Covid-19 Sentry

Contents

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

From Preprints

• Impact of reference design on estimating SARS-CoV-2 lineage abundances from wastewater sequencing data -
  Sequencing of SARS-CoV-2 RNA from wastewater samples has emerged as a valuable tool for detecting the presence and relative abundances of SARS-CoV-2 variants in a community. By analyzing the viral genetic material present in wastewater, public health officials can gain early insights into the spread of the virus and inform timely intervention measures. The construction of reference datasets from known SARS-CoV-2 lineages and their mutation profiles has become state-of-the-art for assigning viral lineages and their relative abundances from wastewater sequencing data. However, the selection of reference sequences or mutations directly affects the predictive power. Here, we show the impact of a mutation- and sequence-based reference reconstruction for SARS-CoV-2 abundance estimation. We benchmark three data sets: 1) synthetic 'spike-in' mixtures, 2) German samples from early 2021, mainly comprising Alpha, and 3) samples obtained from wastewater at an international airport in Germany from the end of 2021, including first signals of Omicron. The two approaches differ in sub-lineage detection, with the marker-mutation-based method, in particular, being challenged by the increasing number of mutations and lineages. However, the estimations of both approaches depend on selecting representative references and optimized parameter settings. By performing parameter escalation experiments, we demonstrate the effects of reference size and alternative allele frequency cutoffs for abundance estimation. We show how different parameter settings can lead to different results for our test data sets, and illustrate the effects of virus lineage composition of wastewater samples and references. Here, we compare a mutation- and sequence-based reference construction and assignment for SARS-CoV-2 abundance estimation from wastewater samples. Our study highlights current computational challenges, focusing on the general reference design, which significantly and directly impacts abundance allocations. We illustrate advantages and disadvantages that may be relevant for further developments in the wastewater community and in the context of higher standardization.
  🖺 Full Text HTML: Impact of reference design on estimating SARS-CoV-2 lineage abundances from wastewater sequencing data
• Civil society initiatives addressing COVID-19 in Rio de Janeiro (PT) -
  Handwashing is key for stemming COVID-19 transmission, but many communities around the world lack access to water, sanitation, and hygiene (WASH). This research investigated the work that civil society organizations (CSO) developed with vulnerable populations in Rio de Janeiro, Brazil, during the COVID-19 pandemic. We interviewed 15 CSO leaders working in the region. This study had three research questions: 1. How do leaders of civil society organizations perceive the impacts of the COVID-19 pandemic on populations with limited access to safe WASH in Brazil? 2. What actions have CSOs implemented to support vulnerable populations during the COVID-19 pandemic? 3. What is the perceived level of success of these actions according to CSO leaders? Our key findings revealed that: 1. Vulnerable populations faced generalized fear and confusion, high rates of COVID-19 infections and income loss. Additionally, CSO leaders noted an increase and diversification in people seeking assistance, as well as rising police and domestic violence. 2. CSOs focused on providing relief aid by donating food, water, hygiene kits, and personal protection equipment (PPE). They invested too in partnering with other organizations and raising awareness about COVID-19, hygiene practices, and public health measures. 3. Initiatives perceived as successful included the construction of water infrastructure and fundraising. Compliance with public health measures, on the other hand, had significant limitations.
  🖺 Full Text HTML: Civil society initiatives addressing COVID-19 in Rio de Janeiro (PT)
• Hospital vulnerability to spread of respiratory infections: close contact data collection and mathematical modelling -

  The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions. However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all those present in a clinical ward over a 36-hour period, across 15 wards in three hospitals in spring 2020. Data were collected from 2114 participants. These data were combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied twenty-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.

  🖺 Full Text HTML: Hospital vulnerability to spread of respiratory infections: close contact data collection and mathematical modelling
• Disruptiveness of COVID-19: Differences in Course Engagement, Self-appraisal, and Learning -
  We investigated how the transition to remote instruction amidst the COVID-19 pandemic affected students’ engagement, self-appraisals, and learning in advanced placement (AP) Statistics courses. Participants included 681 (Mage=16.7 years, SDage=.90; %female=55.4) students enrolled in the course during 2017-2018 (N=266), 2018-2019 (N=200), and the pandemic-affected 2019-2020 (N=215) year. Students enrolled during the pandemic-affected year reported a greater improvement in affective engagement but a decrease in cognitive engagement in the spring semester relative to a previous year. Females enrolled in the pandemic-affected year experienced a greater negative change in affective and behavioral engagement. Students enrolled during the pandemic-affected year reported a greater decrease in their anticipated AP exam scores and received lower scores on a practice exam aligned with the AP exam compared to a prior year. Though resilient in some respects, students’ self-appraisal and learning appeared negatively affected by pandemic circumstances.
  🖺 Full Text HTML: Disruptiveness of COVID-19: Differences in Course Engagement, Self-appraisal, and Learning
• Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study -

  Background: Vaccination is an effective strategy to reduce morbidity and mortality from coronavirus disease 2019 (COVID-19). However, the uptake of COVID-19 vaccination has varied across and within countries. Switzerland has had lower levels of COVID-19 vaccination uptake in the general population than many other high-income countries. Understanding the socio-demographic factors associated with vaccination uptake can help to inform future vaccination strategies to increase uptake. Methods: We conducted a longitudinal online survey in the Swiss population, consisting of six survey waves from June to September 2021. Participants provided information on socio-demographic characteristics, history of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), social contacts, willingness to be vaccinated, and vaccination status. We used a multivariable Poisson regression model to estimate the adjusted rate ratio (aRR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake. Results: We recorded 6,758 observations from 1,884 adults. For the regression analysis, we included 3,513 observations from 1,883 participants. By September 2021, 600 (75%) of 806 study participants had received at least one vaccine dose. Participants who were older, male, and students, had a higher educational level, household income, and number of social contacts, and lived in a household with a medically vulnerable person were more likely to have received at least one vaccine dose. Female participants, those who lived in rural areas and smaller households, and people who perceived COVID-19 measures as being too strict were less likely to be vaccinated. We found no significant association between previous SARS-CoV-2 infections and vaccination uptake. Conclusions: Our results suggest that socio-demographic factors as well as individual behaviours and attitudes played an important role in COVID-19 vaccination uptake in Switzerland. Therefore, appropriate communication with the public is needed to ensure that public health interventions are accepted and implemented by the population. Tailored COVID-19 vaccination strategies in Switzerland that aim to improve uptake should target specific subgroups such as women, people from rural areas or people with lower socio-demographic status. Keywords: Vaccine, COVID-19, contact survey, social contact, socio-demographic characteristics, Switzerland.

  🖺 Full Text HTML: Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study
• Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation -

  Background: Social determinants of health are non-medical factors that influence health outcomes (SDOH). There is a wealth of SDOH information available via electronic health records, clinical reports, and social media, usually in free text format, which poses a significant challenge and necessitates the use of natural language processing (NLP) techniques to extract key information. Objective: The objective of this research is to advance the automatic extraction of SDOH from clinical texts. Setting and Data: The case reports of COVID-19 patients from the published literature are curated to create a corpus. A portion of the data is annotated by experts to create gold labels, and active learning is used for corpus re-annotation. Methods: A named entity recognition (NER) framework is developed and tested to extract SDOH along with a few prominent clinical entities (diseases, treatments, diagnosis) from the free texts. Results: The proposed NER implementation achieves an accuracy (F1-score) of 92.98% on our test set and generalizes well on benchmark data. A careful analysis of case examples demonstrates the superiority of the proposed approach in correctly classifying the named entities. Conclusions: NLP can be used to extract key information, such as SDOH from free texts. A more accurate understanding of SDOH is needed to further improve healthcare outcomes.

  🖺 Full Text HTML: Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation
• Suspensions of prominent accounts minimally impact platform engagement -
  Health-related misinformation online poses threats to individual well-being and undermines public health efforts. In response, many social media platforms have temporarily or permanently suspended accounts that spread misinformation, at the risk of losing traffic vital to platform revenue. Here we examine the impact on platform engagement following removal of six prominent accounts during the COVID-19 pandemic. Focused on those who engaged with the removed accounts, we find that suspension did not meaningfully reduce activity on the platform. Moreover, we find that removal of the prominent accounts minimally impacted the diversity of information sources consumed.
  🖺 Full Text HTML: Suspensions of prominent accounts minimally impact platform engagement
• Complex Adaptive Systems and Human Resource Management: Fostering a Thriving Workforce in the Post-Pandemic Era -
  The outbreak of COVID-19 has presented unparalleled difficulties for both companies and their staff, resulting in a state of emergency that jeopardizes the welfare of employees and the prosperity of organizations. The present article delves into the prospects of human resource management (HRM) in promoting a workforce that is sustainable and thrives in diverse situations or paradigms through the lens of complex adaptive systems. An examination of the current body of literature indicates deficiencies in comprehending the function of HRM in fostering employee thriving, particularly within the framework of broader and more remote organizational contexts. The article utilizes the framework of complex adaptive systems to suggest various human resource strategies, policies, practices, systems, and processes that can enhance the thriving of the workforce. These strategies include initiatives aimed at promoting employee well-being, flexible working arrangements, and leadership that fosters inclusivity. The significance of HR executives in steering organizations through periods of crisis and recuperation is underscored, along with the imperative to reevaluate the definition of thriving in the context of the pandemic and its enduring ramifications. The article’s final remarks entail the identification of potential avenues for future research and practice in the field of HRM. The significance of HRM in fostering a workforce that is capable of thriving sustainably, both during and post-pandemic, is underscored.
  🖺 Full Text HTML: Complex Adaptive Systems and Human Resource Management: Fostering a Thriving Workforce in the Post-Pandemic Era
• Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis -
  Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find broad based lipidomic storm driven predominantly by secretory (s) phospholipase A2 (sPLA2) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD2 and PGI2, and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.
  🖺 Full Text HTML: Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis
• AGILE Platform: A Deep Learning-Powered Approach to Accelerate LNP Development for mRNA Delivery -
  Ionizable lipid nanoparticles (LNPs) have seen widespread use in mRNA delivery for clinical applications, notably in SARS-CoV-2 mRNA vaccines. Despite their successful use, expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored to different target cell types. The traditional process of LNP development remains labor-intensive and cost-inefficient, relying heavily on trial and error. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines the iterative development of ionizable lipids, crucial components for LNP-mediated mRNA delivery. This approach brings forth three significant features: efficient design and synthesis of combinatorial lipid libraries, comprehensive in silico lipid screening employing deep neural networks, and adaptability to diverse cell lines. Using AGILE, we were able to rapidly design, synthesize, and evaluate new ionizable lipids for mRNA delivery in muscle and immune cells, selecting from a library of over 10,000 candidates. Importantly, AGILE has revealed cell-specific preferences for ionizable lipids, indicating the need for different tail lengths and head groups for optimal delivery to varying cell types. These results underscore the potential of AGILE in expediting the development of customized LNPs. This could significantly contribute to addressing the complex needs of mRNA delivery in clinical practice, thereby broadening the scope and efficacy of mRNA therapies.
  🖺 Full Text HTML: AGILE Platform: A Deep Learning-Powered Approach to Accelerate LNP Development for mRNA Delivery
• NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing -
  The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
  🖺 Full Text HTML: NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
• Combinatorial Regimens Augment Drug Monotherapy for SARS-CoV-2 Clearance in Mice -
  Direct acting antivirals (DAAs) represent critical tools for combating SARS-CoV-2 variants of concern (VOCs) that evolve to escape spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or Main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy did not eliminate SARS-CoV-2 in mice. However, targeting two viral enzymes by combining molnupiravir with nirmatrelvir resulted in superior efficacy and virus clearance. Furthermore, combining molnupiravir with Caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma yielded rapid virus clearance and 100% survival. Thus, our study provides insights into treatment efficacies of DAAs and other effective combinations to bolster COVID-19 therapeutic arsenal.
  🖺 Full Text HTML: Combinatorial Regimens Augment Drug Monotherapy for SARS-CoV-2 Clearance in Mice
• The HLA-II immunopeptidome of SARS-CoV-2 -
  Targeted synthetic vaccines have the potential to transform our response to viral outbreaks; yet the design of these vaccines requires a comprehensive knowledge of viral immunogens, including T-cell epitopes. Having previously mapped the SARS-CoV-2 HLA-I landscape, here we report viral peptides that are naturally processed and loaded onto HLA-II complexes in infected cells. We identified over 500 unique viral peptides from canonical proteins, as well as from overlapping internal open reading frames (ORFs), revealing, for the first time, the contribution of internal ORFs to the HLA-II peptide repertoire. Most HLA-II peptides co-localized with the known CD4+ T cell epitopes in COVID-19 patients. We also observed that two reported immunodominant regions in the SARS-CoV-2 membrane protein are formed at the level of HLA-II presentation. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and non-structural and non-canonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize the vaccine effectiveness.
  🖺 Full Text HTML: The HLA-II immunopeptidome of SARS-CoV-2
• Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures -
  The advent of single-cell multi-omics sequencing technology makes it possible for researchers to leverage multiple modalities for individual cells and explore cell heterogeneity. However, the high dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Most of the existing computational methods for single-cell data analysis are either limited to single modality or lack flexibility and interpretability. In this study, we propose an interpretable deep learning method called multi-omic embedded topic model (moETM) to effectively perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder for efficient variational inference and then employs multiple linear decoders to learn the multi-omic signatures of the gene regulatory programs. Through comprehensive experiments on public single-cell transcriptome and chromatin accessibility data (i.e., scRNA+scATAC), as well as scRNA and proteomic data (i.e., CITE-seq), moETM demonstrates superior performance compared with six state-of-the-art single-cell data analysis methods on seven publicly available datasets. By applying moETM to the scRNA+scATAC data in human bone marrow mononuclear cells (BMMCs), we identified sequence motifs corresponding to the transcription factors that regulate immune gene signatures. Applying moETM analysis to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omic biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.
  🖺 Full Text HTML: Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures
• Geospatially-resolved public-health surveillance via wastewater sequencing -

  Wastewater, which contains everything from pathogens to pollutants, is a geospatially- and temporally-linked microbial fingerprint of a given population. As a result, it can be leveraged for monitoring multiple dimensions of public health across locales and time. Here, we integrate targeted and bulk RNA sequencing (n=1,419 samples) to track the viral, bacterial, and functional content over geospatially distinct areas within Miami Dade County from 2020-2022. First, we used targeted amplicon sequencing (n=966) to track diverse SARS-CoV-2 variants across space and time, and we found a tight correspondence with clinical caseloads from University students (N = 1,503) and Miami-Dade County hospital patients (N = 3,939 patients), as well as an 8-day earlier detection of the Delta variant in wastewater vs. in patients. Additionally, in 453 metatranscriptomic samples, we demonstrate that different wastewater sampling locations have clinically and public-health-relevant microbiota that vary as a function of the size of the human population they represent. Through assembly, alignment-based, and phylogenetic approaches, we also detect multiple clinically important viruses (e.g., norovirus) and describe geospatial and temporal variation in microbial functional genes that indicate the presence of pollutants. Moreover, we found distinct profiles of antimicrobial resistance (AMR) genes and virulence factors across campus buildings, dorms, and hospitals, with hospital wastewater containing a significant increase in AMR abundance. Overall, this effort lays the groundwork for systematic characterization of wastewater to improve public health decision making and a broad platform to detect emerging pathogens.

  🖺 Full Text HTML: Geospatially-resolved public-health surveillance via wastewater sequencing

From Clinical Trials

• Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 - Condition:   COVID-19
  Intervention:   Procedure: Extracorporeal photopheresis
  Sponsor:   Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
  Recruiting

• A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes - Condition:   COVID-19
  Interventions:   Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation;   Biological: Bivalent COVID-19 mRNA Vaccine;   Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation
  Sponsors:   Zhongnan Hospital;   Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
  Recruiting

• The Effect of Special Discharge Training in the COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Other: COVID-19 Discharge Education
  Sponsor:   Kilis 7 Aralik University
  Completed

• Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19 - Conditions:   COVID-19 Vaccine;   COVID-19
  Interventions:   Biological: 50 μg Baiya SARS-CoV-2 Vax 2;   Other: Placebo
  Sponsor:   Baiya Phytopharm Co., Ltd.
  Not yet recruiting

• Physiotherapy in Mutated COVID-19 Patients - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Physiotherapy
  Sponsor:   Giresun University
  Completed

• Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19 - Conditions:   SARS-CoV Infection;   COVID-19
  Interventions:   Drug: Mitoquinone/mitoquinol mesylate;   Other: Placebo
  Sponsor:   University of Texas Southwestern Medical Center
  Not yet recruiting

• To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment. - Conditions:   Fecal Microbiota Transplantation;   COVID-19 Infection
  Intervention:   Procedure: Fecal microbiota transplantation
  Sponsor:   Shanghai 10th People’s Hospital
  Completed

• Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2373;   Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant
  Sponsor:   Novavax
  Active, not recruiting

• A Study to Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883. - Condition:   COVID-19
  Intervention:   Drug: PF-07817883
  Sponsor:   Pfizer
  Not yet recruiting

• Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study - Condition:   COVID-19
  Interventions:   Drug: AZD3152;   Other: Placebo
  Sponsor:   AstraZeneca
  Recruiting

• Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: QTP104 1ug;   Biological: QTP104 5ug;   Biological: QTP104 25ug
  Sponsor:   Quratis Inc.
  Active, not recruiting

• Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) - Conditions:   Long COVID;   Post-Acute Sequela of COVID-19;   Post-Acute COVID-19
  Interventions:   Drug: AER002;   Other: Placebo
  Sponsors:   Michael Peluso, MD;   Aerium Therapeutics
  Not yet recruiting

• COVID Frequent Antigen Testing - Condition:   COVID-19 Respiratory Infection
  Intervention:   Diagnostic Test: SARS CoV-2 antigen tests
  Sponsors:   IDX20 Inc;   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study - Conditions:   Postural Orthostatic Tachycardia Syndrome;   COVID-19;   Post COVID-19 Condition;   Post-Acute COVID-19 Syndrome
  Intervention:   Other: Individual tailored exercise
  Sponsors:   Karolinska Institutet;   Karolinska University Hospital
  Enrolling by invitation

• Fluvoxamine for Long COVID-19 - Condition:   Long COVID
  Intervention:   Drug: Fluvoxamine
  Sponsors:   Washington University School of Medicine;   Balvi COVID Fund
  Recruiting

From PubMed

• Isolation of Anti-SARS-CoV-2 Natural Products Extracted from Mentha canadensis and the Semi-synthesis of Antiviral Derivatives - Traditional herbal medicine offers opportunities to discover novel therapeutics against SARS-CoV-2 mutation. The dried aerial part of mint (Mentha canadensis L.) was chosen for bioactivity-guided extraction. Seven constituents were isolated and characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Syringic acid and methyl rosmarinate were evaluated in drug combination treatment. Ten amide derivatives of methyl rosmarinate were synthesized, and the dodecyl (13) and…

• Computational design of medicinal compounds to inhibit RBD-hACE2 interaction in the Omicron variant: unveiling a vulnerable target site - The COVID-19 pandemic, caused by SARS-CoV-2, has globally affected both human health and economy. Several variants with a high potential for reinfection and the ability to evade immunity were detected shortly after the initial reported case of COVID-19. A total of 30 mutations in the spike protein (S) have been reported in the SARS-CoV-2 (BA.2) variant in India and South Africa, while half of these mutations are in the receptor-binding domain and have spread rapidly throughout the world. Drug…

• In silico screening, ADMET analysis and MD simulations of phytochemicals of Onosma bracteata Wall. as SARS CoV-2 inhibitors - Being attracted with their cardiotonic, antidiabetic, cough relieving activity, treatment of fever, absorbent, anti-asthmatic, etc. activities reported in ancient Ayurvedic literature, phytochemicals of Onosma bracteata wall should be evaluated for their activity against SARS-CoV-2 virus. The main objective of this study is to identify a hit molecule for the inhibition of entry, replication, and protein synthesis of SARS CoV-2 virus into the host. To achieve given objective, computational…

• In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors - <b>Background and Objective:</b> The COVID-19, which has been circulating since late 2019, is caused by SARS-CoV-2. Because of its high infectivity, this virus has spread widely throughout the world. Spike glycoprotein is one of the proteins found in SARS-CoV-2. Spike glycoproteins directly affect infection by forming ACE-2 receptors on host cells. Inhibiting glycoprotein spikes could be one method of treating COVID-19. In this study, the antivirus marketed as a database will be…

• PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3β-N-nsp3 cascade - The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3β to facilitate its replication….

• Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19 - It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID-19. As a result, it was found that the isolation efficiency of…

• A Facile Strategy to Construct Anti-Swelling, Antibacterial and Antifogging Coatings for Protection of Medical Goggles - During the COVID-19 pandemic, traditional medical goggles are not only easy to attach bacteria and viruses in long-term exposure, but also easy to fogged up, which increases the risk of infection and affects productivity. Bacterial adhesion and fog can be significantly inhibited through the hydrogel coatings, owing to their super hydrophilic properties. But on the one hand, hydrophilic hydrogel coatings are easy to absorb water and swell in wet environment, resulting in reduced mechanical…

• Secreted ORF8 induces monocytic pro-inflammatory cytokines through NLRP3 pathways in patients with severe COVID-19 - Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe COVID-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in symptomatic patients with COVID-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14^(+) monocytes to…

• Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex - To facilitate selfish replication, viruses halt host gene expression in various ways. The nuclear export of mRNA is one such process targeted by many viruses. SARS-CoV-2, the etiological agent of severe acute respiratory syndrome, also prevents mRNA nuclear export. In this study, Nsp14, a bifunctional viral replicase subunit, was identified as a novel inhibitor of mRNA nuclear export. Nsp14 induces poly(A)+ RNA nuclear accumulation and the dissolution/coalescence of nuclear speckles. Genome-wide…

• In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 - Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening analysis was carried out employing 5852 ligands (from Zinc databases), and performing an ADMET analysis, remaining a set of 2155 compounds. Furthermore, docking analysis was performed on specific sites…

• Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir - Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as…

• Discovery of Polyphenolic Natural Products as SARS-CoV-2 M^pro Inhibitors for COVID-19 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a…

• Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan - Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or…

• Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19 - Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been…

• Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M^pro) - The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (M^(pro)) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 M^(pro) inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior…

From Patent Search