Covid-19 Sentry

Contents

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

From Preprints

• Moral responses to the COVID-19 crisis -
  The COVID-19 pandemic has raised complex moral dilemmas that have been the subject of extensive public debate. Here, we study how people judge a set of controversial actions related to the crisis: relaxing data privacy standards to allow public control of the pandemic, forbidding public gatherings, denouncing a friend who violated COVID-19 protocols, prioritizing younger over older patients when medical resources are scarce, and reducing animal rights to accelerate vaccine development. We collected acceptability judgements in an initial large-scale study with participants from 10 Latin American countries (N=15,420). A formal analysis of the intrinsic correlations between responses to different dilemmas revealed that judgements were organized in two dimensions: one that reflects a focus on human life expectancy and one that cares about the health of all sentient lives in an equitable manner. These stereotyped patterns of responses were stronger in people who endorsed utilitarian decisions in a standardized scale. A second pre-registered study performed in the United States (N=1,300) confirmed the replicability of these findings. Finally, we show how the prioritization of public health correlated with several contextual, personality, and demographic factors. Overall, this research sheds light on the relationship between utilitarian decision-making and moral responses to the COVID-19 crisis.
  🖺 Full Text HTML: Moral responses to the COVID-19 crisis
• Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2 -
  The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
  🖺 Full Text HTML: Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2
• Identification of SGLT2 inhibitor Ertugliflozin as a treatment for COVID-19 using computational and experimental paradigm -
  Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The RBD domain of SARS-CoV-2 Spike protein is a promising drug target due to its pivotal role in viral-host attachment. These specific structural domains can be targeted with small molecules or drug to disrupt the viral attachment to the host proteins. In this study, FDA approved Drugbank database were screened using a virtual screening approach and computational chemistry methods. Five drugs were short listed for further profiling based on docking score and binding energies. Further these selected drugs were tested for their in vitro biological activity. There was significant correlation between the prediction from computational studies and the actual RBD-ACE2 binding inhibition by the drugs. Then, we performed a series of studies that mimic some of the biological events seen in COVID-19 patients such as secretion of IL1{beta}, presentation of a more thrombogenic endothelium by production of thrombomodulin and accumulation of inflammatory cells such as monocytes in the lungs. Of all the drugs, most promising drug was Ertugliflozin which is used for type-2 diabetes. This drug possesses several desired properties and may be a good candidate for immediate repurposing for treatment of COVID-19.
  🖺 Full Text HTML: Identification of SGLT2 inhibitor Ertugliflozin as a treatment for COVID-19 using computational and experimental paradigm
• Influence of viral transport media and freeze-thaw cycling on the sensitivity of qRT-PCR detection of SARS-CoV-2 nucleic acids -
  The events of the last year have highlighted the complexity of implementing large-scale molecular diagnostic testing for novel pathogens. The purpose of this study was to determine the chemical influences of sample collection media and storage on the stability and detection of viral nucleic acids by qRT-PCR. We studied the mechanism(s) through which viral transport media (VTM) and number of freeze-thaw cycles influenced the analytical sensitivity of qRT-PCR detection of SARS-CoV-2. Our goal is to reinforce testing capabilities and identify weaknesses that could arise in resource-limited environments that do not have well-controlled cold chains. The sensitivity of qRT-PCR analysis was studied in four VTM for synthetic single-stranded RNA (ssRNA) and double-stranded DNA (dsDNA) simulants of the SARS-CoV-2 genome. The sensitivity and reproducibility of qRT-PCR for the synthetic ssRNA and dsDNA were found to be highly sensitive to VTM with the best results observed for ssRNA in HBSS and PBS-G. Surprisingly, the presence of epithelial cellular material with the ssRNA increased the sensitivity of the qRT-PCR assay. Repeated freeze-thaw cycling decreased the sensitivity of the qRT-PCR with two noted exceptions. The choice of VTM is critically important to defining the sensitivity of COVID-19 molecular diagnostics assays and this study suggests they can impact upon the stability of the SARS-CoV-2 viral genome. This becomes increasingly important if the virus structure is destabilised before analysis, which can occur due to poor storage conditions. This study suggests that COVID-19 testing performed with glycerol-containing PBS will produce a high level of stability and sensitivity. These results are in agreement with clinical studies reported for patient-derived samples.
  🖺 Full Text HTML: Influence of viral transport media and freeze-thaw cycling on the sensitivity of qRT-PCR detection of SARS-CoV-2 nucleic acids
• No evidence of SARS-CoV-2 infection in Neotropical Primates sampled during COVID-19 pandemic in Minas Gerais and Rio Grande do Sul, Brazil. -
  In 2019, a new coronavirus disease (COVID-19) was detected in China. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was capable to infect domestic and captive mammals like cats, tigers and minks. Due to genetic similarities, concern about the infection of Non-Human Primates (NHPs) and the establishment of a sylvatic cycle has grown in the Americas. In this study, neotropical primates (NP) were sampled in different areas from Brazil to investigate whether they were infected by SARS-CoV-2. A total of 89 samples from 51 NP of four species were examined. No positive samples were detected via RT-qPCR, regardless of the NHP species, tissue or habitat tested. This work provides the first report on the lack of evidence of circulation of SARS-CoV-2 in NP. The expand of wild animals sampling is necessary to understand their role in the epidemiology of SARS-CoV-2.
  🖺 Full Text HTML: No evidence of SARS-CoV-2 infection in Neotropical Primates sampled during COVID-19 pandemic in Minas Gerais and Rio Grande do Sul, Brazil.
• A novel bivalent DNA vaccine encoding both spike protein receptor-binding domain and nucleocapsid protein of SARS-CoV-2 to elicit T cell and neutralising antibody responses that cross react with variants -
  The efficacy of vaccines targeting SARS-CoV-2 is becoming apparent now that the mRNA and adenovirus vector vaccines that have been approved for emergency use are showing promise. However, the longevity of the protective immune response and its efficacy against emerging variants remains to be determined. To improve longevity and future protection against variants, we have designed a DNA vaccine encoding both the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and its nucleocapsid (N) protein, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4 Th1 and CD8 T-cell responses to both proteins, with these responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain. We have shown that the vaccine also stimulates high titre antibody responses to RBD which efficiently neutralise in both a pseudotype and live virus neutralisation assay and show cross reactivity with S proteins from the emerging variants Alpha (B.1.1.7) and Beta (B.1.351). This DNA platform can be easily adapted to target variant RBD and N proteins and we show that a vaccine variant encoding the B.1.351 RBD sequence stimulates cross-reactive humoral and T-cell immunity. These data support the translation of this DNA vaccine platform into the clinic, thereby offering a particular advantage for targeting emerging SARS-CoV-2 variants.
  🖺 Full Text HTML: A novel bivalent DNA vaccine encoding both spike protein receptor-binding domain and nucleocapsid protein of SARS-CoV-2 to elicit T cell and neutralising antibody responses that cross react with variants
• Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients -
  Infection with SARS-CoV-2 is associated with thromboinflammation, involving thrombotic and inflammatory responses, in many COVID-19 patients. In addition, immune dysfunction occurs in patients characterized by T cell exhaustion and severe lymphopenia. We investigated the distribution of phosphatidylserine (PS), a marker of dying cells, activated platelets, and platelet-derived microparticles (PMP), during the clinical course of COVID-19. We found an unexpectedly high amount of blood cells loaded with PS+ PMPs for weeks after the initial COVID-19 diagnosis. Elevated frequencies of PS+PMP+ PBMCs correlated strongly with increasing disease severity. As a marker, PS outperformed established laboratory markers for inflammation, leucocyte composition, and coagulation, currently used for COVID-19 clinical outcome prognosis. PS+ PMPs preferentially bound to CD8+ T cells with gene expression signatures of proliferating effector rather than memory T cells. As PS+ PMPs carried programmed death-ligand 1 (PD-L1), they may affect T cell expansion or function. Our data provide a novel marker for disease severity and show that PS, which can trigger the blood coagulation cascade, the complement system, and inflammation, resides on activated immune cells. Therefore, PS may serve as a beacon to attract thromboinflammatory processes toward lymphocytes and cause immune dysfunction in COVID-19.
  🖺 Full Text HTML: Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients
• Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses -
  Determining how antibodies interact with the spike (S) protein of the SARS-CoV-2 virus is critical for combating COVID-19. Structural studies typically employ simplified, truncated constructs that may not fully recapitulate the behaviour of the original complexes. Here, we combine two single particle mass analysis techniques (mass photometry and charge-detection mass spectrometry) to enable measurement of full IgG binding to the trimeric SARS-CoV-2 S ectodomain. Our experiments reveal that antibodies targeting the S-trimer typically prefer stoichiometries lower than the symmetry-predicted 3:1 binding. We determine that this behaviour arises from the interplay of steric clashes and avidity effects that are not reflected in common antibody constructs (i.e. Fabs). Surprisingly, these sub-stoichiometric complexes are fully effective at blocking ACE2 binding despite containing free receptor binding sites. Our results highlight the importance of studying antibody/antigen interactions using complete, multimeric constructs and showcase the utility of single particle mass analyses in unraveling these complex interactions.
  🖺 Full Text HTML: Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses
• A Robust High-throughput Fluorescent Polarization Assay for the Evaluation and Screening of SARS-CoV-2 Fusion Inhibitors -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious threat to global health. One attractive antiviral target is the membrane fusion mechanism employed by the virus to gain access to the host cell. Here we report a robust protein-based fluorescent polarization assay, that mimicking the formation of the six-helix bundle (6-HB) process during the membrane fusion, for the evaluation and screening of SARS-CoV-2 fusion Inhibitors. The IC50 of known inhibitors, HR2P, EK1, and Salvianolic acid C (Sal C) were measured to be 6 nM, 2.5 nM, and 8.9 uM respectively. In addition, we found Sal A has a slightly lower IC50 (3.9 uM) than Sal C. Interesting, simple caffeic acid can also disrupt the formation of 6-HB with sub-mM concentration. A pilot high throughput screening (HTS) a small marine natural product library validates the assay with a Z factor close to 0.8. We envision the current assay provides a convenient way to screen SARS-CoV-2 fusion inhibitor and assess their binding affinity.
  🖺 Full Text HTML: A Robust High-throughput Fluorescent Polarization Assay for the Evaluation and Screening of SARS-CoV-2 Fusion Inhibitors
• Cross-reactive antibodies after SARS-CoV-2 infection and vaccination -

  Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11 to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2 to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 S protein immunization in macaques, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

  🖺 Full Text HTML: Cross-reactive antibodies after SARS-CoV-2 infection and vaccination
• Spatially refined time-varying reproduction numbers of SARS-CoV-2 in Arkansas and Kentucky and their relationship to population size and public health policy, March - November, 2020 -

  Purpose: To examine the time-varying reproduction number, R_t, for COVID-19 in Arkansas and Kentucky and investigate the impact of policies and preventative measures on the variability in R_t. Methods: Arkansas and Kentucky county-level COVID-19 cumulative case count data (March 6-November 7, 2020) were obtained. R_t was estimated using the R package 9EpiEstim9, by county, region (Delta, non-Delta, Appalachian, non-Appalachian), and policy measures. Results: The R_t was initially high, falling below 1 in May or June depending on the region, before stabilizing around 1 in the later months. The median R_t for Arkansas and Kentucky at the end of the study were 1.15 (95% credible interval [CrI], 1.13, 1.18) and 1.10 (95% CrI, 1.08, 1.12), respectively, and remained above 1 for the non-Appalachian region. R_t decreased when facial coverings were mandated, changing by -10.64% (95% CrI, -10.60%, -10.70%) in Arkansas and -5.93% (95% CrI, -4.31%, -7.65%) in Kentucky. The trends in R_t estimates were mostly associated with the implementation and relaxation of social distancing measures. Conclusions: Arkansas and Kentucky maintained a median R_t above 1 during the entire study period. Changes in R_t estimates allows quantitative estimates of potential impact of policies such as facemask mandate.

  🖺 Full Text HTML: Spatially refined time-varying reproduction numbers of SARS-CoV-2 in Arkansas and Kentucky and their relationship to population size and public health policy, March - November, 2020
• The Spectre of SARS-CoV-2 in the Ambient Urban Natural Water in Ahmedabad and Guwahati: A Tale of Two Cities -

  COVID-19 positive patients can egest live SARS-CoV-2 virus through fecal matter and urine, raising concerns about viral transmission through the fecal-oral route and/or contaminated aerosolized water. These worries are heightened in many low and middle-income nations, where raw sewage is often dumped into surface waterways and open defecation betide. In this manuscript we attempt to discern the presence of SARS-CoV-2 genetic material (ORF-1ab, N and S genes) in two urban cities of India viz., Ahmedabad, in western India with ~12 WWTPs and Guwahati, in the northeast of the country with no such plants. 100% and 20% of the surface water samples had detectable SARSCoV-2 RNA load in Ahmedabad and Gandhinagar, respectively. N-gene>S-gene>ORF-1ab-gene were readily detected in the surface water of Ahmedabad, whereas, no such significant trend was found in the case of Guwahati. The high concentration of gene (ORF-1ab 800 copies/L for Sabarmati river, Ahmedabad and S-gene 565 copies/L for Bharalu urban river, Guwahati) found in natural waters indicates low sanitation and have various health and ecological consequences that should be investigated further.

  🖺 Full Text HTML: The Spectre of SARS-CoV-2 in the Ambient Urban Natural Water in Ahmedabad and Guwahati: A Tale of Two Cities
• Early Epidemiological Evidence of Public Health Value of WA Notify, a Smartphone-based Exposure Notification Tool: Modeling COVID-19 Cases Averted in Washington State -

  Background: Secure and anonymous smartphone-based exposure notification tools are recently developed public health interventions that aim to reduce COVID-19 transmission and supplement traditional public health suriveillance. We assessed the impact of Washington State9s exposure notification tool, WA Notify, in mitigating the spread of COVID-19 during its first four months of implementation. Methods: Due to the constraints of privacy-preservation, aggregate metrics and disparate data sources were utilized to estimate the number of COVID-19 cases averted based on a modelling approach adapted from Wymant et al (2021) using the following parameters: number of notifications generated; the probability that a notified individual goes on to become a case; expected fraction of transmissions preventable by strict quarantine after notification; actual adherence to quarantine; and expected size of the full transmission chain if a contact had not been notified. Results: The model was run on a range of secondary attack rates (5.1%-13.706%) and quarantine effectiveness (53% and 64%). Assuming a 12.085% secondary attack rate and 53% quarantine effectiveness, the model shows that 5,500 cases (central 95% range of sensitivity analyses 2,800-8,200) were averted statewide during the first four months of its implementation. Based on an estimated COVID-19 case fatality of 1.4%, WA Notify saved 40-115 lives during the study period. Conclusions: These findings demonstrate the value of exposure notification tools as a novel public health intervention to mitigate the spread of COVID-19 in the U.S. As new variants emerge and non-essential travel bans are lifted, exposure notification tools may continue to play a valuable role in limiting the spread of COVID-19.

  🖺 Full Text HTML: Early Epidemiological Evidence of Public Health Value of WA Notify, a Smartphone-based Exposure Notification Tool: Modeling COVID-19 Cases Averted in Washington State
• Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells -

  Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 COVID-19 patients longitudinally up to eight months and find durable broad-based immune responses. SARS-CoV-2 spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. SARS-CoV-2 infection also boosts antibody titers to SARS-CoV-1 and common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well for a rapid antibody response upon virus re-exposure or vaccination. Virus-specific CD4+ and CD8+ T cells are polyfunctional and maintained with an estimated half-life of 200 days. Interestingly, CD4+ T cell responses equally target several SARS-CoV-2 proteins, whereas the CD8+ T cell responses preferentially target the nucleoprotein, highlighting the potential importance of including the nucleoprotein in future vaccines. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.

  🖺 Full Text HTML: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
• Comparative Genomic Study for Revealing the Complete Scenario of COVID-19 Pandemic in Bangladesh -

  As the COVID-19 pandemic continues to ravage across the globe and take millions of lives and like many parts of the world, the second wave of the pandemic hit Bangladesh, this study aimed at understanding its causative agent, SARS-CoV-2 at the genomic and proteomic level and provide precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of Mid-June 2021, over 1500 SARS-CoV-2 genomes have been sequenced across the country. From our analyses, it was discovered that the wave-2 samples had a significantly greater average rate of mutation/sample (30.79%) than the wave-1 samples (12.32%). Wave-2 samples also had a higher frequency of deletion, and transversion events. During the first wave, the GR clade was the most predominant but it was replaced by the GH clade in the latter wave. The B.1.1.25 variant showed the highest frequency in wave-1 while in case of wave-2, the B.1.351.3 variant, was the most common one. A notable presence of the delta variant, which is currently at the center of concern, was also observed. Comparison of the Spike protein found in the reference and the 3 most common lineages found in Bangladesh namely, B.1.1.7, B.1.351, B.1.617 in terms of their ability to form stable complexes with ACE2 receptor revealed that B.1.617 had the potential to be more transmissible than others. Importantly, no indigenous variants have been detected so far which implies that the successful prevention of import of foreign variants can diminish the outbreak in the country.

  🖺 Full Text HTML: Comparative Genomic Study for Revealing the Complete Scenario of COVID-19 Pandemic in Bangladesh

From Clinical Trials

• Ivermectin Treatment Efficacy in Covid-19 High Risk Patients - Condition:   COVID-19
  Intervention:   Drug: Ivermectin 0.4mg/kg/day for 5 days
  Sponsor:   Clinical Research Centre, Malaysia
  Not yet recruiting

• Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: XAV-19;   Drug: Placebo
  Sponsor:   Xenothera SAS
  Recruiting

• Study of Codivir in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: One Step Test;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: RT-PCR SARS-CoV-2;   Diagnostic Test: Screening blood test;   Diagnostic Test: ECG;   Diagnostic Test: Medical evaluation;   Diagnostic Test: NEWS-2 score;   Diagnostic Test: WHO score
  Sponsors:   Code Pharma;   Zion Medical
  Active, not recruiting

• Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Vitamin C;   Drug: N-acetylcysteine (NAC);   Drug: NAC + Bromhexine (BMX)
  Sponsors:   Universidade Federal do Ceara;   Paulista School of Medicine-EPM, UNIFESP;   Health Surveillance Secretariat - SVS;   Central Laboratory of Public Health of Ceara - LACEN-CE;   Leonardo da Vinci Hospital - HLV;   São José Hospital for Infectious Diseases - HSJ;   Ceará Health Secretariat - SESA;   Municipal Health Secretary - SMS-Fortaleza
  Not yet recruiting

• Augmentation of Immune Response to COVID-19 mRNA Vaccination Through OMT With Lymphatic Pumps - Condition:   Covid19
  Intervention:   Other: Osteopathic Manipulative Treatment (OMT)
  Sponsors:   Western University of Health Sciences;   American College of Osteopathic Physicians;   American Osteopathic Foundation;   Osteopathic Physicians and Surgeons of California;   Xavier-Nichols Foundation
  Recruiting

• Nervous System Symptoms Associated With COVID 19 - Condition:   Covid19
  Interventions:   Other: NEURO +;   Other: NEURO -
  Sponsor:   University Hospital, Toulouse
  Completed

• Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
  Sponsor:   Peking Union Medical College Hospital
  Recruiting

• Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test - Condition:   Covid-19 Testing
  Intervention:   Diagnostic Test: Biozek Covid-19 Antigen Rapid Test (Saliva)
  Sponsor:   Mach-E B.V.
  Recruiting

• Community-based Post-exposure Prophylaxis for COVID-19 - Condition:   Covid19
  Interventions:   Other: Guduchi Ghanvati;   Other: Standard guidelines
  Sponsors:   NMP Medical Research Institute;   Aarogyam UK;   Dr. Sarvepalli Radhakrishnan Rajasthan Ayurved University;   Samta Ayurveda Prakoshtha, India;   Padmanabhama Ayurveda Hospital and Research Centre
  Completed

• Vitamin A Supplementation in Children With Moderate to Severe COVID-19 - Condition:   Covid19
  Intervention:   Dietary Supplement: Vitamin A supplement
  Sponsor:   Shiraz University of Medical Sciences
  Not yet recruiting

• Cerebral Autoregulation and COVID-19 - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   COVID-19 Pneumonia
  Intervention:   Other: NIRS (Near-Infrared Spectroscopy)
  Sponsor:   University of Athens
  Not yet recruiting

• Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19 - Condition:   Covid19
  Interventions:   Drug: Favipiravir;   Drug: Nitazoxanide;   Other: Nitazoxanide Placebo
  Sponsors:   Coordinación de Investigación en Salud, Mexico;   University College, London;   Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV);   Universidad Autonoma de Guadalajara;   Siegfried Rhein S.A. de C.V.;   Strides Pharma Science Limited;   Hakken Enterprise
  Not yet recruiting

• Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients - Condition:   Covid19
  Interventions:   Biological: Dupilumab;   Drug: Placebo
  Sponsors:   University of Virginia;   PBM C19 Research, LLC (a COVID-19 research entity of the Paul Manning Foundation);   Virginia Catalyst, Virginia Biosciences Health Research Corporation (VBHRC)
  Recruiting

• Impact of Moderate Exercise Training on Vitals and Peak VO2 in Different Age Categories of Adult in COVID-19. - Condition:   Covid19
  Interventions:   Other: Moderate Exercise Training (Age Group 1; Young adult 17 -30 years);   Other: Moderate Exercise Training (Age Group 2; 31 to 45 years);   Other: Moderate Exercise Training (Age Group 3; Above 45 years)
  Sponsor:   Riphah International University
  Recruiting

• Infliximab in the Treatment of Patients With Severe COVID-19 Disease - Condition:   COVID-19
  Interventions:   Drug: Infliximab;   Other: Standard of Care
  Sponsors:   Jena University Hospital;   German Federal Ministry of Education and Research;   Celltrion
  Not yet recruiting

From PubMed

• Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals - The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Here, we show that lysosome-deficient T cells rely on late endosomes rather than lysosomes as an…

• Fear in the Chinese Population: Influential Patterns in the Early Stage of the COVID-19 Pandemic - Major global public health emergencies challenge public mental health. Negative emotions, and especially fear, may endanger social stability. To better cope with epidemics and pandemics, early emotional guidance should be provided based on an understanding of the status of public emotions in the given circumstances. From January 27 to February 11, 2020 (during which the cases of COVID-19 were increasing), a national online survey of the Chinese public was conducted. A total of 132,482…

• An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants - The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might…

• Melatonin and other indoles show antiviral activities against swine Coronaviruses in vitro at pharmacological concentrations - The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights major gaps in our knowledge on the prevention control and cross-species transmission mechanisms of animal coronaviruses. Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta-coronavirus (PDCoV) are three common swine coronaviruses and have similar clinical features. In absence of effective treatments, they…

• Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection - Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs….

• Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions - In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting…

• Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia - COVID-19 (coronavirus disease 2019) represents a pandemic, and several vaccines have been produced to prevent infection and/or severe sequelae associated with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. There have been several reports of infrequent post vaccine associated thrombotic events, in particular for adenovirus-based vaccines. These have variously been termed VIPIT (vaccine-induced prothrombotic immune thrombocytopenia), VITT (vaccine-induced [immune]…

• An in vitro antiviral activity of iodine complexes against SARS-CoV-2 - Since the emergence of COVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule)of an Iodine-complex (Renessans). First, cell cytotoxicity of Renessans on the Vero cells was determined using MTT assay. Afterwards, the antiviral activity of Renessans was determined using viral inhibition assays and TCID(50). For this, nontoxic…

• Correction to “Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir” - [This corrects the article DOI: 10.1021/acsptsci.1c00022.].

• Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection - The 2019-2020 winter was marked by the emergence of a new coronavirus (SARS-CoV-2) related disease (COVID-19), which started in Wuhan, China. Its high human-to-human transmission ability led to a worldwide spread within few weeks and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this…

• Humoral Response after SARS-Cov-2 mRNA Vaccine in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients - Background Kidney transplant recipients and patients receiving hemodialysis are immunocompromised populations that are prioritized for COVID-19 vaccination but were excluded from clinical trials of SARS-CoV-2 mRNA vaccines. Antibody titers and rates of seroconversion following vaccination are lower among patients with chronic kidney disease and those taking immunosuppressants compared with controls. Data are lacking regarding their humoral response to vaccination to prevent COVID-19. Methods…

• Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity - Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway….

• Higher Levels of Harsh Parenting During the COVID-19 Lockdown in the Netherlands - Previous studies on the impact of COVID-19 indicate that pandemic-related distress increases risks for child maltreatment, although data on the scope of this problem are still scarce. Here, we assessed whether parents with toddlers (n = 206) more often used harsh discipline during the lockdown in the Netherlands compared to a matched parent sample collected prior to the pandemic (n = 1,030). Parents were matched on background characteristics using propensity score matching. We found that harsh…

• Humoral and cellular immune responses against SARS-CoV-2 variants and human coronaviruses after single BNT162b2 vaccination - CONCLUSION: These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.

• Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1 - Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.25-Å resolution. Further functional assays showed that the N terminus of SARS-CoVs Nsp1 alone loses the ability to colocalize with ribosomes…

From Patent Search

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

• COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19 - - link

• METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link

• Erweiterbare Desinfektionsvorrichtung -

  Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.

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• Einfache Sterilisationsvorrichtung -

  Einfache Sterilisationsvorrichtung, mit einem Hauptkörper (11), der in Längsrichtung einen ersten Plattenabschnitt (111) und in Querrichtung einen zweiten Plattenabschnitt (112) aufweist, wobei der erste Plattenabschnitt (111) und der zweite Plattenabschnitt (112) L-förmig miteinander verbunden sind; und einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist.

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• Klemmarme aufweisende Desinfektionsvorrichtung -

  Klemmarme aufweisende Desinfektionsvorrichtung, umfassend: einen Hauptkörper; eine Desinfektionslampe, die im Hauptkörper angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; einen Klemmabschnitt, der auf einer Seite des Hauptkörpers angeordnet ist, wobei der Klemmabschnitt zwei gegenüberliegende Greifbacken umfasst, wobei mindestens eine der beiden Greifbacken mit einer Schwenkachse versehen ist, wobei ein Klemmraum durch passgenaues Schließen der beiden Greifbacken entsteht und die beiden Greifbacken jeweils mit einem Durchgangsloch versehen sind; einen Befestigungsabschnitt, der durch die Durchgangslöcher der beiden Greifbacken hindurchgeführt ist;und ein Schild, das auf einer Seite des Klemmabschnitts angeordnet und mit einem Aufnahmeloch versehen ist.

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• Aufhängbare Sterilisationsvorrichtung -

  Aufhängbare Sterilisationsvorrichtung, mit einem Hauptkörper (11); einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist; einem Klemmabschnitt (13), der an einer Seite des Hautpkörpers (11) angeordnet ist und zwei gegenüberliegend angeordnete Klemmbacken (131) aufweist, wobei mindestens eine der beiden Klemmbacken (131) mit einem Achsbolzen (132) versehen ist, wobei die beiden Klemmbacken (131) beim Schließen einen Klemmraum (134) bilden, und wobei die beiden Klemmbacken (131) jeweils mit einem Durchgangsloch (135) versehen sind; und einem Befestigungselement (14), das durch die Durchgangslöcher (135) der beiden Klemmbacken (131) hindurchgeführt wird.

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• Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung -

  Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung, umfassend: einen Hauptkörper, der eine erste Oberfläche, eine von der ersten Oberfläche abgewandte zweite Oberfläche und ein Aufnahmeloch aufweist, wobei die zwei Seiten des Hauptkörpers jeweils mit einem Durchgangsloch versehen sind, wobei die Durchgangslöcher mit dem Aufnahmeloch durchgängig verbunden sind; eine Desinfektionslampe, die auf der zweiten Oberfläche des Hauptkörpers angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; und ein Befestigungsteil, das durch die Durchgangslöcher und das Aufnahmeloch des Hauptkörpers hindurchgeführt ist.

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• IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link