Covid-19 Sentry

Contents

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

From Preprints

• Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network -

  Background The second-wave of CVOID-19 pandemic is anticipated to be worse than the initial one and will strain the healthcare systems even more during the winter months. Our aim was to develop a machine learning-based model to predict mortality using the Neo-V framework. We hypothesized this novel machine learning approach could be applied to COVID-19 patients to predict mortality successfully and high accuracy. Methods The current Deep-Neo-V model is built on our previously statistically rigorous machine learning framework [Fahad-Liaqat-Ahmad Intensive Machine (FLAIM) framework] that evaluates the statistically significant risk factors, generate new combined variables and then supply these risk factors to deep neural network to predict mortality in RT-PCR positive COVID-19 patients in the inpatient setting. We analyzed adult patients (≥18 years) admitted to the Aga Khan University Hospital with a working diagnosis of COVID-19 infection (n=1228). We excluded patients that were negative on COVID-19 on RT-PCR, had incomplete or missing health records. The first phase selection of risk factor was done using Cox-regression univariate and multivariate analyses. In the second phase, we generated new variables and tested those statistically significant for mortality and in the third and final phase we applied deep neural networks and other traditional machine learning models like Decision Tree Model, k-nearest neighbor models and others. Results A total of 1228 cases were diagnosed as a COVID-19 infection, we excluded 14 patients after the exclusion criteria and (n=)1214 patients were analyzed. We observed that several clinical and laboratory-based variables were statistically significant for both univariate and multivariate analyses while others were not. With most significant being septic shock (hazard ratio [HR], 4.30; 95% confidence interval [CI], 2.91-6.37), supportive treatment (HR, 3.51; 95% CI, 2.01-6.14), abnormal international normalized ratio (INR) (HR, 3.24; 95% CI, 2.28-4.63), admission to the intensive care unit (ICU) (HR, 3.24; 95% CI, 2.22-4.74), treatment with invasive ventilation (HR, 3.21; 95% CI, 2.15-4.79) and laboratory lymphocytic derangement (HR, 2.79; 95% CI, 1.6-4.86). Machine learning results showed our DNN (Neo-V) model outperformed all conventional models (Neo-V) and Deep-FLAIM models with test set accuracy of 99.53%, sensitivity of 89.87%, and specificity of 95.63%; positive predictive value, 50.00%; negative predictive value, 91.05%; and area under the curve of the receiver-operator curve of 88.5. Conclusion Our novel Deep-Neo-V model outperformed all other machine learning models. The model is easy to implement, user friendly and with high accuracy.

  🖺 Full Text HTML: Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
• Compliance and Self-Reporting during the COVID-19 Pandemic: A Cross-Cultural Study of Trust and Self-Conscious Emotions in the United States, Italy and South Korea -
  The coronavirus COVID-19 pandemic is an unprecedented health crisis. Many governments around the world have responded by implementing lockdown measures of various degrees of intensity. To be effective, these measures must rely on citizens’ cooperation. In the present study, we drew samples from the United States (N = 597), Italy (N = 606) and South Korea (N = 693) and examined predictors of compliance with social distancing and intentions to report the infection to both authorities and acquaintances. Data were collected between April 6th and 8th 2020. We investigated the role of cultural orientations of horizontal and vertical individualism and collectivism, self-conscious emotions of shame and guilt related to the infection and trust in the government’s action. Across all countries, vertical collectivism predicted stronger shame, whereas horizontal collectivism predicted stronger trust in the government. Only in the United States, vertical collectivism was associated with stronger trust. Stronger feelings of shame predicted lower compliance and intentions to report the infection to both authorities and acquaintances. In contrast, guilt was associated with stronger intentions to report the infection to the authorities. Finally, trust was associated with stronger compliance and intentions to report the infection to the authorities. Unlike Italy and South Korea, the association between trust on compliance was not statistically significant in the United States, Implications of the findings, and directions for future research are discussed.
  🖺 Full Text HTML: Compliance and Self-Reporting during the COVID-19 Pandemic: A Cross-Cultural Study of Trust and Self-Conscious Emotions in the United States, Italy and South Korea
• Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination -

  Background Vaccines remain the cornerstone for containing the SARS-CoV-2 pandemic. mRNA vaccines provide protection in clinical trials using a two-dose approach, separated by a three to four week gap. UK policy in 2021 is to extend the dosing interval from three to twelve weeks. There is a paucity of data in the elderly, even though these individuals are the first to receive vaccines due to risk of severe disease. Here we assessed real world immune responses following vaccination with mRNA-based vaccine BNT162b2. Methods: We did a prospective cohort study of individuals presenting for first dose vaccination. Following the first and second doses of the BNT162b2 vaccine, we measured IFNgamma; T cell responses, as well as binding antibody (IgA, IgG and IgG1-4) responses to Spike and Spike RBD. We also measured neutralising antibody responses to Spike in sera using a lentiviral pseudotyping system. We correlated age with immune responses and compared responses after the first and second doses. Findings Median age was 63.5 years amongst 42 participants. Three weeks after the first dose a lower proportion of participants over 80 years old achieved adequate neutralisation titre of >1:20 for 50% neutralisation as compared to those under 80 (8/17 versus 19/24, p=0.03). Geometric mean neutralisation titres in this age group after the first dose were lower than in younger individuals (p<0.001). Binding IgA and IgG1 and 3 responses developed post vaccination, as observed in natural infection. T- cell responses were not different in those above or below 80 years. Following the second dose, 50% neutralising antibody titres were above 1:20 in all individuals and there was no longer a difference by age grouping. Interpretation A high proportion of individuals above the age of 80 have suboptimal neutralising antibody responses following first dose vaccination with BNT162b2, cautioning against extending the dosing interval in this high risk population.

  🖺 Full Text HTML: Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination
• Genomic epidemiology of COVID-19 in care homes in the East of England -

  COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, we report on 6,600 COVID-19 cases from the East of England, 1,167 of which were identified as residents from 337 care homes. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data we defined 409 viral clusters within the 292 homes, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study period, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission between care home residents should be a key target for infection control to reduce COVID-19 mortality in this population.

  🖺 Full Text HTML: Genomic epidemiology of COVID-19 in care homes in the East of England
• Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers -

  Here, we develop a simple molecular test for SARS-CoV-2 in saliva based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The test has two steps: 1) heat saliva with a stabilization solution, and 2) detect virus by incubating with a primer/enzyme mix. After incubation, saliva samples containing the SARS-CoV-2 genome turn bright yellow. Because this test is pH dependent, it can react falsely to some naturally acidic saliva samples. We report unique saliva stabilization protocols that rendered 295 healthy saliva samples compatible with the test, producing zero false positives. We also evaluated the test on 278 saliva samples from individuals who were infected with SARS-CoV-2 but had no symptoms at the time of saliva collection, and from 54 matched pairs of saliva and anterior nasal samples from infected individuals. The Saliva TwoStep test described herein identified infections with 94% sensitivity and >99% specificity in individuals with sub-clinical (asymptomatic or pre-symptomatic) infections.

  🖺 Full Text HTML: Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers
• New York City Jails: COVID Discharge Policy, Data Transparency, and Reform -
  During the early stages of the COVID-19 pandemic in 2020, Mayor Bill de Blasio ordered the release of New York City jail inmates who were at high risk of contracting the disease and at low risk of committing criminal reoffense. Using public information, we construct and analyze a database of nearly 350,000 incarceration episodes in the city jail system from 2014 - 2020. In concordance with de Blasio’s stated policy, inmates discharged immediately after his order were at a lower risk of reoffense than inmates discharged during the same calendar week in previous years. The inmates in the former group were also slightly older, on average, than those in the latter group, although the overall age distributions of the two groups were quite similar. Additionally, the inmates of the former group had spent dramatically longer in jail than those in the latter group. With the release of long-serving inmates demonstrated to be feasible, we also examine how the jail population would have looked over the past six years had caps in incarceration been in place. With a cap of one year, the system would experience a 15% decrease in incarceration. With a cap of 100 days, incarceration would be just under 50% of the realized value. Because our results are only as accurate as New York City’s public-facing jail data, we discuss numerous challenges with this data and suggest improvements. These improvements would address issues including inmate age, gender, and race. Finally, we discuss policy implications of our work, highlight some opportunities and challenges posed by incarceration caps, and suggest key areas for reform. It is striking that the de Blasio administration was able to identify inmates at low risk of reoffense and was willing to release them. Their success with discharge during the early stages of COVID-19 suggests that low-risk inmates could be discharged sooner in general.
  🖺 Full Text HTML: New York City Jails: COVID Discharge Policy, Data Transparency, and Reform
• SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients -
  The SARS-CoV-2 pandemic has elicited a unique international mobilization of the scientific community to better understand this coronavirus and its associated disease and to develop efficient tools to combat infection. Similar to other coronavirae, SARS-CoV-2 hijacks the host cell complex secretory machinery to produce properly folded viral proteins that will compose the nascent virions; including Spike, Envelope and Membrane proteins, the most exposed membrane viral proteins to the host immune system. Antibody response is part of the anti-viral immune arsenal that infected patients develop to fight viral particles in the body. Herein, we investigate the immunogenic potential of Spike (S), Envelope (E) and Membrane (M) proteins using a human cell-based system to mimic membrane insertion and N-glycosylation. We show that both S and M proteins elicit the production of specific IgG, IgM and IgA in SARS-CoV-2 infected patients. Elevated Ig responses were observed in COVID+ patients with moderate and severe forms of the disease. Finally, when SARS-CoV-2 Spike D614 and G614 variants were compared, reduced Ig binding was observed with the Spike G614 variant. Altogether, this study underlines the needs for including topological features in envelop proteins to better characterize the serological status of COVID+ patients, points towards an unexpected immune response against the M protein and shows that our assay could represent a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.
  🖺 Full Text HTML: SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients
• Broad-spectrum antiviral activity of 3D8, a nucleic acid-hydrolyzing single chain variable fragment (scFv), targeting SARS-CoV-2 and multiple coronaviruses in vitro -
  The current pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a critical public health threat worldwide. Coronaviruses (subfamily Orthocoronavirinae, family Coronaviridae, order Nidovirales) are a group of enveloped positive-sense single-stranded RNA viruses. Six pathogenic human coronaviruses, likely zoonotic viruses, cause the common cold in humans. A new emerging coronavirus, SARS-CoV-2, become a crucial etiology for the Coronavirus-induced disease 19 (COVID-19). However, effective therapeutics and vaccines against multiple coronaviruses remain unavailable. This study aimed to investigate an antiviral molecule, single chain variable fragment (scFv), against SARS-CoV-2 and other coronaviruses. 3D8, a recombinant scFv, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. Here, we report that 3D8 scFv inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the absence of coronavirus nucleoproteins and infectious particles in 3D8 scFv-treated cells, respectively. In addition, we observed the antiviral effects of 3D8 against HCoV-OC43 and PEDV. In conclusion, this study provides insights into the broad-spectrum antiviral agent of 3D8 scFv; thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.
  🖺 Full Text HTML: Broad-spectrum antiviral activity of 3D8, a nucleic acid-hydrolyzing single chain variable fragment (scFv), targeting SARS-CoV-2 and multiple coronaviruses in vitro
• Bromodomain and Extraterminal Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection (Pre-Clinical) -
  Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined, but could be direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory cytokine-storm, a cocktail of interferon gamma, interleukin 1B; and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids and hearts of SARS-CoV-2 infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCO and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the FDA breakthrough designated drug apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.
  🖺 Full Text HTML: Bromodomain and Extraterminal Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection (Pre-Clinical)
• Jumper Enables Discontinuous Transcript Assembly in Coronaviruses -
  Genes in SARS-CoV-2 and, more generally, in viruses in the order of Nidovirales are expressed by a process of discontinuous transcription mediated by the viral RNA-dependent RNA polymerase. This process is distinct from alternative splicing in eukaryotes, rendering current transcript assembly methods unsuitable to Nidovirales sequencing samples. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLY problem of finding transcripts T and their abundances c given an alignment R under a maximum likelihood model that accounts for varying transcript lengths. Underpinning our approach is the concept of a segment graph, a directed acyclic graph that, distinct from the splice graph used to characterize alternative splicing, has a unique Hamiltonian path. We provide a compact characterization of solutions as subsets of non-overlapping edges in this graph, enabling the formulation of an efficient mixed integer linear program. We show using simulations that our method, JUMPER, drastically outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1 and SARS-CoV-2 samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are well supported by direct evidence from long-read data, presence in multiple, independent samples or a conserved core sequence. JUMPER enables detailed analyses of Nidovirales transcriptomes.
  🖺 Full Text HTML: Jumper Enables Discontinuous Transcript Assembly in Coronaviruses
• SARS-CoV-2 and SARS-CoV spike-mediated cell-cell fusion differ in the requirements for receptor expression and proteolytic activation -
  The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infects cells through interaction of its spike protein (SARS2-S) with Angiotensin-converting enzyme 2 (ACE2) and activation by proteases, in particular transmembrane protease serine 2 (TMPRSS2). Viruses can also spread through fusion of infected with uninfected cells. We compared the requirements of ACE2 expression, proteolytic activation, and the sensitivity to inhibitors for SARS2-S-mediated and SARS-CoV-S(SARS1-S)-mediated cell-cell fusion. SARS2-S-driven fusion was moderately increased by TMPRSS2 and strongly by ACE2, while SARS1-S-driven fusion was strongly increased by TMPRSS2 and less so by ACE2 expression. In contrast to SARS1-S, SARS2-S-mediated cell-cell fusion was efficiently activated by Batimastat-sensitive metalloproteases. Mutation of the S1/S2 proteolytic cleavage site reduced effector-target-cell fusion when ACE2 or TMPRSS2 were limiting and rendered SARS2-S-driven cell-cell fusion more dependent on TMPRSS2. When both ACE2 and TMPRSS2 were abundant, initial target-effector-cell fusion was unaltered compared to wt SARS2-S, but syncytia remained smaller. Mutation of the S2’ site specifically abrogated activation by TMPRSS2 for both cell-cell fusion and SARS2-S-driven pseudoparticle entry but still allowed for activation by metalloproteases for cell-cell fusion and by cathepsins for particle entry. Finally, we found that the TMPRSS2 inhibitor Bromhexine was unable to reduce TMPRSS2-activated cell-cell fusion by SARS1-S and SARS2-S as opposed to the inhibitor Camostat. Paradoxically, Bromhexine enhanced cell-cell fusion in the presence of TMPRSS2, while its metabolite Ambroxol exhibited inhibitory activity in some conditions. On Calu-3 lung cells, Ambroxol weakly inhibited SARS2-S-driven lentiviral pseudoparticle entry, and both substances exhibited a dose-dependent trend towards weak inhibition of authentic SARS-CoV-2.
  🖺 Full Text HTML: SARS-CoV-2 and SARS-CoV spike-mediated cell-cell fusion differ in the requirements for receptor expression and proteolytic activation
• Complete Protection of Nasal and Lung Airways Against SARS-CoV-2 Challenge by Antibody Plus Th1 Dominant N- and S-Specific T-Cell Responses to Subcutaneous Prime and Thermally-Stable Oral Boost Bivalent hAd5 Vaccination in an NHP Study -
  We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike (S-Fusion) protein and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) with the potential to increase MHC class I/II responses. The adenovirus serotype 5 platform used, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity, can be delivered in an oral formulation that overcomes cold-chain limitations. The hAd5 S-Fusion + N-ETSD vaccine was evaluated in rhesus macaques showing that a subcutaneous prime followed by oral boosts elicited both humoral and Th1 dominant T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.
  🖺 Full Text HTML: Complete Protection of Nasal and Lung Airways Against SARS-CoV-2 Challenge by Antibody Plus Th1 Dominant N- and S-Specific T-Cell Responses to Subcutaneous Prime and Thermally-Stable Oral Boost Bivalent hAd5 Vaccination in an NHP Study
• Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19 -
  The COVID-19 pandemic is expected to have an adverse effect on the progression of multiple cancers, including prostate cancer, due to the ensuing cytokine storm and associated oncogenic signaling. Epidemiological data showing increased severity and mortality of COVID-19 in men suggests a potential role for androgen in SARS-CoV-2 infection. Here, we present evidence for the transcriptional regulation of SARS-CoV-2 host cell receptor ACE2 and co-receptor TMPRSS2 by androgen in mouse tissues and human prostate and lung cell lines. Additionally, we demonstrate the endogenous interaction between TMPRSS2 and ACE2 in human cells and validate ACE2 as a TMPRSS2 substrate. In an overexpression model, and the prostate and lung cells, Camostat - a TMPRSS2 inhibitor, blocked the cleavage of pseudotype SARS-CoV-2 surface Spike without disrupting TMPRSS2-ACE2 interaction. Thus providing evidence for the first time a direct role of TMPRSS2 in priming the SARS-CoV-2 Spike protein, required for viral fusion to the host cell. Importantly, androgen-deprivation, anti-androgens such as enzalutamide/AR-PROTAC, or Camostat treatment attenuated the SARS-CoV-2 S-mediated entry in lung and prostate cells. Together, our preclinical data provide a strong rationale for clinical evaluations of the TMPRSS2 inhibitors, androgen-deprivation therapy and androgen receptor antagonists alone or in combination with anti-viral drugs as early as clinically possible to prevent inflammation driven COVID-19 progression.
  🖺 Full Text HTML: Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19
• Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19. -
  COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2, a recently emerged coronavirus that has rapidly caused a pandemic. Coalescence of a second wave of this virus with seasonal respiratory viruses, particularly influenza virus is a possible global health concern. To investigate this, transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) were first infected with IAV followed by SARS-CoV-2. The host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 only. Infection of mice with each individual virus resulted in a disease phenotype compared to control mice. Although, SARS-CoV-2 RNA synthesis appeared significantly reduced in the sequentially infected mice, these mice had a more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to singly infected or control mice. The sequential infection also exacerbated the extrapulmonary manifestations associated with SARS-CoV-2. This included a more severe encephalitis. Taken together, the data suggest that the concept of “twinfection” is deleterious and mitigation steps should be instituted as part of a comprehensive public health response to the COVID-19 pandemic.
  🖺 Full Text HTML: Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19.
• Separable Associations Between Perceived Positive and Negative Online Experiences and Loneliness in Peruvian Adolescents During Physical Isolation in Response to COVID-19 -
  COVID-19 lockdowns around the world have markedly disrupted adolescents’ in-person social networks, putting them at risk for social isolation, loneliness and their detrimental consequences. During lockdown, social media can help adolescents to maintain and develop relationships across distance, particularly with peers. In this longitudinal, observational study following 735 Peruvian adolescents (11-17 years old) from low-to-middle income urban settings, we investigated whether online experiences relate to loneliness during initial stages of lockdown in Perú. We found that loneliness generally did not change between week six and week eleven of lockdown, was higher for females and similar for all grades. Both positive and negative online experiences were more frequent for older students, and females experienced more negative online experiences than males. Loneliness was negatively associated with positive online experiences, with the reverse pattern for negative online experiences, when controlling for family social support and screen time. Our results highlight the association between online experiences and well-being, suggesting that positive online experiences can be an important vehicle for peer relationships in the face of lockdown.
  🖺 Full Text HTML: Separable Associations Between Perceived Positive and Negative Online Experiences and Loneliness in Peruvian Adolescents During Physical Isolation in Response to COVID-19

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

• An Effectiveness Study of the Sinovac’s Adsorbed COVID-19 (Inactivated) Vaccine - Condition:   Covid19
  Intervention:   Biological: Adsorbed COVID-19 (Inactivated) Vaccine
  Sponsor:   Butantan Institute
  Enrolling by invitation

• 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

• Effect of Prone Position onV/Q Matching in Non-intubated Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: prone position
  Sponsor:   Southeast University, China
  Not yet recruiting

• Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection - Conditions:   Covid19;   SARS-CoV 2
  Intervention:   Other: Sampling by venipuncture
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Recruiting

• COVID-19 Convalescent Plasma Therapy - Conditions:   SARS-CoV-2 Infection;   COVID-19 Infection
  Intervention:   Biological: Convalescent plasma
  Sponsors:   Angelica Samudio;   Consejo Nacional de Ciencias y Tecnología, Paraguay;   Ministerio de Salud Pública y Bienestar Social, Paraguay;   Centro de información y recursos para el desarrollo, Paraguay
  Completed

• A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Condition:   Coronavirus Disease 2019 (COVID-19)
  Interventions:   Drug: Placebo;   Drug: Prothione™ (6g)
  Sponsor:   Prothione, LLC
  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

• Telerehabilitation in Covid-19 After Hospital Discharge - Condition:   Covid19
  Interventions:   Other: Standard Physiotherapy program;   Other: Telerehabilitation
  Sponsor:   Universidad de Granada
  Not yet recruiting

• AGILE (Early Phase Platform Trial for COVID-19) - Condition:   Covid19
  Interventions:   Drug: CST-2: EIDD-2801;   Drug: CST-2: Placebo
  Sponsors:   University of Liverpool;   University of Southampton;   Liverpool School of Tropical Medicine;   Lancaster University;   Liverpool University Hospitals NHS Foundation Trust
  Recruiting

• Enriched Heparin Anti COVID-19 Trial - Condition:   Covid19
  Interventions:   Drug: Heparin sodium;   Drug: Placebo
  Sponsor:   UPECLIN HC FM Botucatu Unesp
  Not yet recruiting

• Pulmonary Rehabilitation of Patients With a History of COVID-19 - Condition:   Covid19
  Intervention:   Procedure: Pulmonary rehabilitation
  Sponsor:   University of Rzeszow
  Enrolling by invitation

• Respiratory Aerosols in Patients With COVID-19 and Healthy Controls - Conditions:   SARS-CoV-2 Infection;   Covid19
  Interventions:   Diagnostic Test: Resp-Aer-Meter;   Diagnostic Test: Spirometry;   Diagnostic Test: Qualitative and quantitative virus PCR of respiratory secretions in patients with high aerosol concentrations
  Sponsors:   Johann Wolfgang Goethe University Hospital;   Palas GmbH
  Recruiting

• Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US - Condition:   Covid19
  Intervention:   Other: Social Network Strategy + COVID-19 messaging
  Sponsor:   University of Chicago
  Not yet recruiting

From PubMed

• Effect of Chloroquine and Hydroxychloroquine on COVID-19 Virological Outcomes: An Updated Meta-Analysis - As anti-malarial drugs have been found to inhibit Corona viruses in vitro, studies have evaluated the effect of these drugs inCOVID-19 infection. We conducted an updated meta-analysis of clinical trials and observational studies published till June 2020. Patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) infection were included. The drugs used in the intervention group are Chloroquine (CQ)/Hydroxychloroquine…

• EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro - COVID-19 pandemic results in record high deaths in many countries. Although a vaccine for SARS-CoV-2 is now available, effective antiviral drugs to treat coronavirus diseases are not available yet. Recently, EGCG, a green tea polyphenol, was reported to inhibit SARS-CoV-2 3CL-protease, however the effect of EGCG on coronavirus replication is unknown. In this report, human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus) were used to examine the effect of EGCG on…

• Discovery and structural optimization of 3-O-beta-chacotriosyl oleanane-type triterpenoids as potent entry inhibitors of SARS-CoV-2 virus infections - Currently, SARS-CoV-2 virus is an emerging pathogen that has posed a serious threat to public health worldwide. However, no agents have been approved to treat SARS-CoV-2 infections to date, underscoring the great need for effective and practical therapies for SARS-CoV-2 outbreaks. We reported that a focused screen of OA saponins identified 3-O-β-chacotriosyl OA benzyl ester 2 as a novel small molecule inhibitor of SARS-CoV-2 virus entry, via binding to SARS-CoV-2 glycoprotein (S). We performed…

• Neutralizing antibodies targeting the SARS-CoV-2 receptor binding domain isolated from a naive human antibody library - Infection with SARS-CoV-2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naïve antibody libraries are a viable means for discovery of novel SARS-CoV-2 neutralizing antibodies. Here, we used a yeast surface-display library of human naïve…

• Quantitative Assays Reveal Cell Fusion at Minimal Levels of SARS-CoV-2 Spike Protein and Fusion-from-Without - Cell entry of the pandemic virus SARS-CoV-2 is mediated by its spike protein S. As main antigenic determinant, S protein is in focus of various therapeutic strategies. Besides particle-cell fusion, S mediates fusion between infected and uninfected cells resulting in syncytia formation. Here we present sensitive assay systems with a high dynamic range and high signal-to-noise ratios covering not only particle-cell and cell-cell fusion, but also fusion-from-without (FFWO). In FFWO, S-containing…

• Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy - Detailed knowledge of the molecular biology of SARS-CoV-2 infection is crucial for understanding of viral replication, host responses and disease progression. Here, we report gene expression profiles of three SARS-CoV and SARS-CoV-2 infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation of the innate immune response compared to SARS-CoV in the human epithelial cell line Calu-3, including induction of miRNA-155. Single-cell RNA sequencing of infected cells…

• Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease - The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (M^(pro)/3CL(pro)), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of M^(pro) conformational changes, with molecular modeling and 1-μs MD simulations. Long-scale MD…

• Screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus using network pharmacology - The majority of the bioactives under investigation were predicted to target TNF receptor-associated factor 5 in the Janus kinase/signal transducers and activators of the transcription pathway. Similarly, druglikeness prediction identified vitexilactone to possess the highest druglikeness score, i.e., 0.88. Furthermore, proteins targeted in the Janus kinase/signal transducers and activators of transcription pathway were also predicted to regulate multiple pathways, i.e., ErbB, AGE-RAGE, NF-kappa…

• Development of Plant-Produced Recombinant ACE2-Fc Fusion Protein as a Potential Therapeutic Agent Against SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease (COVID-19) which has recently emerged as a potential threat to global public health. SARS-CoV-2 is the third known human coronavirus that has huge impact on the human population after SARS-CoV and MERS-CoV. Although some vaccines and therapeutic drugs are currently in clinical trials, none of them are approved for commercial use yet. As with SARS-CoV, SARS-CoV-2 utilizes…

• Complement Activation in Kidneys of Patients With COVID-19 - Most patients who became critically ill following infection with COVID-19 develop severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of critically ill patients with COVID-19. Apart…

• HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons - The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD…

• Nasal Delivery of Hesperidin/Chitosan Nanoparticles Suppresses Cytokine Storm Syndrome in a Mouse Model of Acute Lung Injury - The cytokine storm or cytokine storm syndrome (CSS) is associated with high mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), for example following sepsis or infectious diseases including COVID-19. However, there are no effective treatments for CSS-associated ALI or ALI/ARDS. Thus, there remains an urgent need to develop effective drugs and therapeutic strategies against CSS and ALI/ARDS. Nasal and inhaled drug delivery methods represent a…

• Computational search for drug repurposing to identify potential inhibitors against SARS-COV-2 using Molecular Docking, QTAIM and IQA methods in viral Spike protein - Human ACE2 interface - With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic…

• In silico identification and validation of natural antiviral compounds as potential inhibitors of SARS-CoV-2 methyltransferase - The novel Coronavirus disease 2019 (COVID-19) is potentially fatal and caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Due to the unavailability of any proven treatment or vaccination, the outbreak of COVID-19 is wreaking havoc worldwide. Hence, there is an urgent need for therapeutics targeting SARS-CoV-2. Since, botanicals are an important resource for several efficacious antiviral agents, natural compounds gaining significant attention for COVID-19 treatment. In the…

• Network Meta-analysis on the Mechanisms Underlying Alcohol Augmentation of COVID-19 Pathologies - CONCLUSIONS: Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Medical records of COVID-19 patients are sparse for drinking history. Our findings suggest the importance to caution against alcohol consumption, which has increased during the COVID-19 pandemic, and facilitate further investigation into how alcohol exposure may affect viral infections.

From Patent Search

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link

• 新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒 - 本发明提供一种新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒，所述试剂盒至少包含：包被有链霉亲和素的孔板、生物素标记的抗新冠棘突蛋白抗体1、SULFO标记的抗新冠棘突蛋白抗体2、洗涤液、读数液、新冠病毒S蛋白标准品和新冠病毒RBD蛋白标准品。本发明以生物素标记的抗新冠棘突蛋白的抗体1与链霉亲和素板进行连接作为固定相，以新冠S蛋白、RBD蛋白作为参照品，可被SULFO标记的抗体2识别，从而检测新冠抗原的表达情况。该试剂盒能准确灵敏地定量检测不同基质中的新冠S蛋白、RBD蛋白，样品的前处理过程简单，耗时少，可同时检测大量样品。本发明对于大批量样品的新冠病毒疫苗表达抗原的检测具有重要意义。 - link

• 陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层 - 本发明是关于一种陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层。该涂料包括30_{99.9%无机树脂、0.1}70%氮化硅、0_{10%功能助剂、0}18%无机颜料和0_{2%其他功能助剂；无机树脂由有机烷氧基硅烷、有机溶剂和硅溶胶混合、反应，抽醇，添加去离子水获得；有机烷氧基硅烷、有机溶剂和硅溶胶的质量比为1}1.6：0.5~0.8：1。所要解决的技术问题是如何制备一种贮存稳定性好、可常温固化且膜层的物理化学性能优异的涂料；该涂料VOC含量低，具有良好的安全生产性，且涂料成膜过程中的VOC排放很低，利于环保；该膜层的硬度高、柔韧性好，不易开裂，且可以接触性杀灭病毒和细菌；该涂料既可常温固化，也可加热固化，无需现场两个剂型调配，施工方便，成本节约，从而更加适于实用。 - link

• SARS-CoV-2 antibodies - - link

• SARS-CoV-2 antibodies - - link

• 病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用 - 本发明涉及病毒检测领域，特别涉及病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用。本发明病毒检测装置提供了一种简单易行的病毒核酸提取方法，整个过程大约5‑15分钟，回收纯化的核酸，可用于病毒核酸的检测。包括PCR、NASBA、LAMP、RPA等。相比较于传统的病毒提取方法，本方法病毒核酸回收率高、用时少、操作方便、易于临床推广。本发明涉及单管同时检测新型冠状病毒COVID‑19 N和ORF基因以及人源内参基因的等温扩增引物、探针组合序列和反应缓冲液，该体系特异性好，灵敏度高（50 cp/mL），特异性高，只需20 min的检测时间，最快可在10 min左右报阳性。 - link

• 一种侧链修饰的聚氨基酸及其制备方法和用途 - 本发明提供了一种侧链修饰的聚氨基酸及其制备方法，所述侧链修饰的聚氨基酸具有如下优势：（1）主链和侧链结构及其连接方式都可以灵活选取，使制得的聚合物胶束具有良好生物相容性和靶向递送效率，（2）聚氨基酸主链的电荷极性为电正性，对主链的电荷调节促进胶束的pH值响应，帮助RNA从“溶酶体陷阱”中逃离进入胞浆，（3）通过量化侧链修饰脂肪链的链长、饱和度和脂肪链数量来控制侧链的疏水性部分，精确调节疏水部分的体积和缔合作用强度，（4）由于RNA和DNA在结构和负电性上的相似性，高效构建包裹和递送体，（5）通过双亲性功能高分子的侧链修饰引入不同的生物功能基团，实现递送体系对靶点组织和部位的特异性结合，提高靶向递送效果。 - link

• 靶向SARS-CoV-2冠状病毒的抗体及其诊断和检测用途 - 本发明涉及靶向SARS‑CoV‑2冠状病毒的抗体及其诊断和检测用途。具体涉及特异性结合冠状病毒S蛋白的抗体或其抗原结合片段和抗体对以及包含所述抗体或其抗原结合片段和抗体对的检测产品。本发明还涉及编码所述抗体或抗原结合片段的核酸及包含其的宿主细胞，以及制备所述抗体或抗原结合片段的方法。此外，本发明涉及所述抗体或其抗原结合片段、抗体对的预防、治疗或诊断用途。相较于常规的IgG/IgM检测，该检测方法直接检测样本中病毒的RBD蛋白，可以有效避免可能的样本中无关IgG/IgM对于检测的干扰，有效提高检测的灵敏度。所述抗体或抗体对可用于诊断和/或检测冠状病毒。 - 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