Covid-19 Sentry

Contents

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

From Preprints

• Fc-gamma receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2 -
  Emerging SARS-CoV-2 variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Although vaccine-elicited antibodies can bind Fc gamma receptors and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical COVID-19 outcome, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and Fc-gamma receptor (FcgR) KO mice, we determined the requirement for Fc effector functions to protect against SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcgRs, especially murine FcgR III (CD16), or depleted of alveolar macrophages. After immunization with the preclinical mRNA-1273 vaccine, protection against Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcgR III. Our passive and active immunization studies in mice suggest that Fc-FcgR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.
  🖺 Full Text HTML: Fc-gamma receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2
• Access to Opioid Agonist Treatment during COVID-19 Public Transport Disruptions -
  Public transport disruptions caused by the COVID-19 pandemic had wide-ranging impacts on the ability of individuals to access health care. Individuals with opioid use disorder represent an especially vulnerable population due to the necessity of frequent, supervised doses of opioid agonists. Focused on Toronto, a major Canadian city suffering from the opioid epidemic, this analysis uses novel realistic routing methodologies to quantify how travel times to individuals’ nearest clinics changed due to public transport disruptions from 2019 to 2020. This analysis uses entirely open-source data sources to estimate the vulnerable populations that were impacted by the largest transport disruptions in the city’s history. Individuals seeking opioid agonist treatment face very constrained windows of access due to the need to manage work and other essential activities. As even small changes to travel times can lead to missed appointments and heighten the chances of overdose and death, understanding the distribution of those most impacted can help inform future policy measures to ensure adequate access to care.
  🖺 Full Text HTML: Access to Opioid Agonist Treatment during COVID-19 Public Transport Disruptions
• Fc mediated pan-sarbecovirus protection after alphavirus vector vaccination -
  Two group 2B beta-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. The mechanisms of cross protection driven by the sarbecovirus spike, a dominant immunogen, are less clear yet critically important for pan-sarbecovirus vaccine development. We evaluated the mechanisms of cross-sarbecovirus protective immunity using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination did not prevent virus replication, it protected against lethal heterologous disease outcomes in both SARS-CoV-2 and clade 2 bat sarbecovirus HKU3-SRBD challenge models. The spike vaccines tested primarily elicited a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. We found non-neutralizing antibody functions that mediated cross protection in wild-type mice were mechanistically linked to FcgR4 and spike S2-binding antibodies. Protection was lost in FcR knockout mice, further supporting a model for non-neutralizing, protective antibodies. These data highlight the importance of FcR-mediated cross-protective immune responses in universal pan-sarbecovirus vaccine designs.
  🖺 Full Text HTML: Fc mediated pan-sarbecovirus protection after alphavirus vector vaccination
• SARS-CoV-2 Omicron subvariants Spike recognition and neutralization elicited after the third dose of mRNA vaccine -

  Several SARS-CoV-2 Omicron subvariants have recently emerged, becoming the dominant circulating strains in many countries. These variants contain a large number of mutations in their Spike glycoprotein, raising concerns about vaccine efficacy. In this study, we evaluate the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize these Omicron subvariant Spikes. We observed that BA.4/5 and BQ.1.1 Spikes are markedly less recognized and neutralized compared to the D614G and the other Omicron subvariant Spikes tested. Also, individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against these subvariants.

  🖺 Full Text HTML: SARS-CoV-2 Omicron subvariants Spike recognition and neutralization elicited after the third dose of mRNA vaccine
• The Shift of Percent Excess Mortality during the COVID-19 pandemic (2020-2022) in Singapore, South Korea, Australia, New Zealand and Hong Kong SAR -

  Introduction: With the economic recession and pandemic fatigue, milder viral variants and higher vaccine coverage along the time lay the basis for lifting anti-COVID policies to restore COVID-19 normalcy. However, when and how to adjust the anti-COVID policies remain under debate in many countries. Methods: In this study, four countries (Singapore, South Korea, Australia, and New Zealand) and one region (Hong Kong SAR), that have shifted from the zero-COVID (ZC) policy to or close to the living-with-COVID (LWC) during or after the Omicron outbreak, were selected as research objects. All-cause mortality data were collected for these objects from 2009-2019. The expected mortality was estimated by a simple linear regression method. Excess mortality over time was calculated as the difference between the expected mortality and the observed mortality. Finally, percent excess mortality (PEM) was calculated as the excess mortality divided by the expected mortality. Results: In the examined four countries, PEM fluctuated around 0% and was lower than 10% most of the time under the ZC policy before 2022. After shifting to the LWC policy, all the examined countries increased the PEM. Briefly, countries with high population density (Singapore and South Korea) experienced an average PEM of 20-40% during the first half of 2022, and followed by a lower average PEM of 15-18% during the second half of 2022. For countries with low population density under the LWC policy, Australia experienced an average PEM of 39.85% during the first half of 2022, while New Zealand was the only country in our analysis that achieved no more than 10% in average PEM all the time. On the contrary, Hong Kong SAR under their ZC policy attained an average PEM of 71.14% during the first half of 2022, while its average PEM decreased to 9.19% in the second half of 2022 with LWC-like policy. Conclusion: PEM under different policies within each country/region overtime demonstrated that the mortality burden caused by COVID-19 had been reduced overtime. Moreover, anti-COVID policies are suggested to control the excess mortality to achieve as low as 10% in PEM.

  🖺 Full Text HTML: The Shift of Percent Excess Mortality during the COVID-19 pandemic (2020-2022) in Singapore, South Korea, Australia, New Zealand and Hong Kong SAR
• Extracellular disintegration of viral proteins as an innovative strategy for developing broad-spectrum antivirals against coronavirus -
  The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives worldwide, not to mention innumerable losses in the global economy and disruptions in social relationships. Unfortunately, state-of-the-art treatments still lag behind the fast emergence of new variants of concern. The key to resolve this issue is to develop broad-spectrum antivirals with innovative antiviral mechanisms in which coronaviruses are deactivated regardless of their variant development. Herein, we report a new antiviral strategy involving extracellular disintegration of viral proteins that are indispensable for viral infection with hyperanion-grafted enediyne molecules. The sulfate groups ensure low cellular permeability and rather low cytotoxicity of the molecules, while the core enediyne generates reactive radical species and causes significant damage to the spike (S) protein of coronavirus. The enediyne compounds exhibit antiviral activity at micromolar to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronaviruses, including the SARS-CoV-2 omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic.
  🖺 Full Text HTML: Extracellular disintegration of viral proteins as an innovative strategy for developing broad-spectrum antivirals against coronavirus
• SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects -
  Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than for the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterwards. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines which use spike protein as the generated antigen.
  🖺 Full Text HTML: SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects
• Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic -

  The COVID-19 pandemic has taken a devastating toll around the world. Since January 2020, the World Health Organization estimates 14.9 million excess deaths have occurred globally. Despite this grim number quantifying the deadly impact, the underlying factors contributing to COVID-19 deaths at the population level remain unclear. Prior studies indicate that demographic factors like proportion of population older than 65 and population health explain the cross-country difference in COVID-19 deaths. However, there has not been a holistic analysis including variables describing government policies and COVID-19 vaccination rate. Furthermore, prior studies focus on COVID-19 death rather than excess death to assess the impact of the pandemic. Through a robust statistical modeling framework, we analyze 80 countries and show that actionable public health efforts beyond just the factors intrinsic to each country are necessary to explain the cross-country heterogeneity in excess death.

  🖺 Full Text HTML: Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic
• Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome -
  Currently the world is dealing with the third outbreak of the human-infecting coronavirus with potential lethal outcome, cause by a member of the Nidovirus family, the SARS-CoV-2. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused the last worldwide pandemic. Successful development of vaccines highly contributed to reduce the severeness of the COVID-19 disease. To establish a control over the current and newly emerging coronaviruses of epidemic concern requires development of substances able to cure severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA using antisense oligonucleotides (ASOs) and identify locked nucleic acid gapmers (LNA gapmers) potent to reduce by up to 96% the intracellular viral load in vitro. Our results strongly suggest promise of our preselected ASOs for further development as therapeutic or prophylactic anti-viral agents.
  🖺 Full Text HTML: Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome
• Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants -
  The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
  🖺 Full Text HTML: Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
• Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ1.1 and XBB. -
  Background: The SARS-CoV-2 Omicron variants, dominating in the late 2022 COVID-19 waves, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized so far, and the BQ.1.* sublineages, dominant in the western countries, are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both with at least 3 vaccine doses and also recently recovered from Omicron COVID-19 (VaxCCP) could retain neutralizing activity against such new Omicron lineages. Methods: Here we reviewed BQ.1.1 virus neutralization data from 652 individual patient samples from 32 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination. Findings: More than 97% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, XBB and BF.7 with 100% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50% neutralizing titers (GMT(GMT50) were 201, 52 and 204 for BQ.1.1, XBB and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naive subjects who also recently within 6 months received at least a third vaccine dose had about half of the GMT(GMT50) for all viral variants with percent neutralizations of 82%, 60% and 94% for BQ.1.1, XBB and BF.7, respectively. Interpretation: Boosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB and BF.7 variants. Funding: Department of Defense in collaboration with the Defense Health Agency, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
  🖺 Full Text HTML: Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ1.1 and XBB.
• Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2 -
  Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
  🖺 Full Text HTML: Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2
• Long-term immune protection against SARS-CoV-2 escape variants upon a single vaccination with murine cytomegalovirus expressing the spike protein -
  Vaccines are central to controlling the coronavirus disease 2019 (COVID-19) pandemic but the durability of protection is limited for currently approved COVID-19 vaccines. Further, the emergence of variants of concern (VoCs) that evade immune recognition has reduced vaccine effectiveness, compounding the problem. Here, we show that a single dose of a murine cytomegalovirus (MCMV)-based vaccine, which expresses the spike (S) protein of the virus circulating early in the pandemic (MCMVS), protects highly susceptible K18-hACE2 mice from clinical symptoms and death upon challenge with a lethal dose of D614G SARS-CoV-2. Moreover, MCMVS vaccination controlled two immune-evading VoCs, the Beta (B.1.135) and the Omicron (BA.1) variants in BALB/c mice, and S-specific immunity was maintained for at least 5 months after immunization, where neutralizing titers against all tested VoCs were higher at 5-months than at 1-month post-vaccination. Thus, cytomegalovirus (CMV)-based vector vaccines might allow for long-term protection against COVID-19.
  🖺 Full Text HTML: Long-term immune protection against SARS-CoV-2 escape variants upon a single vaccination with murine cytomegalovirus expressing the spike protein
• Identifying functionally distinctive and threatened species -
  Functional traits determine species’ responses to environmental change and/or determine species’ effects on ecosystem functions. When species with distinctive functional traits are threatened, there is a risk that ecosystem properties are also threatened. This is because functionally distinctive species may be those that have irreplaceable roles in an ecosystem and/or those that would be able to survive unusual environmental disturbances. To include functional distinctiveness as a criterion in conservation strategies, we need formal quantification of the degree of distinctiveness and threat a species exhibits. Starting with previous quantification attempts, we develop a framework that links different viewpoints on functional distinctiveness and accounts for all species’ extinction probabilities. Our framework is particularly relevant at the local scale where species extinctions impact ecosystem functioning and where conservation policies are developed. As a case study, we thus applied our framework to the mammals of Indian dry forests known to be threatened with a drastic decrease in functional diversity. We notably highlight that although some of the functionally distinctive and threatened species we identified, such as the tiger, are charismatic and considered by conservation actions, others are not. This is the case for some rat species and pangolins, whose negative image in the media during the COVID-19 pandemic could be detrimental to attracting public interest in their preservation. From this case study, we note that noncharismatic, less known species that may be key for ecosystems could be revealed by applying our framework to a range of ecosystems and taxa.
  🖺 Full Text HTML: Identifying functionally distinctive and threatened species
• Strengthening response coordination through public health emergency operations centers in Africa: Lessons learned from 56-week webinar sessions, 2020-2021 -

  Background Following the declaration of coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020, in-person events including trainings were canceled to limit the spread of the pandemic. A virtual learning program was established in May 2020 by Africa Centers for Disease Control and Prevention, the World Health Organization, and other partners to strengthen COVID-19 response coordination through the public health emergency operations centers (PHEOCs). We present a review of the webinar series, the experience, and the lessons learned. Method A data extraction tool was developed to retrieve data from the Africa CDC9s webinar data repository. Major findings were synthesized and described per thematic area. Results A total of 12,715 (13% of the 95,230 registrants) attended the 56 PHEOC webinar sessions between June 2020 and December 2021 and 47% of the attendees came from 17 countries. Of those who attended, 8,528 (70%) were from Africa. The webinars provided 97 learning hours with an average length of 1.18 hours per session. On average, there were 235 attendees per session. In addition, there was an average of 26 interactions between participants and facilitators per session. A total of 4,084 (44%) of the participants (9,283) responded to the post-session surveys, with over 95% rating the webinar topics as being relevant to their work, contributed to improving their understanding of PHEOC operationalization, and with extensive ease of comprehension. Conclusion The virtual training served the intended audience given the high number of participants from African member states, with satisfactory feedback on training relevance. We highlighted a just-in-time, progressively adaptive experience in delivering a PHEOC/PHEM virtual learning in Africa with a consequential global audience at the peak of the COVID-19 pandemic.

  🖺 Full Text HTML: Strengthening response coordination through public health emergency operations centers in Africa: Lessons learned from 56-week webinar sessions, 2020-2021

From Clinical Trials

• A Study to Evaluate EDP-235 in Non-hospitalized Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: EDP-235;   Drug: Placebo
  Sponsor:   Enanta Pharmaceuticals, Inc
  Recruiting

• Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: RAY1216;   Drug: Placebo
  Sponsor:   Guangdong Raynovent Biotech Co., Ltd
  Not yet recruiting

• Acute Rehabilitation in Patients With COVID-19 Pneumonia - Conditions:   COVID-19;   Rehabilitation;   Physical Medicine
  Intervention:   Procedure: Acute rehabilitation program
  Sponsor:   Institut za Rehabilitaciju Sokobanjska Beograd
  Recruiting

• A Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells);   Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)
  Sponsor:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
  Recruiting

• Message Communicating Latest Data on COVID Transmission in Patient’s Area - Condition:   COVID-19
  Intervention:   Behavioral: COVID Booster text messages
  Sponsor:   University of Pennsylvania
  Enrolling by invitation

• Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection - Conditions:   Health Behavior;   Child Development;   Adolescent Obesity
  Interventions:   Dietary Supplement: Probiotics;   Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation;   Dietary Supplement: Placebo probiotics
  Sponsors:   Indonesia University;   Gadjah Mada University;   Universitas Airlangga;   University of Melbourne;   The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
  Recruiting

• Phonation Therapy to Improve Symptoms and Lung Physiology in Patients Referred for Pulmonary Rehabilitation - Condition:   COVID-19
  Interventions:   Behavioral: Tonation Breathing Techniques;   Behavioral: Music Driven Vocal Exercises;   Behavioral: Silent Breathing
  Sponsor:   MetroHealth Medical Center
  Recruiting

• Long COVID-19 Intervention Using Digital Health & Technology - Conditions:   Long COVID;   Distress Tolerance
  Intervention:   Behavioral: iENDURE
  Sponsors:   Rhode Island Hospital;   Brown University
  Not yet recruiting

• Xylitol Based Nasal Spray for COVID-19 Treatment - Condition:   Respiratory Viral Infection
  Intervention:   Device: Nasal Spray
  Sponsors:   Xlear, Inc;   Metanoic Health Ltd.
  Not yet recruiting

• Myocardial Protection in Patients With Post-acute Inflammatory Cardiac Involvement Due to COVID-19 - Conditions:   Myocardial Inflammation;   Remodeling, Left Ventricle;   Remodeling, Vascular;   Left Ventricular Dysfunction;   Exercise Intolerance
  Interventions:   Drug: Prednisolone;   Drug: Losartan
  Sponsors:   Valentina Puentmann;   Bayer;   Alcedis GmbH
  Enrolling by invitation

• A Brief Cognitive Task Intervention for NHS Staff Affected by COVID-19 Trauma (GAINS-2 Study) - Condition:   Intrusive Memories of Traumatic Event(s)
  Interventions:   Behavioral: Brief imagery-competing task;   Behavioral: Brief music-listening task;   Other: Treatment As Usual
  Sponsors:   P1vital Products Limited;   Wellcome Trust (Funder);   Uppsala University (Department of Psychology);   Intensive Care Society (Communication Department);   University of Oxford (Department of Biology);   University of Nottingham (Institute of Mental Health)
  Not yet recruiting

• Study to Evaluate Pharmacokinetics, Safety & Tolerability of 101-PGC-005 in Healthy, Adult, Human Subjects - Conditions:   Glucocorticoids Toxicity;   COVID-19;   Infectious Disease;   Virus Diseases
  Intervention:   Drug: 101-PGC-005
  Sponsor:   101 Therapeutics
  Active, not recruiting

• Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen - Condition:   Acute Respiratory Failure
  Interventions:   Drug: Tozorakimab;   Drug: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

From PubMed

• Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms - In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of…

• Onychomadesis in a COVID-19 patient - We report the case of a 67-year-old woman who developed onychomadesis on 9 of her fingers 2 months after recovering from COVID-19, with subsequent full nail regrowth after 4 months. The development of onychomadesis in COVID-19 is probably related to inhibition of nail proliferation due to fever, direct viral damage, or an inflammatory process associated with endothelial damage and obliterative microangiopathy in the nail matrix area. Clinicians should be aware of nail changes and actively seek…

• An evaluation of the convergent validity of a face-to-face and virtual neuropsychological assessment counter balanced - The COVID-19 pandemic has highlighted the need for further research evaluating the validity of conducting a battery of neuropsychological assessments virtually compared with face-to-face administration. Previous research has suggested that some neuropsychological assessments yield valid results when administered virtually, however, much of the previous research focused on older adults. To determine the validity of virtually administered neuropsychological tests, 28 healthy participants were…

• Nintedanib: a review of the properties, function, and usefulness to minimize COVID-19 induced lung injury - INTRODUCTION: In severe COVID-19 patients, acute respiratory distress syndrome (ARDS)-induced lung injury regularly causes a pulmonary fibrotic phase. There is no approved therapy for the COVID-19-induced pulmonary fibrosis. However, administration of an anti-fibrotic agent, in the early acute phase of the severe COVID-19 with ARDS may improve the infection outcomes.

• Reactive-diffusion epidemic model on human mobility networks: Analysis and applications to COVID-19 in China - The complex dynamics of human mobility, combined with sporadic cases of local outbreaks, make assessing the impact of large-scale social distancing on COVID-19 propagation in China a challenge. In this paper, with the travel big dataset supported by Baidu migration platform, we develop a reactive-diffusion epidemic model on human mobility networks to characterize the spatio-temporal propagation of COVID-19, and a novel time-dependent function is incorporated into the model to describe the…

• Home Sweet Home: Working from home and employee performance during the COVID-19 pandemic in the UK - In 2020, many governments responded to the COVID-19 pandemic by encouraging employees to work from home (WFH). Analyzing representative data from the UK, we find that the pandemic-led increases in WFH frequency are associated with a higher self-perceived hourly productivity among employed respondents. Interestingly, changes in WFH frequency are unrelated to the respondents’ weekly working hours and weekly wages during the same period. While the WFH-productivity association is more substantial in…

• Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation - Virus fusion process is evolutionarily conserved and provides a promising pan-viral target. Cell-cell fusion leads to syncytial formation and has implications in pathogenesis, virus spread and immune evasion. Drugs that target these processes can be developed into anti-virals. Here, we have developed sensitive, rapid, adaptable fusion reporter gene assays as models for plasma membrane and alternative fusion pathways as well as syncytial fusion in the severe acute respiratory syndrome coronavirus…

• Review of preclinical data of PF-07304814 and its active metabolite derivatives against SARS-CoV-2 infection - Main protease (M^(pro)) is a superior target for anti-SARS-COV-2 drugs. PF-07304814 is a phosphate ester prodrug of PF-00835231 that is rapidly metabolized into the active metabolite PF-00835231 by alkaline phosphatase (ALP) and then suppresses SARS-CoV-2 replication by inhibiting M^(pro). PF-07304814 increased the bioavailability of PF-00835231 by enhancing plasma protein binding (PPB). P-glycoprotein (P-gp) inhibitors and cytochrome P450 3A (CYP3A) inhibitors increased the efficacy of…

• mRNA-based vaccine technology for HIV - Human immunodeficiency virus (HIV) poses a major health problem around the globe, resulting in hundred-thousands of deaths from AIDS and over a million new infections annually. Although the standard treatment of HIV infection, antiretroviral therapy, has proven effective in preventing HIV transmission, it is unsuitable for worldwide use due to its substantial costs and frequent adverse effects. Besides promoting HIV/AIDS awareness through education, there is hardly an alternative for inhibiting…

• Does ambient air quality standard contribute to green innovation of enterprises in China? Implications for environmental protection and public health - In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of…

• In vitro evaluation of the activity of teriflunomide against SARS-CoV-2 and the human coronaviruses 229E and OC43 - Previous data have suggested an antiviral effect of teriflunomide, including against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent underlying the ongoing COVID-19 pandemic. We undertook an in vitro investigation to evaluate the inhibitory activity of teriflunomide against SARS-CoV-2 in a cell-based assay. Teriflunomide was added to Vero (kidney epithelial) cells that had been infected with SARS-CoV-2. A nucleocapsid immunofluorescence assay was performed to examine…

• Computational screening of natural products to identify potential inhibitors for human neuropilin-1 (NRP1) receptor to abrogate the binding of SARS-CoV-2 and host cell - Recently, a new variant B.1.1.529 or Omicron variant and its sub-variants (BA2.75, BA.5) of SARS-CoV-2 (Severe acute respiratory virus 2) have been reported with a larger number of mutations in the spike protein and particularly in the RBD (receptor-binding domain). The omicron (B.1.1.529) variant has aggravated the pandemic situation further and needs more analysis for therapeutic development. Keeping in view the urgency of the required data, the current study used molecular modeling and…

• Integrative transcriptome analysis of SARS-CoV-2 human-infected cells combined with deep learning algorithms identifies two potential cellular targets for the treatment of coronavirus disease - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread worldwide, leading coronavirus disease 2019 (COVID-19) to hit pandemic level less than 4 months after the first official cases. Hence, the search for drugs and vaccines that could prevent or treat infections by SARS-CoV-2 began, intending to reduce a possible collapse of health systems. After 2 years, efforts to find therapies to treat COVID-19 continue. However, there is still much to be understood about the virus’…

• Single-cell RNA-sequencing data analysis reveals a highly correlated triphasic transcriptional response to SARS-CoV-2 infection - Single-cell RNA sequencing (scRNA-seq) is currently one of the most powerful techniques available to study the transcriptional response of thousands of cells to an external perturbation. Here, we perform a pseudotime analysis of SARS-CoV-2 infection using publicly available scRNA-seq data from human bronchial epithelial cells and colon and ileum organoids. Our results reveal that, for most genes, the transcriptional response to SARS-CoV-2 infection follows a non-linear pattern characterized by…

• Identification of a group of bisbenzylisoquinoline (BBIQ) compounds as ferroptosis inhibitors - Ferroptosis induced by detrimental accumulation of lipid peroxides has been recently linked to a variety of pathological conditions ranging from acute tissue injuries to chronic degenerative diseases and suppression of ferroptosis by small chemical inhibitors is beneficial to the prevention and treatment of these diseases. However, in vivo applicable small chemical ferroptosis inhibitors are limited currently. In this study, we screened an alkaloid natural compound library for compounds that can…

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