Covid-19 Sentry

Contents

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

From Preprints

• In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance. -
  In vitro selection of remdesivir-resistant SARS-CoV-2 revealed the emergence of a V166L substitution, located outside of the polymerase active site of the nsp12 protein, after 9 passages. V166L remained the only nsp12 substitution after 17 passages at a final concentration of 10 M RDV, conferring a 2.3-fold increase in EC50. When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC50 was observed, indicating a high in vitro barrier to RDV resistance.
  🖺 Full Text HTML: In Vitro Selection of Remdesivir- Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance.
• Exponential magnetophoretic gradient for the direct isolation of basophils from whole blood in a microfluidic system -
  Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 L of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. The i-BID isolates basophils with a mean purity of 93.9%{+/-}3.6% and recovery of 95.6%{+/-}3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment.
  🖺 Full Text HTML: Exponential magnetophoretic gradient for the direct isolation of basophils from whole blood in a microfluidic system
• Extensive in vitro and in vivo protein translation via in situ circularized RNAs -
  RNAs are a powerful therapeutic class. However their inherent transience impacts their activity both as an interacting moiety as well as a template. Circularization of RNA has been demonstrated as a means to improve persistence, however simple and scalable approaches to achieve this are lacking. Utilizing autocatalytic RNA circularization, here we engineer in situ circularized RNAs (icRNAs). This approach enables icRNA delivery as simple linear RNA that is circularized upon delivery into the cell, thus making them compatible with routine synthesis, purification, and delivery formulations. We confirmed extensive protein translation from icRNAs both in vitro and in vivo and explored their utility in three contexts: first, we delivered the SARS-CoV-2 Omicron spike protein in vivo as icRNAs and showed corresponding induction of humoral immune responses; second, we demonstrated robust genome targeting via zinc finger nucleases delivered as icRNAs; and third, to enable compatibility between persistence of expression and immunogenicity, we developed a novel long range multiplexed (LORAX) protein engineering methodology to screen progressively deimmunized Cas9 proteins, and demonstrated efficient genome and epigenome targeting via their delivery as icRNAs. We anticipate this highly simple and scalable icRNA methodology could have broad utility in basic science and therapeutic applications.
  🖺 Full Text HTML: Extensive in vitro and in vivo protein translation via in situ circularized RNAs
• Profiling of the most reliable mutations from sequenced SARS-CoV-2 genomes scattered in Uzbekistan -
  Due to rapid mutations in the coronavirus genome over time and re-emergence of multiple novel variants of concerns (VOC), there is a continuous need for a periodic genome sequencing of SARS-CoV-2 genotypes of particular region. This is for on-time development of diagnostics, monitoring and therapeutic tools against virus in the global pandemics condition. Toward this goal, we have generated 18 high-quality whole-genome sequence data from 32 SARS-CoV-2 genotypes of PCR-positive COVID-19 patients, sampled from the Tashkent region of Uzbekistan. The nucleotide polymorphisms in the sequenced sample genomes were determined, including nonsynonymous (missense) and synonymous mutations in coding regions of coronavirus genome. Phylogenetic analysis grouped fourteen whole genome sample sequences (1, 2, 4, 5, 8, 10-15, 17,

32. into the G clade (or GR sub-clade) and four whole genome sample sequences (3, 6, 25, 27) into the S clade. A total of 128 mutations were identified, consisting of 45 shared and 83 unique mutations. Collectively, nucleotide changes represented one unique frameshift mutation, four upstream region mutations, six downstream region mutations, 50 synonymous mutations, and 67 missense mutations. The sequence data, presented herein, is the first coronavirus genomic sequence data from the Republic of Uzbekistan, which should contribute to enrich the global coronavirus sequence database, helping in future comparative studies. More importantly, the sequenced genomic data of coronavirus genotypes of this study should be useful for comparisons, diagnostics, monitoring, and therapeutics of COVID-19 disease in local and regional levels.
    🖺 Full Text HTML: Profiling of the most reliable mutations from sequenced SARS-CoV-2 genomes scattered in Uzbekistan

• Examining the Effects of Prior Acceptance and Commitment Therapy (ACT) Treatment Among Anxious Cancer Survivors During the COVID-19 Pandemic: Evidence from a Randomized Controlled Trial -
  INTRODUCTION: The COVID-19 pandemic has presented population-wide novel stressors. Acceptance and Commitment Therapy (ACT) may be potent for coping with novel, unpredictable stressors, but it is unknown whether pre-pandemic ACT treatment conferred protective benefit during the COVID-19 pandemic. METHODS: Participants (N = 73) from a previous randomized controlled trial of ACT (seven 2-hour group sessions) versus minimally-enhanced usual care (MEUC) for anxious cancer survivors completed measures of anxiety symptoms, fear of cancer recurrence, and emotional approach coping during the trial and again during the pandemic in May, June/July, and November 2020, an average of 2.71 years after completing ACT or MEUC. We estimated hierarchical linear models to test overall and conditional differences over the trial timepoints, in the interval between the trial and May 2020, and between the pandemic timepoints. RESULTS: Compared to MEUC, ACT led to greater improvement on the outcomes during the 8 month trial follow-up, consistent with the main trial findings. Across the entire sample, anxiety symptoms and emotional approach coping worsened from the final trial assessment timepoint to May 2020 (ps < .001). During this period, ACT participants worsened significantly more on emotional approach coping (p = .035) than MEUC participants. No significant condition differences emerged at later pandemic timepoints. CONCLUSIONS: Treatment with ACT several years earlier did not provide protective benefit to anxious cancer survivors during the pandemic, relative to MEUC. ACT interventions may need to be targeted to pandemic-specific stressors, or booster sessions may be required for prior ACT treatment completers when faced with novel stressors.

• Impact of COVID-19 pandemic and anti-pandemic measures on tuberculosis, viral hepatitis, HIV/AIDS and malaria - a systematic review -

  COVID-19 pandemic puts an enormous strain on health care systems worldwide and may have a detrimental effect on prevention, treatment and outcomes of tuberculosis (TB), viral hepatitis, HIV/AIDS and malaria, whose ending is part of the United Nations 2030 Agenda for Sustainable Development. We conducted a systematic review of scientific and grey literature in order to collect wide-ranging evidence with emphasis on quantification of the projected and actual indirect impacts of COVID-19 on the four infectious diseases with a global focus. We followed PRISMA guidelines and the protocol registered for malaria (CRD42021234974). We searched PubMed, Scopus, preView (last search: January 13, 2021) and websites of main (medical) societies and leading NGOs related to each of the four considered infectious diseases. The identified modelling studies warned about under-diagnosis (TB), anti-retroviral therapy interruption/decrease in viral load suppression (HIV), disruptions of insecticide-treated nets (ITN) distribution and access to effective treatment (malaria), and treatment delays and vaccination interruptions (viral hepatitis). The reported disruptions were very heterogeneous both between and within countries. If observed at several points in time, the initial drops (partly dramatic, e.g. TB notifications/cases, or HIV testing volumes decreased up to -80%) were followed by a gradual recovery. However, the often-missing assessment of the changes against the usual pre-pandemic fluctuations hampered the interpretation of less severe ones. Given the recurring waves of the pandemic and the unknown mid- to long-term effects of adaptation and normalisation, the real consequences for the fight against leading infectious diseases will only manifest over the coming years.

  🖺 Full Text HTML: Impact of COVID-19 pandemic and anti-pandemic measures on tuberculosis, viral hepatitis, HIV/AIDS and malaria - a systematic review
• Binding Interactions between RBD of Spike-Protein and Human ACE2 in Omicron variant -
  Emergence of new SARS-CoV-2 Omicron VOC (OV) has exacerbated the COVID-19 pandemic due to a large number of mutations in the spike-protein, particularly in the receptor-binding domain (RBD), resulting in highly contagious and/or vaccine-resistant strain. Herein, we present a systematic analysis based on detailed molecular dynamics (MD) simulations in order to understand how the OV RBD mutations affect the ACE2 binding. We show that the OV RBD binds to ACE2 more efficiently and tightly due predominantly to strong electrostatic interactions, thereby promoting increased infectivity and transmissibility compared to other strains. Some of OV RBD mutations are predicted to affect the antibody neutralization either through their role in the S-protein conformational changes, such as S371L, S373P, and S375F, or through changing its surface charge distribution, such as G339D, N440K, T478K, and E484A. Other mutations, such as K417N, G446S, and Y505H, decrease the ACE2 binding, whereas S447N, Q493R, G496S, Q498R, and N501Y tend to increase it.
  🖺 Full Text HTML: Binding Interactions between RBD of Spike-Protein and Human ACE2 in Omicron variant
• Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment -
  The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron’s receptor-binding domain and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterising, in the receptor-binding domain (RBD), we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and electronegative human angiotensin- converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild type. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N and Y505H.
  🖺 Full Text HTML: Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment
• Molecular Dynamics Simulations Studies On The Effects Of Mutations On The Binding Affinities Between SARS-CoV-2 Spike RBD And Human ACE2 -
  The SARS-CoV-2 viruses had made a great impact on humankind and the world economy. Phylogenetic analysis revealed the newly identified B.1.617.1 and B.1.617.2 lineages possessed with few key mutations predominantly circulating. The signature mutations possessed by these lineages are situated in the RBD motif of S protein. Reports revealed variants L452R, T478K, and E484Q harbours in enhancement with hACE2 binding while P681R situated in furin cleavage site resulting in better transmissibility. To gain a deeper understanding of the impact of these variants (L452R, T478K and E484Q) binding with hACE2, structural dynamics at the interface between S-RBD protein and hACE2 were studied. We performed our dynamics studies with both single mutant complex (L452R, T478K and E484Q) and in the combination of triple mutants (L452R + T478K + E484Q) at 100ns in contrast with the wild type. Interfacial docking interactions and Molecular Mechanics approach exhibited that the spike mutants -L452R, T478K and E484Q harbour with higher binding affinity on hACE2 in contrast with its native spike protein. The presence of interfacial residue, intermolecular contacts such as hydrogen bonding, salt bridge and non-hydrogen bonded interactions might be the reason for its higher binding affinity. Hence the findings from our study unravelled plausible mechanism for the increase in affinities of mutants to hACE2 thus leading to higher transmissibility and infection of emerging variants. Further, the conformational alterations in the course of dynamics at the RBD motif led to enhancement of hACE2 binding and immune escape. These results suggest that the structural changes introduced by these variants enhance the binding affinities of the S protein with the hACE2 that could form the basis to further aid in designing therapeutics that could inhibit at the interface of S protein and hACE2 receptor.
  🖺 Full Text HTML: Molecular Dynamics Simulations Studies On The Effects Of Mutations On The Binding Affinities Between SARS-CoV-2 Spike RBD And Human ACE2
• Time Perspective predicts levels of Anxiety and Depression during the COVID-19 outbreak: A cross-cultural study -
  The COVID-19 outbreak and governmental measures to keep the population safe had a great impact on many aspects of society, including well-being. Using data from N=1281 participants from six countries (Argentina, France, Greece, Italy, Japan, and Turkey), we first explored differences in anxiety, depression (measured with Hospital Anxiety and Depression Scale; HADS) and time perspectives (Zimbardo Time Perspective Inventory; ZTPI), between these countries during the first weeks of the pandemic. We observed that Turkish participants reported the highest levels of anxiety, and Japanese and Greek the lowest. For depression symptoms, the Japanese scored highest and Italians lowest. Next, for each country, we investigated how well the relatively time-stable personality traits of time perspectives, chronotype (reduced Morningness-Eveningness Questionnaire; rMEQ), and Big Five personality traits (short Big Five Inventory; BFI) predicted the levels of anxiety and depression (HADS). The regression analyses showed that negative attitudes towards the past predicted the levels of both anxiety and depression in most of the countries we analyzed. Additionally, in many countries, a Past Positive orientation negatively predicted depression whereas the Present Fatalistic subscale predicted anxiety and depression. The chronotype did not contribute additionally to the models. The Big Five traits (and particularly neuroticism) showed substantial incremental explanatory power for anxiety in some countries but did not consistently predict anxiety levels. For depression, the additional variance accounted for by including the BFI as predictors was rather small. Importantly, the ZTPI subscales were retained as significant predictors in the model still when the BFI and rMEQ were considered as potential predictors. Our results yield evidence that the ZTPI time perspectives are valuable predictors for anxiety and depression levels during the first period of the pandemic.

• Grandparental Childcare During the Pandemic and Effects on Mental Health: Evidence From England -

  Objectives: Policies aiming at reducing rates of hospitalisation and death from COVID-19 encouraged older people to reduce physical interactions. For grandparents in England, this meant that provision of care for grandchildren was allowed only under very limited circumstances. Evidence also suggests that reduced face-to-face interactions took a toll on mental health during the pandemic. This study aims to investigate whether changes in grandchild care provision during the pandemic impacted grandparents9 mental health. Methods: Using pre-pandemic data from Wave 9 (2018/19) and the second Covid-19 sub-study (November/December 2020) of the English Longitudinal Study of Ageing, we first describe changes in grandparenting since the start of the pandemic to then investigate, using regression models, associations between changes in grandparenting and mental health (depression, quality of life, life satisfaction) during the pandemic, while controlling for pre-pandemic levels of the outcome variables. Results: About 10% of grandparents stopped altogether to look after grandchildren during the pandemic, with 22% reporting an overall decrease in the amount of grandchild care provided and 20% an increase or similar levels. Compared to grandparents who mostly maintained unchanged their grandchild care provision, those who stopped altogether and those who mostly reduced the amount of grandchild care provided were more likely to report poorer mental health, even accounting for pre-pandemic health. Discussion: While measures to limit physical contact and shield older people were necessary to reduce the spread of COVID-19, policymakers should acknowledge potential adverse consequences for mental health among grandparents who experienced changes in their roles as grandchild caregivers.

  🖺 Full Text HTML: Grandparental Childcare During the Pandemic and Effects on Mental Health: Evidence From England
• Population immunity to pre-Omicron and Omicron SARS-CoV-2 variants in US states and counties through December 1, 2021 -

  Importance: Prior infection and vaccination both contribute to population-level SARS-CoV-2 immunity. Population- level immunity will influence future transmission and disease burden. Objective: To estimate population immunity to prevalent SARS-CoV-2 variants in the United States over the course of the epidemic until December 1, 2021, and how this changed with the introduction of the Omicron variant. Design, settings, participants: We used daily SARS-CoV-2 infection estimates and vaccination coverage data for each US state and county. We estimated relative rates of vaccination conditional on previous infection status using the Census Bureaus Household Pulse Survey. We used published evidence on natural and vaccine-induced immunity, including waning and immune escape. We used a Bayesian model to synthesize evidence and estimate population immunity outcomes. Main Outcomes and Measures: The fraction of the population with (i) immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received one or more doses of a COVID-19 vaccine), (ii) effective protection against infection, and (iii) effective protection against severe disease, for each US state and county from January 1, 2020, to December 1, 2021. Results: The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of December 1, 2021, was 88.2% (95%CrI: 83.6%-93.5%), compared to 24.9% (95%CrI: 18.5%-34.1%) on January 1, 2021. State-level estimates for December 1, 2021, ranged between 76.9% (95%CrI: 67.6%-87.6%, West Virginia) and 94.4% (95%CrI: 91.2%-97.3%, New Mexico). Accounting for waning and immune escape, the effective protection against the Omicron variant on December 1, 2021, was 21.8% (95%CrI: 20.7%-23.4%) nationally and ranged between 14.4% (95%CrI: 13.2%-15.8%, West Virginia), to 26.4% (95%CrI: 25.3%-27.8%, Colorado). Effective protection against severe disease from Omicron was 61.2% (95%CrI: 59.1%-64.0%) nationally and ranged between 53.0% (95%CrI: 47.3%-60.0%, Vermont) and 65.8% (95%CrI: 64.9%-66.7%, Colorado). Conclusions and Relevance: While over three-quarters of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on December 1, 2021 only a fifth of the population was estimated to have effective protection to infection with the immune- evading Omicron variant.

  🖺 Full Text HTML: Population immunity to pre-Omicron and Omicron SARS-CoV-2 variants in US states and counties through December 1, 2021
• Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination -

  Early in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of post-menopausal people reported breakthrough bleeding. We found increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever, fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon nor dangerous, yet attention to these experiences is necessary to build trust in medicine.

  🖺 Full Text HTML: Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination
• Relation of incident Type 1 diabetes to recent COVID-19 infection: cohort study using e-health record linkage in Scotland -

  Background Studies using claims databases have reported that SARS-CoV-2 infection >30 days earlier increased the incidence of type 1 diabetes (T1DM). Using exact dates of type 1 diabetes diagnosis from the national register in Scotland linked to virology laboratory data we sought to replicate this finding. Methods A cohort of 1849411 individuals aged <35 years without diabetes, including all those of this age in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident T1DM was identified by linkage to the national registry. Cox regression was used to test the association of time-updated infection with incident T1DM. Trends in incidence of T1DM in the total population from 2015-2021 were estimated in a generalized additive model. Results There were 365080 in the cohort with at least one detected SARS-CoV-2 infection during follow-up and 1074 who developed T1DM. The rate ratio for incident T1DM associated with first positive test for SARS-CoV-2 (with no previous infection as reference category) was 0.88 (95% CI 0.63 to 1.23) for infection more than 30 days earlier and 2.62 (95% CI 1.81 to 3.79) for infection in the previous 30 days. However negative and positive SARS-CoV-2 tests were more frequent in the days surrounding T1DM presentation. In those aged 0-14 years incidence of T1DM during 2020-2021 was 20% higher than the 7-year average. Conclusions T1DM incidence in children increased during the pandemic. However the cohort analysis does not support a causal effect of SARS-CoV-2 infection itself on T1DM incidence.

  🖺 Full Text HTML: Relation of incident Type 1 diabetes to recent COVID-19 infection: cohort study using e-health record linkage in Scotland
• Long term antibody response to SARS-CoV-2 in children -

  Almost two years into the pandemic and with vaccination of children significantly lagging behind adults, long- term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2 infections. We screened 6113 children <18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 9 to June 30, 2020. 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44 %), the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow up of household contacts showed incomplete seroconversion in most families, with higher rates in families with adult index cases compared to pediatric index cases (OR: 1.79, P=0.047). Most importantly, children showed sustained seroconversion up to nine months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG Spike children vs. adults 90 days PSO: 1.75, P<0.001, 180 days: 1.38, P=0.01, 270 days: 1.54, P=0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroconversion rates in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

  🖺 Full Text HTML: Long term antibody response to SARS-CoV-2 in children

From Clinical Trials

• Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV). - Condition:   COVID-19
  Interventions:   Biological: Tozinameran - Standard dose;   Biological: Tozinameran - fractional dose;   Biological: Elasomeran - standard dose;   Biological: Elasomeran - fractional dose
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   PATH;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Zofin to Treat COVID-19 Long Haulers - Condition:   COVID-19
  Interventions:   Drug: Zofin;   Other: Placebo
  Sponsors:  
  Organicell Regenerative Medicine;   Proxima Clinical Research, Inc.
  Not yet recruiting

• Effect of Daily Oral Administration of Food Supplement NLC-V in Patients Diagnosed With COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: NLC-V
  Sponsor:  
  Todos Medical, Ltd.
  Completed

• Fourth COVID-19 Vaccine Dose- mRNA1273 - Condition:   COVID-19 Pandemic
  Intervention:   Biological: mRNA1273 vaccine
  Sponsor:   Sheba Medical Center
  Active, not recruiting

• HEART Rate Variability Biofeedback in LOng COVID-19 (HEARTLOC) - Condition:   COVID-19
  Intervention:   Behavioral: Heart Rate Variability Biofeedback (HRV-B)
  Sponsors:   University of Leeds;   University of Manchester;   Leeds Comunity Healthcare NHS Trust
  Recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of MVC-COV1901 or MVC-COV1901(Beta) Against COVID-19 - Condition:   COVID-19 Vaccine
  Interventions:   Biological: MVC-COV1901(Beta);   Biological: MVC- COV1901
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Fourth BNT162b2 COVID-19 Vaccine Dose - Condition:   COVID-19 Pandemic
  Intervention:   Biological: BNT162b2 vaccine
  Sponsor:   Sheba Medical Center
  Active, not recruiting

• Effects of Aerobic Exercise in Patients With Post COVID-19 - Condition:   COVID-19
  Interventions:   Other: High-intensity interval aerobic exercise training;   Other: Control Group
  Sponsor:   Gazi University
  Not yet recruiting

• Immunogenicity and Safety of the SpikoGen COVID-19 Vaccine in Children Aged 5 to <12 Years and 12 to <18 Years Compared With Adults Aged 18 to 40 Years - Condition:   COVID-19
  Interventions:   Biological: Low-dose SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant
  Sponsors:  
  Cinnagen;   Vaxine Pty Ltd
  Not yet recruiting

• Safety and Immunogenicity of COVI-VAC as a Booster Dose in Adults Previously Vaccinated Against COVID-19 - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Biological: COVI-VAC
  Sponsor:  
  Codagenix, Inc
  Not yet recruiting

• Effects of Inspiratory Muscle Training in Patients With Post COVID-19 - Condition:   COVID-19
  Interventions:   Other: Inspiratory Muscle Training Group;   Other: Control Group
  Sponsor:   Gazi University
  Not yet recruiting

• Study Design of the Diacerein in Patients With Covid-19 - Condition:   COVID-19
  Interventions:   Drug: Diacerein;   Drug: placebo capsules
  Sponsors:   University of Campinas, Brazil;   Fundação de Amparo à Pesquisa do Estado de São Paulo
  Not yet recruiting

• Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Ingavirin®, 90 mg capsules;   Drug: Placebo
  Sponsor:   Valenta Pharm JSC
  Recruiting

• Availability and Advice on Test Uptake During the COVID-19 Pandemic: a Vignette Study. - Condition:   COVID-19
  Interventions:   Behavioral: Customised testing advice;   Behavioral: Regular testing advice;   Behavioral: LFT available;   Behavioral: No LFT available
  Sponsor:  
  National Institute for Public Health and the Environment (RIVM)
  Completed

• Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: Quantitative PCR SARS-CoV-2;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: Screening Blood tests;   Diagnostic Test: Electrocardiogram;   Other: NEWS-2 score;   Other: WHO score;   Other: Physical examination;   Other: COVID-19-Related Symptoms assessment
  Sponsor:   Code Pharma
  Recruiting

From PubMed

• Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy - oxidative stress is caused by an abundant generation of reactive oxygen species, associated to a diminished capacity of the endogenous systems of the organism to counteract them. Activation of pro-oxidative pathways and boosting of inflammatory cytokines are always encountered in viral infections, including SARS-CoV-2. So, the importance of counteracting cytokine storm in COVID-19 pathology is highly important, to hamper the immunogenic damage of the endothelium and alveolar membranes….

• Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry - Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental…

• Visualizing a Field of Research for the Coronavirus Replication in Humans with Knowledge Mapping: Evidence from Web of Science - CONCLUSION: Our results indicated that “viral infection,” spike protein," and “mutation” might be future research hotspots on coronavirus replication in humans. The attention should be paid to the mutations of S protein and these mutants carrying mutations.

• Targeting stem-loop 1 of the SARS-CoV-2 5’ UTR to suppress viral translation and Nsp1 evasion - SARS-CoV-2 is a highly pathogenic virus that evades antiviral immunity by interfering with host protein synthesis, mRNA stability, and protein trafficking. The SARS-CoV-2 nonstructural protein 1 (Nsp1) uses its C-terminal domain to block the messenger RNA (mRNA) entry channel of the 40S ribosome to inhibit host protein synthesis. However, how SARS-CoV-2 circumvents Nsp1-mediated suppression for viral protein synthesis and if the mechanism can be targeted therapeutically remain unclear. Here, we…

• Efficient disinfection of SARS-CoV-2-like coronavirus, pseudotyped SARS-CoV-2 and other coronaviruses using cold plasma induces spike protein damage - Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency, and the high transmission of SARS- CoV-2 variants has raised serious concerns. Efficient disinfection methods are crucial for the prevention of viral transmission. Herein, pulse power-driven cold atmospheric plasma (CAP), a novel sterilization strategy, was found to potently inactivate SARS-CoV-2-like coronavirus GX_P2V, six strains of major epidemic SARS-CoV-2 variants and even swine coronavirus PEDV and SADS-CoV…

• Type I interferons and SARS-CoV-2: from cells to organisms - Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The…

• Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function - The COVID-19 pandemic raises significance for a potential influenza therapeutic compound, cetylpyridinium chloride (CPC), which has been extensively used in personal care products as a positively-charged quaternary ammonium antibacterial agent. CPC is currently in clinical trials to assess its effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity. Two published studies have provided mouse and human data indicating that CPC may alleviate influenza infection, and here…

• European Respiratory Society Statement on Long COVID-19 Follow-Up - Patients diagnosed with COVID-19 associated with SARS-CoV-2 infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aim to identify optimal strategies for follow-up care that may positively impact the patient’s quality-of-life (QOL).A European Respiratory Society (ERS) Task Force (TF) convened and prioritised eight clinical questions. A targeted search of the literature defined the time line of long COVID-19 as one to six months post infection and…

• Ruxolitinib attenuates secondary injury after traumatic spinal cord injury - Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were…

• Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro - The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed…

• Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection - The spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We have developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determine the neutralization titers (defined as the maximal serum dilution that inhibited 50% of infectious virus) of patient sera collected at 1-…

• Reconstruction of the unbinding pathways of noncovalent SARS-CoV and SARS-CoV-2 3CLpro inhibitors using unbiased molecular dynamics simulations - The main protease (3CLpro) is one of the essential components of the SARS-CoVs viral life cycle, which makes it an interesting target for overpowering these viruses. Although many covalent and noncovalent inhibitors have been designed to inhibit this molecular target, none have gained FDA approval as a drug. Because of the high rate of COVID-19 pandemic development, in addition to laboratory research, we require in silico methods to accelerate rational drug design. The unbinding pathways of two…

• Centrifugal Microfluidic Method for Enrichment and Enzymatic Extraction of Severe Acute Respiratory Syndrome Coronavirus 2 RNA - The diversification of analytical tools for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is imperative for effective virus surveillance and transmission control worldwide. Development of robust methods for rapid, simple isolation of viral RNA permits more expedient pathogen detection by downstream real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) to minimize stalled containment and enhance treatment efforts. Here, we describe an automatable…

• Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19 - CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.

• A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant - The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on long term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We here have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma and Epsilon, at…

From Patent Search

• SOCIAL NAVIGATION SYSTEM FOR MOBILE ROBOTS IN THE EMERGENCY DEPARTMENT TECHNOLOGY - The emergency department (ED) is a safety-critical environment in which healthcare workers (HCWs) are overburdened, overworked, and have limited resources, especially during the COVID-19 pandemic. One way to address this problem is to explore the use of robots that can support clinical teams, e.g., to deliver materials or restock supplies. However, due to EDs being overcrowded, and the cognitive overload HCWs experience, robots need to understand various levels of patient acuity so they avoid disrupting care delivery. In this invention, we introduce the Safety-Critical Deep Q-Network (SafeDQN) system, a new acuity-aware navigation system for mobile robots. SafeDQN is based on two insights about care in EDs: high-acuity patients tend to have more HCWs in attendance and those HCWs tend to move more quickly. We compared SafeDQN to three classic navigation methods, and show that it generates the safest, quickest path for mobile robots when navigating in a simulated ED environment. We hope this work encourages future exploration of social robots that work in safety-critical, human-centered environments, and ultimately help to improve patient outcomes and save lives. Figure 1. - link

• A SYSTEM BASED ON DEEP LEARNING FOR ANALYZING DELAYED ENHANCEMENT MAGNETIC RESONANCE IMAGING TO IDENTIFY COVID 19 AND METHOD THEREOF - The present invention discloses a system based on deep learning for analyzing delayed enhancement magnetic resonance imaging to identify COVID 19 and method thereof. The method and system include, but not limited to, a processing unit adapted to process the data based on deep learning data modelling in the magnetic resonance imaging associated with the digital image scanning system for diagnosis COVID 19 with the spatial resolution that each frame is deposited is 256 * 256, and being creating that level and vertical resolution respectively are 256 pixels (pixel), the read/write address that the read/write address of each image element, which is controlled by processing unit and forms circuit and finishes; And the data that will be stored in memory are input to a real-time microcontroller, it is characterized in that: analyze and compare by the Multi-source Information Fusion analytical system by using the real-time microcontroller to deliver the D/A changer then, digital signal is become analogue signal output. - link

• FOLDABLE KIDS NEST - The objective of the present invention is to provide a bird’s nest bag which allows a kid to sleep or sit inside. According to the embodiment of the present invention, the bird nest bag is used to isolate kids below 2 years, who are affected by COVID-19. The netted portion of the bag allows a clear visibility to check on the user by the medical assistants, during emergency situations. The children below two years of age can be isolated in the bags for a shorter duration. (Refer Fig. 1) - link

• IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link

• ANTIMICROBIAL SANITIZING FORMULATION - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - link

• A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - link

• RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• 黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用 - 本发明公开了黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用。所述黄芩黄酮活性成分选自下述至少一种：黄芩素、汉黄芩素和千层纸素A。炎症风暴是一种机体对外界刺激的过度免疫反应和炎症反应，以炎症细胞因子的快速大量释放为特征。炎症风暴可由许多感染或非感染性疾病引起，并与疾病的严重程度和多器官功能障碍综合征的发生密切相关。减少炎症风暴的发生有助于降低器官损伤和减缓疾病进程，尤其对危重症患者的治疗至关重要。本发明发现，黄芩素、汉黄芩素、千层纸素A均具有不同程度抑制小鼠细胞因子风暴的作用。黄芩素能改善炎症风暴引发的肺损伤和炎性细胞浸润。因此黄芩黄酮活性成分可用于制备防治炎症风暴的药物。 - link

• 一种预防和/或治疗炎症风暴的药物组合物及其制剂与应用 - 本发明公开了一种预防和/或治疗炎症风暴的药物组合物、制剂及其应用。该药物组合物，由黄芩素、汉黄芩素和千层纸素A组成，其中，黄芩素、汉黄芩素、千层纸素A的质量比为0.25_1.5：0.57：1。本发明提供的自微乳包括下述组分：药物磷脂复合物、油相、乳化剂和助乳化剂；其中，所述药物磷脂复合物由上述药物组合物和磷脂材料复合而成。本发明的实验结果表明在LPS诱导的系统性炎症风暴小鼠模型中，黄芩素、汉黄芩素和千层纸素A的组合物及其自微乳制剂均具有不同程度抑制小鼠细胞因子风暴的作用。本发明为炎症风暴的临床治疗提供了一种安全、有效、经济的解决方案。 - link

• 胸部CT图像识别方法、装置、计算机设备和存储介质 - 本申请涉及一种胸部CT图像识别方法、装置、计算机设备和存储介质。所述方法针对CT图像特点，设计轻量级的胸部CT图像识别网络更快速准确地识别出胸部CT图像。引入X‑DMFF模块，提升模型性能且降低计算成本。在DMS模块中引入Swin‑Transformer与残差学习，提取更多尺度的空间特征信息并对特征信息不断重用，提升模型分类效果。 - link