Covid-19 Sentry

Contents

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

From Preprints

• Refining COVID-19 retrospective diagnosis with continuous serological tests: a Bayesian mixture model -

  COVID-19 serological tests with a “positive”, “intermediate” or “negative” result according to predefined thresholds cannot be directly interpreted as a probability of having been infected with SARS-CoV-2. Based on 81,797 continuous anti-spike tests collected in France after the first wave, a Bayesian mixture model was developed to provide a tailored infection probability for each participant. Depending on the serological value and the context (age and administrative region), a negative or a positive test could correspond to a probability of infection as high as 61.9% or as low as 68.0%, respectively. In infected individuals, the model estimated a proportion of “non-responders” of 14.5% (95% CI, 11.2-18.1%), corresponding to a sub-group of persons who exhibited a weaker serological response to SARS-CoV-2. This model allows for an individual interpretation of serological results as a probability of infection, depending on the context and without any notion of threshold.

  🖺 Full Text HTML: Refining COVID-19 retrospective diagnosis with continuous serological tests: a Bayesian mixture model
• MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity. -
  Background: Despite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics. Methods: In this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi-omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients. Results: As COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods. Conclusions: This approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
  🖺 Full Text HTML: MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity.
• Cooperativity and induced oligomerisation control the interaction of SARS- CoV-2 with its cellular receptor and patient-derived antibodies -
  Viral entry is mediated by oligomeric proteins on the virus and cell surfaces. The association is therefore open to multivalent interactions between these proteins, yet such recognition is typically rationalised as affinity between monomeric equivalents. As a result, assessment of the thermodynamic mechanisms that control viral entry has been limited. Here, we use mass photometry to overcome the analytical challenges consequent to multivalency. Examining the interaction between the spike protein of SARS-CoV-2 and the ACE2 receptor, we find that ACE2 induces oligomerisation of spike in a variant- dependent fashion. We also demonstrate that patient-derived antibodies use induced-oligomerisation as a primary inhibition mechanism or to enhance the effects of receptor-site blocking. Our results reveal that naive affinity measurements are poor predictors of potency, and introduce a novel antibody-based inhibition mechanism for oligomeric targets.
  🖺 Full Text HTML: Cooperativity and induced oligomerisation control the interaction of SARS- CoV-2 with its cellular receptor and patient-derived antibodies
• The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a lipid-enveloped virus that acquires its lipid bilayer from the host cell it infects. SARS-CoV-2 can spread from cell to cell or from patient to patient by undergoing assembly and budding to form new virions. The assembly and budding of SARS-CoV-2 is mediated by several structural proteins known as envelope (E), membrane (M), nucleoprotein (N) and spike (S), which can form virus-like particles (VLPs) when co-expressed in mammalian cells. Assembly and budding of SARS-CoV-2 from the host ER-Golgi intermediate compartment is a critical step in the virus acquiring its lipid bilayer. To date, little information is available on how SARS-CoV-2 assembles and forms new viral particles from host membranes. In this study, we find the N protein can strongly associate with anionic lipids including phosphoinositides and phosphatidylserine. Moreover, lipid binding is shown to occur in the N protein C-terminal domain, which is supported by extensive in silico analysis. Anionic lipid binding occurs for both the free and N oligomeric forms suggesting N can associate with membranes in the nucleocapsid form. Herein we present a lipid-dependent model based on in vitro, cellular and in silico data for the recruitment of N to M assembly sites in the lifecycle of SARS-CoV-2.
  🖺 Full Text HTML: The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes
• Enhanced neutralization of SARS-CoV-2 XBB sub-lineages and BA.2.86 by a tetravalent COVID-19 vaccine booster -
  As the SARS-CoV-2 virus continues to evolve, novel XBB sub-lineages such as XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3, as well as the most recent BA.2.86, have been identified and aroused global concern. Understanding the efficacy of current vaccines and the immune system's response to these emerging variants is critical for global public health. In this study, we evaluated the neutralization activities of sera from participants who received COVID-19 inactivated vaccines, or a booster vaccination of the recently approved tetravalent protein vaccine in China (SCTV01E), or had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Comparative analysis of their neutralization profiles against a broad panel of 30 SARS-CoV-2 sub-lineage viruses revealed that strains such as BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibited heightened resistance to neutralization than previous variants, however, despite the extra mutations carried by emerging XBB sub-lineages and BA.2.86, they did not demonstrate significantly increased resistance to neutralization compared to XBB.1.5. Encouragingly, the SCTV01E booster vaccination consistently induced robust and considerably higher neutralizing titers against all these variants than breakthrough infection did. Cellular immunity assays also showed that the SCTV01E booster vaccination elicited a higher frequency of virus-specific memory B cells but not IFN-{gamma} secreting T cells. Our findings underline the importance of developing novel multivalent vaccines to more effectively combat future viral variants.
  🖺 Full Text HTML: Enhanced neutralization of SARS-CoV-2 XBB sub-lineages and BA.2.86 by a tetravalent COVID-19 vaccine booster
• Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics -
  We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 Spike (S) protein. With this approach, we first identified Candidate Adaptive Polymorphisms (CAPs) of the SARS-CoV-2 Spike protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of S protein compared to the closed form. In particular, the CAP sites control the dynamics binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly compensatory variants. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding.
  🖺 Full Text HTML: Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics
• Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection -

  Abstract: Background Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found that alox genes, involved in eicosanoid synthesis, were up-regulated in high WHO score patients, especially in goblet cells. Herein, we aimed to further understand the roles played by eicosanoids during severe SARS-CoV-2 infection. Methods and findings We performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways. Conclusions Our study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.

  🖺 Full Text HTML: Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection
• Diagnostic testing and the evolution of detection avoidance by pathogens -

  Diagnostic testing is a key tool in the fight against many infectious diseases. The emergence of pathogen variants that are able to avoid detection by diagnostic testing therefore represents a key challenge for public health. In recent years, variants for multiple pathogens have emerged which escape diagnostic testing, including mutations in Plasmodium falciparum (malaria), Chlamydia trachomatis (chlamydia) and SARS-CoV-2 (COVID-19). However, little is currently known about when and the extent to which diagnostic test escape will evolve. Here we use a mathematical model to explore how the frequency of diagnostic testing, combined with variation in compliance and efficacy of quarantining, together drive the evolution of detection avoidance. We derive key thresholds under which a testing regime will (i) select for diagnostic test avoidance, or (ii) drive the pathogen extinct. Crucially, we show that imperfect compliance with diagnostic testing regimes can have marked effects on selection for detection avoidance, and consequently, for disease control. Yet somewhat counterintuitively, we find that an intermediate level of testing can select for the highest level of detection avoidance. Our results, combined with evidence from various pathogens, demonstrate that the evolution of diagnostic testing avoidance should be carefully considered when designing diagnostic testing regimes.

  🖺 Full Text HTML: Diagnostic testing and the evolution of detection avoidance by pathogens
• Assessing the impact of the Gamma variant on COVID-19 Patient admissions in a Southern Brazilian tertiary hospital - A comparison of dual pandemic phases -

  Since the first case of COVID-19, Brazil has undergone infection waves with distinct characteristics. The description of new variants has alerted the emergence of more contagious or virulent viruses. The variant of concern Gamma emerged in Brazil and caused an epidemic wave, but its spread outside the country was limited. We report the clinical epidemiological profile of hospitalized patients with COVID-19 by comparing two periods. A retrospective cohort study was performed. The primary outcome was to assess individuals with COVID-19 admitted in wards and intensive care units at CHC-UFPR between March 2020 and July 2021, correlating demographic, clinical-epidemiologic, and survival data with the most prevalent viral variant found in each period. We used Kaplan?Meier analysis to estimate the probability of survival and receiver operating characteristic curves to evaluate laboratory tests to find a cutoff point for poor outcomes. Data from 2,887 individuals were analyzed, 1,495 and 1,392 from the first and second periods, respectively. Hospitalization predominated among males in both periods, and the median age was significantly lower in the second one. The frequency of comorbidities was similar. Various demographic factors, clinical assessments, and laboratory tests were examined in relation to greater severity. When comparing the two studied periods, we observed predominance of the Wild virus during the first wave and the Gamma variant during the second, with no significant difference in outcomes. The findings suggest that despite the association of many factors with increased severity, the temporal variation between the two periods did not result in a notable divergence in the measured outcomes. The COVID-19 pandemic has lasted for a long time, with periods marked by peaks of cases, often caused by the emergence of viral variants, resulting in higher infection rates and rapid dissemination but, for variant Gamma, no apparent greater virulence.

  🖺 Full Text HTML: Assessing the impact of the Gamma variant on COVID-19 Patient admissions in a Southern Brazilian tertiary hospital - A comparison of dual pandemic phases
• Associations with LGBTQ+ mental health disparities during the COVID-19 pandemic -
  The COVID-19 pandemic has created tremendous, and unequal, burdens on mental and physical health throughout the United States. Prior work suggests that LGBTQ+ individuals have experienced disproportionate harms during the COVID-19 pandemic, but potential mechanisms underlying these disparities remain unclear. In a large (N=893) sample of US LGBTQ+ adults, we examined four theoretically derived risk factors as potential contributors to depression, anxiety, and suicidal ideation during the summer of 2020. Stressors and disruptions due to the COVID-19 pandemic were common, with over 25% of participants experiencing changes in their living situation, 40% reporting interruptions in health care access, and high levels of stress due to social isolation, financial concerns, and increased mental health symptoms. We found that social disconnection, disruptions in health care, financial strain, and efforts to avoid disclosing one’s sexual orientation or gender identity at home were each associated with poorer mental health, with the largest effects evident for identity disclosure avoidance. Transgender and non-binary adults reported poorer mental health overall, but gender identity did not moderate the effects of other tested risk factors. Results highlight the importance of considering LGBTQ+ mental health in the context of minority stressors, in addition to more general social determinants of health.
  🖺 Full Text HTML: Associations with LGBTQ+ mental health disparities during the COVID-19 pandemic
• Outbreak of severe community-acquired bacterial infections from Streptococcus pyogenes, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae among children in North Rhine-Westphalia (Germany), October to December 2022 -

  Background: In late 2022, a surge of severe bacterial infections caused by S. pyogenes was reported in several European countries, including Germany. This study assessed disease burden and severity of hospitalizations for community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in North Rhine-Westphalia (NRW), Germany, during the last quarter of 2022 compared to long-term incidences. Methods: Hospital cases due to bacterial infections between October and December 2022 were collected from 59/62 (95 %) children9s hospitals in NRW and combined with surveillance data (2016 - 2023) from the national reference laboratories for streptococci, N. meningitidis, and H. influenzae. Total cases in NRW and incidence rates from January 2016 to March 2023 were estimated by capture-recapture analyses. Expected annual deaths from the studied pathogens were calculated from national death cause statistics. Results: Between October and December 2022, 153 cases with high overall disease severity were reported with pneumonia being most common (59 %, n = 91). Incidence rates of bacterial infections declined at the beginning of the COVID-19 pandemic. In late 2022 and early 2023 a massive surge to levels unprecedented since 2016 was observed, mainly driven by S. pyogenes and S. pneumoniae. Observed deaths during the study period exceeded the expected number for the entire year in NRW by far (7 vs. 0.9). Discussion: The unprecedented peak of bacterial infections in late 2022 and early 2023 was caused by various mechanisms intertwined that require close surveillance and improved precautionary measures for future outbreaks.

  🖺 Full Text HTML: Outbreak of severe community-acquired bacterial infections from Streptococcus pyogenes, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae among children in North Rhine-Westphalia (Germany), October to December 2022
• Regulation of interferon signaling by transposon exonization -
  Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues, and functions as a decoy receptor that potently inhibits interferon signaling including in cells infected with SARS-CoV-2. Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.
  🖺 Full Text HTML: Regulation of interferon signaling by transposon exonization
• Worldwide case of COVID-19 cabin fever as a motivator for conservation and sustainable action -
  Exposure to nature is increasingly regarded as a key part of human health, and the recognition that urban environments must provide access to green spaces for the wellbeing of citizens. The beginning of the COVID-19 pandemic in 2020 led to many governments issuing stay-at-home orders and closing parks, limiting the options of accessible green spaces for people seeking to safely socialise and cope with stress. Here, we gain a global perspective on the speed people returned to nature (visiting parks and beaches) in comparison to necessities (accessing groceries and pharmaceuticals) and luxury activities (retail purchases and recreation) following COVID-19 lockdowns using Google Mobility data. Globally, we found that people returned to nature 30 days after returning to shop for essentials and 105 days to return to luxuries. Central Asia, Europe, and North America returned to nature before necessities. The rapidity with which people chose to spend time in nature indicates the value of these spaces to people and the need to increase access to them. However, the large-scale return to nature also highlighted the need to promote messages on how to minimise our impacts in these spaces. One strong way to motivate conservation and sustainability action is to ensure that people have access to nature and green spaces, which can foster pro-environmental behaviour.
  🖺 Full Text HTML: Worldwide case of COVID-19 cabin fever as a motivator for conservation and sustainable action
• Predictors of COVID-19 Vaccine Acceptability Among Refugees and Other Migrant Populations: A Systematic Scoping Review -

  Objective. This study aimed to map the existing literature to identify predictors of COVID-19 vaccine acceptability among refugees, immigrants, and other migrant populations. Methods. A systematic search of Medline, Embase, APA PsycInfo and Cumulative Index of Nursing and Allied Health Literature (CINAHL) was conducted up to 31 January 2023 to identify the relevant English peer-reviewed observational studies. Two independent reviewers screened, selected studies, and extracted data. Results. We identified 34 cross-sectional studies, primarily conducted in high income countries (76%). Lower vaccine acceptance was associated with mistrust in the host countries9 government and healthcare system, concerns about the safety and effectiveness of COVID-19 vaccines, limited knowledge of COVID-19 infection and vaccines, lower COVID-19 risk perception, and lower integration level in the host country. Female gender, younger age, lower education level, and being single were associated with lower vaccine acceptance in most studies. Additionally, sources of information about COVID-19 and vaccines and previous history of COVID-19 infection, also influence vaccine acceptance. Vaccine acceptability towards COVID-19 booster doses and various vaccine brands were not adequately studied. Conclusions. Vaccine hesitancy and lack of trust in COVID-19 vaccines became significant public health concerns within migrant populations. These findings may help in providing information for current and future vaccine outreach strategies among migrant populations.

  🖺 Full Text HTML: Predictors of COVID-19 Vaccine Acceptability Among Refugees and Other Migrant Populations: A Systematic Scoping Review
• Clinical Performance of SARS-CoV-2 Rapid Antigen Tests: A Systematic Review and Meta-Analysis -

  Objectives: We conducted a meta-analysis of RAT diagnostic accuracy for SARS-CoV-2 infections, and further evaluated test sensitivity versus the presence of symptoms, days post symptom onset (DPSO), sample viral load, and sample type (i.e. direct swabs versus specimens stored in transport media). Methods: Three databases were searched systematically for performance evaluations of the Roche-distributed SDB SARS-CoV-2 Rapid Antigen Test (Roche/SDB RAT) through March 2022. If the Roche/SDB RAT was compared with any of 9 commonly available antigen tests, data from these tests were also included. Results: Overall sensitivity of RATs among different manufacturers and study cohorts varied between 36.0% (95% CI: 24.0-50.1) and 79.4% (95% CI: 64.8-89.0). Roche/SDB RATs demonstrated a competitive performance with a pooled (including off-label use) sensitivity of 70.0%, and nearly 100% specificity in included studies. The Roche/SDB RATs exhibited reliable sensitivity in patients with a relatively high viral load (96.6% [95% CI: 95.2-98.2] for Ct≤25). Roche/SDB RATs were more sensitive in symptomatic patients within the first 7 DPSO (85.5% [95% CI: 81.2-88.4]), and when used to test direct swabs (74.4% [95% CI: 69.7-80.3]). Conclusion: RATs show reliable performance in clinical settings and should be considered when rapid diagnosis of SARS-CoV-2 infection is critical.

  🖺 Full Text HTML: Clinical Performance of SARS-CoV-2 Rapid Antigen Tests: A Systematic Review and Meta-Analysis

From Clinical Trials

• A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: HH-120;   Drug: placebo
  Sponsor:   Huahui Health
  Completed

• A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Drug: VYD222;   Drug: Normal saline
  Sponsor:   Invivyd, Inc.
  Recruiting

• Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations - Conditions:   Immunosuppression;   COVID-19
  Intervention:   Biological: NVX-CoV2372
  Sponsors:   University of Wisconsin, Madison;   Novavax
  Not yet recruiting

• Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration
  Interventions:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention
  Sponsors:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: LEM-mR203;   Biological: Placebo
  Sponsor:   Lemonex
  Not yet recruiting

• Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults - Condition:   SARS-CoV-2 Infection
  Intervention:   Biological: B/HPIV3/S-6P
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)
  Recruiting

• A Study to Determine the Tolerability of Intranasal LMN-301 - Condition:   COVID-19
  Intervention:   Biological: LMN-301
  Sponsor:   Lumen Bioscience, Inc.
  Not yet recruiting

• Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions:   Fever After Vaccination;   Fever;   Seizures Fever
  Interventions:   Biological: Pfizer-BioNTech COVID-19 Vaccine;   Biological: Routine Childhood Vaccinations
  Sponsors:   Duke University;   Kaiser Permanente;   Columbia University;   Children’s Hospital Medical Center, Cincinnati;   Centers for Disease Control and Prevention
  Not yet recruiting

• The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students - Condition:   Trauma and Stressor Related Disorders
  Intervention:   Other: Cognitive Behavioral Therapy Group
  Sponsor:   Necmettin Erbakan University
  Active, not recruiting

• Long COVID Immune Profiling - Conditions:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction
  Interventions:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31
  Sponsors:   Vanderbilt University Medical Center;   American Heart Association
  Not yet recruiting

From PubMed

• Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation - SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to…

• Outcomes of a social media campaign to promote COVID-19 vaccination in Nigeria - The COVID-19 pandemic has been an historic challenge to public health and behavior change programs. In low -and middle-income countries (LMICs) such as Nigeria, there have been challenges in promoting vaccination. Vaccine hesitancy and social norms related to vaccination may be important factors in promoting or inhibiting not only COVID vaccination, but other routine vaccinations as well. The aim of this study was to conduct a national-level quasi-experimental evaluation of a social media based…

• Phytoconstituents as potential therapeutic agents against COVID-19: a computational study on inhibition of SARS-CoV-2 main protease - The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has become a global health crisis, and the urgent need for effective treatments is evident. One potential target for COVID-19 therapeutics is the main protease (Mpro) of SARS‑CoV‑2, an essential enzyme for viral replication. Natural compounds have been explored as a source of potential inhibitors for Mpro due to their safety and availability. In this study, we employed a…

• Extracellular Vesicles and Endocannabinoid Signaling in Patients with COVID-19 - Introduction: Endocannabinoids in COVID-19 have immunomodulatory and anti-inflammatory properties but the functional role and the regulation of endocannabinoid signaling in this pandemic disorder is controversial. To exercise their biologic function, endocannabinoids need to travel across the intercellular space and within the blood stream to reach their target cells. How the lipophilic endocannabinoids are transported in the vascular system and how these hydrophobic compounds cross cell…

• Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase - Since the outbreak of the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) has become a main target for antiviral therapeutics due to its essential role in viral replication and transcription. Thus, nucleoside analogs structurally resemble the natural RdRp substrate and hold great potential as inhibitors. Until now, extensive experimental investigations have been performed to explore nucleoside analogs to inhibit the RdRp, and…

• Ebselen: A Review on its Synthesis, Derivatives, Anticancer Efficacy and Utility in Combating SARS-COV-2 - Ebselen is a selenoorganic chiral compound with antioxidant properties comparable to glutathione peroxidase. It is also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one. In studies examining its numerous pharmacological activities, including antioxidant, anticancer, antiviral, and anti-Alzheimer’s, ebselen has demonstrated promising results. This review’s primary objective was to emphasize the numerous synthesis pathways of ebselen and their efficacy in fighting cancer. The data were collected…

• Molnupiravir: an antiviral drug against COVID-19 - SARS-CoV-2, the virus responsible for COVID-19, has caused numerous deaths worldwide and poses significant challenges. Researchers have recently studied a new antiviral drug called molnupiravir for treating COVID-19. This review examines the causes and immunopathogenesis of COVID-19, as well as the role of molnupiravir in its treatment. Molnupiravir is a prodrug of β-D-N4-hydroxyctytidine (NHC) and has demonstrated activity against various viruses, including MERS-CoV, SARS-CoV, SARS-CoV-2, and…

• Overreactive macrophages in SARS-CoV-2 infection: The effects of ACEI - Among various factors influencing the course of SARS-CoV-2 infection in humans, macrophage overactivation is considered the main cause of the cytokine storm that leads to severe complications of COVID-19. Moreover, the increased expression of angiotensin converting enzyme 2 (ACE2), an obligatory entry receptor of the coronavirus, caused by treatment with ACE inhibitors (ACEI) lowered overall confidence in the safety of these drugs. However, analysis of the course of coronavirus infection in…

• Omics data analysis reveals common molecular basis of small cell lung cancer and COVID-19 - The impact of COVID-19 infection on individuals with small cell lung cancer (SCLC) poses a serious threat. Unfortunately, the molecular basis of this severe comorbidity has yet to be elucidated. The present study addresses this gap utilizing publicly available omics data of COVID-19 and SCLC to explore the key molecules and associated pathways involved in the convergence of these diseases. Findings revealed 402 genes, that exhibited differential expression patterns in SCLC patients and also play…

• Whole genome CRISPR screening strategy to identify genes contributing to SARS-CoV-2 spike and VSV-G mediated entry - Understanding the cellular host factors that promote and inhibit viral entry is important for identifying viral countermeasures. CRISPR whole-genome screens can be used to rapidly discover host factors that contribute to or impair viral entry. However, when using live viruses and cellular lethality for selection, these screens can identify an overwhelming number of genes without specificity for the stage of the viral infection cycle. New screening methods are needed to identify host machinery…

• On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine - RNA processing plays a key role in gene expression, allowing for increased protein diversity and functional complexity. Consequently, modulating RNA processing can impact gene function. Given HIV-1’s reliance on host RNA processing machinery for viral protein production/replication, modulators of this process could serve as novel anti-virals to complement and/or enhance existing therapies. In this study, screening of several serine-arginine-rich (SR) kinase inhibitors for their impact on HIV-1…

• Association between levels of IgG antibodies from vaccines and Omicron symptomatic infection among children and adolescents in China - CONCLUSION: The risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive…

• Identification of essential genes associated with SARS-CoV-2 infection as potential drug target candidates with machine learning algorithms - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide concern. Several genes associated with the SARS-CoV-2, which are essential for its functionality, pathogenesis, and survival, have been identified. These genes, which play crucial roles in SARS-CoV-2 infection, are considered potential therapeutic targets. Developing drugs against these essential genes to inhibit their regular functions could be a good approach…

• Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets - The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions…

• Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge - Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including…

From Patent Search