Covid-19 Sentry

Contents

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

From Preprints

• Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients -
  The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.
  🖺 Full Text HTML: Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients
• Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning -
  SARS-CoV-2 has continued to evolve throughout the COVID-19 pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2 and BA.2.75. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.
  🖺 Full Text HTML: Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning
• Recombinant Rotavirus Expressing the Glycosylated S1 Protein of SARS-CoV-2 -
  Reverse genetic systems have been used to introduce heterologous sequences into the rotavirus segmented double-stranded (ds)RNA genome, enabling the generation of recombinant viruses that express foreign proteins and possibly serve as vaccine vectors. Notably, insertion of SARS-CoV-2 sequences into the segment 7 (NSP3) RNA of simian SA11 rotavirus was previously shown to result in the production of recombinant viruses that efficiently expressed the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the S1 region of the SARS-CoV-2 spike protein. However, efforts to generate a similar recombinant (r) SA11 virus that efficiently expressed full-length S1 were less successful. In this study, we describe modifications to the S1-coding cassette inserted in the segment 7 RNA that allowed recovery of second-generation rSA11 viruses that efficiently expressed the ~120-kDa S1 protein. The ~120-kDa S1 products were shown to be glycosylated, based on treatment with endoglycosidase H, which reduced the protein to a size of ~80 kDa. Co-pulldown assays demonstrated that the ~120-kDa S1 proteins had affinity for the human ACE2 receptor. Although all the second-generation rSA11 viruses expressed glycosylated S1 with affinity for the ACE receptor, only the S1 product of one virus (rSA11/S1f) was appropriately recognized by anti-S1 antibody, suggesting the rSA11/S1f virus expressed an authentic form of S1. Possibly due to the presence of FLAG tags immediately upstream of their S1 signal peptides, the S1 products of the other viruses (rSA11/3fS1 and rSA11/3fS1-His) may have undergone defective glycosylation, impeding antibody binding. In summary, these results indicate that recombinant rotaviruses can serve as expression vectors of foreign glycosylated proteins, raising the possibility of generating rotavirus-based vaccines that can induce protective immune responses against enteric and mucosal viruses with glycosylated capsid components, including SARS-CoV-2.
  🖺 Full Text HTML: Recombinant Rotavirus Expressing the Glycosylated S1 Protein of SARS-CoV-2
• Klebsiella pneumoniae Co-infection Leads to Fatal Pneumonia in SARS-CoV-2-infected Mice -
  SARS-CoV-2 patients have been reported to have high rates of secondary Klebsiella pneumoniae infections. Klebsiella pneumoniae is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person's immune system is compromised. Despite a high number of K. pneumoniae cases reported in SARS-CoV-2 patients, a co-infection animal model evaluating the pathogenesis is not available. We describe a mouse model to study disease pathogenesis of SARS-CoV-2 and K. pneumoniae co-infection. BALB/cJ mice were inoculated with mouse-adapted SARS-CoV-2 followed by a challenge with K. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in the lungs. The co-infected mice showed severe clinical disease and a higher mortality rate within 48 h of K. pneumoniae infection. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads were similar between co-infected and single-infected mice. Histopathology of co-infected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Collectively, our results demonstrated that co-infection of SARS-CoV-2 with K. pneumoniae causes severe disease with increased mortality in mice.
  🖺 Full Text HTML: Klebsiella pneumoniae Co-infection Leads to Fatal Pneumonia in SARS-CoV-2-infected Mice
• Asymmetry in the peak in Covid-19 daily cases and the pandemic R-parameter -

  Within the context of the standard SIR model of pandemics, we show that the asymmetry in the peak in recorded daily cases during a pandemic can be used to infer the pandemic R-parameter. Using only daily data for symptomatic, confirmed cases, we derive a universal scaling curve that yields: (i) reff , the pandemic R-parameter; (ii) Leff, the effective latency, the average number of days an infected individual is able to infect others and (iii) α, the probability of infection per contact between infected and susceptible individuals. We validate our method using an example and then apply it to estimate these parameters for the first phase of the SARS-Cov-2/Covid-19 pandemic for several countries where there was a well separated peak in identified infected daily cases. The extension of the SIR model developed in this paper differentiates itself from earlier studies in that it provides a simple method to make an a-posteriori estimate of several useful epidemiological parameters, using only data on confirmed, identified cases. Our results are general and can be applied to any pandemic.

  🖺 Full Text HTML: Asymmetry in the peak in Covid-19 daily cases and the pandemic R-parameter
• Analyzing the Impact of the Covid-19 Pandemic on Stock Market Investments -
  The Covid-19 pandemic has had a notable impact on financial markets, prompting individuals to reevaluate their risk and return objectives and modify their investment portfolios. This study aims to examine the pandemic’s influence on the portfolio allocation decisions of individual investors. It investigates investors’ perceptions and preferences concerning different investment strategies both before and during the period of heightened anxiety caused by the Covid-19 pandemic. The data for the study was collected from individual investors residing in Delhi and Mumbai. The Analytical Hierarchy Process (AHP) was utilized to rank the investment choices of the participants. The findings indicate that, owing to the current economic uncertainty associated with the pandemic, investors have started realigning their portfolios. As the predictability of returns on risky assets has decreased, investors are shifting towards more conservative portfolios. Nevertheless, the extent of the transition from high-risk to low-risk assets varies among individual investors.
  🖺 Full Text HTML: Analyzing the Impact of the Covid-19 Pandemic on Stock Market Investments
• COVID-19 in person’s social network: Unravelling the Impact on Youth Motivations and Protective Behaviours during the Initial Stages of the COVID-19 Pandemic -
  The study explores what motivated youth to comply with recommended protective behaviour while being less vulnerable to COVID-19 comparing to other age groups. Additionally, we looked at the relationships between awareness of COVID-19 cases in participants’ social networks and perceptions of risk, motivation, and behaviour in reaction to the pandemic. We applied structural equation modelling on self-reported data from 1,265 undergraduate university students to investigate the role of different motivation types in predicting adherence to a wide range of protective behaviours. The prosocial motivation was equally as strong as the self-interested motivation in explaining young people’s behaviour, while controlled motivation revealed no association. The presence of known COVID-19 cases in people’s social networks affects both perceived risks of disease and motivation to comply. However, while awareness about severe consequences positively affects them, awareness about the mild cases, in contrast, decreases the perceived disease severity.
  🖺 Full Text HTML: COVID-19 in person’s social network: Unravelling the Impact on Youth Motivations and Protective Behaviours during the Initial Stages of the COVID-19 Pandemic
• Published in Early Childhood Education Journal, https://link.springer.com/article/10.1007/s10643-023-01536-1: Interaction quality among children, staff and parents in German ECEC centres in the COVID-19 pandemic - Results from a longitudinal study -
  Early Education and Care (ECEC) centres had implemented a variety of protective and hygiene measures during the COVID-19 pandemic. Some of these measures temporarily restricted the behaviour of pedagogical staff, children and parents, for example keeping distance from each other or wearing face masks. This may have made it difficult for staff to offer high quality interactions with a positive, sensitive attitude towards children and parents, as would be important for good pedagogical work. Long-term effects of these distance measures on the quality of daily interactions in ECEC centres are largely unexplored. Based on a panel survey among German ECEC centre leaders over a period of one and a half years, we provide a long-term assessment of the impact of specific protective measures on different levels of interactions within ECEC centres, namely on staff-child interactions, interactions of children with each other and the cooperation between staff and parents. We found child-child interaction largely unaffected by the measures, while staff-parent interaction suffered the most. Communication with parents and regular implementation of pedagogical practices have a stabilizing effect, while keeping distance from children, face masks and (pandemic-related) staff shortages worsen staff-child interactions.
  🖺 Full Text HTML: Published in Early Childhood Education Journal, https://link.springer.com/article/10.1007/s10643-023-01536-1: Interaction quality among children, staff and parents in German ECEC centres in the COVID-19 pandemic - Results from a longitudinal study
• The Usage of Mindsponge Theory for Explaining the Usefulness of Checklist Confirmation Scheme for Identifying Unreliable COVID-19-related Information -
  The public nowadays can access health information from the internet easily. However, they have difficulty identifying reliable health information from various sources in an infodemic (information and epidemic). Tanemura & Chiba [1] investigated the usefulness of a checklist approach-based confirmation scheme for identifying unreliable COVID-19-related information in 700 Japanese by using test health information related to the efficacy of green tea in preventing COVID-19. Investigated variables were: 1) the usefulness of the developed confirmation scheme for identifying unreliable COVID-19-related health information and 2) the factors that hindered the confirmation scheme’s usefulness. The findings from this study are important for making decisions concerning health in an epidemic. Tanemura & Chiba [1] used the mindsponge theory as the conceptual framework for their study [2]. This theory focuses on the human mind’s information-processing mechanism. Mindsponge comes from the metaphor of sponge, in which the human mind is analogized to a sponge that squeezes out unsuitable values (or information) and absorbs new ones compatible with its core value. The mindsponge mechanism explains how and why an individual observes and ejects values-information conditional on the external setting [3]. According to the mindsponge mechanism, the presence or absence of trust affects information absorption after moving to the multi-filtering system stage [4]. While accessing health information online, the public judge its value with a trust-based subjective evaluation [2]. This determines the perceived benefit of the information and affects individual behavior accordingly. If this developed confirmation scheme for identifying unreliable COVID-19-related health information increased public awareness that health information is unreliable, it may have suppressed the false perception that green tea is effective for preventing COVID-19. However, the explanations with this confirmation scheme in individual-level information filtering systems proved to be insufficient for consumers. Therefore, the most effective strategies involve filtering information at the organizational level rather than the individual level, which should help consumers correctly identify misinformation concerning food and health and promote accurate decision-making [1].
  🖺 Full Text HTML: The Usage of Mindsponge Theory for Explaining the Usefulness of Checklist Confirmation Scheme for Identifying Unreliable COVID-19-related Information
• Targeted Amplification and Genetic Sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 Surface Glycoprotein -
  The SARS-CoV-2 spike protein is a highly immunogenic and mutable protein that is the target of vaccine prevention and antibody therapeutics. This makes the encoding S-gene an important sequencing target. The SARS-CoV-2 sequencing community overwhelmingly adopted tiling amplicon-based strategies for sequencing the entire genome. As the virus evolved, primer mismatches inevitably led to amplicon drop-out. Given the exposure of the spike protein to host antibodies, mutation occurred here most rapidly, leading to amplicon failure over the most insightful region of the genome. To mitigate this, we developed SpikeSeq, a targeted method to amplify and sequence the S-gene. We evaluated 20 distinct primer designs through iterative in silico and in vitro testing to select the optimal primer pairs and run conditions. Once selected, periodic in silico analysis monitor primer conservation as SARS-CoV-2 evolves. Despite being designed during the Beta wave, the selected primers remain > 99% conserved through Omicron as of 2023-04-14. To validate the final design, we compared SpikeSeq data and National SARS-CoV-2 Strain Surveillance whole-genome data for 321 matching samples. Consensus sequences for the two methods were highly identical (99.998%) across the S-gene. SpikeSeq can serve as a complement to whole-genome surveillance or be leveraged where only S-gene sequencing is of interest. While SpikeSeq is adaptable to other sequencing platforms, the Nanopore platform validated here is compatible with low to moderate throughputs, and its simplicity better enables users to achieve accurate results, even in low resource settings.
  🖺 Full Text HTML: Targeted Amplification and Genetic Sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 Surface Glycoprotein
• Improvement of Neisseria gonorrhoeae culture media to enable growth without atmospheric CO2. -
  Bacterial culture is the crucial step in diagnosing Neisseria gonorrhoeae infections and is the gold standard for determining their antimicrobial resistance profile. However, culture of Neisseria spp. can be challenging in resource poor areas, relying on specialist incubators supplying an atmosphere with 5% CO2 for growth of the bacteria. Even when such incubators are available, the CO2 to run them may be scarce; there were CO2 shortages during the COVID-19 pandemic, for example. Although culture jars with gas packs or candles can be used, these are inefficient in terms of use of incubator space and researcher time. To achieve simplicity in culturing of N. gonorrhoeae, the standard Oxoid GC base medium, made with the Kelloggs glucose and iron supplements was improved with the addition of 0.75 g/L sodium bicarbonate (NaHCO3), which is inexpensive and really available. This improved media was able to sustain gonococcal growth as well as standard GC media in 5% CO2. Chocolate agar and Thayer-Martin agar with sodium bicarbonate was also developed, with all showing good growth of N. gonorrhoeae without the need for atmospheric CO2.
  🖺 Full Text HTML: Improvement of Neisseria gonorrhoeae culture media to enable growth without atmospheric CO2.
• Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein -
  Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking host cell processes. Here, we examine the role of RNA-virus sequence diversity in the dynamics of the virus-host interface, by analyzing the uniquely vast sequence record of viable SARS-CoV-2 species with focus on the multi-functional nucleocapsid protein. We observe the abundant presentation of motifs encoding several essential host protein interactions, alongside a majority of possibly non-functional and randomly occurring motif sequences absent in subsets of viable virus species. A large number of motifs emerge ex nihilo through transient mutations relative to the ancestral consensus sequence. The observed mutational landscape implies an accessible motif space that spans at least 25% of known eukaryotic motifs. This reveals motif mimicry as a highly dynamic process with the capacity to broadly explore host motifs, allowing the virus to rapidly evolve the virus-host interface.
  🖺 Full Text HTML: Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein
• Associations between SARS-CoV-2 infection and subsequent economic inactivity and employment status: pooled analyses of five linked longitudinal surveys -

  Background Following the acute phase of the COVID-19 pandemic, record numbers of people became economically inactive (i.e., neither working nor looking for work, e.g., retired), or non-employed (including unemployed job seekers and economically inactive people). A possible explanation is people leaving the workforce after contracting COVID-19. We aim to investigate whether testing positive for SARS-CoV-2 is related to subsequent economic inactivity and non-employment, among people who were in employment prior to the pandemic. Methods The primary source of data are UK longitudinal population studies linked to English NHS digital data, held by the UK Longitudinal Linkage Collaboration (UK LLC). We pooled data from five studies (1970 British Cohort Study, English Longitudinal Study of Ageing, 1958 National Child Development Study, Next Steps, and Understanding Society), established long before the pandemic with between two and eight follow up surveys during the pandemic. The study population comprised people aged 25-65 years during the study period (March 2020 to March 2021) who were employed pre-pandemic. Outcomes were economic inactivity and non-employment status measured at the time of the last follow-up survey (November 2020 to March 2021, depending on study). For participants who could be linked to NHS England data (n=8,174), COVID-19 infection was indicated by a positive SARS-CoV-2 test. For sensitivity analyses, we used a self-reported measure of COVID-19 infection from participants (n=13,881) in the public use files of the five studies. Potential confounders included sociodemographic variables, pre-pandemic self-rated health and occupational class. Logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (95%CIs). Results In adjusted analyses, testing positive for SARS-CoV-2 was very weakly associated with economic inactivity (OR 1.08 95%CI 0.68-1.73) and non-employment status (OR 1.09. 95%CI 0.77-1.55). In sensitivity analyses, self-reported test-confirmed COVID-19 was not associated with either economic inactivity (OR 1.01: 95%CI 0.70 to 1.44) or non-employment status (OR1.03 95%CI 0.79-1.35). Conclusions Among people employed pre-pandemic, testing positive for SARS-CoV-2 was either weakly or not associated with increased economic inactivity or exiting employment. Wide confidence intervals limit the ability to make definitive conclusions, but it appears unlikely that COVID-19 disease explains the increase in economic inactivity among working-age people.

  🖺 Full Text HTML: Associations between SARS-CoV-2 infection and subsequent economic inactivity and employment status: pooled analyses of five linked longitudinal surveys
• Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases -

  ABSTRACT Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. Methods: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness. Results: Plasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock. Conclusion: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

  🖺 Full Text HTML: Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases
• The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records. -

  Background The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Aim Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. Design and setting With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. Method For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. Results In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). Conclusion We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.

  🖺 Full Text HTML: The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.

From Clinical Trials

• Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)
  Sponsor:   Asfendiyarov Kazakh National Medical University
  Not yet recruiting

• Effects of Exercise Training on Patients With Long COVID-19 - Condition:   Long COVID-19
  Intervention:   Behavioral: Exercise training
  Sponsor:   Guangdong Provincial People’s Hospital
  Recruiting

• Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition:   COVID-19
  Intervention:   Procedure: Lymph node aspiration / Blood sampling
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Recruiting

• A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition:   COVID-19
  Interventions:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo
  Sponsor:   GlaxoSmithKline
  Not yet recruiting

• A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
  Sponsor:   Novavax
  Not yet recruiting

• Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome - Conditions:   Fatigue;   Post-Acute COVID-19 Syndrome
  Intervention:   Procedure: Immunoadsorption vs. sham immunoadsorption
  Sponsor:   Hannover Medical School
  Not yet recruiting

• Non-ventilated Prone Positioning in the COVID-19 Population - Conditions:   COVID-19;   Proning;   Oxygenation;   Length of Stay
  Interventions:   Other: Proning group;   Other: Control group
  Sponsor:   Baylor St. Luke’s Medical Center
  Completed

• HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions:   COVID-19;   Delirium;   Critical Illness
  Interventions:   Combination Product: Active HD-tDCS;   Combination Product: Sham HD-tDCS
  Sponsors:   Suellen Andrade;   City University of New York
  Completed

• RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions:   Long COVID-19;   Long COVID
  Interventions:   Drug: Paxlovid 25 day dosing;   Drug: Paxlovid 15 day dosing;   Drug: Control
  Sponsor:   Kanecia Obie Zimmerman
  Not yet recruiting

• A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition:   SARS-CoV-2
  Interventions:   Biological: CV0701 Bivalent High dose;   Biological: CV0701 Bivalent Medium dose;   Biological: CV0701 Bivalent Low dose;   Biological: CV0601 Monovalent High dose;   Biological: Control vaccine
  Sponsors:   GlaxoSmithKline;   CureVac
  Not yet recruiting

• RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

• Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition:   Post Acute Sequelae Covid-19 Hyposmia
  Interventions:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge
  Sponsor:   Duke University
  Not yet recruiting

• PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition:   SARS-CoV-2
  Interventions:   Drug: Upamostat;   Drug: Placebo (PO)
  Sponsors:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited
  Not yet recruiting

• RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

• Impact of COVID-19 on Sinus Augmentation Surgery - Condition:   Bone Loss
  Interventions:   Procedure: Sinus lift in patients with positive COVID-19 history;   Procedure: Sinus lift with negative COVID-19 history
  Sponsor:   Cairo University
  Completed

From PubMed

• Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…

• Structural basis of anti-SARS-CoV-2 activity of HCQ: specific binding to N protein to disrupt its interaction with nucleic acids and LLPS - SARS-CoV-2 nucleocapsid (N) protein plays the essential roles in key steps of the viral life cycle, thus representing a top drug target. Functionality of N protein including liquid-liquid phase separation (LLPS) depends on its interaction with nucleic acids. Only the variants with N proteins functional in binding nucleic acids might survive and spread in evolution and indeed, the residues critical for binding nucleic acids are highly conserved. Hydroxychloroquine (HCQ) was shown to prevent the…

• Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.

• SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…

• Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)’s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPR’s binding pocket…

• Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 M^pro - CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 M^(pro) natural inhibitors.

• Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2 - CONCLUSION: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

• Deuteration for Metabolic Stabilization of SARS-CoV-2 Inhibitors GC373 and Nirmatrelvir - Nirmatrelvir and GC373 inhibit the SARS-CoV-2 3CL protease and hinder viral replication in COVID-19. As nirmatrelvir in Paxlovid is oxidized by cytochrome P450 3A4, ritonavir is coadministered to block this. However, ritonavir undesirably alters the metabolism of other drugs. Hydrogens can be replaced with deuterium in nirmatrelvir and GC373 to slow oxidation. Results show that deuterium slows oxidation of nirmatrelvir adjacent to nitrogen by ∼40% and that the type of warhead can switch the site…

• Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals - The RNA N7-methyltransferase (MTase) activity of SARS-CoV-2’s nsp14 protein is essential for viral replication and is a target for the development of new antivirals. Nsp14 uses S-adenosyl methionine (SAM) as the methyl donor to cap the 5’ end of the SARS-CoV-2 mRNA and generates S-adenosyl homocysteine (SAH) as the reaction byproduct. Due to the central role of histone MTases in cancer, many SAM/SAH analogs with properties of cell permeability have recently been developed for the inhibition of…

• Mega-scale desalination efficacy (Reverse Osmosis, Electrodialysis, Membrane Distillation, MED, MSF) during COVID-19: Evidence from salinity, pretreatment methods, temperature of operation - The unprecedented situation of the COVID-19 pandemic heavily polluted water bodies whereas the presence of SARS-CoV-2, even in treated wastewater in every corner of the world is reported. The main aim of the present study is to show the effectiveness and feasibility of some well-known desalination technologies which are reverse osmosis (RO), Electrodialysis (ED), Membrane Distillation (MD), multi effect distillation (MED), and multi stage flashing (MSF) during the COVID-19 pandemic. Systems’…

• An RBD bispecific antibody effectively neutralizes a SARS-CoV-2 Omicron variant - Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We…

• Effects of official information and rumor on resource-epidemic coevolution dynamics - Epidemic-related information and resources have proven to have a significant impact on the spread of the epidemic during the Corona Virus Disease 2019 (COVID-19) pandemic. The various orientation role of information has different effects on the epidemic spreading process, which will affect the individual’ awareness of resources allocation and epidemic spreading scale. Based on this, a three-layer network is established to describe the dynamic coevolution process among information dissemination,…

• Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches - Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as identifying of virus-host dependencies, offers valuable insights into disease mechanisms and informs the development of effective therapeutic strategies against viral infections. This review delves into the key host factors that facilitate or…

• Antibody response to inactivated COVID-19 vaccine in patients with type 2 diabetes mellitus after the booster immunization - CONCLUSIONS: Patients with T2DM showed impaired antibody responses after booster vaccination for more than 6 months. Decreased anti-BA.4/5 responses give rise to the possibility of breakthrough infections for both patients with T2DM and HCs.

• Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi-organ toxicity - AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an “emerging pollutant”, is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE.

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