Covid-19 Sentry

Contents

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

From Preprints

• Can a pan-coronavirus vaccine limit the threat of SARS-CoV-2 emerging variants and prevent any future pandemic? -
  During coronavirus disease 2019 (COVID-19) pandemic, the initial application of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were deemed to be effective in preventing infection. However, the efficacy of these vaccines was then significantly reduced due to the emergence of SARS-CoV-2 variants that can evade host immune response. Moreover, waning of SARS-CoV-2 neutralizing antibodies (nAbs) level over time represents another challenge to control COVID-19 ongoing waves. The short-term immunity conferred by the currently available vaccines may lead to a never-ending cycle of SARS-CoV-2 variants emergence and ongoing waves of COVID-19. In addition, the presence of animal reservoir for coronaviruses is complicating efforts to eradicate these pathogens. As such, by employing different designs and approaches, broad-spectrum or pan-coronavirus vaccines may represent a potential tool to fight various emergent variants of SARS-CoV-2 through the generation of long-lasting and cross-reactive neutralizing antibodies. The production of these broad-spectrum neutralizing antibodies is currently explored through application of strategies like the use of pathogen conserved (consensus) epitopes, heterologous sequential immunization, and mosaic nanoparticle platform. But the big questions that need answers: Can these proposed broad-spectrum or pan-coronavirus vaccines be effective against the emergent variants for SARS-CoV-2? And can they prevent any future pandemic driven by coronaviruses?
  🖺 Full Text HTML: Can a pan-coronavirus vaccine limit the threat of SARS-CoV-2 emerging variants and prevent any future pandemic?
• MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C) -

  Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. Results: Sixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. Few (8/60) had a prior history of COVID-19, whereas 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. Conclusions: A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.

  🖺 Full Text HTML: MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C)
• M3NetFlow: a novel multi-scale multi-hop multi-omics graph AI model for omics data integration and interpretation -
  The integration and interpretation of multi-omics data play a crucial role in systems biology for prioritizing vital molecular targets and deciphering core signaling pathways of complex diseases, such as cancer, COVID-19 and Alzheimer’s disease. However, it remains a challenge that has not been adequately addressed. Graph neural networks (GNN) have emerged as powerful artificial intelligence models for analyzing data with a graphical structure. Nevertheless, GNN models have not been sufficiently designed for integrative and interpretable multi-omics data analysis. In this study, we propose a novel multi-scale multi-hop multi-omics GNN model, M3NetFlow, to integrate and interpret multi-omics data to rank key targets and infer core signaling pathways. Specifically, we applied the M3NetFlow model to infer cell-line-specific core signaling networks explaining drug combination response. The evaluation and comparison results on drug combination prediction showed that the M3NetFlow model achieved significantly higher prediction accuracy than existing GNN models. Furthermore, M3NetFlow can predict key targets and infer essential signaling networks regulating drug combination response. It is critical for guiding the development of personalized precision medicine for patients with drug resistance. This model can be applied to general multi-omics data-driven research. Aside from that, we developed the visualization tool, NetFlowVis, the better analysis of targets and signaling pathways of drugs and drug combinations.
  🖺 Full Text HTML: M3NetFlow: a novel multi-scale multi-hop multi-omics graph AI model for omics data integration and interpretation
• Frequency and determinants of COVID-19 prevention behaviours: assessment of large-scale programmes in seven countries -

  Pre-existing health and economic challenges mean residents of low- and middle-income countries (LMICs) are likely to be particularly vulnerable to infectious disease pandemics. Limited access to hygiene facilities, water, soap and masks, and dense living environments impeded effective practice of preventive behaviours - handwashing with soap (HWWS), mask wearing and physical distancing - a key line of primary defence against COVID-19. Here we describe a multi-country analysis of prevalence of key hygiene prevention behaviours and their determinants associated with an international non-governmental organisation (WaterAid) hygiene behaviour change programmes for COVID-19 prevention. The goal of this analysis is to inform future outbreak preparedness and pandemic response in LMICs. Cross-sectional household surveys were conducted in October-November 2020 in seven countries where WaterAid worked (Ethiopia, Ghana, Nepal, Nigeria, Rwanda, Tanzania and Zambia). Multivariable mixed-effects regression analyses were used to explore relationships between self-reported behavioural outcomes of interest (handwashing with soap, physical distancing, and mask use) and demographic characteristics, behavioural factors (knowledge, norms, barriers, motives), and exposure to COVID-19 communications. Most respondents (80%) reported increasing their handwashing behaviour after the pandemic, but practice of HWWS at COVID-19-specific prevention moments was low. Mask wearing (58%) and physical distancing (29%) varied substantially between countries. Determinants of key behaviours were identified, including age and socioeconomic status, perceived norms, self-regulation, and the motive of protecting others. These findings highlight that leveraging behaviour-specific emotional drivers and norms, reducing common barriers and promoting targeted messages about specific behaviours and actions individuals can take to reduce risk are necessary to support large-scale behaviour change. Learning from the COVID-19 response to more effectively integrate novel behaviours into existing health promotion will be vital for disease prevention and outbreak resilience.

  🖺 Full Text HTML: Frequency and determinants of COVID-19 prevention behaviours: assessment of large-scale programmes in seven countries
• Sufficient COVID-19 quarantine and testing on international travelers from China -

  Objectives Removal of zeroCOVID restrictions in China led to a surge in COVID19 cases. In response, countries imposed restrictions on Chinese travelers. However, border policies may not provide substantial benefits and their assessment depends on accurate prevalence data. Methods We analyzed quarantines and testing sufficient to prevent additional in country transmission for February 13 to 19, 2023 based on World Health Organization (WHO) and self reported infection rates to estimate prevalence. Results Here we have shown that self-reported prevalence data indicated more stringent border restrictions compared to WHOpublished prevalence statistics. No travel restrictions were required for Singapore for infections to not be greater than in complete border closure, while a 1day quarantine, 2day quarantine, and a 3day quarantine were indicated for England, Germany, and Scotland respectively. A 10day quarantine, 11day quarantine, and 13day quarantine were required for Italy, Japan, and France, respectively, to prevent an increase in the number of within country infections due to travel, while South Korea required a complete border shutdown. Conclusions Our results demonstrated the necessity for accurate and timely reporting of pandemic statistics to prevent an increase in viral spread. Through the minimum quarantine analysis, countries can use science to determine policy, minimize international friction, and improve the cost efficiency of interventions.

  🖺 Full Text HTML: Sufficient COVID-19 quarantine and testing on international travelers from China
• Real-world comparative effectiveness of a third dose of mRNA-1273 versus BNT162b2 among adults aged ≥65 years in the United States -

  Introduction: To compare the real-world effectiveness of a third dose of mRNA-1273 versus a third dose of BNT162b2 against breakthrough COVID-19 hospitalizations among adults age ≥65 years who completed a primary series of an mRNA-based COVID-19 vaccine (regardless of which primary series was received). Materials and methods: This observational comparative vaccine effectiveness (VE) study was conducted using administrative claims data from the US HealthVerity database (September 22, 2021, to August 31, 2022). A third dose of mRNA-1273 versus BNT162b2 was assessed for preventing COVID-19 hospitalizations and medically attended COVID-19 among adults ≥65 years. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) with 95% confidence intervals (CIs) using weighted Cox proportional hazards models were calculated to estimate relative VE for each outcome. Results: Overall, 94,587 and 92,377 individuals received a third dose of mRNA-1273 and BNT162b2, respectively. Among the weighted population, the median age was 69 years (interquartile range, 66-74), 53% were female, and 46% were commercially insured. COVID-19 hospitalization rates per 1000 person-years (PYs) were 5.61 (95% CI, 5.13-6.09) for mRNA-1273 and 7.06 (95% CI, 6.54-7.57) for BNT162b2 (HR, 0.82; 0.69-0.98). Medically attended COVID-19 rates per 1000 PYs (95% CI) were 95.05 (95% CI, 93.03-97.06) for mRNA-1273 and 106.55 (95% CI, 104.53-108.57) for BNT162b2 (HR, 0.93; 0.89-0.98). Conclusions: Results from this observational comparative VE database study provide evidence that among older adults, a third dose of mRNA-1273 was more effective in preventing breakthrough COVID-19 hospitalization and medically attended COVID-19 infection compared with a third dose of BNT162b2.

  🖺 Full Text HTML: Real-world comparative effectiveness of a third dose of mRNA-1273 versus BNT162b2 among adults aged ≥65 years in the United States
• Virological characteristics of the SARS-CoV-2 BA.2.86 variant -
  In late 2023, a lineage of SARS-CoV-2 emerged and was named the BA.2.86 variant. BA.2.86 is phylogenetically distinct from other Omicron sublineages identified so far, displaying an accumulation of over 30 amino acid mutations in its spike protein. Here, we performed multiscale investigations to reveal the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Experimental studies showed that four clinically-available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 is significantly lower than that of BA.2 in both in vitro cell cultures and in vivo, it is suggested that the attenuated pathogenicity of BA.2.86 is due to its decreased replication capacity.
  🖺 Full Text HTML: Virological characteristics of the SARS-CoV-2 BA.2.86 variant
• Leveraging a self-cleaving peptide for tailored control in proximity labeling proteomics -
  Protein-protein interactions play an important biological role in every aspect of cellular homeostasis and functioning. Proximity labeling mass spectrometry-based proteomics overcomes challenges typically associated with other methods, and has quickly become the current state-of-the-art in the field. Nevertheless, tight control of proximity labeling enzymatic activity and expression levels is crucial to accurately identify protein interactors. Here, we leverage a T2A self-cleaving peptide and a non-cleaving mutant to accommodate the protein-of-interest in the experimental and control TurboID setup. To allow easy and streamlined plasmid assembly, we built a Golden Gate modular cloning system to generate plasmids for transient expression and stable integration. To highlight our T2A Split-link design, we applied it to identify protein interactions of the glucocorticoid receptor and SARS-CoV-2 nucleocapsid and NSP7 proteins by TurboID proximity labeling. Our results demonstrate that our T2A split-link provides an opportune control that builds upon previously established control requirements in the field.
  🖺 Full Text HTML: Leveraging a self-cleaving peptide for tailored control in proximity labeling proteomics
• Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04 -
  Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, in the 3C-like protease (3CLpro) that confer resistance to a novel non-covalent inhibitor, WU-04. Crystallographic analysis indicates that the M49K mutation destabilizes the WU-04 binding pocket, impacting the binding of WU-04 more significantly than the binding of 3CLpro substrates. The M165V mutation directly interferes with WU-04 binding. The S301P mutation, which is far from the WU-04 binding pocket, indirectly affects WU-04 binding by restricting the rotation of 3CLpro's C-terminal tail and impeding 3CLpro dimerization. We further explored 3CLpro mutations that confer resistance to two clinically used inhibitors: ensitrelvir and nirmatrelvir, and revealed a trade-off between the catalytic activity, thermostability, and drug resistance of 3CLpro. We found that mutations at the same residue (M49) can have distinct effects on the 3CLpro inhibitors, highlighting the importance of developing multiple antiviral agents with different skeletons for fighting SARS-CoV-2. These findings enhance our understanding of SARS-CoV-2 resistance mechanisms and inform the development of effective therapeutics.
  🖺 Full Text HTML: Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04
• OASIS: An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery -
  Contingency tables, data represented as counts matrices, are ubiquitous across quantitative research and data-science applications. Existing statistical tests are insufficient however, as none are simultaneously computationally efficient and statistically valid for a finite number of observations. In this work, motivated by a recent application in reference-free genomic inference (Chaung et. al. 2022), we develop OASIS (Optimized Adaptive Statistic for Inferring Structure), a family of statistical tests for contingency tables. OASIS constructs a test-statistic which is linear in the normalized data matrix, providing closed form p-value bounds through classical concentration inequalities. In the process, OASIS provides a decomposition of the table, lending interpretability to its rejection of the null. We derive the asymptotic distribution of the OASIS test statistic, showing that these finite-sample bounds correctly characterize the test statistic’s p-value up to a variance term. Experiments on genomic sequencing data highlight the power and interpretability of OASIS. The same method based on OASIS significance calls detects SARS-CoV-2 and Mycobacterium Tuberculosis strains de novo, which cannot be achieved with current approaches. We demonstrate in simulations that OASIS is robust to overdispersion, a common feature in genomic data like single cell RNA-sequencing, where under accepted noise models OASIS still provides good control of the false discovery rate, while Pearson’s X² test consistently rejects the null. Additionally, we show on synthetic data that OASIS is more powerful than Pearson’s X² test in certain regimes, including for some important two group alternatives, which we corroborate with approximate power calculations.
  🖺 Full Text HTML: OASIS: An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery
• Forecasting COVID-19 New Cases Using Transformer Deep Learning Model -

  Making accurate forecasting of COVID-19 cases is essential for healthcare systems, with more than 650 million cases as of 4 January,1 making it one of the worst in history. The goal of this research is to improve the precision of COVID-19 case predictions in Russia, India, and Brazil, a transformer-based model was developed. Several researchers have implemented a combination of CNNs and LSTMs, Long Short-Term Memory (LSTMs), and Convolutional Neural Networks (CNNs) to calculate the total number of COVID-19 cases. In this study, an effort was made to improve the correctness of the models by incorporating recent advancements in attention-based models for time-series forecasting. The resulting model was found to perform better than other existing models and showed improved accuracy in forecasting. Using the data from different countries and adapting it to the model will enhance its ability to support the worldwide effort to combat the pandemic by giving more precise projections of cases.

  🖺 Full Text HTML: Forecasting COVID-19 New Cases Using Transformer Deep Learning Model
• Serum Antibody Fingerprinting for SARS-CoV-2 Variants in Infected and Vaccinated Subjects by Label-Free Microarray Biosensor -

  Both viral infection and vaccination affect the antibody repertoire of a person. Here we demonstrate that the analysis of serum antibodies carries information not only on the virus type that caused the infection, but also on the specific virus variant. We developed a rapid multiplex assay providing a fingerprint of serum antibodies against five different SARS-CoV-2 variants, based on a microarray of virus antigens immobilized on the surface of a label-free reflectometric biosensor. We analyzed serum from plasma of convalescent subjects and vaccinated volunteers and extracted individual antibody profiles of both total immunoglobulin Ig and IgA fraction. We found that Ig level profiles were strongly correlated with the specific variant of infection or vaccination and that vaccinated subjects displayed larger quantity of total Ig and lower fraction of IgA relative to the population of convalescent unvaccinated subjects.

  🖺 Full Text HTML: Serum Antibody Fingerprinting for SARS-CoV-2 Variants in Infected and Vaccinated Subjects by Label-Free Microarray Biosensor
• The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response -

  Protection against SARS-CoV-2 wanes over time, and booster uptake has been low, in part because of concern about side effects. We examined the relationships between local and systemic symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 364) who received two doses of either BNT162b2 or mRNA-1273. Serum nAB concentration was measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater increases in skin temperature and heart rate after the second dose predicted higher nAB levels at both time points, but skin temperature change was more predictive of durable (6 month) nAB response than of short-term (1 month) nAB response. In the context of low ongoing vaccine uptake, our convergent symptom and biometric findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.

  🖺 Full Text HTML: The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response
• Urban and rural disparities in life expectancy drops during the COVID-19 pandemic were not uniform across European countries -
  This paper explores differences in mortality dynamics between urban and rural areas of 20 European countries during the two pandemic years 2020 and 2021. The link between population density and the spread of communicable diseases is a well-established phenomenon, yet to what extent this results in a mortality gap after years of ongoing epidemics is a less explored question. We find pronounced and significant differences, with urban areas being harder hit by COVID-19 mortality in most countries.
  🖺 Full Text HTML: Urban and rural disparities in life expectancy drops during the COVID-19 pandemic were not uniform across European countries
• Non-generalizability of biomarkers for mortality in SARS-CoV-2: a meta-analyses series -

  Rationale: Sophisticated prognostic scores have been proposed for SARS-CoV-2 but do not always perform consistently. We conducted these meta-analyses to uncover why and to investigate the impact of vaccination and variants. Methods: We searched the PubMed database for the keywords: SARS-CoV-2 with biomarker and mortality. All studies published from 01/12/2020 to 31/03/2023 were surveyed. To aggregate the data, the meta library in R was used, and a random effects model fitted to obtain pooled AUCs and 95% confidence intervals for the European/North American, Asian, and overall datasets. Results: Biomarker effectiveness varies significantly in different continents. Admission CRP levels are a good prognostic marker for mortality in Asian countries, with a pooled area under curve (AUC) of 0.83 (95%CI 0.80-0.85), but only an average predictor of mortality in Europe/North America, with a pooled AUC of 0.67 (95%CI 0.63-0.71, P<0.0001). We observed the same pattern for D-dimer and IL-6. This variability explains why the proposed prognostic scores did not perform evenly. Notably, urea and troponin had pooled AUCs ≥0.78 regardless of location, implying that end-organ damage at presentation is a key prognostic factor. Very little data is available for vaccinated and variant cohorts but it appears that inflammatory biomarkers are performing less well. We note a significant lag from the pandemic advent to data availability and this has no doubt impacted on patient care. Conclusions: Biomarker efficacies vary considerably by region. It is imperative that the infrastructure for collecting clinical data should be put in place ahead of a future pandemic.

  🖺 Full Text HTML: Non-generalizability of biomarkers for mortality in SARS-CoV-2: a meta-analyses series

From Clinical Trials

• A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection
  Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
  Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.
  Recruiting

• Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting - Conditions: Post COVID-19 Condition (PCC)
  Interventions: Device: RDX-19
  Sponsors: KNOWBio Inc.; NAMSA
  Recruiting

• CPAP Therapy Through a Helmet or an Oronasal Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study - Conditions: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia
  Interventions: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate
  Sponsors: I.M. Sechenov First Moscow State Medical University
  Recruiting

• Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease - Conditions: COVID-19 Pneumonia; Virus Diseases; COVID-19
  Interventions: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment
  Sponsors: AVB Biotechnology
  Recruiting

• A PhaseⅠ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection
  Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
  Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital
  Recruiting

• SAFE Workplace Intervention for People With IDD - Conditions: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm
  Interventions: Behavioral: SAFE Employment Training
  Sponsors: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research
  Recruiting

• Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms - Conditions: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame
  Interventions: Behavioral: EMDR
  Sponsors: University of Pisa
  Completed

• Lithium Long COVID Dose-finding Study - Conditions: Long COVID
  Interventions: Dietary Supplement: Lithium
  Sponsors: State University of New York at Buffalo
  Not yet recruiting

• Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function - Conditions: COVID-19 Pneumonia
  Interventions: Drug: GST-HG171 Tablets
  Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
  Recruiting

• Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic - Conditions: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children
  Interventions: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education
  Sponsors: Chung Shan Medical University
  Completed

• Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function - Conditions: COVID-19 Pneumonia
  Interventions: Drug: GST-HG171 Tablets
  Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
  Completed

• Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2 - Conditions: SARS-CoV-2 Infection; COVID-19; Coronavirus
  Interventions: Device: eBAM Cov Testing
  Sponsors: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE
  Not yet recruiting

• Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult - Conditions: COVID-19
  Interventions: Biological: EG-COVII
  Sponsors: EyeGene Inc.
  Recruiting

• Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers - Conditions: Viral Infection COVID-19
  Interventions: Drug: Aterixen
  Sponsors: Valenta Pharm JSC
  Not yet recruiting

• Long COVID Brain Fog: Cognitive Rehabilitation Trial - Conditions: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome
  Interventions: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring
  Sponsors: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research
  Not yet recruiting

From PubMed

• Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon - Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo. Moreover, lipin-2 also acts as a regulator of…

• Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia - Nitric oxide (NO), a gaseous free radical produced from L-arginine catalyzed by NO synthase, functions as an important signaling molecule in the human body. Its antiviral activity was confirmed in the 1990s, and has been studied more extensively since the outbreak of the SARS pandemic in 2003. In the fight against the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some recent studies have revealed the potential of NO in the treatment of coronavirus disease 2019…

• Understanding psychology students’ perspective on video psychotherapy and their intention to offer it after graduation: a mixed-methods study - INTRODUCTION: Video psychotherapy (VPT) demonstrated strong clinical efficacy in the past, with patients and psychotherapists expressing satisfaction with its outcomes. Despite this, VPT only gained full recognition from the German healthcare system during the COVID-19 pandemic. As society increasingly relies on new media, it seems likely that VPT will become even more relevant. Previous studies surveyed practicing psychotherapists and patients about advantages and disadvantages of VPT. In…

• Oral mucosa immunity: ultimate strategy to stop spreading of pandemic viruses - Global pandemics are most likely initiated via zoonotic transmission to humans in which respiratory viruses infect airways with relevance to mucosal systems. Out of the known pandemics, five were initiated by respiratory viruses including current ongoing coronavirus disease 2019 (COVID-19). Striking progress in vaccine development and therapeutics has helped ameliorate the mortality and morbidity by infectious agents. Yet, organism replication and virus spread through mucosal tissues cannot be…

• Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation associated transcription factors - The novel coronavirus SARS-CoV-2, responsible for COVID-19, can trigger dysregulated immune responses known as cytokine release syndrome (CRS), leading to severe organ dysfunction and respiratory distress. Our study focuses on developing an improved cell-permeable nuclear import inhibitor, iCP-NI, capable of blocking the nuclear transport of inflammation-associated transcription factors (IATFs), specifically nuclear factor kappa B (NF-κB). By fusing advanced macromolecule transduction domains…

• Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice - Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus…

• The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus - Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei)…

• Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story - Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory…

• Veratramine Inhibits Porcine Epidemic Diarrhea Virus Entry through Macropinocytosis by Suppressing PI3K/Akt Pathway - Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50% inhibitory concentration (IC(50)) of ∼ 5 µM. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virus…

• Promising role of Vitamin D and plant metabolites against COVID-19: Clinical trials review - Vitamin D possesses immunomodulatory qualities and is protective against respiratory infections. Additionally, it strengthens adaptive and cellular immunity and boosts the expression of genes involved in oxidation. Experts suggested taking vitamin D supplements to avoid and treat viral infection and also COVID-19, on the other hand, since the beginning of time, the use of plants as medicines have been vital to human wellbeing. The WHO estimates that 80 % of people worldwide use plants or herbs…

• Plant-Derived Antioxidants for Management of COVID-19: A Comprehensive Review of Molecular Mechanisms - We aimed to review the literature to introduce some effective plant-derived antioxidants to prevent and treat COVID-19. Natural products from plants are excellent sources to be used for such discoveries. Among different plant-derived bioactive substances, components including luteolin, quercetin, glycyrrhizin, andrographolide, patchouli alcohol, baicalin, and baicalein were investigated for several viral infections as well as SARS-COV-2. The mechanisms of effects detected for these agents were…

• SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was…

• A novel cell-permeable peptide prevents protein SUMOylation and supports the mislocalization and aggregation of TDP-43 - SUMOylation is a post-translational modification (PTM) that exerts a regulatory role in different cellular processes, including protein localization, aggregation, and biological activities. It consists of the dynamic formation of covalent isopeptide bonds between a family member of the Small Ubiquitin Like Modifiers (SUMOs) and the target proteins. Interestingly, it is a cellular mechanism implicated in several neurodegenerative pathologies and potentially it could become a new therapeutic…

• Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions - CONCLUSIONS: The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.

• Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis - Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe COVID-19 upon infection with SARS-CoV-2. The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis. Serum from 53 SARS-CoV-2 unexposed and unvaccinated individuals, with decompensated liver…

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