Covid-19 Sentry

Contents

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

From Preprints

• Religious Identity Cues Increase Vaccination Intentions and Trust in Medical Experts among American Christians -
  Containing the COVID-19 pandemic in the U.S. requires mobilizing a large majority of the mass public to vaccinate, but many Americans are hesitant or opposed to vaccination. A significant predictor of vaccine attitudes in the U.S. is religiosity, with more religious individuals expressing more distrust in science and being less likely to get vaccinated. Here, we test whether explicit cues of common religious identity can help medical experts build trust and increase vaccination intentions. In a pre-registered survey experiment conducted with a sample of unvaccinated American Christians (N=1,765), we presented participants with a vaccine endorsement from a prominent medical expert (NIH Director, Francis Collins) and a short essay about doctors’ and scientists’ endorsement of the vaccines. In the common religious identity condition, these materials also highlighted the religious identity of Collins and many medical experts. Unvaccinated Christians in the common identity condition expressed higher trust in medical experts, greater intentions to vaccinate, and greater intentions to promote vaccination to friends and family than those who did not see the common identity cue. These effects were moderated by religiosity, with the strongest effects observed among the most religious participants, and statistically mediated by heightened perceptions of shared values with the medical expert endorsing the vaccine. These findings demonstrate the efficacy of common identity cues for promoting vaccination in a vaccine-hesitant subpopulation. More generally, the results illustrate how trust in science can be built through the invocation of common group identities, even identities often assumed to be in tension with science.
  🖺 Full Text HTML: Religious Identity Cues Increase Vaccination Intentions and Trust in Medical Experts among American Christians
• COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina -

  In December 2019, a novel illness called coronavirus disease 2019 (COVID 19) was described in China and became pandemic in a few months. The first case was detected in Argentina on March 3, 2020. A multicentre prospective observational cohort study on hospitalized patients with COVID 19 was conducted in 4 hospitals in San Isidro district from March 1, 2020 to October 31. Data was obtained by the attendant physician. 668 patients were included, the median age was 54 years, and 42.7% were female. Male sex and older age were associated with COVID 19 disease and more strongly with severity. Most frequent symptoms were fever and cough followed by dyspnoea, myalgia, odynophagia, headache, anosmia, and diarrhoea. Nonsevere patients had more upper respiratory symptoms while severe patients had mainly lower respiratory symptoms on admission. Most common comorbidities were arterial hypertension, diabetes, and cardiovascular disease. A great proportion of patients had normal thorax X ray and ground-glass opacity in tomography. In severe patients, radiography and tomography had a predominant ground glass pattern, but normal radiography and tomography on presentation were present in 22% and 5.9%, respectively. The absence of fever and normal radiology on admission neither excluded the disease nor further severity. PCR elevation was related with COVID 19 disease and with severity, while lymphopenia was more related with the disease and leukocytosis and thrombocytopenia with severity. 8, 4% of patients were health care workers. The mortality rate was 12.4%, 32.7% in severe patients and 61.2% in ventilated patients. Mortality was higher in the public hospital, probably associated with patients with older age and more comorbidities. All these observations can contribute to the knowledge of this disease in terms of diagnosis and prognosis.

• MALDI-ToF Protein Profiling as Potential Rapid Diagnostic Platform for COVID-19 -

  More than a year after the COVID-19 pandemic has been declared, the need still exists for accurate, rapid, inexpensive and non-invasive diagnostic methods that yield high specificity and sensitivity towards the current and newly emerging SARS-CoV-2 strains. Several studies have since established saliva as a more amenable specimen type for early detection of SARS-CoV-2 as compared to nasopharyngeal swabs. Considering the limitations and high demand for COVID-19 testing, we employed MALDI-ToF mass spectrometry for the analysis of 60 gargle samples from human donors and compared the spectra with their COVID-19 status. Several standards including isolated human serum immunoglobulins and controls such as pre-COVID-19 saliva and heat inactivated SARS-CoV-2 virus were simultaneously analyzed to provide a relative view of the saliva and viral proteome as they would appear in this works methodology. Five potential biomarker peaks were established that demonstrated high concordance with COVID-19 positive individuals. Overall, the agreement of these results with RT-qPCR testing on NP swabs was no less than 90% for the studied cohort, which consisted of young and largely asymptomatic student athletes. From a clinical standpoint, the results from this pilot study are promising and suggest that MALDI-ToF can be used to develop a relatively rapid and inexpensive COVID-19 assay.

  🖺 Full Text HTML: MALDI-ToF Protein Profiling as Potential Rapid Diagnostic Platform for COVID-19
• Screening of cell-virus, cell-cell, gene-gene interactions among kingdoms of life at single cell resolution -
  The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) issued a significant and urgent threat to global health. The exact animal origin of SARS-CoV-2 remains obscure and understanding its host range is vital for preventing interspecies transmission of this virus. Previously, we have assessed the target cell profiles of SARS-CoV-2 in pets, livestock, poultry and wild animals. With the reverse zoonotic transmission of SARS-CoV-2 to farm animals. Herein, we expand this investigation to a wider range of animal species and viruses to provide it is urgent to expand the a comprehensive source for large-scale susceptible host screening of potential virus hosts to a larger scale. Therefore, we constructed the single cell atlas for several representative mammalian species (alpaca, hamster, hedgehog, chinchilla etc.), as well as comparative atlas for lung, brain and peripheral blood mononuclear cells (PBMC) for various lineages of animals were constructed, from which we systemically analyzed the virus entry factors for SARS-CoV-2 to identify potential host species. Moreover, to fully apply these resources to the prevention of other infectious diseases, we further evaluated the target cells for 113 viruses over 10 million single cells covering 102 species from mammalians, birds, reptiles, amphibians and invertebrates. Conserved cellular connectomes and regulomes were also identified, with great implication for revealing the fundamental cell-cell and gene-gene cross-talks between these species. Overall, our study could help understand the transmission identify the potential host range and tissue tropism of SARS-CoV-2 and, as well as many other diverse set of viruses and, revealing the host-virus co-evolution footprints and throw light upon the control and prevention of current and future pandemics.
  🖺 Full Text HTML: Screening of cell-virus, cell-cell, gene-gene interactions among kingdoms of life at single cell resolution
• A diabetic milieu increases cellular susceptibility to SARS-CoV-2 infections in engineered human kidney organoids and diabetic patients -
  SARS-CoV-2 infections lead to a high risk of hospitalization and mortality in diabetic patients. Why diabetic individuals are more prone to develop severe COVID-19 remains unclear. Here, we established a novel human kidney organoid model that mimics early hallmarks of diabetic nephropathy. High oscillatory glucose exposure resulted in metabolic changes, expansion of extracellular membrane components, gene expression changes determined by scRNAseq, and marked upregulation of angiotensin-converting enzyme 2 (ACE2). Upon SARS-CoV-2 infection, hyperglycemic conditions lead to markedly higher viral loads in kidney organoids compared to normoglycemia. Genetic deletion of ACE2, but not of the candidate receptor BSG/CD147, in kidney organoids demonstrated the essential role of ACE2 in SARS-CoV-2 infections and completely prevented SARS-CoV-2 infection in the diabetogenic microenvironment. These data introduce a novel organoid model for diabetic kidney disease and show that diabetic-induced ACE2 licenses the diabetic kidney to enhanced SARS- CoV-2 replication.
  🖺 Full Text HTML: A diabetic milieu increases cellular susceptibility to SARS-CoV-2 infections in engineered human kidney organoids and diabetic patients
• Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant -
  SARS-CoV-2 Delta variant has rapidly replaced the Alpha variant around the world. The mechanism that drives this global replacement has not been defined. Here we report that Delta spike mutation P681R plays a key role in the Alpha- to-Delta variant replacement. In a replication competition assay, Delta SARS-CoV-2 efficiently outcompeted the Alpha variant in human lung epithelial cells and primary human airway tissues. Delta SARS-CoV-2 bearing the Alpha-spike glycoprotein replicated less efficiently than the wild-type Delta variant, suggesting the importance of Delta spike in enhancing viral replication. The Delta spike has accumulated mutation P681R located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduced the replication of Delta variant, to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhanced the cleavage of the full-length spike to S1 and S2, leading to increased infection via cell surface entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the spike cleavage from purified Alpha virions was reduced compared to the Delta spike. Collectively, our results indicate P681R as a key mutation in enhancing Delta variant replication via increased S1/S2 cleavage. Spike mutations that potentially affect furin cleavage efficiency must be closely monitored for future variant surveillance.
  🖺 Full Text HTML: Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant
• Secreted SARS-CoV-2 ORF8 modulates the cytokine expression profile of human macrophages -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still adapting to its new human host. Attention has focussed on the viral spike protein, but substantial variation has been seen in the ORF8 gene. Here, we show that SARS- CoV-2 ORF8 protein undergoes signal peptide-mediated processing through the endoplasmic reticulum and is secreted as a glycosylated, disulphide-linked dimer. The secreted protein from the prototype SARS-CoV-2 virus had no major effect on viability of a variety of cell types, or on IFN or NF-{kappa}B; signalling. However, it modulated cytokine expression from primary CSF1-derived human macrophages, most notably by decreasing IL-6 and IL-8 secretion. Furthermore, a sequence polymorphism L84S that appeared early in the pandemic associated with the Clade S lineage of virus, showed a markedly different effect, of increasing IL-6 production. We conclude that ORF8 sequence polymorphisms can potentially affect SARS-CoV-2 virulence and should therefore be monitored in sequencing-based surveillance.
  🖺 Full Text HTML: Secreted SARS-CoV-2 ORF8 modulates the cytokine expression profile of human macrophages
• Conserved T-cell epitopes predicted by bioinformatics in SARS-COV-2 variants -
  Background: Finding conservative T cell epitopes in the proteome of numerous variants of SARS-COV-2 is required to develop T cell activating SARS-COV-2 capable of inducing T cell responses against SARS-COV-2 variants. Methods: A computational workflow was performed to find HLA restricted CD8+ and CD4+ T cell epitopes among conserved amino acid sequences across the proteome of 474727 SARS-CoV-2 strains. Results: A batch of covserved regions in the amino acid sequences were found in the proteome of the SARS-COV-2 strains. 2852 and 847 peptides were predicted to have high binding affinity to distint HLA class I and class II molecules. Among them, 1456 and 484 peptides are antigenic. 392 and 111 of the antigenic peptides were found in the conseved amino acid sequences. Among the antigenic-conserved peptides, 6 CD8+ T cell epitopes and 7 CD4+ T cell epitopes were identifed. The T cell epitopes could be presented to T cells by high-affinity HLA molecules which are encoded by the HLA alleles with high population coverage. Conclusions: The T cell epitopes are conservative, antigenic and HLA presentable, and could be constructed into SARS-COV-2 vaccines for inducing protective T cell immunity against SARS-COV-2 and their variants.
  🖺 Full Text HTML: Conserved T-cell epitopes predicted by bioinformatics in SARS-COV-2 variants
• SARS-CoV-2 Neutralization in Commercial Lots of Plasma-derived Immunoglobulin -
  Introduction: Patients suffering from primary or secondary immunodeficiency face times of increased insecurity and discomfort in the light of the raging Covid-19 pandemic, not knowing if and to what extend their comorbidities impact a potential Covid-19 course of disease. Furthermore, recently available vaccination options might not be amenable or effective for all patients of this heterogeneous population. Therefore, these patients often rely on passive immunization with plasma-derived, intravenous or subcutaneous immunoglobulin (IVIG/SCIG). Whether the ongoing Covid-19 pandemic and/or the progress in vaccination programs lead to increased and potentially protective titers in plasma- derived immunoglobulins (Ig) indicated e.g. for humoral immunodeficiency remains a pressing question for this patient population. Purpose: Here we investigated SARS-CoV-2 reactivity of US plasma-derived IVIG/SCIG products from the end of 2020 until 06/2021 as well as in convalescent plasma (CP) from 05/2020 to 08/2020. Methods: Final containers of IVIG/SCIG and CP donations were analyzed by commercial ELISA for SARS-CoV-2 S1-RBD IgG as well as microneutralization assay using a patient-derived SARS-CoV-2 (D614G) isolate. Neutralization capacities of 313 plasma single donations and 119 plasma-derived IVIG/SCIG lots were determined. Results obtained from both analytical methods were normalized against the international WHO standard. Finally, based on dense pharmacokinetic profiles of an IVIG preparation from previously published investigations, possible steady-state plasma levels of SARS-CoV-2 neutralization capacities were approximated based on currently measured anti-SARS-CoV-2 potencies in IVIG/SCIG preparations. Results: CP donations presented with a high variability with regards to anti-SARS-reactivity in ELISA as well as in neutralization testing. While approximately 50% of convalescent donations were none/low neutralizing, approximately 10% were at or above 1000 IU/ml. IVIG/SCIG lots derived from pre-pandemic plasma donations did not show neutralizing capacities of SARS-CoV-2. Lots produced between 12/2020 and 06/2021, entailing plasma donations after emergence of SARS-CoV-2 showed a rapid and constant increase in anti-SARS-CoV-2 reactivity and neutralization capacity over time. Neutralization capacity increased from a mean of 20 IU/ml in 12/2020 to 505 IU/ml in 06/2021, while lot-to-lot variability was substantial. Pharmacokinetic (PK) extrapolations based on non-compartmental superposition principles using steady-state reference profiles from previously published PK investigations on IVIG in PID, yielded potential steady-state trough plasma levels of 16 IU/ml based on the average final container concentration from 05/2021 with 216 IU/ml. Maximum extrapolated trough levels could reach 64 IU/ml based on the latest maximal final container potency tested in 06/2021. Conclusions: SARS- CoV-2 reactivity and neutralization capacity in IVIG/SCIG produced from US plasma rapidly and in part exponentially increased in the first half of 2021. The observed increase of final container potencies is likely trailing the serological status of the US donor population in terms of Covid-19 convalescence and vaccination by at least 5 months due to production lead times and should in principle continue at least until fall 2021. In summary, the data support rapidly increasing levels of SARS-COV-2 antibodies in IVIG/SCIG products implicating that a certain level of protection could be possible against COVID-19 for regularly substituted PID/SID patients. Nevertheless, more research to confirm, which plasma levels are needed for protection against SARS-CoV-2 infection of immune-compromised patients is still needed.
  🖺 Full Text HTML: SARS-CoV-2 Neutralization in Commercial Lots of Plasma-derived Immunoglobulin
• Covid-19 vaccine immunogenicity in people living with HIV-1 -
  Introduction: COVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals. Methods: HIV-positive individuals (n=121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naive to SARS CoV-2 was used. The participants Anti-RBD IgG responses were measured by ELISA at baseline and 3 to 4 weeks after receiving the first dose of an mRNA vaccine. Results: Eleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between between the HIV negative control group (n=20) and the combined HIV+ group (n=106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p<0.0001). Increasing age was independently associated with decreased immunogenicity. Conclusion: HIV-positive individuals with CD4 counts over 250 cells/mm3 have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV- positive individuals, depending on their response to the second dose.
  🖺 Full Text HTML: Covid-19 vaccine immunogenicity in people living with HIV-1
• SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact -
  The trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, is responsible for binding to human ACE2 receptors. The binding process is initiated when the receptor binding domain (RBD) of at least one protomer switches from a “down” (closed) to an “up” (open) state. Here, we used molecular dynamics simulations and two- dimensional replica exchange umbrella sampling calculations to investigate the transition between the two S-protein conformations with and without glycosylation. We show that the glycosylated spike has a higher barrier to opening than the non-glycosylated one with comparable populations of the down and up states. In contrast, we observed that the up conformation is favored without glycans. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state. We also identify roles for glycans at N165 and N343 in stabilizing the down and up states. Finally we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the epitope of the BD-368-2 antibody remains exposed irrespective of the S-protein conformation, explaining the high efficacy of this antibody.
  🖺 Full Text HTML: SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact
• Rapid antigen testing as a reactive public health response to surges in SARS-CoV-2 outbreak risk in healthcare settings -

  Background: Surges in community SARS-CoV-2 incidence increase risk of importation and subsequent transmission in healthcare facilities. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health and economic benefits as a reactive intervention in healthcare settings are unclear. Methods: We used stochastic, individual-based modelling to simulate SARS-CoV-2 transmission in a long-term care facility with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). In contrast to routine symptomatic testing using reverse-transcriptase polymerase chain reaction (RT-PCR), we evaluated the efficacy and health-economic efficiency of single or repeated population-wide Ag-RDT screening interventions implemented in response to surges in nosocomial outbreak risk. Results: Depending on the baseline containment measures in place, nosocomial SARS-CoV-2 incidence was reduced by up to 40-47% (range of means) with routine RT-PCR testing, 59-63% with the addition of a timely round of Ag- RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4 to 5 days between the first and second rounds was optimal for transmission prevention. Efficacy varied depending on test sensitivity, subpopulations targeted, and SARS-CoV-2 incidence in the community. Efficiency, however, varied primarily depending on the other containment measures in place: surveillance costs for a combined strategy of routine RT-PCR testing and reactive Ag-RDT screening ranged from a mean €420-€10,260/infection averted across scenarios (default unit costs: €5/Ag-RDT test, €50/RT-PCR test). Interpretation: Reactive Ag-RDT screening complements routine RT-PCR testing, and systematic two-round screening helps overcome limited, time-varying diagnostic sensitivity. Health-economic gains scale significantly with underlying nosocomial outbreak risk.

  🖺 Full Text HTML: Rapid antigen testing as a reactive public health response to surges in SARS-CoV-2 outbreak risk in healthcare settings
• How did people cope during the COVID-19 pandemic? A Structural Topic Modelling Analysis of Free-Text Data from 11,000 UK Adults -

  Background: The COVID-19 pandemic has had substantial impacts on lives across the globe. Job losses have been widespread, and individuals have experienced significant restrictions on their usual activities, including extended isolation from family and friends. While studies suggest population mental health worsened from before the pandemic, not all individuals appear to have experienced poorer mental health. This raises the question of how people managed to cope during the pandemic. Methods: To understand the coping strategies individuals employed during the COVID-19 pandemic, we used structural topic modelling, a text mining technique, to extract themes from free-text data on coping from over 11,000 UK adults, collected between 14 October and 26 November 2020. Results: We identified 16 topics. The most discussed coping strategy was 9thinking positively9 and involved themes of gratefulness and positivity. Other strategies included engaging in activities and hobbies (such as doing DIY, exercising, walking and spending time in nature), keeping routines, and focusing on one day at a time. Some participants reported more avoidant coping strategies, such as drinking alcohol and binge eating. Coping strategies varied by respondent characteristics including age, personality traits and sociodemographic characteristics and some coping strategies, such as engaging in creative activities, were associated with more positive lockdown experiences. Conclusion: A variety of coping strategies were employed by individuals during the COVID-19 pandemic. The coping strategy an individual adopted was related to their overall lockdown experiences. This may be useful for helping individuals prepare for future lockdowns or other events resulting in self-isolation.

  🖺 Full Text HTML: How did people cope during the COVID-19 pandemic? A Structural Topic Modelling Analysis of Free-Text Data from 11,000 UK Adults
• Healthcare presentations with self-harm and the association with COVID-19: an e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016 - March 2021 -

  Background Multi-setting population-based studies on healthcare service presentations with self-harm covering the first 12 months of the COVID-19 pandemic are yet to be published. Aims Ascertain changes across settings in healthcare service presentations with self-harm during Waves 1 and 2 of the COVID-19 pandemic. Method E-cohort study using individual-level linked routine healthcare data from Wales, UK, 2016-March 2021. We measured weekly proportion of self-harm contacts and people who self-harmed in contact with general practice (GP), emergency department (ED) and hospital admissions. We modelled weekly trends using linear regression and generalised estimated equations, quantifying time differences using difference-in-difference (DiD). Results We included 3,552,210 Welsh residents aged ≥10 years. Counts of self-harm presentations across settings was at a minimum at the start of stay-at-home restrictions during both waves and recovered compared to previous years in 3-5 months. Those who self-harmed in April 2020 were more likely to be seen in GP compared to other settings and previous years - mean rate of OR=1.2, although actual numbers fell. The proportion of self-harm ED contacts admitted to hospital dropped from June 2020 (1.9 [1.5-2.3] pp/month). Self-harm and COVID-19 infection had a bidirectional effect - self-harm history had OR=1.4 [1.2-1.6] and incidence had DiD=1.1 [0.8-1.4]. Conclusions Those that self-harmed and sought help during the COVID-19 pandemic potentially encountered stringent criteria for hospitalisation, particularly in Wave 2, while in Wave 1 they preferentially presented to GP. Reductions in contacts likely resulted in unmet healthcare needs which may later emerge placing further burden on individuals and healthcare services.

  🖺 Full Text HTML: Healthcare presentations with self-harm and the association with COVID-19: an e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016 - March 2021
• Another step toward final call on Remdesivir efficacy as a treatment for hospitalized COVID-19 patients: a multicenter open-label trial -

  Introduction: After emerging the global pandemic of SARS-CoV2 some preliminary studies demonstrated the efficacy of antiviral treatments. But shortly thereafter, inconsistencies in the results of further clinical trials raised doubts on the efficacy of these agents. In this study, we aimed to evaluate the effect of Remdesivir on hospitalized COVID-19 patients9 outcomes. Material and methods: This study was an open-label, single-armed, clinical trial on hospitalized patients diagnosed with COVID-19 who had progressive respiratory symptoms despite receiving standard care. All patients received Remdesivir and their characteristics, outcomes, time of treatment initiation, and respiratory support stages during hospitalization were registered and followed up for 14 days. Results: 145 patients with a mean age of 52.89 +- 1.12 years enrolled in this study, 38 (26.2%) died at the end of 14 days period. The mean time interval from the onset of the symptoms to antiviral treatment was 10.63+-0.56 days. Thirty deceased patients (78.9%) were men, showing 2.8 times higher mortality chance compared to women (ORadj=2.77; 95%CI=1.08-7.09). The type of respiratory support on the first day of treatment initiation showed a significantly lower mortality chance in patients receiving O2 only than those who needed non-invasive and/or mechanical ventilation (ORadj=3.91; 95%CI=1.64-9.32). The start time (early vs late administration) and duration (less or more than 7 days) of antiviral treatment had no statistically significant association with mortality or ventilation escalation among the patients (p-value > 0.05). Conclusion: In this study, we showed that Remdesivir probably is not effective on the outcome of hospitalized COVID-19 patients.

  🖺 Full Text HTML: Another step toward final call on Remdesivir efficacy as a treatment for hospitalized COVID-19 patients: a multicenter open-label trial

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

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

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

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

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

• 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

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

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

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

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

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

• 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

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

From PubMed

• In-vivo protection from SARS-CoV-2 infection by ATN-161 in k18-hACE2 transgenic mice - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5β1, and human ACE2 to…

• EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus - In the search for anti-SARS-CoV-2 drugs, much attention is given to safe and widely available native compounds. The green tea component epigallocatechin 3 gallate (EGCG) is particularly promising because it reportedly inhibits viral replication and viral entry in vitro. However, conclusive evidence for its predominant activity is needed. We tested EGCG effects on the native virus isolated from COVID-19 patients in two independent series of experiments using VERO cells and two different treatment…

• Involvement of Inflammation in Venous Thromboembolic Disease: An Update in the Age of COVID-19 - The inflammatory process is strongly involved in the pathophysiology of venous thromboembolism (VTE) and has a significant role in disease prediction. Inflammation most probably represents a common denominator through which classical and nonclassical risk factors stimulate thrombotic process. Inflammation of the venous wall promotes the release of tissue factor, inhibits the release of anticoagulant factors, and hampers endogenous fibrinolysis. Systemic inflammatory response also inhibits…

• GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2 - Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike…

• Levamisole Therapy in COVID-19 - Coronavirus disease 2019 (COVID-19) a global infectious disease caused by severe acute respiratory coronavirus 2 (SARS- CoV-2) affects various organs, primarily the respiratory system, and presented with pulmonary manifestations such as acute lung injury (ALI) and acute respiratory distress syndrome. Levamisole (LVM) is an anthelminthic drug; it has immune-modulating effects through induction of type 1 immune response. Based on these findings several recent studies highlighted that LVM might be…

• Machine Learning Models Identify Inhibitors of SARS-CoV-2 - With the rapidly evolving SARS-CoV-2 variants of concern, there is an urgent need for the discovery of further treatments for the coronavirus disease (COVID-19). Drug repurposing is one of the most rapid strategies for addressing this need, and numerous compounds have already been selected for in vitro testing by several groups. These have led to a growing database of molecules with in vitro activity against the virus. Machine learning models can assist drug discovery through prediction of the…

• ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication - Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin 1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete…

• Synthesis and molecular docking study of novel COVID-19 inhibitors - In 2020, the world tried to combat the corona virus (COVID-19) pandemic. A proven treatment method specific to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is still not found. In this study, seven new antiviral compounds were designed for COVID-19 treatment. The ability of these compounds to inhibit COVID-19’s RNA processing was calculated by the molecular docking study. It has been observed that the compounds can have high binding affinities especially against NSP12 (between…

• Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms - No abstract

• The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS) - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019), which is associated with high morbidity and mortality, especially in elder patients. Acute respiratory distress syndrome (ARDS) is a life-threatening complication of COVID-19 and has been linked with severe hyperinflammation. Dexamethasone has emerged as standard of care for COVID-19 associated respiratory failure. In a non-randomized prospective phase II multi- center study, we asked whether…

• Potent prophylactic and therapeutic efficacy of recombinant human ACE2-Fc against SARS-CoV-2 infection in vivo - The current COVID-19 pandemic, caused by SARS-CoV-2, poses a serious public health threat. Effective therapeutic and prophylactic treatments are urgently needed. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS- CoV-2, which binds to the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Here, we developed recombinant human ACE2-Fc fusion protein (hACE2-Fc) and a hACE2-Fc mutant with reduced catalytic activity. hACE2-Fc and the hACE2-Fc mutant both efficiently…

• Summary report of seven cases of COVID-19 infection in renal transplant recipients - The coronavirus disease 2019 (COVID-19) has swept the world, posing a serious threat to people’s lives and health. Several cases of COVID-19 infection in renal transplant recipients (RTRs) have been reported, but the treatment and prognosis have not been fully elucidated. We followed-up with RTRs infected with SARS-CoV2 in our center and classified them as five clinical types-asymptomatic, mild, moderate, severe, and critical. The immunosuppressive agents were not adjusted in asymptomatic…

• Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIbeta) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus and Human Rhinoviruses - Over half a century since the description of the first antiviral drug, “old” re-emerging viruses and “new” emerging viruses still represent a serious threat for global health. Their high mutation rate and rapid selection of resistance towards common antiviral drugs, together with the increasing number of co-infections, make the war against viruses quite challenging. Here we report a host-targeted approach, based on the inhibition of the lipid kinase PI4KIIIβ, as a promising strategy for…

• The rapid diagnosis and effective inhibition of coronavirus using spike antibody attached gold nanoparticles - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease that began in 2019 (COVID-19), has been responsible for 1.4 million deaths worldwide as of 13 November 2020. Because at the time of writing no vaccine is yet available, a rapid diagnostic assay is very urgently needed. Herein, we present the development of anti-spike antibody attached gold nanoparticles for the rapid diagnosis of specific COVID-19 viral antigen or virus via a simple colorimetric…

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

From Patent Search

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

• Cabina de desinfección de doble carga exterior - - link

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

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

• 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 - - link

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

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