Covid-19 Sentry

Contents

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

From Preprints

• Solitary and Joint Online Pornography Use During the First COVID-19 Lockdown in Portugal: Intrapersonal and Interpersonal Correlates -
  The onset of the COVID-19 pandemic forced several people into social isolation and research has shown a paradoxical effect on people’s sexual functioning. Some people experienced decreases in sexual desire and sexual satisfaction, whereas others experienced heightened sexual desire and made new additions to their sexual repertoire, including more online pornography use during the lockdown. Yet, studies failed to examine its interpersonal and intrapersonal correlates, distinguish between solitary and joint use, or explore differences between partnered and single people. We examined if changes in solitary or joint online pornography use since the lockdown were associated with sexual functioning, sexual satisfaction, perceived health, and sleep quality. We conducted an online cross-sectional study with convenience sampling in Portugal (N = 303 participants; 56.3% men; Mage = 31.32, SD = 10.55; 70.8% in a relationship) during May and July 2020. Partnered participants who reported increases in solitary online pornography use also reported decreases in their sex life quality. For partnered and single participants, increases in joint online pornography use were associated with increases in sex life quality. Single participants who reported increases in solitary online pornography use also perceived better health and sleep quality, and those who reported increases in joint online pornography use also reported more intimacy with casual partner(s) and better sleep quality. These findings suggest that online pornography was sometimes used as a sexual pleasure tool to connect with a stable or casual partner(s) in a time when social interactions were restricted.
  🖺 Full Text HTML: Solitary and Joint Online Pornography Use During the First COVID-19 Lockdown in Portugal: Intrapersonal and Interpersonal Correlates
• CAN DISASTERS IMPROVE THE TOURISM INDUSTRY? The role of normative, cognitive and relational expectations in shaping industry response to disaster-induced disruption -
  COVID-19 led to the hibernation of tourism activities globally, causing substantial economic loss and putting at risk the survival of many tourism businesses. At the same time, the reduction in travel activity led to an immediate and unprecedented reduction of global carbon emissions. Many academics argue that the tourism industry should be rebuilt in a more sustainable way post-COVID-19. Based on the sociological theory on response to disruption, the present study provides initial empirical evidence that long-lasting environmental benefits are unlikely to result from the pandemic. Recovery guidelines issued by the UNWTO and six member-based industry associations from different geographical locations and representing different types of tourism businesses form the basis of the empirical analysis. Member-based industry associations represent key information brokers during the pandemic; they convey information and advice to their member businesses. The result of the content analysis indicates the dominant impact of normative expectations, which exclusively focus on re-establishing the pre-COVID-19 status. While there is little indication that cognitive expectations – which view the pandemic as an opportunity to transform business operations to be more environmentally sustainable – will be leveraged. This stands in stark contrast to the collective hope that the tourism industry will become more sustainable after the pandemic.
  🖺 Full Text HTML: CAN DISASTERS IMPROVE THE TOURISM INDUSTRY? The role of normative, cognitive and relational expectations in shaping industry response to disaster-induced disruption
• SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate -
  The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for almost two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Although the structure of the RdRp complex has been determined, the function of RdRp has not been fully characterized. Here we reveal that in addition to RNA dependent RNA polymerase activity, RdRp also shows exoribonuclease activity and consequently proofreading activity. We observed that RdRp and nsp14-ExoN, when combined, exhibit higher proofreading activity compared to RdRp alone. Moreover, RdRp can recognize and utilize nucleoside diphosphate (NDP) as substrate to synthesize RNA and can also incorporate {beta}-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir as substrate.
  🖺 Full Text HTML: SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate
• IFITM dependency of SARS-CoV-2 variants of concern -
  We have recently shown that a SARS-CoV-2 strain isolated in the Netherlands in February 2020 (NL-02-2020) hijacks interferon-induced transmembrane proteins, especially IFITM2, as entry cofactors for efficient infection. Here, we examined whether SARS-CoV-2 ‘variants of concern’ (VOCs), including the currently dominating delta variant, maintained the dependency on IFITMs for efficient replication. Depletion of IFITM2 reduced viral RNA production from 31- (B.1.1.7) to 755-fold (P.1). In comparison, silencing of IFITM1 had little effect, while knock-down of IFITM3 resulted in an intermediate phenotype. Strikingly, silencing of IFITM2 generally reduced infectious virus production in Calu-3 cells to near background levels. An antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells. In conclusion, endogenously expressed IFITM proteins (especially IFITM2) are important cofactors for replication of genuine SARS-CoV-2 VOCs, including the Delta variant.
  🖺 Full Text HTML: IFITM dependency of SARS-CoV-2 variants of concern
• Global Mutational Sweep of SARS-CoV-2: from Chaos to Order -
  Analysis of large-scale genome sequences demonstrates the mutation of SARS-CoV-2 has been undergoing significant sweeps. Driven by emerging variants, global sweeps are accelerated and purified over time. This may prolong the pandemic with repeating epidemics, presenting challenges to the control and prevention of SARS-CoV-2.
  🖺 Full Text HTML: Global Mutational Sweep of SARS-CoV-2: from Chaos to Order
• Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naive sheep was not highly efficient; hovewer, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.
  🖺 Full Text HTML: Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant
• Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice -
  Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ~50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-{lambda} and Tnf-) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease.
  🖺 Full Text HTML: Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice
• The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells -
  Interferons are a major part of the anti-viral innate defense system. Successful pathogens, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), need to overcome these defenses to establish an infection. Early induction of interferons (IFNs) protects against severe coronavirus disease 2019 (COVID-19). In line with this, SARS- CoV-2 is inhibited by IFNs in vitro, and IFN-based therapies against COVID-19 are investigated in clinical trials. However, SARS-CoV-2 continues to adapt to the human population resulting in the emergence of variants characterized by increased transmission fitness and/or decreased sensitivity to preventive or therapeutic measures. It has been suggested that the efficient spread of these so-called “Variants of Concern” (VOCs) may also involve reduced sensitivity to IFNs. Here, we examined whether the four current VOCs (Alpha, Beta, Gamma and Delta) differ in replication efficiency or IFN sensitivity from an early isolate of SARS-CoV-2. All viruses replicated in a human lung cell line and in iPSC-derived alveolar type II cells (iAT2). The Delta variant showed accelerated replication kinetics and higher infectious virus production compared to the early 2020 isolate. Replication of all SARS-CoV-2 VOCs was reduced in the presence of exogenous type I, II and III IFNs. On average, the Alpha variant was the least susceptible to IFNs and the Alpha, Beta and Gamma variants show increased resistance against type III IFN. Although the Delta variant has outcompeted all other variants in humans it remained as sensitive to IFNs as an early 2020 SARS-CoV-2 isolate. This suggests that increased replication fitness rather than IFN resistance may be a reason for its dominance. Our results may help to understand changes in innate immune susceptibility of VOCs, and inform clinical trials exploring IFN-based COVID-19 therapies.
  🖺 Full Text HTML: The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells
• Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells. -
  SARS-CoV-2 entry into host cells is mediated by the binding of its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor, highly expressed in several organs, but very low in the brain. The mechanism through which SARS-CoV-2 infects neurons is not understood. Tunneling nanotubes (TNTs), actin-based intercellular conduits that connect distant cells, allow the transfer of cargos, including viruses. Here, we explored the neuroinvasive potential of SARS-CoV-2 and whether TNTs are involved in its spreading between cells in vitro. We report that neuronal cells, not permissive to SARS-CoV-2 through an exocytosis/endocytosis dependent pathway, can be infected when co-cultured with permissive infected epithelial cells. SARS-CoV-2 induces TNTs formation between permissive cells and exploits this route to spread to uninfected permissive cells in co-culture. Correlative Cryo-electron tomography reveals that SARS-CoV-2 is associated with the plasma membrane of TNTs formed between permissive cells and virus-like vesicular structures are inside TNTs established both between permissive cells and between permissive and non-permissive cells. Our data highlight a potential novel mechanism of SARS-CoV-2 spreading which could serve as route to invade non-permissive cells and potentiate infection in permissive cells.
  🖺 Full Text HTML: Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells.
• BSG/CD147 and ACE2 receptors facilitate SARS-CoV-2 infection of human iPS cell-derived kidney podocytes -
  Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the Coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease has caused more than 5.1 million deaths worldwide. While cells in the respiratory system are frequently the initial target for SARS-CoV-2, clinical studies suggest that COVID-19 can become a multi-organ disease in the most severe cases. Still, the direct affinity of SARS-CoV-2 for cells in other organs such as the kidneys, which are often affected in severe COVID-19, remains poorly understood. Method: In this study, we employed a human induced pluripotent stem (iPS) cell- derived model to investigate the affinity of SARS-CoV-2 for kidney glomerular podocytes. We studied uptake of the live SARS-CoV-2 virus as well as pseudotyped viral particles by human iPS cell derived podocytes using qPCR, western blot, and immunofluorescence. Global gene expression and qPCR analyses revealed that human iPS cell-derived podocytes express many host factor genes (including ACE2, BSG/CD147, PLS3, ACTR3, DOCK7, TMPRSS2, CTSL CD209, and CD33) associated with SARS-CoV-2 binding and viral processing. Result: Infection of podocytes with live SARS-CoV-2 or spike-pseudotyped lentiviral particles revealed viral uptake by the cells at low Multiplicity of Infection (MOI of 0.01) as confirmed by RNA quantification and immunofluorescence studies. Our results also indicate that direct infection of human iPS cell- derived podocytes by SARS-CoV-2 virus can cause cell death and podocyte foot process retraction, a hallmark of podocytopathies and progressive glomerular diseases including collapsing glomerulopathy observed in patients with severe COVID-19 disease. Additionally, antibody blocking experiments identified BSG/CD147 and ACE2 receptors as key mediators of spike binding activity in human iPS cell-derived podocytes. Conclusion: These results show that SARS-CoV-2 can infect kidney glomerular podocytes in vitro. These results also show that the uptake of SARS-CoV-2 by kidney podocytes occurs via multiple binding interactions and partners, which may underlie the high affinity of SARS-CoV-2 for kidney tissues. This stem cell-derived model is potentially useful for kidney-specific antiviral drug screening and mechanistic studies of COVID-19 organotropism.
  🖺 Full Text HTML: BSG/CD147 and ACE2 receptors facilitate SARS-CoV-2 infection of human iPS cell-derived kidney podocytes
• Predicting SARS-CoV-2 epitope-specific TCR recognition using pre-trained protein embeddings -
  The COVID-19 pandemic is ongoing because of the high transmission rate and the emergence of SARS-CoV-2 variants. The P272L mutation in SARS-Cov-2 S-protein is known to be highly relevant to the viral escape associated with the second pandemic wave in Europe. Epitope-specific T-cell receptor (TCR) recognition is a key factor in determining the T-cell immunogenicity of a SARS-CoV-2 epitope. Although several data-driven methods for predicting epitope-specific TCR recognition have been proposed, they remain challenging owing to the enormous diversity of TCRs and the lack of available training data. Self-supervised transfer learning has recently been demonstrated to be powerful for extracting useful information from unlabeled protein sequences and increasing the predictive performance of the fine-tuned models in downstream tasks. Here, we present a predictive model based on Bidirectional Encoder Representations from Transformers (BERT), employing self-supervised transfer learning, to predict SARS-CoV-2 T-cell epitope-specific TCR recognition. The fine-tuned model showed notably high predictive performance for independent evaluation using the SARS- CoV-2 epitope-specific TCR CDR3{beta} sequence datasets. In particular, we found the proline at position 4 corresponding to the P272L mutation in the SARS-CoV-2 S-protein269-277 epitope (YLQPRTFLL) may contribute substantially to TCR recognition of the epitope through interpreting the output attention weights of our model. We anticipate that our findings will provide new directions for constructing a reliable data-driven model to predict the immunogenic T-cell epitopes using limited training data and help accelerate the development of an effective vaccine in response to SARS- CoV-2 variants.
  🖺 Full Text HTML: Predicting SARS-CoV-2 epitope- specific TCR recognition using pre-trained protein embeddings
• Effectiveness of Localized Lockdowns in the SARS-CoV-2 Pandemic -

  Non-pharmaceutical interventions, such as social distancing and lockdowns, have been essential to control the COVID-19 pandemic. In particular, localized lockdowns in small geographic areas have become an important policy intervention to prevent viral spread in cases of resurgence. These localized lockdowns can result in lower social and economic costs compared to larger-scale suppression strategies. Using an integrated dataset from Chile (March 3 through June 15, 2020) and a novel synthetic control approach, in this paper we estimate the effect of localized lockdowns, disentangling its direct and indirect causal effects on SARS-CoV-2 transmission. Our results show that the effects of localized lockdowns are strongly modulated by their duration and are influenced by indirect effects from neighboring geographic areas. Our estimates suggest that extending localized lockdowns can slow down the pandemic; however, localized lockdowns on their own are insufficient to control pandemic growth in the presence of indirect effects from contiguous neighboring areas that do not have lockdowns. These results provide critical empirical evidence about the effectiveness of localized lockdowns in interconnected geographic areas.

  🖺 Full Text HTML: Effectiveness of Localized Lockdowns in the SARS-CoV-2 Pandemic
• Epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus- induced asthma exacerbations and COVID-19 -

  Rhinoviruses (RV) and inhaled allergens, such as house dust mite (HDM) are the major agents responsible for asthma onset, its life-threatening exacerbations and progression to severe disease. The role of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in exacerbations of asthma or the influence of preexisting viral or allergic airway inflammation on the development of coronavirus disease 2019 (COVID-19) is largely unknown. To address this, we compared molecular mechanisms of HDM, RV and SARS-CoV-2 interactions in experimental RV infection in patients with asthma and healthy individuals. RV infection was sensed via retinoic acid-inducible gene I (RIG-I) helicase, but not via NLR family pyrin domain containing 3 (NLRP3), which led to subsequent apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) recruitment, oligomerization and RIG-I inflammasome activation. This phenomenon was augmented in bronchial epithelium in patients with asthma, especially upon pre-exposure to HDM, which itself induced a priming step, pro-IL-1β release and early inhibition of RIG-I/TANK binding kinase 1/IκB kinase ϵ/type I/III interferons (RIG-I/TBK1/IKKϵ/IFN-I/III) responses. Excessive activation of RIG-I inflammasomes was partially responsible for the alteration and persistence of type I/III IFN responses, prolonged viral clearance and unresolved inflammation in asthma. RV/HDM-induced sustained IFN I/III responses initially restricted SARS-CoV-2 replication in epithelium of patients with asthma, but even this limited infection with SARS-CoV-2 augmented RIG-I inflammasome activation. Timely inhibition of the epithelial RIG-I inflammasome and reduction of IL-1β signaling may lead to more efficient viral clearance and lower the burden of RV and SARS-CoV-2 infection.

  🖺 Full Text HTML: Epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus-induced asthma exacerbations and COVID-19
• SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021 -

  The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.

  🖺 Full Text HTML: SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021
• COVID-19 first and delta waves in relation to ACEI, ARB, Influenza vaccination, and comorbidity in a North Metropolitan Barcelona Health Consortium -

  BACKGROUND: Some authors have reported that angiotensin converter enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improve clinical outcomes in hypertensive COVID-19 patients, and others have proposed cross- protection for influenza vaccination. This study explores the impact of these variables on the evolution of hospitalized patients, focusing in the first wave and the Delta wave. METHODS: Hospitalizations (n=1888) from March 1, 2020, to July 31, 2021, in the Hospital of Terrassa, the referral center for the free access Terrassa Health Consortium in the North Metropolitan Barcelona Health Region (population=167,386) were studied. The number of chronic treatments and conditions of patients from the initial outbreak (n=184) and the Delta outbreak (n=158) were recorded. RESULTS: Of the non-survivors, 96.3% were aged >60 years in the first wave and 100% were aged >70 years in the Delta wave. In non-survival hospitalized patients aged >60 years, the percentage treated with ACEI was similar to general population but was significantly different for ARB treatments of influenza vaccination, although associated to a higher comorbidity and age. In July 2021, the number of hospitalizations for patients aged <50 years was higher than March 2020 and 22% of hospitalized patients without chronic treatments and conditions needed admission to the intensive care unit. Mortality was reduced in the groups with most comorbidities who received influenza and SARS-CoV2 vaccination. CONCLUSIONS: In COVID-19 infection, age and comorbidity are related to survival, ACEI use is safe. A high proportion of patients without comorbidity require hospitalization and intensive care.

  🖺 Full Text HTML: COVID-19 first and delta waves in relation to ACEI, ARB, Influenza vaccination, and comorbidity in a North Metropolitan Barcelona Health Consortium

From Clinical Trials

• BREATHE: Virtual Self-management for Long COVID-19 - Condition:   COVID-19
  Intervention:   Other: BREATHE
  Sponsor:  
  University of Calgary
  Not yet recruiting

• Mesenchymal Stem Cell Secretome In Severe Cases of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Injection of secretome - mesenchymal stem cell;   Other: Placebo;   Drug: Standard treatment of Covid-19
  Sponsor:   Indonesia University
  Completed

• Adding Colchicine to Tocilizumab in Patients With Severe COVID-19 Pneumonia. - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Colchicine
  Sponsor:  
  Hamad Medical Corporation
  Recruiting

• Partnerships to Address COVID-19 Inequities - Condition:   COVID-19
  Interventions:   Behavioral: Crowdsourced campaign package;   Behavioral: Standard information
  Sponsor:   Duke University
  Not yet recruiting

• Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Candesartan Cilexetil;   Drug: Repagermanium;   Drug: Candesartan Placebo;   Drug: Repagermanium Placebo
  Sponsors:  
  University of Sydney;   The George Institute for Global Health, India
  Not yet recruiting

• Pharmacokinetics, Pharmacodynamics, and Safety of Single-dose Sotrovimab in High-risk Pediatric Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Sotrovimab
  Sponsors:  
  GlaxoSmithKline;   Vir Biotechnology, Inc.
  Not yet recruiting

• PREVENT-COVID-19: A Q-Griffithsin Intranasal Spray - Condition:   COVID-19 Prevention
  Interventions:   Drug: Q-Griffithsin;   Other: Placebo
  Sponsors:   Kenneth Palmer;   United States Department of Defense
  Recruiting

• the Safety and Efficacy of Meplazumab in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Meplazumab for Injection;   Drug: Sterile normal saline (0.9%)
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Health Information Technology for COVID-19 Testing in Schools (SCALE-UP Counts) - Condition:   COVID-19
  Interventions:   Behavioral: Text Messaging (TM);   Behavioral: Text Messaging + Health Navigation (TM+HN)
  Sponsors:   University of Utah;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell) - Condition:   COVID-19
  Intervention:   Biological: Experimental Group
  Sponsor:  
  Sinovac Biotech Co., Ltd
  Not yet recruiting

• Intranasal INNA-051 for Prevention of COVID-19 in Adults - Condition:   COVID-19 Pandemic
  Interventions:   Drug: INNA-051;   Other: Placebo
  Sponsor:   ENA Respiratory Pty Ltd
  Not yet recruiting

• Feasibility Pilot Clinical Trial of Omega-3 Supplement vs. Placebo for Post Covid-19 Recovery Among Health Care Workers - Condition:   COVID-19
  Interventions:   Drug: Omega-3 (EPA+DHA);   Drug: Placebo
  Sponsor:   Hackensack Meridian Health
  Not yet recruiting

• Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo - Conditions:   COVID-19 Vaccine Knowledge;   COVID-19 Vaccine Beliefs
  Interventions:  
  Behavioral: COVID-19 Vaccine IVR Training;   Behavioral: Control Condition
  Sponsors:   Stanford University;   Viamo
  Not yet recruiting

• A Clinical Trial to Evaluate the Efficacy of RUTI® to Reduce the Severity of SARS-CoV-2 Infection (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: RUTI® vaccine;   Biological: Placebo
  Sponsors:   RUTI Immunotherapeutics S.L.;   Archivel Farma S.L.
  Not yet recruiting

• Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Vaccine (IN-B009) in Healthy Adults (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: IN-B009 (Low-dose);   Biological: IN-B009 (High- dose)
  Sponsor:   HK inno.N Corporation
  Recruiting

From PubMed

• Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury - CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

• The role of microRNAs in solving COVID-19 puzzle from infection to therapeutics: A mini-review - Nowadays, one of the major global health concerns is coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous treatments and vaccines to combat this virus are currently under development, the detailed molecular mechanisms underlying the pathogenesis of this disease are yet to be elucidated to design future therapeutic tools against SARS-CoV-2 variants. MicroRNAs (miRNAs) are small (20-24 nucleotides),…

• Contribution of autophagy machinery factors to HCV and SARS-CoV-2 replication organelle formation - Positive-strand RNA viruses replicate in close association with rearranged intracellular membranes. For hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these rearrangements comprise endoplasmic reticulum (ER)-derived double membrane vesicles (DMVs) serving as RNA replication sites. Cellular factors involved in DMV biogenesis are poorly defined. Here, we show that despite structural similarity of viral DMVs with autophagosomes, conventional macroautophagy…

• IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study - No abstract

• Interleukin-1 blocking agents as promising strategy for prevention of anticancer drug-induced cardiotoxicities: possible implications in cancer patients with COVID-19 - Cytokines in cardiac tissue plays a key role in progression of cardiometabolic diseases and cardiotoxicity induced by several anticancer drugs. Interleukin-1β is one on the most studied regulator of cancer progression, survival and resistance to anticancer treatments. Recent findings indicate that interleukin1-β exacerbates myocardial damages in cancer patients treated with chemotherapies and immune check-point inhibitors. Interleukin1-β blocking agent canakinumab reduces major adverse…

• All hands on deck: SARS-CoV-2 proteins that block early anti-viral interferon responses - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is responsible for the current pandemic coronavirus disease 2019 (COVID-19). Like other pathogens, SARS-CoV-2 infection can elicit production of the type I interferon (IFN) cytokines by the innate immune response. A rapid and robust type I and III IFN response can curb viral replication and improve clinical outcomes of SARS-CoV-2 infection. To effectively replicate in the host, SARS-CoV-2 has evolved mechanisms for evasion of…

• Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells - Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease…

• Antiviral and cytotoxic effects of a traditional drug KanthaRasaVillai with a cocktail of metallic nanoparticles - CONCLUSION: The anticancer and antiviral properties in the ancient herbomineral drug with a cocktail of metal nanoparticles acknowledge the traditional medical practice as a pioneering approach for present-day ailments. However, the study concludes that the use of KRV depends on safety dosage and genuine preparation as described by ancient saints.

• Assessment of proarrhythmogenic risk for chloroquine and hydroxychloroquine using the CiPA concept - Chloroquine and hydroxychloroquine have been proposed recently as therapy for SARS-CoV-2-infected patients, but during 3 months of extensive use concerns were raised related to their clinical effectiveness and arrhythmogenic risk. Therefore, we estimated for these compounds several proarrhythmogenic risk predictors according to the Comprehensive in vitro Proarrhythmia Assay (CiPA) paradigm. Experiments were performed with either CytoPatch™2 automated or manual patch- clamp setups on HEK293T cells…

• Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-kappaB signaling pathway - CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

• Absent antibody production following COVID19 vaccination with mRNA in patients under immunosuppressive treatments - Patients undergoing immunosuppressive treatments have a higher need for protection against coronavirus disease (COVID19) that follows infection with the SARS-CoV-2 virus but their ability to respond sufficiently to COVID vaccines is uncertain. We retrospectively evaluated SARS-CoV-2 spike subunit 1 (S1)-specific antibody levels after two mRNA doses in 242 patients with underlying chronic inflammatory, hematooncological or metabolic diseases and in solid organ transplant recipients. S1-specific…

• A comparison between virus- versus patients-centred therapeutic attempts to reduce COVID-19 mortality - AbstractSince December 2019, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has changed our lives. Elderly, and those with comorbidities represent the vast majority of patients hospitalized with severe COVID-19 symptoms, including acute respiratory disease syndrome, and cardiac dysfunction. Despite a huge effort of the scientific community, improved treatment modalities limiting the severity and mortality of…

• Lipid droplet accumulation occurs early following Salmonella infection and contributes to intracellular bacterial survival and replication - Salmonellosis is a public health problem caused by Salmonella sp., a highly adapted facultative intracellular pathogen. After internalization, Salmonella sp. manipulates several host processes, mainly through the activation of the type III secretion system (T3SS), including modification of host lipid metabolism and lipid droplet (LD) accumulation. LDs are dynamic and complex lipid-rich organelles involved in several cellular processes. The present study investigated the mechanism involved in LD…

• SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis - The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS- CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2…

• Impact of COVID-19 lockdowns on hospital presentations and admissions in the context of low community transmission: evidence from time series analysis in Melbourne, Australia - CONCLUSIONS: Our analyses suggest citizens were willing and able to present with life-threatening conditions during Melbourne’s lockdowns, and that switching to telemedicine did not cause widespread spill-over from primary care into ED. During a pandemic, lockdowns may not inhibit appropriate hospital attendance where rates of infectious disease are low.

From Patent Search

• A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link

• A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link

• Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients. - - link

• ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - link

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• Secured Health monitoring system using cloud computing - As used in public health surveillance, the invention generally relates to remote health monitoring systems with cloud computing. This is particularly relevant about a multi-user remote health monitoring system that can detect and gather data from healthcare professionals on the ground and systems in laboratories and hospitals to help the public health sector. It is possible to utilize the system for tracking, monitoring, and collecting patient data and for querying and collecting more information on the health of the people. - link

• SPIRAL GROOVES SQUEEZER - The present invention relates to squeezer that extracts the most of the juice or pulp from the citrus fruits like lemon, orange, etc. because of its design. The present invention works on the principle of reamer having left hand spiral. In general, Left hand spiral reamers have the tendency to push chips and coolant in front of the cut, pushing coolant into the hole and the reamer back out of the hole. The concept of the left hand spiral is used the subject squeezer to design the groves of squeezer to get maximum juice and to help prevent grabbing and binding of the fruit. It will release all the juice extracted from the fruit and will also be easy to remove the waste fruit skin from squeezer. - link

• 基于拉曼光谱的新型冠状病毒核酸检测试剂盒及方法 - 本发明公开了一种基于拉曼光谱的新型冠状病毒核酸检测试剂盒及方法，所述试剂盒包括正向引物，和纳米银针SERS基底，所述纳米银针SERS基底由5’端有巯基修饰的反向引物和纳米银针共价连接而得。其检测方法为：先采集纳米银针SERS基底的拉曼光谱信号；在包含待检测样品的反应溶液中插入所述纳米银针SERS基底，恒温扩增；取出纳米银针SERS基底，采集拉曼光谱信号，检测两次拉曼光谱信号的位移差异。相比起根据拉曼峰强度定量检测核酸的方法，本发明的新型冠状病毒核酸检测方法可以实现定性检测核酸，检测方法更简单、更准确、更可靠。 - link

• Infektionsschutz-Ausrüstung und das ihr zugrundeliegende System -

  Antivirusausrüstung, hergestellt aus einem mehrschichtigen Fasermaterial und ausgestattet mit Bindungen und einem antiviral wirkenden Element, das sich dadurch auszeichnet, dass das antiviral wirkende Element mindestens eine Gewebeschicht enthält, die mit dem Aerosol einer Emulsion bearbeitet wurde, das eine Aprotinin-Lösung enthält.

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