Covid-19 Sentry

Contents

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

From Preprints

• Impairment of T cells’ antiviral and anti-inflammation immunities dominates death from COVID-19 -

  Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analyzing the multi-level clinical data, including viral dynamics, immune response, and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses demonstrates that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells leads to more significant inflammation, proposing an explanation for the monotonous increase of COVID-19 mortality with age and higher mortality for males. We conclude that T cells play a crucial role in the immunity against COVID-19, which reveals a new direction—-improvement of T cell number for advancing current prevention and treatment.

  🖺 Full Text HTML: Impairment of T cells’ antiviral and anti-inflammation immunities dominates death from COVID-19
• Antibody mediated neutralization of authentic SARS-CoV-2 B.1.617 variants harboring L452R and T478K/E484Q -

  The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.5-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which however, might be circumvented by a combination therapy with casirivimab together.

  🖺 Full Text HTML: Antibody mediated neutralization of authentic SARS-CoV-2 B.1.617 variants harboring L452R and T478K/E484Q
• Electronic Computer-Based Model of Combined Ventilation Using a New Medical Device -

  Introduction The increased demand for mechanical ventilation caused by the SARS-CoV-2 pandemic could generate a critical situation where patients may lose access to mechanical ventilators. Combined ventilation, in which two patients are ventilated simultaneously but independently with a single ventilator has been proposed as a life-saving bridge while waiting for new ventilators availability. New devices have emerged to facilitate this task and allow individualization of ventilatory parameters in combined ventilation. In this work we run computer-based electrical simulations of combined ventilation. We introduce an electrical model of a proposed mechanical device which is designed to individualize ventilatory parameters, and tested it under different circumstances. Materials and Methods With an electronic circuit simulator applet, an electrical model of combined ventilation is created using resistor-capacitor circuits. A device is added to the electrical model which is capable of individualizing the ventilatory parameters of two patients connected to the same ventilator. Through computational simulation, the model is tested in different scenarios with the aim of achieving adequate ventilation of two subjects under different circumstances: 1) two identical subjects; 2) two subjects wiIth the same size but different lung compliance; and 3) two subjects with different sizes and compliances. The goal is to achieve the established charge per unit of size on each capacitor under different levels of end-expiratory voltage (as an end-expiratory pressure analog). Data collected included capacitor charge, voltage, and charge normalized to the weight of the simulated patient. Results Simulations show that it is possible to provide the proper charge to each capacitor under different circumstances using an array of electrical components as equivalents to a proposed mechanical device for combined ventilation. If the pair of connected capacitors have different capacitances, adjustments must be made to the source voltage and/or the resistance of the device to provide the appropriate charge for each capacitor under initial conditions. In pressure control simulation, increasing the end- expiratory voltage on one capacitor requires increasing the source voltage and the device resistance associated with the other simulated patient. On the other hand, in the volume control simulation, it is only required to intervene in the device resistance. Conclusions Under simulated conditions, this electrical model allows individualization of combined mechanical ventilation. Keywords: SARS-CoV-2, pandemic, mechanical ventilation, medical device, computational simulation, electrical model.

  🖺 Full Text HTML: Electronic Computer-Based Model of Combined Ventilation Using a New Medical Device
• An extended SEIARD model for COVID-19 vaccination in Mexico: analysis and forecast -

  In this study, we propose and analyze an extended SEIARD model with vaccination. We compute the control reproduction number R_c of our model and study the stability of equilibria. We show that the set of disease- free equilibria is locally asymptotically stable when R_c<1 and unstable when R_c>1, and we provide a sufficient condition for its global stability. Furthermore, we perform numerical simulations using the reported data of COVID-19 infections and vaccination in Mexico to study the impact of different vaccination, transmission and efficacy rates on the dynamics of the disease.

  🖺 Full Text HTML: An extended SEIARD model for COVID-19 vaccination in Mexico: analysis and forecast
• Durability of SARS-CoV-2-specific T cell responses at 12-months post-infection -
  Background. Characterizing the longevity and quality of cellular immune responses to SARS-CoV-2 is critical to understanding immunologic approaches to protection against COVID-19. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Further analysis of the function, durability, and diversity of the cellular response long after natural infection, over a wider range of ages and disease phenotypes, is needed to further identify preventative and therapeutic interventions. Methods. We identified participants in our multi-site longitudinal, prospective cohort study 12-months post SARS-CoV-2 infection representing a range of disease severity. We investigated the function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry. In parallel, the magnitude of SARS-CoV-2-specific antibodies was compared. Results. SARS-CoV-2-specific antibodies and T cells were detected at 12-months post-infection. Severity of acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12-months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity. Conclusions. Our data show that SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12-months post-infection, with higher frequency noted in those who originally experienced severe disease.
  🖺 Full Text HTML: Durability of SARS-CoV-2-specific T cell responses at 12-months post-infection
• SARS-CoV-2 Spike S1 glycoprotein is a TLR4 agonist, upregulates ACE2 expression and induces pro-inflammatory M1 macrophage polarisation. -
  Background and aims: TLR4 is an important innate immune receptor that recognizes bacterial LPS, viral proteins and other pathogen associated molecular patterns (PAMPs). It is expressed on tissue-resident and immune cells. We previously proposed a model whereby SARS-CoV-2 activation of TLR4 via its spike glycoprotein S1 domain increases ACE2 expression, viral loads and hyperinflammation with COVID-19 disease [1]. Here we test this hypothesis in vitro and demonstrate that the SARS-CoV-2 spike S1 domain is a TLR4 agonist in rat and human cells and induces a pro-inflammatory M1 macrophage phenotype in human THP-1 monocyte-derived macrophages. Methods: Adult rat cardiac tissue resident macrophage-derived fibrocytes (rcTMFs) were treated with either bacterial LPS or recombinant SARS-CoV-2 spike S1 glycoprotein. The expression of ACE2 and other inflammatory and fibrosis markers were assessed by immunoblotting. S1/TLR4 co- localisation/binding was assessed by immunocytochemistry and proximity ligation assays on rcTMFs and human HEK-293 HA- TLR4-expressing cells. THP-1 monocytes were differentiated into M1 or M2 macrophages with LPS/IFN-{gamma}, S1/IFN-{gamma} or IL-4 and RNA was extracted for RT-qPCR of M1/M2 markers and ACE2. Results: TLR4 activation by spike S1 or LPS resulted in the upregulation of ACE2 in rcTMFs as shown by immunoblotting. Likewise, spike S1 caused TLR4-mediated induction of the inflammatory/wound healing marker COX-2 and concomitant downregulation of the fibrosis markers CTGF and Col3a1, similar to LPS. The specific TLR4 TIR domain signalling inhibitor CLI-095 (Resatorvid), blocked the effects of spike S1 and LPS, confirming that spike S1 is a TLR4 agonist and viral PAMP (VAMP). ACE2 expression was also inhibited by the dynamin inhibitor Dynasore, suggesting ACE2 expression is mediated by the alternative endosomal/{beta}-interferon pathway. Confocal immunofluorescence microscopy confirmed 1:1 stoichiometric spike S1 co- localisation with TLR4 in rat and human cells. Furthermore, proximity ligation assays confirmed spike S1 and TLR4 binding in human and rat cells. Spike S1/IFN-{gamma} treatment of THP-1-derived macrophages induced pro-inflammatory M1 polarisation as shown by an increase in IL-1-{beta} and IL-6 mRNA. Conclusions: These results confirm that TLR4 is activated by the SARS-CoV-2 spike protein S1 domain and therefore TLR4 may be a receptor/accessory factor for the virus. By binding to and activating TLR4, spike S1 caused upregulation of ACE2, which may facilitate viral entry into cells. In addition, pro-inflammatory M1 macrophage polarisation via TLR4 activation, links TLR4 activation by spike S1 to inflammation. The clinical trial testing of CLI-095 (Resatorvid) and other TLR4 antagonists in severe COVID-19, to reduce both viral entry into cells and hyperinflammation, is warranted. Our findings likely represent an important development in COVID-19 pathophysiology and treatment, particularly regarding cardiac complications and the role of macrophages.
  🖺 Full Text HTML: SARS-CoV-2 Spike S1 glycoprotein is a TLR4 agonist, upregulates ACE2 expression and induces pro-inflammatory M1 macrophage polarisation.
• Cross-sectional genomic perspective of epidemic waves of SARS-CoV-2: a pan India study -
  COVID-19 has posed unforeseen circumstances and throttled major economies worldwide. India has witnessed two waves affecting around 31 million people representing 16% of the cases globally. To date, the epidemic waves have not been comprehensively investigated to understand pandemic progress in India. In the present study, we aim for a cross- sectional analysis since its first incidence up to 26th July 2021. We have performed the pan Indian evolutionary study using 20,086 high-quality complete genomes of SARS-CoV-2. Based on the number of cases reported and mutation rates, we could divide the Indian epidemic into seven different phases. First, three phases constituting the pre-first wave had a very less average mutation rate (<11), which increased in the first wave to 17 and then doubled in the second wave (~34). In accordance with the mutation rate, variants of concern (alpha, beta, gamma and delta) and interest (eta and kappa) also started appearing in the first wave (1.5% of the genomes), which dominated the second (~96% of genomes) and post-second wave (100% of genomes) phases. Whole genome-based phylogeny could demarcate the post-first wave isolates from previous ones by the point of diversification leading to incidences of VOCs and VOIs in India. Nation-wide mutational analysis depicted more than 0.5 million events with four major mutations in ~97% of the total 20,086 genomes in the study. These included two mutations in coding (spike (D614G) and NSP 12b (P314L) of RNA dependent RNA polymerase), one silent mutation (NSP3 F106F) and one extragenic mutation (5 UTR 241). Large scale genome-wide mutational analysis is crucial in expanding knowledge on evolution of deadly variants of SARS-CoV-2 and timely management of the pandemic.
  🖺 Full Text HTML: Cross-sectional genomic perspective of epidemic waves of SARS-CoV-2: a pan India study
• Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19 -
  Thrombocytopenia, characterized by reduced platelet count, increases mortality in COVID-19 patients. We performed a computational investigation of antibody-induced cross-reactivity due to molecular mimicry between SARS-CoV-2 Spike protein and human thrombopoietin, the regulator of platelet production, as a mechanism for thrombocytopenia in COVID-19 infections. The presence of a common sequence motif with similar structure and antibody-binding properties for these proteins strongly indicate shared molecular mimicry. Recent reports of antibodies in COVID-19 patients and pre-pandemic samples against epitopes containing the motif offer additional support for the cross-reactivity. Altogether, this suggests cross-reactivity between an antibody with affinity for Spike protein and a human protein. Consideration of cross-reactivity for SARS-CoV-2 is important for therapeutic intervention and when designing the next generation of COVID-19 vaccines to avoid potential autoimmune interference.
  🖺 Full Text HTML: Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19
• Structural Differences In 3C-like protease (Mpro) From SARS-CoV and SARS-CoV-2: Molecular Insights For Drug Repurposing Against COVID-19 Revealed by Molecular Dynamics Simulations. -
  A recent fatal outbreak of novel coronavirus SARS-CoV-2, identified preliminary as a causative agent for series of unusual pneumonia cases in Wuhan city, China has infected more than 20 million individuals with more than 4 million mortalities. Since, the infection crossed geographical barriers, the WHO permanently named the causing disease as COVID-2019 by declaring it a pandemic situation. SARS-CoV-2 is an enveloped single-stranded RNA virus causing a wide range of pathological conditions from common cold symptoms to pneumonia and fatal severe respiratory syndrome. Genome sequencing of SARS-CoV-2 has revealed 96% identity to the bat coronavirus and 79.6% sequence identity to the previous SARS-CoV. The main protease (known as 3C-like proteinase/ Mpro) plays a vital role during the infection with the processing of replicase polyprotein thus offering an attractive target for therapeutic interventions. SARS-CoV and SARS- CoV-2 Mpro shares 97% sequence identity, with 12 variable residues but none of them are present in the catalytic and substrate binding site. With the high level of sequence and structural similarity and absence of any drug/vaccine against SARS-CoV-2, drug repurposing against Mpro is an effective strategy to combat COVID-19. Here, we report a detailed comparison of SARS-CoV-2 Mpro with SARS-CoV Mpro using molecular dynamics simulations to assess the impact of 12 divergent residues on the molecular microenvironment of Mpro. Structural comparison and analysis are made on how these variable residues affect the intra-molecular interactions between key residues in the monomer and biologically active dimer form of Mpro. The present MD simulations study concluded the change in microenvironment of active-site residues at the entrance (T25, T26, M49 and Q189), near the catalytic region (F140, H163, H164, M165 and H172) and other residues in substrate binding site (V35T, N65S, K88R and N180K) due to 12 mutation incorporated in the SARS-CoV-2 Mpro. It is also evident that SARS-CoV-2 dimer is more stable and less flexible state compared to monomer which may be due to these variable residues, mainly F140, E166 and H172 which are involved in dimerization. This also warrants a need for inhibitor design considering the more stable dimer form. The mutation accumulated in SARS-CoV-2 Mpro indirectly reconfigures the key molecular networks around the active site conferring a potential change in SARS-CoV-2, thus posing a challenge in drug repurposing SARS drugs for COVID-19. The new networks and changes in the microenvironment identified by our work might guide attempts needed for repurposing and identification of new Mpro inhibitors.
  🖺 Full Text HTML: Structural Differences In 3C-like protease (Mpro) From SARS-CoV and SARS-CoV-2: Molecular Insights For Drug Repurposing Against COVID-19 Revealed by Molecular Dynamics Simulations.
• Modeling the SARS-CoV-2 mutation based on geographical regions and time -
  The Coronavirus Disease 2019 (COVID-19) epidemic was first detected in late-December 2019 in Wuhan, China. So far, it has caused more than 200 million confirmed cases and over 4.2 million deaths in the world. We collected sequences from 150,659 COVID-19 patients. Based on the previous phylogenomic analysis, we found three major branches of the virus RNA genomic mutation located in Asia, America, and Europe which is consistent with other studies. We selected sites with high mutation frequencies from Asia, America, and Europe. There are only 13 common mutation sites in these three regions. It infers that the viral mutations are highly dependent on their location and different locations have specific mutations. Most mutations can lead to amino acid substitutions, which occurred in 3/5’UTR, S/N/M protein, and ORF1ab/3a/8/10. Thus, the mutations may affect the pathogenesis of the virus. In addition, we applied a ARIMA model to predict the short-term frequency change of these top mutation sites during the spread of the disease. We tested a variety of settings of ARIMA model to optimize the prediction effect of three patterns. This model can provide a good help for predicting short-term mutation frequency changes.
  🖺 Full Text HTML: Modeling the SARS-CoV-2 mutation based on geographical regions and time
• N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2 -
  The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of {beta}-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS- CoV-2.
  🖺 Full Text HTML: N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
• Multiplexed detection of SARS-CoV-2 genomic and subgenomic RNA using in situ hybridization -
  The widespread Coronavirus Disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have a limited toolset available for visualizing SARS-CoV-2 in cells and tissues, particularly in tissues from patients who died from COVID-19. Generally, single-molecule RNA FISH techniques have shown mixed results in formalin fixed paraffin embedded tissues such as those preserved from human autopsies. Here, we present a platform for preparing autopsy tissue for visualizing SARS-CoV-2 RNA using RNA FISH with amplification by hybridization chain reaction (HCR). We developed probe sets that target different regions of SARS-CoV-2 (including ORF1a and N) as well as probe sets that specifically target SARS-CoV-2 subgenomic mRNAs. We validated these probe sets in cell culture and tissues (lung, lymph node, and placenta) from infected patients. Using this technology, we observe distinct subcellular localization patterns of the ORF1a and N regions, with the ORF1a concentrated around the nucleus and the N showing a diffuse distribution across the cytoplasm. In human lung tissue, we performed multiplexed RNA FISH HCR for SARS-CoV-2 and cell-type specific marker genes. We found viral RNA in cells containing the alveolar type 2 (AT2) cell marker gene (SFTPC) and the alveolar macrophage marker gene (MARCO), but did not identify viral RNA in cells containing the alveolar type 1 (AT1) cell marker gene (AGER). Moreover, we observed distinct subcellular localization patterns of viral RNA in AT2 cells and alveolar macrophages, consistent with phagocytosis of infected cells. In sum, we demonstrate the use of RNA FISH HCR for visualizing different RNA species from SARS-CoV-2 in cell lines and FFPE autopsy specimens. Furthermore, we multiplex this assay with probes for cellular genes to determine what cell-types are infected within the lung. We anticipate that this platform could be broadly useful for studying SARS-CoV-2 pathology in tissues as well as extended for other applications including investigating the viral life cycle, viral diagnostics, and drug screening.
  🖺 Full Text HTML: Multiplexed detection of SARS-CoV-2 genomic and subgenomic RNA using in situ hybridization
• SARS-CoV-2 Spike Affinity and Dynamics Exclude the Strict Requirement of an Intermediate Host -
  SARS-CoV-2 proximal origin is still unclear, limiting the possibility of foreseeing other spillover events with pandemic potential. Here we propose an evolutionary model based on the thorough dissection of SARS-CoV-2 and RaTG13 - the closest bat ancestor - spike dynamics, kinetics and binding to ACE2. Our results indicate that both spikes share nearly identical, high affinities for Rhinolophus affinis bat and human ACE2, pointing out to negligible species barriers directly related to receptor binding. Also, SARS-CoV-2 spike shows a higher degree of dynamics and kinetics optimization that favors ACE2 engagement. Therefore, we devise an affinity-independent evolutionary process that likely took place in R. affinis bats and limits the eventual involvement of other animal species in initiating the pandemic to the role of vector.
  🖺 Full Text HTML: SARS-CoV-2 Spike Affinity and Dynamics Exclude the Strict Requirement of an Intermediate Host
• A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC -
  Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric hAdV5 vector. The vaccine (named CoroVaxG.3) is based on three pillars: i) high expression of Spike to enhance its immunodominance by using a potent promoter and a mRNA stabilizer; ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; iii) use of Spike stabilized in a prefusion conformation. Transduction with CoroVaxG.3 expressing Spike (D614G) dramatically enhanced Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3 vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha) and P.1 (gamma) Spikes, as well as an authentic WT and P.1 SARS-CoV-2 isolates. Neutralizing antibodies did not wane even after 5 months making this kind of vaccine a likely candidate to enter clinical trials.
  🖺 Full Text HTML: A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC
• Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants -
  Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as the recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The B.1.617.2 (delta) variant of concern is causing a new wave of infections in many countries, mostly affecting unvaccinated individuals, and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing the impact of individual mutations on immune evasion. Mutations in the B.1.617.1 (kappa) and B.1.617.2 (delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including an unexpected remodeling of the B.1.617.2 (delta) N-terminal domain. The binding affinity of the B.1.617.1 (kappa) and B.1.617.2 (delta) receptor-binding domain for ACE2 is comparable to the ancestral virus whereas B.1.617.2+ (delta+) exhibits markedly reduced affinity. We describe a previously uncharacterized class of N-terminal domain-directed human neutralizing monoclonal antibodies cross-reacting with several variants of concern, revealing a possible target for vaccine development.
  🖺 Full Text HTML: Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants

From Clinical Trials

• Pulmonary Rehabilitation Post-COVID-19 - Condition:   COVID-19
  Intervention:   Other: Exercise program (virtual/remote)
  Sponsors:   University of Manitoba;   Health Sciences Centre Foundation, Manitoba;   Health Sciences Centre, Winnipeg, Manitoba
  Not yet recruiting

• Echinacea Drug for Covid-19 - Condition:   Covid19
  Interventions:   Drug: Equinacea Arkopharma;   Other: Placebo
  Sponsors:   Jesús R. Requena;   IDIS;   SALUD;   Laboratoires Arkopharma
  Recruiting

• Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise - Condition:   Covid19
  Interventions:   Biological: COVI-MSC;   Biological: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique - Condition:   Covid19
  Interventions:   Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell);   Biological: AZD1222 (replication-deficient Ad type 5 vector expressing full-length spike protein)
  Sponsors:   International Vaccine Institute;   The Coalition for Epidemic Preparedness Innovations (CEPI);   Instituto Nacional de Saúde (INS), Mozambique;   University of Antananarivo;   International Centre for Diarrhoeal Disease Research, Bangladesh;   Harvard University;   Heidelberg University
  Not yet recruiting

• Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment - Condition:   Covid19
  Interventions:   Drug: Hydroxychloroquine;   Drug: Favipiravir;   Drug: Favipiravir + Hydroxychloroquine;   Drug: Placebo
  Sponsor:   Health Institutes of Turkey
  Completed

• Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized With Covid-19 - Condition:   COVID-19 Infection
  Intervention:   Drug: Colchcine
  Sponsor:  
  Asociacion Instituto Biodonostia
  Active, not recruiting

• ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Danicopan;   Other: Placebo;   Drug: Remdesivir
  Sponsor:   National Institute of Allergy and Infectious Diseases (NIAID)
  Recruiting

• Project FLUx COntact-CoVID-19 Faculty of Medicine Paris-Saclay - Condition:   Covid19
  Interventions:   Other: Antigenic tests (on saliva samples);   Other: Individual electronic sensor port;   Other: Atmospheric measurements of CO2
  Sponsor:  
  Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose) - Condition:   COVID-19 Lower Respiratory Infection
  Interventions:   Biological: AG0302-COVID19 for Intramuscular Injection;   Biological: AG0302-COVID19 for Intradermal Injection
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Not yet recruiting

• COVID-19 Administration of Single-Dose Subcutaneous or Intramuscular Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition:   COVID-19
  Intervention:   Drug: casirivimab and imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Reactogenicity, Safety, and Immunogenicity of Covid-19 Vaccine Booster - Condition:   Covid19
  Interventions:   Biological: Placebo;   Biological: Inactivated vaccine booster;   Biological: mRNA vaccine booster;   Drug: Viral vector vaccine booster
  Sponsors:   Universidad del Desarrollo;   Ministry of Health, Chile;   University of Chile;   Pontificia Universidad Catolica de Chile
  Active, not recruiting

• Relaxation Exercise in Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: Relaxation technique
  Sponsor:   Beni- Suef University
  Completed

• The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Intervention:   Dietary Supplement: Nigella Sativa capsule twice daily
  Sponsor:   Ain Shams University
  Recruiting

• Clinical Trial to Assess the Efficacy and Safety of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms - Condition:   Covid19
  Intervention:   Drug: Drug, inhalation
  Sponsor:  
  Aquilon Pharmaceuticals S.A.
  Not yet recruiting

• Efficacy, Immunogenicity and Safety of COVID-19 Vaccine , Inactivated in Children and Adolescents - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: Controlled vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Recruiting

From PubMed

• A computational study of cooperative binding to multiple SARS-CoV-2 proteins - Structure-based drug design targeting the SARS-CoV-2 virus has been greatly facilitated by available virus-related protein structures. However, there is an urgent need for effective, safe small-molecule drugs to control the spread of the virus and variants. While many efforts are devoted to searching for compounds that selectively target individual proteins, we investigated the potential interactions between eight proteins related to SARS-CoV-2 and more than 600 compounds from a traditional…

• Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase - There is currently a lack of effective drugs to treat people infected with SARS-CoV-2, the cause of the global COVID-19 pandemic. The SARS-CoV-2 Non-structural protein 13 (NSP13) has been identified as a target for anti-virals due to its high sequence conservation and essential role in viral replication. Structural analysis reveals two “druggable” pockets on NSP13 that are among the most conserved sites in the entire SARS-CoV-2 proteome. Here we present crystal structures of SARS-CoV-2 NSP13…

• Decreased inhibition of exosomal miRNAs on SARS-CoV-2 replication underlies poor outcomes in elderly people and diabetic patients - Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative…

• Designing Self-Inhibitory fusion peptide analogous to viral spike protein against novel severe acute respiratory syndrome (SARS-CoV-2) - COVID-19 is a highly contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is declared pandemic by the World Health Organization (WHO). The spike protein of SARS-CoV-2 is a key component playing a pivotal role in facilitating viral fusion as well as release of genome into the host cell. Till date there is no clinically approved vaccine or drug available against Covid-19. We designed four hydrophobic inhibitory peptides (ITPs) based on WWIHS…

• Targeting Some Enzymes with Repurposing Approved Pharmaceutical Drugs for Expeditious Antiviral Approaches Against Newer Strains of COVID-19 - At present, global vaccination for the SARS-CoV2 virus 2019 (COVID-19) is 95% effective. Generally, viral infections are arduous to cure due to the mutating nature of viral genomes, with the consequent quick development of resistance, posing significant fatalities or hazards. The novel corona viral strains are increasingly lethal than earlier variants, as those evolve faster than imagined. Despite the emergence of several present innovative treatment options, the vaccines, and available drugs,…

• COVID-19 - associated inhibition of energy accumulation pathways in human semen samples - CONCLUSION: Our results may provide molecular basis for the previously observed phenomenon of decreased sperm motility associated with COVID-19 infection. Moreover, identified data would be beneficial for the optimization of preconception care for men who have recently recovered from COVID-19.

• The role of T2E mediated CBF-1/RBP-Jκ signaling in metastatic thyroid cancer - CONCLUSION: This study indicates that the overexpression of ERG co-option has a unique cis-regulatory structure in T2E positive thyroid tumors, which induces drug dependence on CBF-1/RBP-Jκ signal. Our study solved the genetic and epigenetic variation of T2E in metastatic thyroid cancer for the first time. It is worth noting that further functional and clinical validation is needed as our study is a bioinformatics analysis.

• Transmissible gastroenteritis virus ORF3b up-regulates miR-885-3p to counteract TNF-alpha production via inhibiting NF-kappaB pathway - Transmissible gastroenteritis (TGE) is an acute viral disease and characterized as severe acute inflammation response that leads to diarrhea, vomiting, and high lethality of piglets. Transmissible gastroenteritis virus (TGEV), a member of coronavirus, is the pathogen of TGE. We previously found NF-κB pathway was activated and 65 miRNAs were changed in response to inflammation caused by TGEV in cell line porcine intestinal epithelial cells-jejunum 2 (IPEC-J2). Bioinformatics results showed that…

• The use of pseudotyped coronaviruses for the screening of entry inhibitors: Green tea extract inhibits the entry of SARS-CoV-1, MERS-CoV, and SARS-CoV-2 by blocking receptor-spike interaction - CONCLUSION: In summary, we demonstrated that pseudotyped viruses are an ideal tool for studying viral entry, quantification of neutralizing antibodies, and screening of entry inhibitors in a BSL-2 facility. Moreover, green tea might be a promising natural remedy against emerging coronaviruses.

• In Vitro Inhibition of Alphaviruses by Lycorine - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 μmol/L without apparent…

• Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review - CONCLUSIONS AND RELEVANCE: Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

• Dietary foods containing nitric oxide donors can be early curators of SARS-CoV-2 infection: A possible role in the immune system - Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a lethal virus that causes COVID-19 (Coronavirus disease 2019), the respiratory illness that has caused the COVID-19 pandemic. Even though multiple pharmacological trials are ongoing, there is no proof that any treatment will effectively cure or prevent COVID-19. Currently, COVID-19-infected patients are being managed with non-specific medications to suppress the symptoms and other associated co-morbidities. Nitric oxide is a…

• Management of COVID-19-induced cytokine storm by Keap1-Nrf2 system: a review - The natural pathway of antioxidant production is mediated through Kelch-like erythroid cell-derived protein with Cap and collar homology [ECH]-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) system. Keap1 maintains a low level of Nrf2 by holding it in its protein complex. Also, Keap1 facilitates the degradation of Nrf2 by ubiquitination. In other words, Keap1 is a down-regulator of Nrf2. To boost the production of biological antioxidants, Keap1 has to be inhibited…

• Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern - Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1…

• Unfolded Protein Response Inhibition Reduces Middle East Respiratory Syndrome Coronavirus-Induced Acute Lung Injury - Tissue- and cell-specific expression patterns are highly variable within and across individuals, leading to altered host responses after acute virus infection. Unraveling key tissue-specific response patterns provides novel opportunities for defining fundamental mechanisms of virus-host interaction in disease and the identification of critical tissue- specific networks for disease intervention in the lung. Currently, there are no approved therapeutics for Middle East respiratory syndrome…

From Patent Search

• 자외선살균등 - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - link

• Camellia nitidissima C.W.Chi Caffeine and Chlorogenic acid composition for anti-SARS-CoV-2 and preparation method and application thereof - - link

• A Novel Method COVID -19 infection using Deep Learning Based System - - link

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Mascarilla impermeable - - link

• 基于细胞膜展示冠状病毒免疫原以诱导中和抗体的方法 - 本申请公开了一种基于细胞膜展示冠状病毒免疫原以诱导中和抗体的方法。具体而言，本公开中提供了一种在其细胞膜表面展示新型冠状病毒SARS‑CoV‑2刺突蛋白S的细胞，包含所述细胞的针对新型冠状病毒SARS‑CoV‑2的疫苗或疫苗组合，所述细胞在制备用于预防或治疗新型冠状病毒SARS‑CoV‑2的疫苗中的应用及其制备方法。本公开的细胞和疫苗能够在体内高效活化B细胞，诱导中和抗体应答，在预防和降低新冠病毒感染中有广泛的应用前景。 - link

• 硫代咪唑烷酮药物在治疗COVID-19疾病中的用途 - 本发明属于医药技术领域，具体涉及一种硫代咪唑烷酮药物或其药学上可接受的盐在制备用于治疗ACE2和TMPRSS2蛋白失调相关疾病的药物中的用途，尤其是在制备用于治疗COVID‑19疾病的药物中的用途。 - link

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

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

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