Covid-19 Sentry

Contents

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

From Preprints

• Dolezal, L., Rose, A., and Cooper, F. COVID-19, Online Shaming and Healthcare Professionals. -
  As previous pandemics have taught us, coming into contact with, or being associated with, a highly infectious and potentially deadly disease has social consequences. Hence, it is no surprise that stigma and shame have developed around COVID-19. Although there have been outpourings of support and admiration for health-care workers for their work in this pandemic, health professionals have been among those directly affected. This article considers how shame has been part of healthcare workers’ experience during the COVID-19 pandemic because of social media use and instances of online shaming.
  🖺 Full Text HTML: Dolezal, L., Rose, A., and Cooper, F. COVID-19, Online Shaming and Healthcare Professionals.
• Dolezal, L. and Lucas, G. Differential Experiences of Social Distancing: Considering Alienated Embodied Communication and Racism. Puncta: Journal of Critical Phenomenology -
  In this musing we consider how social distancing, the primary public health measure introduced to mitigate the spread of the COVID-19 virus, is creating social encounters characterized by a self-and-other-consciousness and an atmosphere of suspicion, leading to what we call “alienated embodied communication”. Whilst interaction rituals dominated by avoidance, fear and distrust are novel for many individuals who occupy positions of social privilege, Black and ethnic minority writers have demonstrated that the alienated bodily communication of COVID-19 social distancing is “nothing new” for people who routinely experience marginalization as a result of racism. Our aim in this musing, then, is to reflect on how on-going experiences of stigma, shame, and marginalisation can shape how social distancing is registered on an embodied and existential level, and therefore how social distancing may differentially impact individuals with lived experiences of racism.
  🖺 Full Text HTML: Dolezal, L. and Lucas, G. Differential Experiences of Social Distancing: Considering Alienated Embodied Communication and Racism. Puncta: Journal of Critical Phenomenology
• Drug-free nasal spray as a barrier against SARS-CoV-2 infection: safety and efficacy in human nasal airway epithelia -
  Background: For SARS-CoV-2 and other respiratory viruses, the nasal epithelium is a key portal for infection. Therefore, the nose is an important target of prophylactic and therapeutic interventions against these viruses. We developed a nasal spray (AM-301, a medical device marketed as Bentrio) to protect against infection by SARS-CoV-2 and potentially other viruses. Aims of the study: To test the safety and efficacy of AM-301 against SARS-CoV-2 infection. Methods: AM-301 was tested on an in vitro 3D model of primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in prophylaxis and infection mitigation assays. Results: AM-301 did not have any detrimental effect on the nasal epithelium. Prophylactic treatment with AM-301 reduced viral titer significantly vs. controls over 4 days, reaching a maximum reduction of 99%. When treatment with AM-301 was started 24 or 30 h after infection, epithelia that received the formulation had a 12- or 14-fold lower titer than controls. Conclusion: AM-301 was found to be safe in vitro, and it significantly decelerated viral titer growth in experimental models of prophylaxis and mitigation. Its physical (non-pharmaceutical) mechanism of action, safety and efficacy pave the way for further investigation of its possible use against a broad spectrum of viruses, allergens and pollutants.
  🖺 Full Text HTML: Drug-free nasal spray as a barrier against SARS-CoV-2 infection: safety and efficacy in human nasal airway epithelia
• Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada -

  Background: The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants), and then by the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented but data for increased virulence is limited. We used Ontario COVID-19 case data to evaluate the virulence of these VOCs compared to non-VOC SARS-CoV-2 infections, as measured by risk of hospitalization, intensive care unit (ICU) admission, and death. Methods: We created a retrospective cohort of people in Ontarios testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and June 22, 2021 (n=211,197). We constructed mixed effects logistic regression models with hospitalization, ICU admission, and death as outcome variables. Models were adjusted for age, sex, time, comorbidities, and pregnancy status. Health units were included as random intercepts. Results: Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 59% (49-69%) for hospitalization; 105% (82-134%) for ICU admission; and 61% (40-87%) for death. Increases with Delta variant were more pronounced: 120% (93-153%) for hospitalization; 287% (198-399%) for ICU admission; and 137% (50-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-2 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred in the absence of VOC emergence.

• We are not ready yet: limitations of transfer learning for Disease Named Entity Recognition -
  Intense research has been done in the area of biomedical natural language processing. Since the breakthrough of transfer learning-based methods, BERT models are used in a variety of biomedical and clinical applications. For the available data sets, these models show excellent results - partly exceeding the inter-annotator agreements. However, biomedical named entity recognition applied on COVID-19 preprints shows a performance drop compared to the results on available test data. The question arises how well trained models are able to predict on completely new data, i.e. to generalize. Based on the example of disease named entity recognition, we investigate the robustness of different machine learning-based methods - thereof transfer learning - and show that current state-of-the-art methods work well for a given training and the corresponding test set but experience a significant lack of generalization when applying to new data. We therefore argue that there is a need for larger annotated data sets for training and testing.
  🖺 Full Text HTML: We are not ready yet: limitations of transfer learning for Disease Named Entity Recognition
• Identifiability as an “Antidote”: Exploring Emotional Contagion and the Role of Anonymity in Twitter Discussions on Misinformation -
  Misinformation carries both distorted facts and sophisticated emotional signals. Comparing to facts that could be labeled as true or false, we are more concerned about contaminative negative emotions transferring digital-ly among users. In this study, we explored an emotional contagion effect among misinformation discussion participants on Twitter. We analyzed the sentiment of 573 tweets in 192 discussion threads. Our result revealed that highly emotional tweets do not have a universal effect on the online discussions, but it affects those individuals with limited social and personal identity cues (i.e., being anonymous). We found that anonymous members of the online discussion are more susceptible to emotional contagions than those are not. We also suggest coping strategies that protect social media users’ emotional well-being during the era COVID-19.
  🖺 Full Text HTML: Identifiability as an “Antidote”: Exploring Emotional Contagion and the Role of Anonymity in Twitter Discussions on Misinformation
• Heparin for Moderately Ill Patients with Covid-19 -

  Background Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. Methods We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. Results At 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). Conclusions In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days.

  🖺 Full Text HTML: Heparin for Moderately Ill Patients with Covid-19
• Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections -

  Importance: Vaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health. Objective: To determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough. Design: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. Setting: Transmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests. Participants: Following a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination.

  🖺 Full Text HTML: Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections
• The sensitivity improved two-test algorithm “SIT2”: a universal optimization strategy for SARS-CoV-2 serology -

  Background Reliable antibody tests are an essential tool to identify individuals who have developed an adaptive immune response to SARS-CoV-2. However, attempts to maximize the specificity of SARS-CoV-2 antibody tests have come at the cost of sensitivity, exacerbating the total test error with increasing seroprevalence. Here, we present a novel method to maximize specificity while maintaining or even increasing sensitivity: the “Sensitivity Improved Two-Test” or “SIT²” algorithm. Methods SIT² involves confirmatory re-testing of samples with results falling in a predefined retesting-zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1,117 negative, 64 post-COVID positive samples) and validated the algorithm in an independent British cohort (976 negatives, 536 positives). Results The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared to single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralization assay could not detect antibodies. Compared to single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy algorithm to apply to different available SARS-CoV-2 antibody testing systems and can potentially be helpful for the serology of other infectious diseases.

  🖺 Full Text HTML: The sensitivity improved two-test algorithm “SIT2”: a universal optimization strategy for SARS-CoV-2 serology
• Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model -
  Following the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread throughout the world, new viral variants of concern (VOC) have emerged. There is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. Syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (COVID-19). In this study, we show that intranasal inoculation of SARS-CoV-2 into hamsters with the ancestral virus (nCoV-WA1-2020) or VOC first identified in the United Kingdom (B.1.1.7) and South Africa (B.1.351) led to similar gross and histopathologic pulmonary lesions. Although differences in viral genomic copy numbers were noted in the lungs and oral swabs of challenged animals, infectious titers in the lungs were comparable. Antibody neutralization capacities varied, dependent on the original challenge virus and cross-variant protective capacity. Transcriptional profiling indicated significant induction of antiviral pathways in response to all three challenges with a more robust inflammatory signature in response to B.1.1.7. Furthermore, no additional mutations in the spike protein were detected at peak disease. In conclusion, the emerging VOC showed distinct humoral responses and transcriptional profiles in the hamster model compared to the ancestral virus.
  🖺 Full Text HTML: Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model
• Daily sampling of early SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness -

  The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimate viral reproduction and clearance rates, and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Viral genome load often peaked days earlier in saliva than in nasal swabs, indicating strong compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of B.1.1.7 and non-B.1.1.7 viruses were indistinguishable, however B.1.1.7 exhibited a significantly slower pre-peak growth rate in saliva. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

  🖺 Full Text HTML: Daily sampling of early SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness
• SARS-CoV-2 Spike Protein Mutations and Escape from Antibodies: a Computational Model of Epitope Loss in Variants of Concern -
  The SARS-CoV-2 spike (S) protein is exposed on the viral surface and is the first point of contact between the virus and the host. For these reasons it represents the prime target for Covid-19 vaccines. In recent months, variants of this protein have started to emerge. Their ability to reduce or evade recognition by S-targeting antibodies poses a threat to immunological treatments and raises concerns for their consequences on vaccine efficacy. To develop a model able to predict the potential impact of S-protein mutations on antibody binding sites, we performed unbiased multi- microsecond molecular dynamics of several glycosylated S-protein variants and applied a straightforward structure- dynamics-energy based strategy to predict potential changes in immunogenic regions on each variant. We recover known epitopes on the reference D614G sequence. By comparing our results, obtained on isolated S-proteins in solution, to recently published data on antibody binding and reactivity in new S variants, we directly show that modifications in the S-protein consistently translate into the loss of potentially immunoreactive regions. Our findings can thus be qualitatively reconnected to the experimentally characterized decreased ability of some of the Abs elicited against the dominant S-sequence to recognize variants. While based on the study of SARS-CoV-2 Spike variants, our computational epitope-prediction strategy is portable and could be applied to study immunoreactivity in mutants of proteins of interest whose structures have been characterized, helping the development/selection of vaccines and antibodies able to control emerging variants.
  🖺 Full Text HTML: SARS-CoV-2 Spike Protein Mutations and Escape from Antibodies: a Computational Model of Epitope Loss in Variants of Concern
• High rate of mutational events in SARS-CoV-2 genomes across Brazilian geographical regions, February 2020 to June 2021 -
  Brazil has been considered as one of the emerging epicenters of the coronavirus pandemic in 2021, experiencing over 3,000 daily deaths caused by the virus at the peak of the second wave. In total, the country has more than 19.2 million confirmed cases of Covid-19, including over 533,509 fatalities. A set of emerging variants arose in the country, some of them posing new challenges for COVID-19 control. The goal of this study was to describe mutational events across samples from Brazilian SARS-CoV-2 sequences openly publicly obtainable on the Global Initiative on Sharing Avian Influenza Data-EpiCoV (GISAID-EpiCoV) platform and generate an index of new mutant by each genome. A total of 16,953 SARS-CoV-2 genomes were obtained and are not proportionally representative of the five Brazilian geographical regions. A comparative sequence analysis was conducted to identify common mutations located at 42 positions of the genome (38 were in coding regions whereas two in 5’ and two in 3’ UTR). Moreover, 11 were synonymous and 27 missense variants, and more than 44.4% were located in the spike gene. Across the total of single nucleotide variations (SNVs) identified, 32 were found in genomes obtained from all five Brazilian regions. While a high genomic diversity is reported in Europe given the large number of sequenced genomes, Africa is emerging as a hotspot for new variants. In South America, Brazil and Chile, rates are similar to those found in South Africa and India, giving enough space to generate new viral mutations. Genomic surveillance is the central key to identifying the emerging variants of SARS-CoV-2 in Brazil and has shown that the country is one of the “hotspots” in the generation of new variants.
  🖺 Full Text HTML: High rate of mutational events in SARS-CoV-2 genomes across Brazilian geographical regions, February 2020 to June 2021
• Niclosamide reverses SARS-CoV-2 control of lipophagy -
  The global effort to combat COVID-19 rapidly produced a shortlist of approved drugs with antiviral activities for clinical repurposing. However, the jump to clinical testing was lethal in some cases as a full understanding of the mechanism of antiviral activity as opposed to pleiotropic activity/toxicity for these drugs was lacking. Through parallel lipidomic and transcriptomic analyses we observed massive reorganization of lipid profiles of infected Vero E6 cells, especially plasmalogens that correlated with increased levels of virus replication. Niclosamide (NIC), a poorly soluble anti-helminth drug identified for repurposed treatment of COVID-19, reduced the total lipid profile that would otherwise amplify during virus infection. NIC treatment reduced the abundance of plasmalogens, diacylglycerides, and ceramides, which are required for virus pro-duction. Future screens of approved drugs may identify more druggable compounds than NIC that can safely but effectively counter SARS-CoV-2 subversion of lipid metabolism thereby reducing virus replication. However, these data support the consideration of niclosamide as a potential COVID-19 therapeutic given its modulation of lipophagy leading to the reduction of virus egress and the subsequent regulation of key lipid mediators of pathological inflammation.
  🖺 Full Text HTML: Niclosamide reverses SARS-CoV-2 control of lipophagy
• Bereavement from COVID-19, Gender, and Reports of Depression among Older Adults in Europe -
  Objectives: The COVID-19 pandemic has left older adults around the world bereaved by the sudden death of relatives and friends. We examine if COVID-19 bereavement corresponds with older adults’ reporting depression in 27 countries, and test for variation by gender and country context. Methods: We analyze SHARE COVID-19 data collected between June-August 2020 from N=51,383 older adults (age 50–104) living in 27 countries, of whom 1,363 reported the death of a relative or friend from COVID-19. We estimate pooled-multilevel logit regression models to examine if COVID-19 bereavement was associated with self-reported depression and worsening depression, and we test whether national COVID-19 mortality rates moderate these assocations. Results: COVID-19 bereavement is associated with significantly higher probabilities of both reporting depression and reporting worsened depression among older adults. Net of one’s own personal loss, living in a country with the highest COVID-19 mortality rate is associated with women’s reports of worsened depression but not men’s. However, the country’s COVID-19 mortality rate does not moderate associations between COVID-19 bereavement and depression. Discussion: COVID-19 deaths have lingering mental health implications for surviving older adults. Even as the collective toll of the crisis is apparent, bereaved older adults are in particular need of mental health support.
  🖺 Full Text HTML: Bereavement from COVID-19, Gender, and Reports of Depression among Older Adults in Europe

From Clinical Trials

• COVID-19 Vaccinations With a Sweepstakes - Condition:   Covid19
  Intervention:   Behavioral: Philly Vax Sweepstakes
  Sponsors:  
  University of Pennsylvania;   Philadelphia Department of Public Health
  Active, not recruiting

• A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Covid-19 Virtual Recovery Study - Condition:   Covid19
  Interventions:   Behavioral: Strength RMT;   Behavioral: Strength RMT and nasal breathing;   Behavioral: Endurance RMT;   Behavioral: Endurance RMT and nasal breathing;   Behavioral: Low dose RMT
  Sponsor:   Mayo Clinic
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms - Condition:   Covid19
  Intervention:   Other: Exercise Therapy
  Sponsor:  
  Wake Forest University Health Sciences
  Not yet recruiting

• Lipid Emulsion Infusion and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SMOFlipid;   Other: 0.9% saline
  Sponsor:   Assiut University
  Recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Coenzyme Q10 as Treatment for Long Term COVID-19 - Conditions:   Covid19;   Long Term Covid19
  Interventions:   Drug: Coenzyme Q10;   Drug: Placebo
  Sponsors:   Aarhus University Hospital;   University of Aarhus;   Pharma Nord
  Recruiting

• Effect of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Best Standard of Care for the Treatment of Hospitalized COVID-19 Patients and Continued Treatment Following Discharge - Condition:   COVID-19
  Intervention:   Device: NovoTTF-100L
  Sponsor:   NovoCure GmbH
  Completed

• Study to Select the Dose and Evaluate Safety and Efficacy of Monoclonal Antibody in Adult With Recently Diagnosed Asymptomatic to Moderately Severe COVID-19. - Condition:   Covid19
  Interventions:   Drug: MAD0004J08;   Other: Placebo
  Sponsor:  
  Toscana Life Sciences Sviluppo s.r.l.
  Recruiting

• Phase II Clinical Trial of CinnaGen COVID-19 Vaccine (SpikoGen) - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: Saline placebo
  Sponsor:   Cinnagen
  Active, not recruiting

From PubMed

• Cationic Compounds with SARS-CoV-2 Antiviral Activity and their Interaction with OCT/MATE Secretory Transporters - In the wake of the COVID-19 pandemic, drug repurposing has been highlighted for rapid introduction of therapeutics. Proposed drugs with activity against SARS-CoV-2 include compounds with positive charges at physiological pH, making them potential targets for the organic cation (OC) secretory transporters of kidney and liver, i.e., the basolateral Organic Cation Transporters, OCT1 and OCT2; and the apical Multidrug And Toxin Extruders, MATE1 and MATE2-K. We selected several compounds proposed to…

• COVID-19 diagnosis and testing in pediatric heart transplant recipients - Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of…

• Determination of camostat and its metabolites in human plasma - preservation of samples and quantification by a validated UHPLC-MS/MS method - CONCLUSIONS: A methodology was developed that preserves camostat and GBPA in plasma samples and provides accurate and sensitive quantification of camostat, GBPA and GBA by UHPLC-MS/MS.

• Accurate Bulk Quantitation of Droplet Digital Polymerase Chain Reaction - Droplet digital PCR provides superior accuracy for nucleic acid quantitation. The requirement of microfluidics to generate and analyze the emulsions, however, is a barrier to its adoption, particularly in low resource settings or clinical laboratories. Here, we report a novel method to prepare ddPCR droplets by vortexing and readout of the results by bulk analysis of recovered amplicons. We demonstrate the approach by accurately quantitating SARS-CoV-2 sequences using entirely bulk processing…

• Strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors - Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in…

• Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans - As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular…

• Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay - The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be…

• Tocilizumab as a Treatment for ‘Cytokine Storm Syndrome’ in COVID-19: A Case Report - Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases…

• Catalytic Dyad Residues His41 and Cys145 Impact the Catalytic Activity and Overall Conformational Fold of the Main SARS-CoV-2 Protease 3-Chymotrypsin-Like Protease - Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the…

• Pulmonary Covid Fibrosis a New Pharmaceutic Approach - CONCLUSIONS: This study proposes to inhibit phosphodiesterase by vasodilatation of the pulmonary vascular bed and the MUC1 over expression by interleukin6, the Sildenafil with the SGLT2 and N-Acetylcysteine.

• Review of the potential of mesenchymal stem cells for the treatment of infectious diseases - The therapeutic value of mesenchymal stem cells (MSCs) for the treatment of infectious diseases and the repair of disease-induced tissue damage has been explored extensively. MSCs inhibit inflammation, reduce pathogen load and tissue damage encountered during infectious diseases through the secretion of antimicrobial factors for pathogen clearance and they phagocytose certain bacteria themselves. MSCs dampen tissue damage during infection by downregulating the levels of pro-inflammatory…

• RIG-I-Like Receptor-Mediated Recognition of Viral Genomic RNA of Severe Acute Respiratory Syndrome Coronavirus-2 and Viral Escape From the Host Innate Immune Responses - RIG-I-like receptors (RLR), RIG-I and MDA5, are cytoplasmic viral RNA sensors that recognize viral double-stranded RNAs and trigger signals to induce antiviral responses, including type I interferon production. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the coronavirus disease 2019 pandemic. However, the RLR role in innate immune response to SARS-CoV-2 has not been fully elucidated. Here, we studied the roles of RLR in cytokine expression responding to SARS-CoV-2 and…

• Interleukin-1- Receptor Kinase 4 Inhibition: Achieving Immunomodulatory Synergy to Mitigate the Impact of COVID-19 - No abstract

• Case Report: Adult Post-COVID-19 Multisystem Inflammatory Syndrome and Thrombotic Microangiopathy - CONCLUSION: Our case suggests that that TMA could play a central role in the pathophysiology of post-COVID-19 MIS-A, making complement blockers an interesting therapeutic option.

• The MERS-CoV N Protein Regulates Host Cytokinesis and Protein Translation via Interaction With EF1A - Middle East respiratory syndrome coronavirus (MERS-CoV), a pathogen causing severe respiratory disease in humans that emerged in June 2012, is a novel beta coronavirus similar to severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, immunoprecipitation and proximity ligation assays revealed that the nucleocapsid (N) protein of MERS-CoV interacted with human translation elongation factor 1A (EF1A), an essential component of the translation system with important roles in protein…

From Patent Search

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• SARS-CoV-2 anti-viral therapeutic - - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link

• 一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR，并结合Sanger测序，能够快速、准确地获取SARS‑CoV‑2基因信息，从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株，且具备良好的准确性、灵敏度、特异性以及重复性。 - link

• 一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域，公开了一种新冠病毒肺炎重症化预测系统及方法，包括以下步骤：步骤一，采集患者血常规信息和用户信息；步骤二，将患者血常规信息按照用户信息进行等级分类；步骤三，将已经等级分类的患者血常规信息与对应等级的标准信息进行比较；步骤四，当患者血常规信息在标准信息范围内则判定患者为轻症患者，当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link

• MEDIDOR DE SATURACION - - link

• 폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link