopy (TEM) proved deformations in Staphylococcus aureus ATCC 6538….

• N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is highly pathogenic to piglets and poses a major threat to the swine industry. SADS-CoV has a wide cell tropism and pathogenic potential in younger animals. Therefore, understanding how SADS-CoV enters cells is essential for curbing its re-emergence and spread. Here, we report that tunicamycin, an N-linked glycoprotein inhibitor, inhibited the attachment of SADS-CoV to host cells, suggesting that the SADS-CoV receptor may be an N-linked…

• EGR1 functions as a new host restriction factor for SARS-CoV-2 to inhibit virus replication through the E3 ubiquitin ligase MARCH8 - Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an unprecedented public health crisis worldwide. Though the host produces interferons (IFNs) and restriction factors to suppress virus infection, SARS-CoV-2 has evolved multiple strategies to inhibit the antiviral responses. Understanding host restriction factors and viral escape mechanisms is conducive to developing effective anti-SARS-CoV-2 drugs. Here, we constructed SARS-CoV-2…

• In-silico investigation of 4-nitro-N-1H-pyrazol-3-ylbenzamide towards its potential use against SARS-CoV-2: a DFT, molecular docking and molecular dynamics study - In the present research work, we report the synthesis and characterization of novel pyrazole derivative obtained by the condensation reaction of 4-nitro benzaldehyde group with one equivalent of the 2-amino pyrazole yielding 4-nitro-N-1H-pyrazol-3-ylbenzamide with high yield. The two symmetry-independent molecules (molecule A and molecule B) differ about the central C-N bond, with the dihedral angles between the pyrazole ring system and the nitrobenzene ring being 13.90° and 18.64°,…

• Dimeric ACE2-FC Is Equivalent to Monomeric ACE2 in the Surrogate Virus Neutralization Test - Angiotensin-converting enzyme 2 (ACE2) is the main cellular receptor for the dangerous sarbecoviruses SARS-CoV and SARS-CoV-2. Its recombinant extracellular domain is used to monitor the level of protective humoral immune response to a viral infection or vaccine using the surrogate virus neutralization test (sVNT). Soluble ACE2 is also considered as an option for antiviral therapy potentially insensitive to the changes in the SARS-CoV-2 spike protein. Extensive testing of the samples of…

• Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract - CONCLUSIONS: Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract.

• DETECTION OF SARS-COV-2 NEUTRALIZING ANTIBODIES IN RETROPHARYNGEAL LYMPH NODE EXUDATES OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) FROM NEBRASKA, USA - Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for…

• Physiological effects of ivabradine in heart failure and beyond - Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradine’s clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the…

• The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other coronaviruses, replicates their genome in virus-induced cytosolic membrane-bound replication organelles (ROs). SARS-CoV-2 promotes the biogenesis of ROs by inducing the rearrangement of endoplasmic reticulum (ER) membranes. NSP3, NSP4, and NSP6 are transmembrane viral non-structural proteins (NSPs) and essential players in the formation of ROs. To understand how these three NSPs work synergistically with host-binding…

• Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery - CONCLUSION: PDs were significantly larger in COVID-19 patients in all light intensities in the 1^(st) month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the 6^(th) month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction and/or optic nerve and visual pathways alterations following COVID-19.

• An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein - SARS-CoV-2, responsible for the COVID-19 pandemic, invades host cells via its spike protein, which includes critical binding regions, such as the receptor-binding domain (RBD), the S1/S2 cleavage site, the S2 cleavage site, and heptad-repeat (HR) sections. Peptides targeting the RBD and HR1 inhibit binding to host ACE2 receptors and the formation of the fusion core. Other peptides target proteases, such as TMPRSS2 and cathepsin L, to prevent the cleavage of the S protein. However, research has…

• microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host’s Lipid Microenvironment - With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by…

• Protective versus Pathogenic Type I Interferon Responses during Virus Infections - Following virus infections, type I interferons are synthesized to induce the expression of antiviral molecules and interfere with virus replication. The importance of early antiviral type I IFN response against virus invasion has been emphasized during COVID-19 as well as in studies on the microbiome. Further, type I IFNs can directly act on various immune cells to enhance protective host immune responses to viral infections. However, accumulating data indicate that IFN responses can be harmful…

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