Covid-19 Sentry

Contents

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

From Preprints

• Shifting Streets COVID-19 Mobility Data: Findings from a global dataset and a research agenda for transport planning and policy -
  The COVID-19 pandemic brought a dramatic shift in demand for spaces for safe, physically distanced walking, bicycling, and outdoor commerce. Cities around the world responded by instituting a variety of policies and programs meant to address this shift, such as carving out roadway space for non-car uses, putting pedestrian walk signals on recall, reducing speed limits, and subsidizing bike share schemes. The extraordinarily rapid pace and global scale of these responses—and the public’s reactions to them—suggest that the transport planning, policy, and engineering professions may be at an inflection point with respect to equitable accommodation of non-car transport modes. In this paper we describe an effort to support potential shifts in practice by documenting and cataloging over a thousand COVID-19-related mobility responses into a publicly available database. We provide detailed guidance on using the database, along with preliminary summaries of key variables in the database. We also put forth a research agenda intended to build understanding about the processes that led to these actions, their implications for future efforts to design and implement pedestrian and bicycle infrastructure, and ways in which the transport professions might evolve in response to lessons learned during and after the pandemic.
  🖺 Full Text HTML: Shifting Streets COVID-19 Mobility Data: Findings from a global dataset and a research agenda for transport planning and policy
• Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens -
  The ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in the last twenty years. Previously, four other known coronaviruses moved from animal reservoirs into humans and now cause primarily mild-to-moderate respiratory disease. The emergence of these viruses likely involved a period of intense transmission before becoming endemic, highlighting the recurrent threat to human health posed by animal coronaviruses. Enzootic and epizootic coronaviruses of diverse lineages pose a significant threat to livestock, as most recently observed for virulent strains of porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea-associated coronavirus (SADS-CoV). Unique to RNA viruses, coronaviruses encode a proofreading exonuclease (ExoN) that lowers point mutation rates to increase the viability of large RNA virus genomes, which comes with the cost of limiting virus adaptation via point mutation. This limitation can be overcome by high rates of recombination that facilitate rapid increases in genetic diversification. To compare dynamics of recombination between related sequences, we developed an open-source computational workflow (IDPlot) to measure nucleotide identity, locate recombination breakpoints, and infer phylogenetic relationships. We analyzed recombination dynamics among three groups of coronaviruses with impacts on livestock or human health: SARSr-CoV, Betacoronavirus-1, and SADSr-CoV. We found that all three groups undergo recombination with highly diverged viruses, disrupting phylogenetic relationships and revealing contributions of unknown coronavirus lineages to the genetic diversity of established groups. Dynamic patterns of recombination impact inferences of relatedness between diverse coronaviruses and expand the genetic pool that may contribute to future zoonotic events. These results illustrate the limitations of current sampling approaches for anticipating zoonotic threats to human and animal health.
  🖺 Full Text HTML: Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens
• Codon arrangement modulates MHC-I peptides presentation: implications for a SARS-CoV-2 peptide-based vaccine -
  Among various vaccination strategies, peptide-based vaccines appear as excellent candidates because they are cheap to produce, are highly stable and harbor low toxicity. However, predicting which MHC-I Associated Peptide (MAP) will ultimately reach cell surface remains challenging, due to high false discovery rates. Previously, we demonstrated that synonymous codon arrangement (usage and placement) is predictive of, and modulates MAP presentation. Here, we apply CAMAP (Codon Arrangement MAP Predictor), the artificial neural network we used to unveil the role of codon arrangement in MAP presentation, to predict SARS-CoV MAPs. We report that experimentally identified SARS-CoV-1 and SARS-CoV-2 MAPs are associated with significantly higher CAMAP scores. Based on CAMAP scores and binding affinity, we identified 48 non-overlapping MAP candidates for a peptide-based vaccine, ensuring coverage for a high proportion of HLA haplotypes in the US population (>78%) and SARS-CoV-2 strains (detected in >98% of SARS-CoV-2 strains present in the GISAID database). Finally, we built an interactive web portal (https://www.epitopes.world) where researchers can freely explore CAMAP predictions for SARS-CoV-1/2 viruses. Collectively, we present an analysis framework that can be generalizable to empower the rapid identification of virus-specific MAPs, including in the context of an emergent virus, to help accelerate target identification for peptide-based vaccine designs that could be critical in safely attaining group immunity in the context of a global pandemic.
  🖺 Full Text HTML: Codon arrangement modulates MHC-I peptides presentation: implications for a SARS-CoV-2 peptide-based vaccine
• Site-specific O-glycosylation analysis of SARS-CoV-2 spike protein produced in insect and human cells -
  Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures. SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported. The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence difficult to predict. Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S – insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD). In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD. Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites. However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy. This suggests possible complimentary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
  🖺 Full Text HTML: Site-specific O-glycosylation analysis of SARS-CoV-2 spike protein produced in insect and human cells
• Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates -
  Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against it. We analyzed 146,920 SARS-CoV-2 genome assemblies and 2,393 NGS datasets from GISAID, NCBI Virus and NCBI SRA archives focusing on non-synonymous mutations in the spike protein. Only around 13.6% of the samples contained the wild-type spike protein with no variation from the reference. Among the spike protein mutants, we confirmed a low mutation rate exhibiting less than 10 non-synonymous mutations in 99.98% of the analyzed sequences, but the mean and median number of spike protein mutations per sample increased over time. 2,592 distinct variants were found in total. The majority of the observed variants were recurrent, but only nine and 23 recurrent variants were found in at least 0.5% of the mutant genome assemblies and NGS samples, respectively. Further, we found high-confidence subclonal variants in about 15.1% of the NGS data sets with mutant spike protein, which might indicate co-infection with various SARS-CoV-2 strains and/or intra-host evolution. Lastly, some variants might have an effect on antibody binding or T-cell recognition. These findings demonstrate the increasing importance of monitoring SARS-CoV-2 sequences for an early detection of variants that require adaptations in preventive and therapeutic strategies.
  🖺 Full Text HTML: Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates
• People with intellectual disabilities living in care facilities engaging in virtual social contact: A systematic review of the feasibility and effects on well-being -
  During the initial phase of the COVID-19 pandemic, many people with disabilities living in care facilities could not receive visitors. The use of virtual social contact has been recommended by health authorities such as the World Health Organization. This systematic review examined the scientific evidence of the use and feasibility of information and communication technology (ICT) for social contact by people with intellectual disabilities living in care facilities, and potential effects on well-being.
  🖺 Full Text HTML: People with intellectual disabilities living in care facilities engaging in virtual social contact: A systematic review of the feasibility and effects on well-being
• Is Commitment Getting Infected Too? How COVID-19 Stay-Home Orders Influence Workgroup Commitment -
  The COVID-19 pandemic and associated “Stay-Home” restrictions in the United States have disrupted employees’ lives. We leverage the change brought on by the Stay-Home restrictions to examine corresponding changes in employees’ commitment to their workgroup. Specifically, we advance and test a model predicting that the Stay-Home restrictions prevented workgroups from engaging in rigidly performed, meaningful workplace activities (i.e., ritualistic workplace activities), which subsequently made members feel that the group was less cohesive and ultimately reduced members’ workgroup commitment. We also compare changes in workgroup commitment to changes in workgroup identification, hypothesizing that commitment to one’s group erodes more than identification when workgroups are perceived to be less cohesive. We test our model in a four-wave panel survey of 772 U.S. employees at the onset of the Stay-Home restrictions, which allows us to examine within-person changes to commitment over time. Consistent with our hypotheses, commitment decreased as the duration of Stay-Home restrictions increased, which was mediated by corresponding declines in engaging in ritualistic workplace activities and perceptions of the workgroup’s cohesiveness. Further, commitment to one’s workgroup declined more than did identification with the workgroup, due to the stronger relationship between perceived group cohesion and commitment (vs. identification). We replicated these results in a separate, preregistered cross-sectional survey. Our findings shed light on the mechanisms underlying workgroup commitment, demonstrating that engagement in ritualistic activities, which enhance workgroup cohesion, is linked to stronger commitment— more so than identification—over time.
  🖺 Full Text HTML: Is Commitment Getting Infected Too? How COVID-19 Stay-Home Orders Influence Workgroup Commitment
• Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of Nsp1, Nsp2, and Nucleocapsid proteins from SARS-CoV-2 -
  Atomic structures of several proteins from the coronavirus family are still partial or unavailable. A possible reason for this gap is the instability of these proteins outside of the cellular context, thereby prompting the use of in-cell approaches. In situ cross-linking and mass spectrometry (in situ CLMS) can provide information on the structures of such proteins as they occur in the intact cell. Here, we applied targeted in situ CLMS to structurally probe Nsp1, Nsp2, and Nucleocapsid (N) proteins from SARS-CoV-2, and obtained cross-link sets with an average density of one cross-link per twenty residues. We then employed integrative modeling that computationally combined the cross-linking data with domain structures to determine full-length atomic models. For the Nsp2, the cross-links report on a complex topology with long-range interactions. Integrative modeling with structural prediction of individual domains by the AlphaFold2 system allowed us to generate a single consistent all-atom model of the full-length Nsp2. The model reveals three putative metal binding sites, and suggests a role for Nsp2 in zinc regulation within the replication-transcription complex. For the N protein, we identified multiple intra- and inter-domain cross-links. Our integrative model of the N dimer demonstrates that it can accommodate three single RNA strands simultaneously, both stereochemically and electrostatically. For the Nsp1, cross-links with the 40S ribosome were highly consistent with recent cryo-EM structures. These results highlight the importance of cellular context for the structural probing of recalcitrant proteins and demonstrate the effectiveness of targeted in situ CLMS and integrative modeling.
  🖺 Full Text HTML: Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of Nsp1, Nsp2, and Nucleocapsid proteins from SARS-CoV-2
• Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules -
  Coronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2 arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2 and autophagy expression.
  🖺 Full Text HTML: Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules
• Molnupiravir (EIDD-2801) inhibits SARS-CoV-2 replication and enhances the efficacy of favipiravir in a Syrian hamster infection model -
  Since its emergence in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide resulting in a global pandemic with >2 million deaths within a year of the emergence of the virus. In the search for small molecule inhibitors of SARS-CoV-2 Molnupiravir (EIDD-2801), an orally bioavailable nucleoside analog that was originally developed as an antiviral against influenza viruses but that exerts also activity against a number of other RNA viruses, including SARS-CoV2 and other coronaviruses. We here report on the effect of EIDD-2801 in a well-established Syrian hamster SARS-CoV-2 infection model. Oral treatment of SARS-CoV-2-infected hamsters with EIDD-2801 for four consecutive days, starting from the day of infection, significantly reduced infectious virus titers and viral RNA loads in the lungs and markedly improved lung histopathology in a dose-dependent manner when assessed at 4 dpi. When onset of treatment with 500 mg/kg/dose was delayed until 24h post-infection, a modest but significant antiviral effect was observed. When suboptimal doses of both favipiravir (300 mg/kg, BID) and EIDD-2801 (150 mg/kg, BID) were combined, a complete reduction (~5 log10) of infectious virus titers was observed in the lungs of most of the combo-treated animals whereas either compound alone resulted in a reduction of respectively 1.2 and 1.3 log10. The potential of EIDD-2801 for the treatment and/or prevention of SARS-CoV-2 alone or in combination with favipiravir deserves further attention.
  🖺 Full Text HTML: Molnupiravir (EIDD-2801) inhibits SARS-CoV-2 replication and enhances the efficacy of favipiravir in a Syrian hamster infection model
• Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH -
  The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize viral RNA directly in infected cells are critical to analyze its replication cycle, screen for therapeutic molecules or study infections in human tissue. Here, we report the design, validation and initial application of fluorescence in situ hybridization (FISH) probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy (EM). We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening and diagnostics.
  🖺 Full Text HTML: Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH
• A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium. -
  SARS-CoV-2, causative agent of the COVID-19 pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, 3 histidine residues in S2 are consistently predicted as destabilising in pre-fusion (all 3) and post-fusion (2 of 3) structures. Other predicted features include the more moderate energetics of surface salt-bridge interactions, and sidechain-mainchain interactions. Two aspartic acid residues in partially buried salt-bridges (D290-R273 and R355-D398) have pKas that are calculated to be elevated and destabilising in more open forms of the spike trimer. These aspartic acids are most stabilised in a tightly closed conformation that has been observed when linoleic acid is bound, and which also affects the interactions of D614. The D614G mutation is known to modulate the balance of closed to open trimer. It is suggested that D398 in particular contributes to a pH-dependence of the open/closed equilibrium, potentially coupled to the effects of linoleic acid binding and D614G mutation, and possibly also A570D mutation. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.
  🖺 Full Text HTML: A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium.
• One Year of Evidence on Mental Health Disorders in China during the COVID-19 Crisis - A Systematic Review and Meta-Analysis -

  ABSTRACT Objective: This paper provides a systematic review and meta-analysis on the prevalence rate of mental health issues of the major population, including general population, general healthcare workers (HCWs), and frontline healthcare workers (HCWs), in China over one year of the COVID-19 crisis. Design: A systematic review and meta-analysis. Data sources: articles in PubMed, Embase, Web of Science, and medRxiv up to November 16, 2020, one year after the first publicly known confirmed COVID-19 case. Eligibility criteria and data analysis: any COVID-19 and mental disorders relevant English studies with frontline/general healthcare workers, general adult population sample, using validated scales. We pooled data using random-effects meta-analyses to estimate the prevalence rates of anxiety, depression, distress, general psychological symptoms (GPS), insomnia, and PTSD and ran meta-regression to tease out the heterogeneity. Results: The meta-analysis includes 131 studies and 171 independent samples. The overall prevalence of anxiety, depression, distress, GPS, insomnia, and PTSD are 11%, 13%, 20%, 13%, 19%, and 20%, respectively. The meta-regression results uncovered several predictors of the prevalence rates, including severity (e.g., above severe vs. above moderate, p<0.01; above moderate vs. above mild, p<0.01) and type of mental issues (e.g., depression vs. anxiety, p=0.04; insomnia vs. anxiety p=0.04), population (frontline HCWs vs. general HCWs, p<0.01), sampling location (Wuhan vs. non-Wuhan, p=0.04), and study quality (p=0.04). Limitations: First, we only focus on China population, which may limit the generalizability of the results. Second, 96.2% studies included in this meta-analysis were cross-sectional. Last, since we only included studies published in English, we expect to have a language bias. Conclusion: Our pooled prevalence rates are significantly different from, yet largely between, the findings of previous meta-analyses, suggesting the results of our larger study are consistent with, yet fine-tune, the findings of the smaller, previous meta-analyses. Hence, this meta-analysis not only provides a significant update on the mental health prevalence rates in COVID-19 but also suggests the need to update meta-analyses continuously to provide more accurate estimates of the prevalence of mental illness during this ongoing health crisis. While prior meta-analyses focused on the prevalence rates of mental health disorders based on one level of severity (i.e., above mild), our findings also suggest a need to examine the prevalence rates at varying levels of severity. The one-year cumulative evidence on sampling locations (Wuhan vs. non-Wuhan) corroborates the typhoon eye effect theory. Our finding that the prevalence rates of distress and insomnia and those of frontline healthcare workers are higher suggest future research and interventions should pay more attention to those mental outcomes and populations. Keywords: systematic review; meta-analysis; COVID-19; mental health; epidemic; general population; healthcare workers; frontline healthcare workers

  🖺 Full Text HTML: One Year of Evidence on Mental Health Disorders in China during the COVID-19 Crisis - A Systematic Review and Meta-Analysis
• Vaccinating Australia: How long will it take? -

  The Australian Government9s COVID-19 vaccine rollout strategy is scheduled to commence in late February 2021 and aims to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people within this timeframe presents considerable logistical challenges. Key to meeting this target is the rate of vaccine delivery: the number of vaccine doses that can be administered per day. In the opening phase, high priority groups will receive the Pfizer/BioNTech vaccine through hospital hubs at an initial rate of 80,000 doses per week. However, pending regulatory approval, the currently announced plan appears to be to distribute the AstraZeneca vaccine to the bulk of the popluation through a combination of general practices and community pharmacies. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration as well as the schedule for second doses and prevalence of vaccine hesitancy. Our analysis highlights the ambitious rate of vaccine administration that will be neccessary to meet the Australian Government completion target of October 2021. A rate of 200,000 doses per day would comfortably meet that target; 80,000 doses a day would see roll-out extended until mid-2022. Speed is of the essence when it comes to vaccine rollout: protecting the population quickly will minimise the risk of sporadic and costly lockdowns lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. The government should gather all its resources to maximise the daily vaccination rate, ideally aiming to ramp up administration to at least 200,000 doses per day as quickly as possible. Quickly achieving and maintaining this pace will likely require dedicated large-scale vaccination sites that are capable of delivering thousands of doses a week in addition to the enthusiastic participation of GP practices and community pharmacies around the country. Lessons on the neccessary logistical planning, including coordination of delivery, ultra-cold-chain storage and staffing, can potentially be learned from Israel, where between 7,000 and 20,000 vaccinations per million population have been delivered daily throughout January.

  🖺 Full Text HTML: Vaccinating Australia: How long will it take?
• Dynamics of SARS-CoV-2 with Waning Immunity in the UK Population -

  The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48-142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than one year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalised individuals, a year for hospitalised individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387,000 infectious individuals and 125,000 daily new cases; three-fold greater than in a scenario with permanent immunity. Our models suggests that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent.

  🖺 Full Text HTML: Dynamics of SARS-CoV-2 with Waning Immunity in the UK Population

From Clinical Trials

• Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

• Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition:   Covid19
  Interventions:   Drug: Placebo;   Drug: Fluvoxamine
  Sponsor:   SigmaDrugs Research Ltd.
  Recruiting

• TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition:   Covid19
  Intervention:   Drug: Tocilizumab
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• Convalescent Plasma in the Treatment of Covid-19 - Condition:   Covid19
  Interventions:   Biological: Convalescent plasma from COVID-19 donors;   Biological: Placebo
  Sponsors:   Helsinki University Central Hospital;   Finnish Red Cross
  Recruiting

• A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19 - Condition:   Severe COVID-19
  Interventions:   Drug: VB-201 + Standard of care;   Drug: Standard of care
  Sponsor:   Vascular Biogenics Ltd. operating as VBL Therapeutics
  Recruiting

• Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition:   Covid-19
  Intervention:   Other: ivermectin impregnated mask
  Sponsor:   South Valley University
  Recruiting

• An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition:   Covid19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Doxycycline Tablets;   Drug: Placebo
  Sponsor:   Max Health, Subsero Health
  Recruiting

• COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition:   Covid19
  Interventions:   Biological: Omalizumab;   Other: Placebo
  Sponsor:   McGill University Health Centre/Research Institute of the McGill University Health Centre
  Not yet recruiting

• CPI-006 Plus Standard of Care Versus Placebo Plus Standard of Care in Mild to Moderately Symptomatic Hospitalized Covid-19 Patients - Condition:   Covid-19
  Interventions:   Drug: CPI-006 2 mg/kg + SOC;   Drug: CPI-006 1 mg/kg + SOC;   Drug: Placebo + SOC
  Sponsor:   Corvus Pharmaceuticals, Inc.
  Recruiting

• Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Biological: Placebo
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   West China Hospital
  Not yet recruiting

• Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Ivermectin
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition:   Covid-19
  Interventions:   Drug: Famotidine;   Drug: Placebo
  Sponsors:   Northwell Health;   Cold Spring Harbor Laboratory
  Recruiting

• Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 - Conditions:   Severe Acute Respiratory Syndrome Coronavirus 2;   COVID-19
  Interventions:   Drug: SNG001;   Drug: Placebo
  Sponsor:   Synairgen Research Ltd.
  Recruiting

From PubMed

• In silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19 - Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of…

• Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir - No abstract

• Potent and Selective Knockdown of Tyrosine Kinase 2 by Antisense Oligonucleotides - Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor tyrosine kinase, together with JAK1, JAK2, and JAK3. JAKs are important signaling mediators of many proinflammatory cytokines and represent compelling pharmacological targets for autoimmune and inflammatory diseases. Pan-acting small-molecule JAK inhibitors were approved for the treatment of rheumatoid arthritis and ulcerative colitis. However, their limited selectivity among JAK members have led to undesirable side effects,…

• A Neutralization Assay Based on Pseudo-Typed Lentivirus with SARS CoV-2 Spike Protein in ACE2-Expressing CRFK Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic zoonotic virus that spreads rapidly. In this work, we improve the hitherto existing neutralization assay system to assess SARS-CoV-2 inhibitors using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein (LpVspike +) and angiotensin-converting enzyme 2 (ACE2)-transfected cat Crandell-Rees feline kidney (CRFK) cells as the host cell line. Our method was 10-fold more sensitive compared to the typical…

• Mechanisms of Coronavirus Nsp1-Mediated Control of Host and Viral Gene Expression - Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three…

• SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study - The coronavirus disease (COVID-19) is spreading between human populations mainly through nasal droplets. Currently, the vaccines have great hope, but it takes years for testing its efficacy in human. As there is no specific drug treatment available for COVID-19 pandemic, we explored in silico repurposing of drugs with dual inhibition properties by targeting transmembrane serine protease 2 (TMPRSS2) and human angiotensin-converting enzyme 2 (ACE2) from FDA-approved drugs. The TMPRSS2 and ACE2…

• An Urgent Industrial Scheme both for Total Synthesis, and for Pharmaceutical Analytical Analysis of Umifenovir as an Anti-Viral API for Treatment of COVID-19 - CONCLUSION: The most important pharmaceutical analytical methods containing OVI test (mainly ethanol (about 171 ppm) much lower than the limits, by gas chromatography-Flame Ionization Detector (GC-FID) instrument), Assay content (about 99.6% by potentiometric titration), and related purity analysis (by High performance liquid chromatography-Ultraviolet Detector (HPLC-UV)) (about 99.8%) were performed and described to give a more clear industrial scheme.

• Ethical Dilemma: An Unprecedented Strike by Health care Workers in Early February 2020 in Hong Kong - Urging the government to exercise a complete border closure to inhibit the spread of the novel coronavirus from Mainland China, about 8,000 health care workers participated in a 5-day strike in early February 2020 in Hong Kong. Despite gaining 61% support from the public, dissenters criticised that the participants violated professional ethics and abandoned their accountabilities, which led to moral distress. However, the participants were guided by the four fundamental medical principles…

• Complement inhibition initiated recovery of a severe myasthenic crisis with COVID-19 - We report on a patient with refractory Myasthenia gravis with acetylcholine receptor antibodies with two prior myasthenic crises suffering from COVID-19 with rapid evolving weakness and respiratory failure. Respiratory failure developed and prolonged mechanical ventilation was necessary. After plasmapheresis, residual, severe generalized and bulbar weakness persisted. Complement inhibition with eculizumab was, therefore, introduced and lead to rapid recovery. In refractory myasthenic crisis…

• Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study - A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness…

• Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity - Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the…

• Genome-scale metabolic modeling reveals SARS-CoV-2-induced host metabolic reprogramming and identifies metabolic antiviral targets - Tremendous progress has been made to control the COVID-19 pandemic, including the development and approval of vaccines as well as the drug remdesivir, which inhibits the SARS-CoV-2 virus that causes COVID-19. However, remdesivir confers only mild benefits to a subset of patients, and additional effective therapeutic options are needed. Drug repurposing and drug combinations may represent practical strategies to address these urgent unmet medical needs. Viruses, including coronaviruses, are known…

• Analogue discovery of safer alternatives to HCQ and CQ drugs for SAR-CoV-2 by computational design - COVID-19 outbreak poses a severe health emergency to the global community. Due to availability of limited data, the selection of an effective treatment is a challenge. Hydroxychloroquine (HCQ), a chloroquine (CQ) derivative administered for malaria and autoimmune diseases, has been shown to be effective against both Severe Acute Respiratory Syndrome (SARS-CoV-1) and SARS-CoV-2. Apart from the known adverse effects of these drugs, recently the use of CQ and HCQ as a potential treatment for…

• Repurposing of Tetracyclines for COVID-19 Neurological and Neuropsychiatric Manifestations: A Valid Option to Control SARS-CoV-2-Associated Neuroinflammation? - The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not…

• SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4 - Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in…

From Patent Search

• SARS-CoV-2 antibodies - - link

• SARS-CoV-2 antibodies - - link

• A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link

• TREATMENT OF COVID-19 WITH REBAMIPIDE - - link

• METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link

• A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link

• Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -

  Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.

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• 一种医用可佩戴式防护口鼻的微型气幕系统 - 本发明公开了一种医用可佩戴式防护口鼻的微型气幕系统，包括框柱，框柱一侧开凿有气幕送风口和呼吸用送风口，气幕送风口和呼吸用送风口内分别连接有软管一和软管二，框柱内开凿有水平条缝和垂直条缝，水平条缝与垂直条缝均与气幕送风口相连通，框柱靠近水平条缝的一侧贯穿开凿有出风口，出风口内设有滤网，出风口贯穿框柱的一端连接有高效过滤器，滤网与高效过滤器之间连接有吸气泵，框柱靠近出风口的一侧连接有电池和开关。本发明通过提出一种在口腔处应用洁净空气幕阻挡气溶胶传播的可佩戴装置，可以在口腔类相关诊疗过程，保护医生和周围人的健康，避免引起可能引发的呼吸道疾病交叉感染。 - link

• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• Vorrichtung umfassend einen Schutzschirm und einen Filter zum Herausfiltern von Viren aus einem Schall erzeugenden Luftstrom -

  Vorrichtung (10) umfassend einen Schutzschirm (12) und einen Filter (14) zum Herausfiltern von Viren (16) aus einem Schall erzeugenden Luftstrom (18), der von einem Musiker (20) beim Musizieren mit einem Musikinstrument oder beim Singen erzeugt wird, wobei der Schutzschirm (12) zur Verringerung des Risikos einer Infektion mit den Viren (16) dafür vorgesehen ist, wenigstens einen Teil der mit dem Luftstrom transportierten Viren (16) aufzufangen, der Schutzschirm (12) eine erste Seite (22) und eine zweite Seite (24) aufweist, die voneinander abgewandt sind, und der Schutzschirm (12) wenigstens einen sich von der ersten (22) bis zu der zweiten Seite (24) erstreckenden Durchlass (26) aufweist, wobei dieser Durchlass (26) zum Durchströmen mit wenigstens einem Teil des beim Musizieren erzeugten Luftstroms (18) vorgesehen ist und der Filter (14) zum Herausfiltern von Viren (16) aus dem Luftstrom (18) in dem Durchlass (26) des Schutzschirms (12) angeordnet ist.

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