Covid-19 Sentry

Contents

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

From Preprints

• Hybrid immunity elicits potent cross-variant ADCC against SARS-CoV-2 through a combination of anti-S1 and S2 antibodies -
  Antibodies capable of neutralising SARS-CoV-2 have been well studied, but the Fc receptor-dependent antibody activities that also significantly impact the course of infection have not been studied in such depth. SARS-CoV-2 infection induces antibody-dependent NK cell responses targeting multiple antigens, however, as most vaccines induce only anti-spike antibodies, we investigated spike-specific antibody-dependent cellular cytotoxicity (ADCC). Vaccination produced antibodies that only weakly induced ADCC, however, antibodies from individuals who were infected prior to vaccination (hybrid immunity) elicited much stronger anti-spike ADCC. Quantitative and qualitative aspects of humoral immunity contributed to this capability, with infection skewing IgG antibody production towards S2, vaccination skewing towards S1 and hybrid immunity evoking strong responses against both domains. The capacity for hybrid immunity to provide superior spike-directed ADCC was associated with selectively increased antibody responses against epitopes within both S1 and S2. Antibodies targeting both spike domains were important for strong antibody-dependent NK cell activation, with three regions of antibody reactivity outside the receptor-binding domain (RBD) corresponding with potent anti-spike ADCC. Consequently, ADCC induced by hybrid immunity with ancestral antigen was conserved against variants containing neutralisation escape mutations in the RBD [Delta and Omicron (BA.1)]. Induction of antibodies recognizing a broad range of spike epitopes and eliciting strong and durable ADCC may partially explain why hybrid immunity provides superior protection against infection and disease than vaccination alone, and demonstrates that spike-only subunit vaccines would benefit from strategies to induce a combination of S1- and S2-specific antibody responses.
  🖺 Full Text HTML: Hybrid immunity elicits potent cross-variant ADCC against SARS-CoV-2 through a combination of anti-S1 and S2 antibodies
• Covid-19 impact on food insecurity in Uganda: a dynamic analysis -

  Lockdowns were used as a tool to avoid excessive social contact and thus limit the spread of Covid-19. However, the true welfare effects of this policy action are still being determined. This paper studies the impact of these lockdowns on the food security outcomes of households in Uganda using a dynamic probit model. We find that the most consequential determinant of whether a household9s food security was severely impacted by the lockdown was the initial status of whether a family was food insecure to begin with. Also, an increase in a household9s economic resources (log consumption per person) significantly influences a reduction in the probability of being severely food insecure. Over time, this creates a wedge of greater inequality between the food security of households who were initially food secure and those who were not. This is despite the use of government cash transfers which have turned out to be ineffective.

  🖺 Full Text HTML: Covid-19 impact on food insecurity in Uganda: a dynamic analysis
• Archetypal analysis of COVID-19 in Montana, USA, March 13, 2020 to April 26, 2022 -

  Given the potential consequences of infectious diseases, it is important to understand how broad scale incidence variability influences the probability of localized outbreaks. Often, these infectious disease data can involve complex spatial patterns intermixed with temporal trends. Archetypal Analysis is a method to mine complex spatiotemporal epidemiological data, and can be used to discover the dynamics of spatial patterns. The application of Archetypal Analysis to epistemological data is relatively new, and here we present one of the first applications using COVID-19 data from March 13, 2020 to April 26, 2022 in the counties of Montana, USA. We present three views of the data set with Archetypal Analysis. First, we evaluate the entire 56 county data set. Second, we compute mutual information of the 56 counties’ time series to remove counties whose dynamics are mainly independent from most of the other counties. We choose the top 17 counties ranked in terms of increasing total mutual information. Finally, to compare how population size might influence results, we conducted an analysis with 10 of the largest counties. Using the Archetypal Analysis results, we analyze the disease outbreaks across Montana, comparing and contrasting the three different cases and showing how certain counties can be found in distinct sets of archetypes. Using the reconstruction time series, we show how each outbreak had a unique trajectory across the state in terms of the archetypes.

  🖺 Full Text HTML: Archetypal analysis of COVID-19 in Montana, USA, March 13, 2020 to April 26, 2022
• What the analysis of causes of death in France in 2020 reveals about the impact of the Covid-19 epidemic -

  Context: In 2020, the French population lived under the threat of the Covid-19 epidemic, which would allegedly cause an exceptional excess mortality rate. Mortality data by cause of death for the year 2020 are now available. These data allow us to quantify and qualify the impact of the epidemic. This analysis presents the evolution of the main mortality indicators by cause and by age group. It is intended to demonstrate how 2020 was an exceptional year. Materials and methods: In France, causes of death are labeled according to the International Classification of Diseases (ICD-10) based on medical death certificates. The study focuses on aggregated data for the year 2020 as well as complete data from 1979 to 2017 available online. To estimate excess mortality by cause of death, mortality data were standardized to 2020 to take into account changes in the age structure of the population. Results: The year 2020 is marked, on the one hand, by the introduction of “Covid-19” as a cause of death, which accounts for 10.4% of deaths; and, on the other hand, by a strong downward trend in most other causes of death. Discussion: In 2020, we show that the overall number of additional deaths due to the Covid-19 epidemic is paradoxically lower than the number of deaths caused by this disease. According to official sources, the number of Covid-19-labeled deaths is nearly 50% higher than the number of additional deaths. Besides excess mortality in 2020 being modest compared to other years that saw health events and it affecting only individuals over 65 years of age, what could explain that this disease has caused more deaths than additional deaths? This analysis shows that the emergency implementation of the “Covid-19” classification led to many biases. A significant number of deaths, usually labeled for other major causes (e.g., neoplasm, circulatory system diseases) were, in a way, transferred to this new label. This analysis of mortality by cause of death provides quantitative answers to the overestimation of the impact of the Covid-19 epidemic in France.

  🖺 Full Text HTML: What the analysis of causes of death in France in 2020 reveals about the impact of the Covid-19 epidemic
• Characterization of Long COVID among U.S. Medicare Beneficiaries using Claims Data -

  This retrospective study utilized healthcare claims data to investigate the incidence, patient demographics, and concurrent diagnoses associated with long COVID in the U.S. Medicare population. Nearly 194,000 (0.6%) beneficiaries had post-COVID condition diagnoses, with higher rates among nursing home residents. Of those medically attended for COVID-19, 3-5% were diagnosed with post-COVID conditions. We observed minimal demographic differences between those with and without long COVID. When comparing diagnoses concurrent with long COVID and COVID-19, certain codes (G72 and J84) for myopathies and interstitial pulmonary diseases were disproportionately present with long COVID.

  🖺 Full Text HTML: Characterization of Long COVID among U.S. Medicare Beneficiaries using Claims Data
• The impact of signal variability on epidemic growth rate estimation from wastewater surveillance data -

  Background: Testing samples of waste water for markers of infectious disease became a widespread method of surveillance during the COVID-19 pandemic. While these data generally correlate well with other indicators of national prevalence, samples that cover localised regions tend to be highly variable over short time scales. Methods: We introduce a procedure for estimating the real-time growth rate of pathogen prevalence using time series data from wastewater sampling. The number of copies of a target gene found in a sample is modelled as time-dependent random variable whose distribution is estimated using maximum likelihood. The output depends on a hyperparameter that controls the sensitivity to variability in the underlying data. We apply this procedure to data reporting the number of copies of the N1 gene of SARS-CoV-2 collected at water treatment works across Scotland between February 2021 and February 2023. Results: The real-time growth rate of the SARS-CoV-2 prevalence is estimated at 121 wastewater sampling sites covering a diverse range of locations and population sizes. We find that the sensitivity of the fitting procedure to natural variability determines its reliability in detecting the early stages of an epidemic wave. Applying the procedure to hospital admissions data, we find that changes in the growth rate are detected an average of 2 days earlier in wastewater than in hospital admissions data. Conclusion: We provide a robust method to generate reliable estimates of epidemic growth from highly variable data. Applying this method to samples collected at wastewater treatment works provides highly responsive situational awareness to inform public health.

  🖺 Full Text HTML: The impact of signal variability on epidemic growth rate estimation from wastewater surveillance data
• Dosing of convalescent plasma and hyperimmune anti-SARS-CoV-2 1 immunoglobulins: a phase I/II dose finding study -

  Background: During the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing neutralizing antibody (Nab) titers following the administration of ConvP or hyperimmune globulins(COVIg). Methods: Immunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination received a range of anti-SARS-CoV-2 antibodies in the form of COVIg or ConvP infusion. The popPK analysis was performed using NONMEM v7.4. Monte Carlo simulations were performed to assess potential COVIg and ConvP dosing regimens for prevention of COVID-19. Results: 44 patients were enrolled, and data from 42 were used for constructing the popPK model. A two-compartment elimination model with mixed residual error best described the Nab-titers after administration. Inter individual variation was associated to CL (44.3%), V1 (27.3%), and V2 (29.2%). Lean body weight and type of treatment (ConvP/COVIg) were associated with V1 and V2, respectively. Median elimination half-life was 20 days (interquartile-range: 17-25 days). Simulations demonstrated that even monthly infusions of 600ml of the ConvP or COVIg used in this trial would not achieve potentially protective serum antibody levels for >90% of the time. However, as a result of hybrid immunity and/or repeated vaccination plasma donors with extremely high Nab-titers are now readily available, and a >90% target attainment should be possible. Conclusion: The results of this study may inform future intervention studies on the prophylactic and therapeutic use of antiviral antibodies in the form of ConvP or COVIg.

  🖺 Full Text HTML: Dosing of convalescent plasma and hyperimmune anti-SARS-CoV-2 1 immunoglobulins: a phase I/II dose finding study
• Early transcriptional responses of human nasal epithelial cells to infection with Influenza A and SARS-CoV-2 virus differ and are influenced by physiological temperature -
  Influenza A (IAV) and SARS-CoV-2 (SCV2) viruses represent an ongoing threat to public health. Both viruses target the respiratory tract, which consists of a gradient of cell types, receptor expression, and temperature. Environmental temperature has been an understudied contributor to infection susceptibility and understanding its impact on host responses to infection could help uncover new insights into severe disease risk factors. As the nasal passageways are the initial site of respiratory virus infection, in this study we investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SCV2 in vitro infection models. We demonstrate that temperature affects SCV2, but not IAV, viral replicative fitness and that SCV2 infected cultures are slower to mount an infection-induced response, likely due to suppression by the virus. Additionally, we show that that temperature not only changes the basal transcriptomic landscape of epithelial cells, but that it also impacts the response to infection. The induction of interferon and other innate immune responses were not drastically affected by temperature, suggesting that while the baseline antiviral response at different temperatures remains consistent, there may be metabolic or signaling changes that affect how well the cultures are able to adapt to new pressures such as infection. Finally, we show that hNECs respond differently to IAV and SCV2 infection in ways that give insight into how the virus is able to manipulate the cell to allow for replication and release. Taken together, these data give new insight into the innate immune response to respiratory infections and can assist in identifying new treatment strategies for respiratory infections.
  🖺 Full Text HTML: Early transcriptional responses of human nasal epithelial cells to infection with Influenza A and SARS-CoV-2 virus differ and are influenced by physiological temperature
• COVID-19 as a continuous-time stochastic process -
  In this article a mathematical treatment of Covid-19 as a stochastic process is discussed. The chance of extinction and the consequences of introducing new Covid-19 infectives into the population are evaluated by using certain approximate arguments. It is shown, in general terms, that the stochastic formulation of a recurrent epidemic like Covid-19 leads to the prediction of a permanent succession of undamped outbreaks of disease. It is also shown that one is able to derive certain useful conclusions about Covid-19 without consideration of immune individuals in a population.
  🖺 Full Text HTML: COVID-19 as a continuous-time stochastic process
• Generation of a SARS-CoV-2 reverse genetics system and novel human lung cell lines that exhibit high virus-induced cytopathology -
  The global COVID-19 pandemic continues with an increasing number of cases worldwide and the emergence of new SARS-CoV-2 variants. In our study, we have developed novel tools with applications for screening antivirals, identifying virus-host dependencies, and characterizing viral variants. Using reverse genetics, we rescued SARS-CoV-2 Wuhan1 (D614G variant) wild type (WTFL) and reporter virus (NLucFL) using molecular BAC clones. The replication kinetics, plaque morphology and titers were comparable between rescued molecular clones and a clinical isolate (VIDO strain), thus providing confidence that the rescued viruses can be used as effective replication tools. Furthermore, the reporter SARS-CoV-2 NLucFL virus exhibited robust luciferase values over the time course of infection and was used to develop a rapid antiviral assay using remdesivir as proof-of-principle. In addition, as a tool to study lung-relevant virus-host interactions, we established novel human lung cell lines that support SARS-CoV-2 infection with high virus-induced cytopathology. Six lung cell lines (NCI-H23, A549, NCI-H1703, NCI-H520, NCI-H226, and HCC827) and HEK293T cells, were transduced to stably express ACE2 and tested for their ability to support virus infection. A549ACE2 B1 and HEK293TACE2 A2 cell lines exhibited more than 70% virus-induced cell death and a novel lung cell line NCI-H23ACE2 A3 showed about ~99% cell death post-infection. These cell lines are ideal for assays relying on live-dead selection and are currently being used in CRISPR knockout and activation screens in our lab.
  🖺 Full Text HTML: Generation of a SARS-CoV-2 reverse genetics system and novel human lung cell lines that exhibit high virus-induced cytopathology
• Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor -
  SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an alpha-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease-inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the alpha-ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials (https://clinicaltrials.gov/ct2/show/NCT05620160) to test real-world therapeutic efficacy against COVID-19.
  🖺 Full Text HTML: Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor
• Giving a voice to adults with COVID-19: An analysis of open-ended comments from smell longhaulers and non-longhaulers -

  Smell disorders are commonly reported with COVID-19 infection. Some patients show prolonged smell-related issues, even after the respiratory symptoms are resolved. To explore the concerns of patients, and to provide an overview for each specific smell disorder, we explored the longitudinal survey that was conducted by 1, and contained self-reports on the changes of smell that participants experienced at two time points. People who still suffered from smell disorders at the second time point, hence named longhaulers, were compared to those who were not, hence named non-longhaulers. Specifically, three aims were pursued in this study. First, to classify smell disorders based on the participants self-reports. Second, to classify the sentiment of each self-report using a machine learning approach, and third, to find specific keywords that best describe the smell dysfunction in those self-reports. We found that the prevalence of parosmia and hyposmia was higher in longhaulers than in non-longhaulers. Furthermore, the results suggest that longhaulers stated self-reports with more negative sentiment than non-longhaulers. Finally, we found specific keywords that were more typical for either longhaulers compared to non-longhaulers. Taken together, our work shows consistent findings with previous studies, while at the same time, provides new insights for future studies investigating smell disorders.

  🖺 Full Text HTML: Giving a voice to adults with COVID-19: An analysis of open-ended comments from smell longhaulers and non-longhaulers
• An Explainable Host Genetic Severity Predictor Model for COVID-19 Patients -

  Understanding the COVID-19 severity and why it differs significantly among patients is a thing of concern to the scientific community. The major contribution of this study arises from the use of a voting ensemble host genetic severity predictor (HGSP) model we developed by combining several state-of-the-art machine learning algorithms (decision tree-based models: Random Forest and XGBoost classifiers). These models were trained using a genetic Whole Exome Sequencing (WES) dataset and clinical covariates (age and gender) formulated from a 5-fold stratified cross-validation computational strategy to randomly split the dataset to overcome model instability. Our study validated the HGSP model based on the 18 features (i.e., 16 identified candidate genetic variants and 2 covariates) identified from a prior study. We provided post-hoc model explanations through the ExplainerDashboard - an open-source python library framework, allowing for deeper insight into the prediction results. We applied the Enrichr and OpenTarget genetics bioinformatic interactive tools to associate the genetic variants for plausible biological insights, and domain interpretations such as pathways, ontologies, and disease/drugs. Through an unsupervised clustering of the SHAP feature importance values, we visualized the complex genetic mechanisms. Our findings show that while age and gender mainly influence COVID-19 severity, a specific group of patients experiences severity due to complex genetic interactions.

  🖺 Full Text HTML: An Explainable Host Genetic Severity Predictor Model for COVID-19 Patients
• Immunological imprinting of humoral immunity to SARS-CoV-2 in children -
  Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We determined immune responses following Omicron BA.1/2 infection in children aged 6-14 years and related this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicited a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicited increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primed for robust antibody responses following Omicron infection but these remained primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses were robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.
  🖺 Full Text HTML: Immunological imprinting of humoral immunity to SARS-CoV-2 in children
• N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2 -
  The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of {beta}-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.
  🖺 Full Text HTML: N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

From Clinical Trials

• A Phase 3 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: QLS1128;   Drug: Placebo
  Sponsor:   Qilu Pharmaceutical Co., Ltd.
  Not yet recruiting

• Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients - Condition:   COVID-19
  Intervention:   Other: breathing exercise
  Sponsor:   Basma Mosaad Abd-elrahman Abushady
  Completed

• Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine - Conditions:   Vaccine Reaction;   COVID-19
  Interventions:   Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech);   Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)
  Sponsors:   Assistance Publique - Hôpitaux de Paris;   IREIVAC/COVIREIVAC Network
  Not yet recruiting

• Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection - Condition:   COVID-19 Infection
  Interventions:   Drug: WPV01;   Drug: Placebo
  Sponsor:   Westlake Pharmaceuticals (Hangzhou) Co., Ltd.
  Not yet recruiting

• ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19) - Condition:   COVID-19 Vaccine
  Interventions:   Biological: Gamma Variant RBD-based ARVAC-CG vaccine;   Biological: Omicron Variant RBD-based ARVAC-CG vaccine;   Biological: Bivalent RBD-based ARVAC-CG vaccine;   Other: Placebo
  Sponsors:   Mónica Edith Lombardo;   Universidad Nacional de San Martín (UNSAM);   National Council of Scientific and Technical Research, Argentina;   Laboratorio Pablo Cassará S.R.L.
  Recruiting

• A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Intervention:   Drug: HH-120 Nasal Spray
  Sponsor:   Beijing Ditan Hospital
  Completed

• Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients - Conditions:   COVID-19 Pneumonia;   Neoplasms Malignant
  Interventions:   Drug: EGCG;   Drug: Placebo
  Sponsor:   Shandong Cancer Hospital and Institute
  Recruiting

• The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial. - Conditions:   Xerostomia;   COVID-19;   Long COVID;   Persistent COVID-19
  Interventions:   Combination Product: Institutional standard treatment for xerostomia and Long Covid;   Radiation: Photobiomodulation Therapy;   Radiation: Placebo Photobiomodulation Therapy
  Sponsor:   University of Nove de Julho
  Recruiting

• A Phase 1/2 Study to Assess the Safety and Immunogenicity of JCXH-221, an mRNA-based Broadly Protective COVID-19 Vaccine - Conditions:   COVID-19;   Infectious Disease
  Interventions:   Biological: JCXH-221;   Biological: Active Comparator;   Other: Placebo
  Sponsors:   Immorna Biotherapeutics, Inc.;   ICON plc
  Not yet recruiting

• Acupuncture for Post COVID-19 Fatigue - Conditions:   Acupuncture;   Post COVID-19 Condition;   Fatigue
  Interventions:   Device: Acupuncture;   Device: Sham Acupuncture
  Sponsor:   Guang’anmen Hospital of China Academy of Chinese Medical Sciences
  Not yet recruiting

• Evaluation of Telemedicine Practices for Contraceptive Counseling During the COVID-19 Pandemic: A Randomized Controlled Trial - Conditions:   Family Planning Services;   Telemedicine;   Pregnant Women;   Women’s Health;   COVID-19 Pandemic
  Intervention:   Behavioral: Video call sessions
  Sponsor:   Fenerbahce University
  Completed

• Clinical and Imaging Biomarkers Associated With Plasma ad Cellular Determinants of Cardiovascular Disease at the Time of COVID 19 - Condition:   Cardiovascular Diseases
  Intervention:   Other: sample blood
  Sponsor:   Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  Active, not recruiting

• Lactoferrin for COVID-19-Induced Taste or Smell Abnormality - Conditions:   Covid19;   Taste Disorder, Secondary;   Taste Disorders;   Dysgeusia;   Smell Disorder;   Ageusia;   Anosmia
  Intervention:   Dietary Supplement: Lactoferrin
  Sponsor:   Wake Forest University Health Sciences
  Withdrawn

• tDCS in Post-COVID Syndrome: Comparison of Two Targets - Conditions:   COVID-19;   Post-COVID-19 Syndrome;   Post COVID-19 Condition
  Intervention:   Device: transcranial current direct stimulation
  Sponsor:   Hospital San Carlos, Madrid
  Recruiting

• In Vivo Investigation on Mitochondrial Dysfunction in Post-COVID Fatigue and Cancer Fatigue. - Conditions:   Mitochondrial Dysfunction;   COVID-19;   Fatigue
  Interventions:   Other: MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS);   Other: Chalder Fatigue Scale;   Other: Health Questionnaire (EQ-5D-5L);   Other: Hamilton Depression Rating Scale
  Sponsors:   National University Hospital, Singapore;   National University of Singapore
  Recruiting

From PubMed

• Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips - SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct…

• SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy - Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus. Interleukin-18, an inflammasome-induced cytokine, has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown. Based on a screening panel, IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19. Supporting clinical data, administration of SARS-CoV-2 Spike 1 (S1)…

• Korupensamine A, but not its atropisomer, korupensamine B, inhibits SARS-CoV-2 in vitro by targeting its main protease (M^pro) - By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we…

• Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection - The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are enhancing the treatment of numerous diseases with unprecedented potency, duration of effect, and safety. Through the systematic screening of hundreds of oligonucleotide sequences, we identified fully chemically stabilized siRNAs and ASOs that target regions of…

• Analysis of the incidence of central precocious puberty treated with gonadotropin-releasing hormone analogs. Impact of the COVID-19 pandemic - Introduction. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, consultations of girls with idiopathic central precocious puberty (ICPP) increased in several countries, but there were no data from Argentina. This increase may be related to changes in lifestyle and stress levels resulting from the lockdown, which particularly affected the child population. Objectives. 1) To describe the progression of the incidence of ICPP requiring inhibition of the…

• In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach - CONCLUSION: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required.

• SARS-CoV-2 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan-coronavirus fusion inhibitors - Numerous emerging SARS-CoV-2 Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high…

• Reactive oxygen species are associated with the inhibitory effect of N-(4-hydroxyphenyl)-retinamide on the entry of the severe acute respiratory syndrome-coronavirus 2 - N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits the dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity. We previously reported that 4-HPR suppresses the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spike protein-mediated membrane fusion through a decrease in membrane fluidity in a DEGS1-independent manner. However, the precise mechanism underlying the inhibition of viral entry by 4-HPR remains unclear. In this study, we examined the role of reactive oxygen species (ROS)…

• Autophagy is induced by swine acute diarrhea syndrome coronavirus through the cellular IRE1-JNK-Beclin 1 signaling pathway after an interaction of viral membrane-associated papain-like protease and GRP78 - Autophagy plays an important role in the infectious processes of diverse pathogens. For instance, cellular autophagy could be harnessed by viruses to facilitate replication. However, it is still uncertain about the interplay of autophagy and swine acute diarrhea syndrome coronavirus (SADS-CoV) in cells. In this study, we reported that SADS-CoV infection could induce a complete autophagy process both in vitro and in vivo, and an inhibition of autophagy significantly decreased SADS-CoV production,…

• Erratum to “Targeting SARS-CoV-2 by synthetic dual-acting thiol compounds that inhibit Spike/ACE2 interaction and viral protein production” - No abstract

• Incremental innovation in healthcare in Spain during the COVID-19 pandemic - CONCLUSIONS: In general, incremental innovations require less investment and shorter technology maturation times, which had made it possible to respond, in some cases successfully, to situations of initial shortages of many medical devices, such as ventilators and protective equipment.

• Bioinspired Antimicrobial PLA with Nanocones on the Surface for Rapid Deactivation of Omicron SARS-CoV-2 - Bioinspired bactericidal surfaces are artificial surfaces that mimic the nanotopography of insect wings and are capable of inhibiting microbial growth by a physicomechanical mechanism. The scientific community has considered them an alternative method to design polymers with surfaces that inhibit bacterial biofilm formation, suitable for self-disinfectant medical devices. In this contribution, poly(lactic acid) (PLA) with nanocone patterns was successfully produced by a novel two-step procedure…

• Inhibitory activity of a sulfated oligo-porphyran from Pyropia yezoensis against SARS-CoV-2 - COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-β-d-Gal-(1 → 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more…

• The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics - In December 2019, the global coronavirus disease 2019 (COVID-19) pandemic began in Wuhan, China. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells primarily through the angiotensin-converting enzyme 2 (ACE2) receptor. In addition to ACE2, several studies have shown the importance of heparan sulfate (HS) on the host cell surface as a co-receptor for SARS-CoV-2-binding. This insight has driven research into antiviral therapies, aimed…

• Work-related experiences of consultant psychiatrists during the COVID-19 response: qualitative analysis - CONCLUSIONS: The challenges of leading mental health services were evident in the increased complexity involved in caring for vulnerable patients during the pandemic, contributing to uncertainty, loss of control and moral distress among participants. These dynamics worked synergistically with pre-existing system-level failures, eroding capacity to mount an effective response. The longer-term psychological well-being of consultant psychiatrists - as well as the pandemic preparedness of healthcare…

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