Covid-19 Sentry

Contents

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

From Preprints

• Regulation of coronavirus nsp15 cleavage specificity by RNA structure -
  SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, has had an enduring impact on global public health. However, SARS-CoV-2 is only one of multiple pathogenic human coronaviruses (CoVs) to have emerged since the turn of the century. CoVs encode for several nonstructural proteins (NSPS) that are essential for viral replication and pathogenesis. Among them is nsp15, a uridine-specific viral endonuclease that is important in evading the host immune response and promoting viral replication. Despite the established function of nsp15 as a uridine-specific endonuclease, little is known about other determinants of its cleavage specificity. In this study we investigate the role of RNA secondary structure in SARS-CoV-2 nsp15 endonuclease activity. Using a series of in vitro endonuclease assays, we observed that thermodynamically stable RNA structures were protected from nsp15 cleavage relative to RNAs lacking stable structure. We leveraged the s2m RNA from the SARS 3'UTR as a model for our structural studies as it adopts a well-defined structure with several uridines, two of which are unpaired and thus high probably targets for nsp15 cleavage. We found that SARS-CoV-2 nsp15 specifically cleaves s2m at the unpaired uridine within the GNRNA pentaloop of the RNA. Further investigation revealed that the position of uridine within the pentaloop also impacted nsp15 cleavage efficiency, suggesting that positioning within the pentaloop is necessary for optimal presentation of the scissile uridine and alignment within the nsp15 catalytic pocket. Our findings indicate that RNA secondary structure is an important determinant of nsp15 cleavage and provides insight into the molecular mechanisms of recognition of RNA by nsp15.
  🖺 Full Text HTML: Regulation of coronavirus nsp15 cleavage specificity by RNA structure
• Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform -
  Reverse genetic systems enable engineering of RNA virus genomes and are instrumental to study RNA virus biology. With the recent outbreak of the COVID-19 pandemic, already established methods were challenged by the large genome of SARS-CoV-2. Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA-viruses with high sequence fidelity, using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment (harboring all heterologous sequences) viral RNA can directly serve as template for manipulation and rescue of recombinant mutant virus, without any cloning-step needed. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate its biology.
  🖺 Full Text HTML: Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform
• Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design -

  Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

  🖺 Full Text HTML: Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design
• Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work -
  This paper presents the findings from a detailed study investigating UK undergraduate students’ experience of practical science in their post-16 studies during the COVID-19 pandemic. It also examines the perceived confidence and preparedness of the students in relation to areas of practical science skills at the start of their degree courses. The study employed an exploratory sequential mixed methods design, with the findings from focus groups with students at the end of their post-16 studies used to support the development of a comprehensive quantitative survey for incoming undergraduate students. Survey data were collected in September and October 2021 from 275 students commencing Biological Science/Life Science, Chemistry, Physics and Natural Science degrees at two universities in England. The research is significant for its finding that although almost all students had the opportunity to undertake practical work as part of their post-16 studies during the COVID-19 pandemic, there was significant variation in students’ experiences. The data indicate that students’ self-efficacy in relation to practical science was impacted by the closures of post-16 education establishments, ongoing social distancing and the removal of the assessment criteria for students to have ‘routinely and consistently’ undertaken each of the practical assessment requirements. The research presents important considerations which are relevant for educators supporting students’ transition from post-16 to Higher Education.
  🖺 Full Text HTML: Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work
• Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study -

  Objectives To quantify healthcare resource utilisation (HCRU) and costs to the National Health Service (NHS) associated with acute COVID-19 in adults in England. Design Population-based retrospective cohort study, using Clinical Practice Research Datalink (CPRD) Aurum primary care electronic medical records linked when available to Hospital Episode Statistics (HES) secondary care administrative data. Setting Patients registered to primary care practices in England. Population 1,706,368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13,105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1,693,263 within the primary care cohort indexed between August 2020 and January 2022. Main outcome measures Primary and secondary care HCRU and associated costs during the acute phase of COVID-19 (≤4 weeks following positive test), stratified by age group, risk of severe COVID-19 and immunocompromised status. Results Among the hospitalised cohort, average total length of stay, as well as in critical care wards, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75 - 84 (£8,942) and ≥85 years (£8,835) than in those aged <50 years (£7,703). Whilst few (6.0%) patients in critical care required mechanical ventilation, its use was higher in older adults (50 - 74 years: 8.3%; <50 years: 4.3%). HCRU and associated costs were often greater in those at higher risk of severe COVID-19 when compared to the overall cohort, although minimal differences in HCRU were found across the three different high-risk definitions implemented. Among the primary care cohort, GP or nurse consultations were more frequent among older adults and the immunocompromised. Conclusions COVID-19 related hospitalisations in older adults, particularly critical care admissions, were the primary drivers of high resource use of COVID-19 in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.

  🖺 Full Text HTML: Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study
• Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine -
  Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS-CoV-2 vaccines require an initial two-shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations-scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune-escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, we developed a single immunization SARS-CoV-2 subunit vaccine that could rapidly generate potent, broad, and durable humoral immunity. We leveraged injectable polymer-nanoparticle (PNP) hydrogels as a depot technology for the sustained delivery of a nanoparticle COVID antigen displaying multiple copies of the SARS-CoV-2 receptor-binding-domain (RBD NP), and potent adjuvants including CpG and 3M052. Compared to a clinically relevant prime-boost regimen with soluble vaccines formulated with CpG/Alum or 3M052/Alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single-immunization hydrogel-based vaccines elicited potent and consistent neutralizing responses. Overall, we show that PNP hydrogels elicit improved anti-COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance our overall pandemic readiness.
  🖺 Full Text HTML: Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine
• Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in four metropolitan areas of the United States -

  To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.5x to 2.4x. The estimated Alpha takeoff times ranged from February 10 (for New York City, which was evidently impacted much earlier than the other regions) to March 23, 2021. The estimated Delta takeoff times were more tightly clustered, ranging from June 8 to June 24, 2021. Estimated takeoff times are consistent with genomic surveillance data.

  🖺 Full Text HTML: Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in four metropolitan areas of the United States
• SOCIODEMOGRAPHIC CHARACTERISTICS AND COVID-19 TESTING RATES: SPATIO-TEMPORAL PATTERNS AND IMPACT OF TEST ACCESSIBILITY IN SWEDEN -

  Background: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. Here, we aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with COVID-19 testing rates. Methods: We included information on 421 542 patient-initiated COVID-19 PCR tests from Uppsala County in Sweden from 24 June, 2020 to 9 February, 2022. Using Poisson regression analyses, we investigated whether the Care Need Index (CNI; median 1.0, IQR 0.8, 1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with aggregated COVID-19 daily testing rates after adjustments for community transmission. We further assessed if distance to the nearest testing station influenced testing. Lastly, we performed a difference-in-difference analysis of the opening of a testing station targeting a disadvantaged neighbourhood. Results: We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants aged 5-69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5-14 years) ranging from 0.56 (95% CI 0.47-0.66) to 0.88 (95% CI 0.81-0.95) across the three pandemic waves. Longer distance to testing station was linked to lower testing rates, foremost in less densely populated areas. Furthermore, the opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70-105, supporting an intervention effect. Conclusions: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease differences and inequalities in testing.

  🖺 Full Text HTML: SOCIODEMOGRAPHIC CHARACTERISTICS AND COVID-19 TESTING RATES: SPATIO-TEMPORAL PATTERNS AND IMPACT OF TEST ACCESSIBILITY IN SWEDEN
• Biorefinery Innovation in Increasing the Effectiveness of COVID-19 Vaccine Production -
  The COVID-19 pandemic has highlighted the importance of innovation in the fight against infectious diseases. Biorefinery offers a promising platform for the production of vaccines that is more cost-effective, efficient, and scalable than traditional methods. By using advanced fermentation and purification techniques and genetic engineering, biorefinery can improve the efficacy of vaccines and enable their production on a large scale. While there are challenges that need to be addressed, biorefinery has the potential to revolutionize the way we produce vaccines and other bioproducts, and contribute to a more sustainable and resilient future.
  🖺 Full Text HTML: Biorefinery Innovation in Increasing the Effectiveness of COVID-19 Vaccine Production
• Metabolic alterations unravel the materno fetal immune responses with disease severity in pregnant women infected with SARS-CoV-2 -
  Background: Pregnancy being immune compromised state, COVID-19 disease poses a high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome, and immune cells in COVID-19-positive pregnant mothers and cord blood. Methods: COVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mothers blood and cord blood (n=80) was analyzed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry. Results: In asymptomatic SARS-CoV-2 infection, the amino acid metabolic pathways such as glycine, serine, L-lactate, and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+ metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-alpha, IFN-alpha, IFN-gamma, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+ metabolic pathways along with IL-9 and IFN-gamma had an impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+ T cells. Cord blood mimicked the mothers metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+ and riboflavin metabolism in mild and moderate disease subjects. Conclusions: Our results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- gamma regulated pyruvate, lactate TCA metabolism, and riboflavin metabolism with context to disease severity are hallmarks of this materno-fetal metabolome.
  🖺 Full Text HTML: Metabolic alterations unravel the materno fetal immune responses with disease severity in pregnant women infected with SARS-CoV-2
• D614G and Omicron SARS-CoV-2 variant spike proteins differ in the effects of N-glycan modifications on spike expression, virus infectivity, and neutralization by some therapeutic antibodies -
  The SARS-CoV-2 spike glycoprotein has 22 potential N-linked glycosylation sites per monomer that are highly conserved among diverse variants, but how individual glycans affect virus entry and neutralization of Omicron variants has not been extensively characterized. Here we compared the effects of specific glycan deletions or modifications in the Omicron BA.1 and D614G spikes on spike expression, processing, and incorporation into pseudoviruses, as well as on virus infectivity and neutralization by therapeutic antibodies. We found that loss of potential glycans at spike residues N717 and N801 each conferred a loss of pseudovirus infectivity for Omicron but not for D614G or Delta variants. This decrease in infectivity correlated with decreased spike processing and incorporation into Omicron pseudoviruses. Oligomannose-enriched Omicron pseudoviruses generated in GnTI- cells or in the presence of kifunensine were non-infectious, whereas D614G or Delta pseudoviruses generated under similar conditions remained infectious. Similarly, authentic SARS-CoV-2 grown in the presence of kifunensine decreased titers more for the BA.1.1 variant than Delta or D614G variants relative to their respective, untreated controls. Finally, we found that loss of some N-glycans, including N343 and N234, increased the maximum percent neutralization by the class 3 S309 monoclonal antibody against D614G but not BA.1 variants, while these glycan deletions altered the neutralization potency of the class 1 COV2-2196 and Etesevimab monoclonal antibodies without affecting maximum percent neutralization. The maximum neutralization by some antibodies also varied with the glycan composition, with oligomannose-enriched pseudoviruses conferring the highest percent neutralization. These results highlight differences in the interactions between spike glycans and residues among SARS-CoV-2 variants that can affect spike expression, virus infectivity, and susceptibility of variants to antibody neutralization.
  🖺 Full Text HTML: D614G and Omicron SARS-CoV-2 variant spike proteins differ in the effects of N-glycan modifications on spike expression, virus infectivity, and neutralization by some therapeutic antibodies
• Mild/Asymptomatic Maternal SARS-CoV-2 Infection Leads to Immune Paralysis in Fetal Circulation and Immune Dysregulation in Fetal-Placental Tissues -
  Few studies have addressed the impact of maternal mild/asymptomatic SARS-CoV-2 infection on the developing neonatal immune system. In this study, we analyzed umbilical cord blood and placental chorionic villi from newborns of unvaccinated mothers with mild/asymptomatic SARS-CoV-2 infection during pregnancy using flow cytometry, single-cell transcriptomics, and functional assays. Despite the lack of vertical transmission, levels of inflammatory mediators were altered in cord blood. Maternal infection was also associated with increased memory T, B cells, and non-classical monocytes as well as increased activation. However, ex vivo responses to stimulation were attenuated. Finally, within the placental villi, we report an expansion of fetal Hofbauer cells and infiltrating maternal macrophages and rewiring towards a heightened inflammatory state. In contrast to cord blood monocytes, placental myeloid cells were primed for heightened antiviral responses. Taken together, this study highlights dysregulated fetal immune cell responses in response to mild maternal SARS-CoV-2 infection during pregnancy.
  🖺 Full Text HTML: Mild/Asymptomatic Maternal SARS-CoV-2 Infection Leads to Immune Paralysis in Fetal Circulation and Immune Dysregulation in Fetal-Placental Tissues
• Factors associated with the near miss of pregnant and postpartum women hospitalized by Covid-19 -

  Objective To analyze the factors associated with maternal near miss due to Covid-19 in Brazil. Method cross-sectional study that assessed the cases of pregnant and postpartum women hospitalized with SARS due to Covid-19, aged between 10 and 49 years and from March 2020 to March 2022. Secondary data available in the Influenza Epidemiological Surveillance Information System (SIVEP-Flu) were used. Data were analyzed using SPSS statistical software, with univariate analysis followed by logistic regression. Results the significant independent factors associated with near miss in pregnant postpartum women due to Covid-19 were black/brown race, O2 saturation <95%, dyspnea, comorbidities, need for invasive and non-invasive ventilatory support. Conclusion the factors associated with near misses in pregnant and postpartum women with covid-19 reveal characteristics and risks inherent to the pathophysiology of the disease that contribute to worsening the condition.

  🖺 Full Text HTML: Factors associated with the near miss of pregnant and postpartum women hospitalized by Covid-19
• Reconciling the efficacy and effectiveness of masking on epidemic outcomes -

  Mask wearing in public settings has been broadly implemented as a means to mitigate the COVID-19 pandemic. However, the reported effectiveness of masking has been much lower than laboratory measures of efficacy, and this large discrepancy has cast doubt on the utility of masking. Here, we develop an agent-based model that comprehensively accounts for individual masking behaviors and infectious disease dynamics, and test the impact of masking on epidemic outcomes. Using realistic inputs of mask efficacy and contact data at the individual level, the model reproduces the lower effectiveness as reported in randomized controlled trials. Model results demonstrate that transmission within households, where masks are rarely used, can substantially lower effectiveness, and reveal the interaction of nonlinear epidemic dynamics, control measures (e.g., masking and social distancing), and potential measurement biases. Overall, model results show that, at the individual level, consistent masking can reduce the risk of first infection, and, over time, reduce the frequency of repeated infection. At the population level, masking can provide direct protection to mask wearers, as well as indirect protection to non-wearers, collectively reducing epidemic intensity. These findings suggest it is prudent for individuals to use masks during an epidemic, and for policy makers to recognize the less-than-ideal effectiveness of masking when devising public health interventions.

  🖺 Full Text HTML: Reconciling the efficacy and effectiveness of masking on epidemic outcomes
• Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation -

  Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

  🖺 Full Text HTML: Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation

From Clinical Trials

• The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Glucocorticoid
  Sponsor:   Huashan Hospital
  Not yet recruiting

• Arginine Replacement Therapy in COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Arginine Hydrochloride
  Sponsor:   Emory University
  Not yet recruiting

• Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults - Condition:   COVID-19
  Interventions:   Biological: Intramuscularly administered Ad5-nCoV vaccine;   Biological: Aerosolized Ad5-nCoV;   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: SYS6006
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Not yet recruiting

• Long COVID-19 Syndrome Lifestyle Intervention Study - Condition:   Long COVID-19 Syndrome
  Intervention:   Dietary Supplement: Low carbohydrate diet intervention
  Sponsor:   University of Southern California
  Not yet recruiting

• A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment - Condition:   Post COVID-19 Cognitive Impairment
  Interventions:   Device: Vielight Neuro RX Gamma active device;   Device: Vielight Neuro RX Gamma sham device
  Sponsor:   Vielight Inc.
  Not yet recruiting

• PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway - Conditions:   Post COVID-19 Condition, Unspecified;   SARS-CoV2 Infection;   COVID-19
  Interventions:   Drug: Nirmatrelvir/ritonavir;   Drug: Placebo
  Sponsors:   Haukeland University Hospital;   University of Bergen
  Not yet recruiting

• Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement - Condition:   COVID-19
  Interventions:   Other: mHealth Outreach;   Other: Care Coordination
  Sponsors:   University of California, San Diego;   San Ysidro Health Center
  Not yet recruiting

• Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response - Condition:   COVID-19 Respiratory Infection
  Intervention:   Combination Product: Vitamin-D
  Sponsor:   Sulaimany Polytechnic university
  Completed

• Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention - Condition:   Sars-CoV-2 Infection
  Interventions:   Drug: Alveavax-v1.2;   Drug: Janssen Ad26.COV2.S
  Sponsor:   Alvea Holdings, LLC
  Completed

• COVID-19 Vaccination Detoxification in LDL-C - Conditions:   COVID-19 Stress Syndrome;   COVID-19 Vaccine Adverse Reaction;   COVID-19-Associated Thromboembolism;   COVID-19 Post-Intensive Care Syndrome;   COVID-19-Associated Stroke;   COVID-19 Respiratory Infection
  Intervention:   Combination Product: Atorvastatin Calcium Tablets
  Sponsor:   Yang I. Pachankis
  Active, not recruiting

• Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial - Conditions:   Post-Acute COVID-19 Syndrome;   Dysautonomia
  Interventions:   Procedure: Rehabilitation;   Procedure: Standard of Care
  Sponsors:   Evangelismos Hospital;   National and Kapodistrian University of Athens;   LONG COVID GREECE;   414 Military Hospital of Special Diseases
  Recruiting

• Exercise for Health in Patients With Post-acute Sequelae of COVID-19 - Condition:   Long COVID
  Intervention:   Other: Rehabilitation program
  Sponsors:   Campus docent Sant Joan de Déu-Universitat de Barcelona;   Hospital de Mataró;   University of Barcelona
  Active, not recruiting

• Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome. - Condition:   Post-COVID Syndrome
  Interventions:   Behavioral: RehabCovid_Telematic;   Behavioral: RehabCovid_ImmersiveVR;   Behavioral: Control_Condition
  Sponsors:   Consorci Sanitari de Terrassa;   University of Barcelona;   Universitat de Girona;   Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment;   Politecnic University of Catalonia;   Corporación Fisiogestión
  Recruiting

• A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558 - Condition:   COVID-19
  Interventions:   Drug: ALG-097558;   Drug: Placebo;   Drug: Midazolam;   Drug: Itraconazole;   Drug: Carbamazepine;   Drug: ALG-097558 in solution formulation;   Drug: ALG-097558 in tablet formulation
  Sponsor:   Aligos Therapeutics
  Not yet recruiting

• Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome - Conditions:   Post-COVID-19 Syndrome;   Post-COVID Syndrome;   Post COVID-19 Condition
  Interventions:   Device: Immunoadsorption;   Device: Sham-apheresis
  Sponsor:   University Medical Center Mainz
  Recruiting

From PubMed

• Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport - Lifeways of worldwide people have changed dramatically amid the coronavirus disease 2019 (COVID-19) pandemic, and public health is at stake currently. In the early stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, fibrinolytic system is mostly inhibited, which is responsible for the development of hypofibrinolysis, promoting disseminated intravascular coagulation, hyaline membrane formation, and pulmonary edema. Whereas the common feature and risk factor at…

• Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults - CONCLUSION: The inhibitory effect for CYP3A was confirmed after the last dose of ensitrelvir, and the effect diminished over time. In addition, ensitrelvir at 375/125 mg showed CYP3A inhibitory potential similar to that at 750/250 mg. These findings can be used as a clinical recommendation for prescribing ensitrelvir with regard to concomitant medications.

• Mapping early serum proteome signatures of liver regeneration in living donor liver transplant cases - The liver is the only solid organ capable of regenerating itself to regain 100% of its mass and function after liver injury and/or partial hepatectomy (PH). This exceptional property represents a therapeutic opportunity for severe liver disease patients. However, liver regeneration (LR) might fail due to poorly understood causes. Here, we have investigated the regulation of liver proteome and phosphoproteome at a short time after PH (9 h), to depict a detailed mechanistic background of the early…

• Long-term consequences of COVID-19 on mental health and the impact of a physically active lifestyle: a narrative review - CONCLUSIONS: Preventive measures must be undertaken, such as the vaccination of the entire population, vaccination hesitancy discouragement by creating awareness among individuals, and people’s engagement in a physically active lifestyle, since being physically active is a low-cost and effective measure to restore or inhibit the negative outcomes from COVID-19 on mental health.

• Cruciferous vegetable-derived indole-3-carbinol prevents coronavirus cell egression mechanisms in tracheal and intestinal 3D in vitro models - The potential antiviral effects of indole-3-carbinol (I3C), a phytochemical found in Cruciferous vegetables, were investigated. Fibroblasts and epithelial cells were co-cultured on Alvetex® scaffolds, to obtain ad hoc 3D in vitro platforms able to mimic the trachea and intestinal mucosae, which represent the primary structures involved in the coronavirus pathogenesis. The two barriers generated in vitro were treated with various concentrations of I3C for different incubation periods. A…

• Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities - Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. These biological effects have been attributed to certain structural features, including molecular…

• Luteolin inhibits spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binding to angiotensin-converting enzyme 2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that poses a serious threat to global public health. In an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike (S) protein to engage with angiotensin-converting enzyme 2 (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, with luteolin being a flavonoid that can significantly…

• Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation - In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and…

• Designer DNA NanoGripper - DNA has shown great biocompatibility, programmable mechanical properties, and structural addressability at the nanometer scale, making it a versatile material for building high precision nanorobotics for biomedical applications. Herein, we present design principle, synthesis, and characterization of a DNA nanorobotic hand, called the “NanoGripper”, that contains a palm and four bendable fingers as inspired by human hands, bird claws, and bacteriophages evolved in nature. Each NanoGripper finger…

• Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice - CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

• 90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection - Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein…

• SARS-CoV-2 S1 Subunit Booster Vaccination Elicits Robust Humoral Immune Responses in Aged Mice - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concerns about reduced vaccine effectiveness and the increased risk of infection, and while repeated homologous booster shots are recommended for elderly and immunocompromised individuals, they cannot completely protect against breakthrough infections. In our previous study, we assessed the immunogenicity of an adenovirus-based vaccine expressing SARS-CoV-2 S1 (Ad5.S1) in mice, which induced robust…

• Frontline Worker Safety in the Age of COVID-19: A Global Perspective - The third annual Health Watch USAsm webinar conference assembled 16 speakers from 4 continents who shared information regarding frontline worker safety in the age of COVID-19. The U.S. Bureau of Labor Statistics reported a nearly 4000% increase in workplace illness in 2020 compared with 2019. It is estimated that 2% of the U.S. workforce is not working because of long COVID. In addition, the impact is growing with each surge. After the acute illness, patients are often described as recovered,…

• Reparixin improves survival in critically ill and transplant patients: A meta-analysis - CONCLUSIONS: The findings of this meta-analysis indicate that reparixin, an anti-inflammatory drug, improved survival in critically ill or transplant patients (including both COVID-19 and non-COVID-19 patients) without increasing the risk of infection.

• Bioinformatics approach to analyse COVID-19 biomarkers accountable for generation of intracranial aneurysm in COVID-19 patients - COVID-19 became a health emergency on January 30, 2020. SARS-CoV-2 is the causative agent of the coronavirus disease known as COVID-19 and can develop cardiometabolic and neurological disorders. Intracranial aneurysm (IA) is considered the most significant reason for hemorrhagic stroke,and it accounts for approximately 85% of all subarachnoid hemorrhages (SAH). Retinoid signaling abnormalities may explain COVID-19’s pathogenesis with inhibition of AEH2, from which COVID-19 infection may enhance…

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