Covid-19 Sentry

Contents

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

From Preprints

• Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera -
  Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
  🖺 Full Text HTML: Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera
• Care-full Collectives and their Care Practices -
  In my dissertation, I examine different collectives and their practices through different applied theories of care and theorize on new organizational structures and rituals. This is a study of how people came together during the first wave of Covid-19, myself included. It studies these coming-togethers through different “do-ings” and “be–ings” and juxtaposes them with different theories of care. Theories that include Annemarie Mol’s “Logic of Care”, Ella Myers’ “Worldly things”, Jenna Grant’s “Repair as Care”, Sara Ahmed’s “Fragile Connections” and Lucy Suchman’s “Relocating Innovation”. These different theories come from places like medical anthropology, STS, queer theory, and more. I give an honest account of my journey through these collectives and these theories. I also start to propose an alternate way of organizing institutions for mutual aid through two tools - archetypes and axioms.
  🖺 Full Text HTML: Care-full Collectives and their Care Practices
• Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals. -

  Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination.  In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population.  Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse.  Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities.  Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2.  In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

  🖺 Full Text HTML: Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.
• The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence -
  A randomized survey experiment (N=2,868) was conducted at the onset of the COVID-19 pandemic to examine the effects of information provision on individuals’ cooperation with social distancing measures. Employing a 2 × 2 factorial design, the study examined the influence of social comparison and a powerful messenger. Using an online sample of approximately 3,000 Japanese respondents, it was found that participants demonstrated greater cooperation with social distancing measures when they perceived that they had spent a relatively long time outside the home compared with prevailing social norms in the previous week. Conversely, individuals who spent a relatively short time outside the home, exhibited the opposite effect. However, these results were observed solely in conjunction with the influence of a powerful messenger. The study also explored heterogeneous responses based on personality traits. In conclusion, the results highlight the challenges of changing behavior through informational interventions, emphasizing the role of both the characteristics of the sender and recipient of the information.
  🖺 Full Text HTML: The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence
• Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19 -
  The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.
  🖺 Full Text HTML: Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19
• Within-host genetic diversity of SARS-CoV-2 across animal species -
  Infectious disease transmission to different host species makes eradication very challenging and expands the diversity of evolutionary trajectories taken by the pathogen. Since the beginning of the ongoing COVID-19 pandemic, SARS-CoV-2 has been transmitted from humans to many different animal species, and viral variants of concern could potentially evolve in a non-human animal. Previously, using available whole genome consensus sequences of SARS-CoV-2 from four commonly sampled animals (mink, deer, cat, and dog) we inferred similar numbers of transmission events from humans to each animal species but a relatively high number of transmission events from mink back to humans (Naderi et al., 2023). Using a genome-wide association study (GWAS), we identified 26 single nucleotide variants (SNVs) that tend to occur in deer – more than any other animal – suggesting a high rate of viral adaptation to deer. Here we quantify intra-host SARS-CoV-2 across animal species and show that deer harbor more intra-host SNVs (iSNVs) than other animals, providing a larger pool of genetic diversity for natural selection to act upon. Within-host diversity is particularly high in deer lymph nodes compared to nasopharyngeal samples, suggesting tissue-specific differences in viral population sizes or selective pressures. Neither mixed infections involving more than one viral lineage nor large changes in the strength of selection are likely to explain the higher intra-host diversity within deer. Rather, deer are more likely to contain larger viral population sizes, to be infected for longer periods of time, or to be systematically sampled at later stages of infections. Combined with extensive deer-to-deer transmission, the high levels of within-deer viral diversity help explain the apparent rapid adaptation of SARS-CoV-2 to deer.
  🖺 Full Text HTML: Within-host genetic diversity of SARS-CoV-2 across animal species
• Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology -
  Background: Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods: We used a bioinformatics and systems biology approach to investigate the relationship between GC and COVID-19. The gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results: A total of 209 shared DEGs were identified to explore the linkages between COVID-19 and GC. Functional analyses showed that Immune-related pathway collectively participated in the development and progression of COVID-19 and GC. In addition, there are selected 10 hub genes including CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, and IFIT2. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This study also provides insight into the diseases most associated with mutual DEGs, which may provide new ideas for research on the treatment of COVID-19. Conclusions: This research has the possibility to be contributed to effective therapeutic in COVID-19 and GC.
  🖺 Full Text HTML: Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology
• Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19 -
  The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discovered a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with leads revealed that the residues E164 and Q269 around the S2 site are critical for improving the inhibitor's potency. The lead compound GZNL-P36 not only inhibited SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibited HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 M, respectively. Oral administration of the compound resulted in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitor is a promising SARS-CoV-2 therapy.
  🖺 Full Text HTML: Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19
• Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle -
  Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose a significant threat to public health globally. Notably, SARS-CoV-2 demonstrates a unique capacity to infect various non-human animal species, documented in captive and free-living animals. However, experimental studies revealed low susceptibility of domestic cattle (Bos taurus) to ancestral B.1 lineage SARS-CoV-2 infection, with limited viral replication and seroconversion. Despite the emergence of viral variants with potentially altered host tropism, recent experimental findings indicate greater permissiveness of cattle to SARS-CoV-2 Delta variant infection compared to other variants, though with limited seroconversion and no clear evidence of transmission. While some studies detected SARS-CoV-2 antibodies in cattle in Italy and Germany, there is no evidence of natural SARS-CoV-2 infection in cattle from the United States or elsewhere. Since serological tests have inherent problems of false positives and negatives, we conducted a comprehensive assessment of multiple serological assays on over 600 cattle serum samples, including pre-pandemic and pandemic cattle sera. We found that SARS-CoV-2 pseudovirus neutralization assays with a luciferase reporter system can produce false positive results, and care must be taken to interpret serological diagnosis using these assays. We found no serological evidence of natural SARS-CoV-2 infection or transmission among cattle in the USA. Hence, it is critical to develop more reliable serological assays tailored to accurately detect SARS-CoV-2 antibodies in cattle populations and rigorously evaluate diagnostic tools. This study underscores the importance of robust evaluation when employing serological assays for SARS-CoV-2 detection in cattle populations.
  🖺 Full Text HTML: Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle
• Visualization Guardrails: Designing Interventions Against Cherry-Picking in Interactive Data Explorers -
  The growing popularity of interactive time series exploration platforms has made visualizing data of public interest more accessible to general audiences. At the same time, the democratized access to professional-looking explorers with preloaded data enables the creation of convincing visualizations with carefully cherry-picked items. Prior research shows that people use data explorers to create and share charts that support their potentially biased or misleading views on public health or economic policy and that such charts have, for example, contributed to the spread of COVID-19 misinformation. Interventions against misinformation have focused on post hoc approaches such as fact-checking or removing misleading content, which are known to be challenging to execute. In this work, we explore whether we can use visualization design to impede cherry-picking—one of the most common methods employed by deceptive charts created on data exploration platforms. We describe a design space of guardrails—interventions against cherry-picking in time series explorers. Using our design space, we create a prototype data explorer with four types of guardrails and conduct two crowd-sourced experiments. In the first experiment, we challenge participants to create cherry-picked charts. We then use these charts in a second experiment to evaluate the guardrails’ impact on the perception of cherry-picking. We find evidence that guardrails—particularly superimposing relevant primary data—are successful at encouraging skepticism in a subset of experimental conditions but come with limitations. Based on our findings, we propose recommendations for developing effective guardrails for visualizations.
  🖺 Full Text HTML: Visualization Guardrails: Designing Interventions Against Cherry-Picking in Interactive Data Explorers
• Misleading Beyond Visual Tricks: How People Actually Lie with Charts -
  Data visualizations can empower an audience to make informed decisions. At the same time, deceptive representations of data can lead to inaccurate interpretations while still providing an illusion of data-driven insights. Existing research on misleading visualizations primarily focuses on examples of charts and techniques previously reported to be deceptive. These approaches do not necessarily describe how charts mislead the general population in practice. We instead present an analysis of data visualizations found in a real-world discourse of a significant global event—Twitter posts with visualizations related to the COVID-19 pandemic. Our work shows that, contrary to conventional wisdom, violations of visualization design guidelines are not the dominant way people mislead with charts. Specifically, they do not disproportionately lead to reasoning errors in posters’ arguments. Through a series of examples, we present common reasoning errors and discuss how even faithfully plotted data visualizations can be used to support misinformation online.
  🖺 Full Text HTML: Misleading Beyond Visual Tricks: How People Actually Lie with Charts
• Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes -

  A substantial proportion of acute SARSCoV2 infection cases exhibit gastrointestinal symptoms, yet the genetic determinants of these extrapulmonary manifestations are poorly understood. Using survey data from 239,866 individuals who tested positively for SARSCoV2, we conducted a multi-ancestry GWAS of 80,289 cases of diarrhea occurring during acute COVID19 infection (33.5%). Six loci (CYP7A1, LZFTl1/CCR9, TEME182, NALCN, LFNG, GCKR) met genomewide significance in a trans-ancestral analysis. The top significant GWAS hit mapped to the CYP7A1 locus, which plays an etiologic role in bile acid metabolism and is in high LD (r2= 0.93) with the SDCBP gene, which was previously implicated in antigen processing and presentation in the COVID-19 context. Another association was observed with variants in the LZTFL1/CCR9 region, which is a known locus for COVID19 susceptibility and severity. PheWAS showed a shared association across three of the six SNPs with irritable bowel syndrome (IBS) and its subtypes. Mendelian randomization showed that genetic liability to IBS-diarrhea increased (OR=1.40,95%,CI[1.33,1.47]), and liability to IBS-constipation decreased (OR=0.86, 95%CI[0.79,0.94]) the relative odds of experiencing COVID19+ diarrhea. Our genetic findings provide etiological insights into the extrapulmonary manifestations of acute SARSCoV2 infection.

  🖺 Full Text HTML: Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes
• Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study -

  Abstract: Objectives: This study aimed to assess the safety and preliminary efficacy of MiSaver stem cells in enhancing left ventricular ejection function and functional activity among patients with acute myocardial infarction (AMI). Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with heart attacks and strokes accounting for a significant portion of deaths. Recovery of left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is crucial for prognosis, as patients with poor LVEF recovery face increased risks of sudden cardiac arrest events and mortality. Stem cell therapy offers regenerative potential for cardiovascular diseases, yet accessibility remains limited. This study investigates the safety and efficacy of MiSaver, a prefabricated stem cell investigational product, in recent AMI patients, aiming to enhance accessibility and patient outcomes. Methods: Patients who were admitted for AMI within 7 days and had reduced LVEF (≤45%) were eligible for the study. MiSaver were matched for blood group and administered in participants in cohorts of five, each receiving escalating dosages (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg, respectively). Patients were assessed for symptoms of graft-versus-host disease (GVHD) and treatment-related adverse events (AE). LVEF measured by echocardiographic on admission, at 6 months, and at 12 months after treatment. Patients functional activity status evalution ( using the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classification systems. Results: Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved left ventricular ejection fraction (LVEF), accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline. Conclusion: Intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups, suggesting potential for improving left ventricular function following AMI. However, further research with larger cohorts and controlled placebos is necessary to confirm these findings and address trial limitations encountered.

  🖺 Full Text HTML: Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study
• Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia -

  Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters, which suggests that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms.

  🖺 Full Text HTML: Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia
• Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study -

  Abstract: Objectives: This study aimed to assess the safety and preliminary efficacy of MiSaver stem cells in enhancing left ventricular ejection function and functional activity among patients with acute myocardial infarction (AMI). Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with heart attacks and strokes accounting for a significant portion of deaths. Recovery of left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is crucial for prognosis, as patients with poor LVEF recovery face increased risks of sudden cardiac arrest events and mortality. Stem cell therapy offers regenerative potential for cardiovascular diseases, yet accessibility remains limited. This study investigates the safety and efficacy of MiSaver, a prefabricated stem cell investigational product, in recent AMI patients, aiming to enhance accessibility and patient outcomes. Methods: Patients admitted for AMI with reduced LVEF (≤45%) were eligible. MiSaver stem cells, matched for blood group, were administered to participants in cohorts of five, with escalating dosages (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg) 2-5 days post-AMI onset. Echocardiographic assessments were conducted upon admission, at 6 months, and at 12 months post-treatment. Results: Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved left ventricular ejection fraction (LVEF), accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline. Conclusion: Intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups, suggesting potential for improving left ventricular function following AMI. However, further research with larger cohorts and controlled placebos is necessary to confirm these findings and address trial limitations encountered.

  🖺 Full Text HTML: Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study

From Clinical Trials

• Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID - Conditions: Long COVID; Brain Fog; Cognitive Change
  Interventions: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose
  Sponsors: Taipei Veterans General Hospital, Taiwan
  Not yet recruiting

• Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19
  Interventions: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF).
  Sponsors: University of the State of Santa Catarina; Larissa Sinhorim
  Recruiting

• Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure - Conditions: Acute Respiratory Failure
  Interventions: Behavioral: Standard of Care; Behavioral: Rehabilitation
  Sponsors: Hospital Israelita Albert Einstein
  Not yet recruiting

• Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD) - Conditions: Post-Acute Sequelae of COVID-19
  Interventions: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program
  Sponsors: University of Minnesota
  Recruiting

From PubMed

• DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients - Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and…

• Immunoglobulin G4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant - CONCLUSION: Heterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

• Toll like receptor 4 mediates the inhibitory effect of SARS-CoV-2 spike protein on proximal tubule albumin endocytosis - Tubular proteinuria is a common feature in COVID-19 patients, even in the absence of established acute kidney injury. SARS-CoV-2 spike protein (S protein) was shown to inhibit megalin-mediated albumin endocytosis in proximal tubule epithelial cells (PTECs). Angiotensin-converting enzyme type 2 (ACE2) was not directly involved. Since Toll-like receptor 4 (TLR4) mediates S protein effects in various cell types, we hypothesized that TLR4 could be participating in the inhibition of PTECs albumin…

• Coordination chemistry suggests that independently observed benefits of metformin and Zn(2+) against COVID-19 are not independent - Independent trials indicate that either oral Zn^(2+) or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn^(2+) deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn^(2+) is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn^(2+) bioavailability and active absorption by cation transporters known to transport…

• SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system…

• Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses - BACKGROUND: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms.

• Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-β). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and…

• TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency - INTRODUCTION: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition.

• Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19 - CONCLUSIONS: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.

• Quercetin inhibition of porcine intestinal alpha coronavirus in vitro and in vivo - CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.

• Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques - CONCLUSIONS: We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.

• A rigorous theoretical and numerical analysis of a nonlinear reaction-diffusion epidemic model pertaining dynamics of COVID-19 - The spatial movement of the human population from one region to another and the existence of super-spreaders are the main factors that enhanced the disease incidence. Super-spreaders refer to the individuals having transmitting ability to multiple pathogens. In this article, an epidemic model with spatial and temporal effects is formulated to analyze the impact of some preventing measures of COVID-19. The model is developed using six nonlinear partial differential equations. The infectious…

• A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV) - CONCLUSION: Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.

• SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling - Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse…

• Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19? - The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and…

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