Covid-19 Sentry

Contents

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

From Preprints

• Social influence matters: We follow pandemic guidelines most when our close circle does -
  Why do we adopt new rules, such as social distancing? Although human sciences research stresses the key role of social influence in behaviour change, most COVID-19 campaigns emphasise the disease’s medical threat. In a global dataset (n= 6675), we investigated how social influences predict people’s adherence to distancing rules during the pandemic. Bayesian regression analyses controlling for stringency of local measures showed that people distanced most when they thought their close social circle did. Such social influence mattered more than people thinking distancing was the right thing to do. People’s adherence also aligned with their fellow citizens’, but only if they felt deeply bonded with their country. Self-vulnerability to the disease predicted distancing more for people with larger social circles. Collective efficacy and collectivism also significantly predicted distancing. To achieve behavioural change during crises, policymakers must emphasise shared values and harness the social influence of close friends and family.

• Examining Saudi EFL University Students’ Readiness for Online Learning at the Onset of Covid-19 Pandemic -
  Nowadays, especially after the COVID-19 crisis lockdown, the heavy reliance on technology and online platforms led to a greater expectation of more learning autonomy among English learners in EFL contexts such as Saudi Arabia. The sudden shift to online learning requires an investigation into students’ readiness and willingness for such a mode of learning. This can provide educators with many prospects about learning outcomes achievement and assessment, test performance, and interaction during classes. Therefore, the current study seeks to contribute to the well-known area of learner autonomy research, which is still lacking in the context of the study, by exploring the readiness of Saudi first-year undergraduate English learners towards online education. Participants’ level of readiness is identified according to their autonomous behaviors and activities. The study will also assess the investigated concept considering the influence of gender and field of study of the participants on their autonomy levels. A total of 802 students participated in this study. It was found that Saudi first-year university students are moderately autonomous, that both males and females have similar levels of aptitude and readiness for taking responsibility for their learning, and that English-major and non-English-major groups showed comparatively similar levels across different learning autonomy dimensions. Yet interestingly, English-major participants displayed a relatively lower autonomy level than students of other majors.
  🖺 Full Text HTML: Examining Saudi EFL University Students’ Readiness for Online Learning at the Onset of Covid-19 Pandemic
• Saudi EFL Students’ Use and Perceptions of Blackboard before and during Online Learning Amid COVID-19 -
  Online learning becomes the means of education during COVID-19. Blackboard is one of the learning management systems that has been widely used before and during the pandemic. This study focuses on English as a Foreign Language (EFL) students’ use and perceptions of Blackboard. It explores and compares EFL students’ use and perceptions of Blackboard considering three phases: before COVID-19 in 2019, during online learning in 2020, and during online learning in 2021. A questionnaire and semi-structured interviews were used to collect the data. A total of 381 Saudi EFL students participated in the study. The results show that there are statistically significant differences in EFL students’ use of Blackboard between the three phases. EFL students’ use of Blackboard increased during online learning in 2020 compared to 2019, especially concerning the frequency of visiting Blackboard and the time students spent using it. Further, EFL students’ use of Blackboard increased significantly during online learning in 2021 compared to 2019 with regard to visit frequencies, time spent, and Blackboard tools used. Considering perceptions, the results indicate that there are statistically significant differences in students’ perceptions of Blackboard in terms of easiness and usefulness between the three phases. Interestingly, students had more positive perceptions of Blackboard before COVID-19 in 2019 and during online learning in 2021. The technical problems that students faced while using Blackboard during 2020 might have affected their perceptions. The study results of students’ use and perceptions of Blackboard are discussed in light of institutional policies and support.
  🖺 Full Text HTML: Saudi EFL Students’ Use and Perceptions of Blackboard before and during Online Learning Amid COVID-19
• XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 Spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants. -
  Amino acid substitutions and deletions in Spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBM), in direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Therefore, in Spike/ACE2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study with the Beta strain on Vero E6 cells conducted over 1 month, no mutation was associated with addition of increasing doses XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in a phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (Covid-19) including the different variants of concern identified so far.
  🖺 Full Text HTML: XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 Spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants.
• Modeling Coronavirus Spike Protein Dynamics: Implications for Immunogenicity and Immune Escape -
  The ongoing COVID-19 pandemic is a global public health emergency requiring urgent development of efficacious vaccines. While concentrated research efforts are underway to develop antibody-based vaccines that would neutralize SARS-CoV-2, and several first-generation vaccine candidates are currently in Phase III clinical trials or have received emergency use authorization, it is forecasted that COVID-19 will become an endemic disease requiring second-generation vaccines. The SARS-CoV-2 surface Spike (S) glycoprotein represents a prime target for vaccine development because antibodies that block viral attachment and entry, i.e. neutralizing antibodies, bind almost exclusively to the receptor binding domain (RBD). Here, we develop computational models for a large subset of S proteins associated with SARS-CoV-2, implemented through coarse-grained elastic network models and normal mode analysis. We then analyze local protein domain dynamics of the S protein systems and their thermal stability to characterize structural and dynamical variability among them. These results are compared against existing experimental data, and used to elucidate the impact and mechanisms of SARS-CoV-2 S protein mutations and their associated antibody binding behavior. We construct a SARS- CoV-2 antigenic map and offer predictions about the neutralization capabilities of antibody and S mutant combinations based on protein dynamic signatures. We then compare SARS-CoV-2 S protein dynamics to SARS-CoV and MERS-CoV S proteins to investigate differing antibody binding and cellular fusion mechanisms that may explain the high transmissibility of SARS-CoV-2. The outbreaks associated with SARS-CoV, MERS-CoV, and SARS-CoV-2 over the last two decades suggest that the threat presented by coronaviruses is ever-changing and long-term. Our results provide insights into the dynamics-driven mechanisms of immunogenicity associated with coronavirus S proteins, and present a new approach to characterize and screen potential mutant candidates for immunogen design, as well as to characterize emerging natural variants that may escape vaccine-induced antibody responses.
  🖺 Full Text HTML: Modeling Coronavirus Spike Protein Dynamics: Implications for Immunogenicity and Immune Escape
• Effects of Hydroxychloroquine and Azithromycin on iPSC-derived Cardiomyocytes: Considerations for the Treatment of COVID-19 Patients -
  Despite known adverse effects of hydroxychloroquine (HCQ) and azithromycin (AZM) on cardiac function, HCQ and AZM have been used as combination therapy in the treatment of COVID-19 patients. Recent clinical data indicate higher complication rates with HCQ/AZM combination treatment in comparison to monotherapy. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to systematically investigate the effects of HCQ and AZM individually and in combination. The clinically observed QT prolongation caused by treatment with HCQ could be recapitulated in iPSC-CMs based on prolonged field potential duration (FPDc). Interestingly, HCQ-induced FPDc prolongation was strongly enhanced by combined treatment with AZM, although AZM alone slightly shortened FPDc in iPSC- CMs. Furthermore, combined treatment with AZM and HCQ leads to higher cardiotoxicity, more severe structural disarrangement, and more pronounced contractile and electrophysiological dysfunctions, compared to respective mono- treatments. First mechanistic insights underlying the synergistic effects of AZM and HCQ on iPSC-CM functionality are provided based on increased Cx43- and Nav1.5-protein levels. Taken together, our results highlight that combined treatment with HCQ and AZM strongly enhances the adverse effects on cardiomyocytes, providing mechanistic evidence for the high mortality in patients receiving HCQ/AZM combination treatment.
  🖺 Full Text HTML: Effects of Hydroxychloroquine and Azithromycin on iPSC-derived Cardiomyocytes: Considerations for the Treatment of COVID-19 Patients
• Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus -
  Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both EBOV and COVID-19 infection cohorts. We also show unique characteristics absent in RSV infection or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risks off-target effects.
  🖺 Full Text HTML: Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus
• Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaii Lineage B.1.243 -
  SARS-CoV-2 worldwide emergence and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired clinical samples, analyzed SARS-CoV-2 genomes, used the most worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the SARS-CoV-2 vaccine platform. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson’s correlation determines exponential emergence. The SARS-CoV-2 genome evaluation indicated 49 mutations. Nine of the ten most worldwide prevalent (>70%) spike protein changes have r-values >0.9. The tenth, D614G, has a prevalence >99% and r-value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. SARS-CoV-2 is predicted to remain endemic and continues to evolve, so must SARS-CoV-2 monitoring and next-generation vaccine design.
  🖺 Full Text HTML: Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaii Lineage B.1.243
• Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens -
  Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim- II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.
  🖺 Full Text HTML: Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
• Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells -
  The SARS-CoV-2 (SC2) virus has caused a worldwide pandemic because of the virus’s ability to transmit efficiently human-to-human. A key determinant of infection is the attachment of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Because of the presumed zoonotic origin of SC2, there is no practical way to assess every species susceptibility to SC2 by direct challenge studies. In an effort to have a better predictive model of animal host susceptibility to SC2, we expressed the ACE2 and/or transmembrane serine protease 2 (TMPRSS2) genes from humans and other animal species in the avian fibroblast cell line, DF1, that is not permissive to infection. We demonstrated that expression of both human ACE2 and TMPRSS2 genes is necessary to support SC2 infection and replication in DF1 and a non-permissive sub-lineage of MDCK cells. Titers of SC2 in these cell lines were comparable to those observed in control Vero cells. To further test the model, we developed seven additional transgenic cell lines expressing the ACE2 and TMPRSS2 derived from Felis (cat), Equus (horse), Sus (pig), Capra (goat), Mesocricetus (Golden hamster), Myotis lucifugus (Little Brown bat) and Hipposideros armiger (Great Roundleaf bat) in DF1 cells. Results demonstrate permissive replication of SC2 in cat, Golden hamster, and goat species, but not pig or horse, which correlated with the results of reported challenge studies. The development of this cell culture model allows for more efficient testing of the potential susceptibility of many different animal species for SC2 and emerging variant viruses.
  🖺 Full Text HTML: Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells
• Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence -
  SARS-CoV-2 has infected over 200 million and caused more than 4 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID-19 beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive immune activation that differed in character by age (young vs. old). We then characterized signals associated with recovery and convalescence to define and validate a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS- CoV-2 infection (PASC).
  🖺 Full Text HTML: Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence
• ACE2-Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker -
  The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS- CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 knock-in mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and alanine walk studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and broad-spectrum management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
  🖺 Full Text HTML: ACE2-Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker
• Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents -

  Nursing home residents often fail to mount robust responses to vaccinations and recent reports of breakthrough infections, particularly from variants of concern, raise questions about whether vaccination regimens elicit a sufficient humoral immune response or if booster doses are warranted. We examined SARS-CoV-2 antibody levels and neutralizing capacity in nursing home residents 3-5 months after 2 doses of mRNA-1273 or BNT163b2 vaccination as per recommended schedules. Nursing home residents were recruited from eight long-term care homes in Ontario, Canada, between March and July 2021. Antibody levels and neutralization capacity from a previously published convalescent cohort were used as a comparator. Serum SARS-CoV-2 IgA/G/M against spike (S) protein and its receptor-binding domain (RBD) were measured by validated ELISA, with assay cut-off at the mean and 3 standard deviations of a pre-COVID-19 population from the same geographic region. Antibody neutralization was measured against the wild-type strain of SARS-CoV-2 and the beta variant of concern (B.1.351). No neutralizing antibodies were detected in ~20% of residents to the wild-type virus (30/155; 19%) or beta variant (27/134; 20%). Residents that received BNT163b2 had a ~4-fold reduction in neutralization to the wild-type strain, and a ~2-fold reduction in neutralization to the beta variant relative to those who received mRNA-1273. Current mRNA SARS-CoV-2 vaccine regimens may not have equivalent efficacy in nursing home residents. Our findings imply that differences in the humoral immune response may contribute to breakthrough infections, and suggest that consideration of the type of vaccine administered to older adults will have a positive impact on the generation of protective immunity.

  🖺 Full Text HTML: Antibody Responses 3-5 Months Post- Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents
• App-based COVID-19 surveillance and prediction: The COVID Symptom Study Sweden -

  Background The app-based COVID Symptom Study was launched in Sweden to disseminate real-time estimates of disease spread and to collect prospective data for research. The aim of this study was to describe the project, develop models for estimation of COVID-19 prevalence and to evaluate it for prediction of hospital admissions for COVID-19. Methods We enrolled 143 531 study participants (≥18 years) throughout Sweden, who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Data from 19 161 self-reported PCR tests were used to create a symptom-based algorithm to estimate daily prevalence of symptomatic COVID-19. The prediction model was validated using external datasets and used to forecast subsequent new hospital admissions. Results A prediction model for symptomatic COVID-19 based on 17 symptoms, age, and sex yielded an area under the ROC curve of 0.78 (95% CI 0.74-0.83) in an external validation dataset. App-based surveillance proved particularly useful for predicting hospital trends in times of insufficient testing capacity and registration delays. During the first wave, our prediction model estimates demonstrated a lower mean error (0.38 average new daily hospitalizations per 100 000 inhabitants per week (95% CI 0.32, 0.45)) for subsequent hospitalizations in the ten most populated counties, than a model based on confirmed case data (0.72 (0.64, 0.81)). Conclusions The experience of the COVID Symptom Study highlights the important role citizens can play in real-time monitoring of infectious diseases, and how app-based data collection may be used for data-driven rapid responses to public health challenges.

  🖺 Full Text HTML: App-based COVID-19 surveillance and prediction: The COVID Symptom Study Sweden
• Repeated Testing Necessary: Assessing Negative Predictive Value of SARS-CoV-2 qPCR in a Population of Young Adults -

  Determining when individuals should be released from quarantine is critical for successfully managing a COVID-19 outbreak and local protocols frequently call for testing during the quarantine period, generally after a reasonable incubation period, which raises a question about the interpretation of test results during the quarantine period. We report the negative predictive value of SARS-CoV-2 qPCR tests based on a retrospective longitudinal analysis of 5349 qPCR tests collected from 1227 US service members infected with COVID-19 aboard the USS Theodore Roosevelt (CVN-71) aircraft carrier. In our retrospective evaluation of recovering qPCR-positive quarantined crew members undergoing repeated testing, the negative predictive value is 80% for tests occurring as late as seven weeks following an initial positive qPCR test result. Repeated qPCR testing is necessary to ensure that a once-infected person is no longer shedding viral RNA. When deciding the stringency of exit criteria, we recommend considering local operational and community risk factors.

  🖺 Full Text HTML: Repeated Testing Necessary: Assessing Negative Predictive Value of SARS-CoV-2 qPCR in a Population of Young Adults

From Clinical Trials

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

• To Evaluate Efficacy & Safety of Proxalutamide in Hospitalized Covid-19 Subjects - Condition:   Covid19
  Interventions:   Drug: GT0918;   Drug: Standard of care;   Drug: Matching placebo
  Sponsors:   Suzhou Kintor Pharmaceutical Inc,;   IQVIA Biotech
  Not yet recruiting

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

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

• Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease - Condition:   COVID-19
  Intervention:   Drug: leflunomide
  Sponsor:  
  Ashford and St. Peter’s Hospitals NHS Trust
  Active, not recruiting

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

• COVID-19 Methylene Blue Antiviral Treatment - Condition:   Covid19
  Interventions:   Drug: Methylene Blue;   Drug: Saline nasal spray
  Sponsors:   Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences;   Irkutsk State Medical University
  Recruiting

• Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose) - Condition:   COVID-19 Lower Respiratory Infection
  Interventions:   Biological: AG0302-COVID19 for Intramuscular Injection;   Biological: AG0302-COVID19 for Intradermal Injection
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Recruiting

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

• Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector, Ad5-nCoV) in Adults Living With HIV - Condition:   Covid19
  Intervention:   Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV)
  Sponsors:   Fundación Huésped;   Canadian Center for Vaccinology;   CanSino Biologics Inc.;   Hospital Fernandez
  Recruiting

• Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study). - Condition:   Covid19
  Interventions:   Drug: C1 Inhibitor Human;   Drug: Icatibant Injection;   Other: Placebo
  Sponsor:   GCS Ramsay Santé pour l’Enseignement et la Recherche
  Completed

• Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition:   Covid19
  Interventions:   Drug: Standard of care;   Dietary Supplement: combination of curcumin, quercetin and Vitamin D
  Sponsor:   Ayub Teaching Hospital
  Not yet recruiting

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

• A Study to Evaluate the Safety and Efficacy of Artemisinin- a Herbal Supplement on COVID-19 Subjects - Condition:   Covid19
  Interventions:   Dietary Supplement: Artemisinin;   Drug: Dexamethasone
  Sponsors:   Mateon Therapeutics;   Windlas Biotech Private Limited
  Completed

• Efficacy of PJS-539 for Adult Patients With SARS-Cov-2. - Conditions:   Covid19;   COVID-19 Pneumonia
  Interventions:   Drug: PJS-539 Dose 1;   Drug: PJS-539 Dose 2;   Drug: Placebo
  Sponsors:   Hospital do Coracao;   Covicept
  Not yet recruiting

From PubMed

• Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19 - The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious…

• An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19) - INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment.

• Efficient inactivation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in human apheresis platelet concentrates with amotosalen and ultraviolet A light - CONCLUSION: SARS-CoV-2 was efficiently inactivated in platelet concentrates by amotosalen/UVA treatment. These results are in line with previous inactivation data for SARS-CoV-2 in plasma as well as MERS-CoV and SARS-CoV-1 in platelets and plasma, demonstrating efficient inactivation of human coronaviruses.

• Osteopathic interventions via telehealth in a pediatric population: a retrospective case series - CONCLUSIONS: In our small retrospective case series, osteopathic interventions via telehealth resulted in decreased average pain scores following treatment while minimizing risk of viral exposure and transmission. Further study is needed to determine if such treatment methods could be effective on a larger scale when distance or illness preclude an in-person OMT visit.

• Deconstructing the Treatment Effect of Remdesivir in the Adaptive COVID-19 Treatment Trial-1: Implications for Critical Care Resource Utilization - CONCLUSIONS: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.

• Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency - Non-covalent inhibitors of the main protease (M^(pro)) of SARS-CoV-2 having a pyridinone core were previously reported with IC(50) values as low as 0.018 μM for inhibition of enzymatic activity and EC(50) values as low as 0.8 μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of M^(pro) and N-methylation of a uracil ring. Free energy perturbation…

• Long Noncoding RNAs as Emerging Regulators of COVID-19 - Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus…

• Auricular Neuromodulation for Mass Vagus Nerve Stimulation: Insights From SOS COVID-19 a Multicentric, Randomized, Controlled, Double-Blind French Pilot Study - Importance: An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light- chain-enhancer of activated B cells…

• Potential of diterpene compounds as antivirals, a review - Viruses cause widely transmitted diseases resulting in pandemic conditions. Currently, the world is being hit by the Covid-19 pandemic caused by the SAR-CoV-2 infection. Countries in the world are competing to develop antivirals to overcome this problem. Diterpene compounds derived from natural ingredients (plants, corals, algae, fungi, sponges) and synthesized products have potential as antivirals. This article summarizes the different types of diterpenes such as daphnane, tiglilane, kaurane,…

• Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease - Repurposing FDA-approved inhibitors able to prevent infection by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) could provide a rapid path to establish new therapeutic options to mitigate the effects of coronavirus disease 2019 (COVID-19). Proteolytic cleavages of the spike S protein of SARS-CoV-2, mediated by the host cell proteases cathepsin and TMPRSS2, alone or in combination, are key early activation steps required for efficient infection. The PIKfyve kinase inhibitor apilimod…

• Diabetes in the COVID-19 pandemic era - CONCLUSIONS: Diabetes mellitus is related to the increased severity and complications of COVID-19. The association between diabetes and COVID-19 creates a devastating double pandemic, as it worsens the prognosis of COVID-19.

• Molecular dynamics simulation, 3D-pharmacophore and scaffold hopping analysis in the design of multi-target drugs to inhibit potential targets of COVID-19 - SARS-CoV-2 has posed serious threat to the health and has inflicted huge costs in the world. Discovering potent compounds is a critical step to inhibit coronavirus. 3CL^(pro) and RdRp are the most conserved targets associated with COVID-19. In this study, three-dimensional pharmacophore modeling, scaffold hopping, molecular docking, structure-based virtual screening, QSAR-based ADMET predictions and molecular dynamics analysis were used to identify inhibitors for these targets. Binding free…

• Antiviral nanoparticles for sanitizing surfaces: a roadmap to self-sterilizing against COVID-19 - Nanoparticles open new opportunities in merging therapeutics and new materials, with current research efforts just beginning to scratch the surface of their diverse benefits and potential applications. One such application, the use of inorganic nanoparticles in antiseptic coatings to prevent pathogen transmission and infection, has seen promising developments. Notably, the high reactive surface area to volume ratio and unique chemical properties of metal-based nanoparticles enables their potent…

• Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl- hydrocarbon receptor signal - Since understanding molecular mechanisms of SARS-CoV-2 infection is extremely important for developing effective therapies against COVID-19, we focused on the internalization mechanism of SARS-CoV-2 via ACE2. Although cigarette smoke is generally believed to be harmful to the pathogenesis of COVID-19, cigarette smoke extract (CSE) treatments were surprisingly found to suppress the expression of ACE2 in HepG2 cells. We thus tried to clarify the mechanism of CSE effects on expression of ACE2 in…

• Computational screening of 645 antiviral peptides against the receptor-binding domain of the spike protein in SARS- CoV-2 - The receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein plays a vital role in binding and internalization through the alpha-helix (AH) of human angiotensin-converting enzyme 2 (hACE2). Thus, it is a potential target for designing and developing antiviral agents. Inhibition of RBD activity of the S protein may be achieved by blocking RBD interaction with hACE2. In this context, inhibitors with large contact surface area are preferable as they can form a potentially stable complex with…

From Patent Search

• SARS-COV-2 BINDING PROTEINS - - link

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

• A Protein chip and kit for detecting SARS-CoV-2 N protein and its preparation method - - link

• Protein chip and kit for detecting the SARS-CoV-2 S antigen - - link

• Cabina de desinfección de doble carga exterior - - link

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

• EMPUNADURA DE RAQUETA O PALA PARA JUEGO DE PELOTA CON DISPENSADOR LIQUIDO POR CAPILARIDAD INSERTADO - - link

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

• System zum computergestützten Nachverfolgen einer von einer Person durchzuführenden Prozedur -

  Ein System (2000) zum computergestützten Nachverfolgen einer von einer Person (1) durchzuführenden Testprozedur, insbesondere für einen Virusnachweistest, bevorzugt zur Durchführung eines SARS-CoV-2 Tests, wobei das System (2000) umfasst:

• eine Identifizierungseinheit eines Endgeräts (30), die eingerichtet ist zum Identifizieren (201) der Person

1. unmittelbar vor einem Durchführen der Testprozedur durch die Person (1);

• wobei die Identifizierungseinheit des Endgeräts (30) weiter eingerichtet ist zum Identifizieren (202) zumindest eines Testobjekts (20), bevorzugt einer Testkassette, insbesondere für einen SARS-CoV-2 Test, mehr bevorzugt eines Teststreifens, weiter bevorzugt ein Reagenz in einem Behälter, weiter bevorzugt eines Testsensors, unmittelbar vor der Durchführung der Testprozedur, die Identifizierungseinheit aufweisend:
• eine Kamera (31) des Endgeräts (30), eingerichtet zum Erfassen (2021) eines Objektidentifizierungsdatensatzes (21) als maschinenlesbaren Datensatz; und
• eine Auswerteeinheit (33) des Endgeräts (30), eingerichtet zum Vergleichen (2022) des erfassten Objektidentifizierungsdatensatzes (21) mit einem Objektdatensatz

420. eines Hintergrundsystems (40);

• eine Nachverfolgungseinheit des Endgeräts (30), die eingerichtet ist zum Nachverfolgen (203) einer oder mehrerer Positionen der Person (1) während der Durchführung der Testprozedur mittels Methoden computergestützter Gesten- und/oder Muster- und/oder Bilderkennung mittels eines Prüfens, ob beide Hände (12) der Person (1) während der gesamten Durchführung der Testprozedur in einem vordefinierten Bereich oder einem von der Kamera (31a) des Endgeräts (30) erfassbaren Bereich sind;
• die Nachverfolgungseinheit des Endgeräts (30), zudem eingerichtet zum Nachverfolgen (203) von einer oder mehreren Positionen des zumindest einen Testobjekts (20) anhand der Form des Objekts während der Durchführung der Testprozedur mittels Methoden computergestützter Gesten- und/oder Muster- und/oder Bilderkennung; und
• einer Anzeigeeinheit (34) des Endgeräts, eingerichtet zum Anleiten (204) der Person (1) zum Durchführen der Testprozedur während der Durchführung der Testprozedur.

• link

• Mascarilla impermeable - Mascarilla impermeable, que comprende un cuerpo de cubrición de la nariz y boca, así como medios de fijación a la cabeza del usuario, se caracteriza por que los medios de cubrición de la zona de la nariz y boca se constituyen a partir de dos cuerpos de distinta naturaleza; una superficie (1) tridimensional superior que cubre la zona de la nariz y la boca, de naturaleza impermeable, que se remata inferiormente en unos medios de filtración (3) interiores, debidamente protegidos superiormente de la humedad a través de la superficie (1). - link