Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 viral RNA levels are not “viral load” -
  Ct values are commonly used as proxy of SARS-CoV-2 “viral load”. Because of the (+)ssRNA nature of coronaviruses, current RT-qPCR target amplification does not distinguish replicative from transcriptional RNA. Although Ct values analyses through time, space and biological backgrounds remain informative, equating Ct with viral load may generate misleading conclusions.
  🖺 Full Text HTML: SARS-CoV-2 viral RNA levels are not “viral load”
• University Students’ Adherence to the COVID-19-guidelines: A Qualitative Study on Facilitators and Barriers -
  Objective. This study aims to explore students’ adherence and reasons behind the (non)adherence to the COVID-19-regulations within a university setting. Methods. A total of 33 students participated in on-site and online focus group interviews (k=8). Discussed topics included the general COVID-19-guidelines of the university, including keeping ≥1.5 m distance, staying at home and getting tested when having symptoms, and wearing facemasks. Additionally, education and psychosocial wellbeing in the times of COVID-19 were discussed. We also conducted online interviews with stewards (2 focus group interviews and 1 individual interview) and security/crowd control officials (1 focus group interview) to learn more about students’ (non)adherence behaviors. Results. The findings of this study show that the interviewed students were willing to adhere to the guidelines within the university buildings. They mentioned several facilitators (e.g., the infrastructure of the buildings and staff) and barriers (e.g., being together with friends and difficulties with telling others to follow the regulations) for their compliance behaviors. Some students also stated that they are not afraid of COVID-19 because they are young, while others adhered to the regulations to protect vulnerable people. Conclusion. To create a safe environment within the university and alleviate the spread of the virus, future interventions require targeting the determinants of students’ non-adherence behaviors, such as lower risk perception (e.g., being young and no perceived threat/low vulnerability) and lower self-efficacy (e.g., for keeping distance, to determine symptoms for testing/isolating and to correct others).
  🖺 Full Text HTML: University Students’ Adherence to the COVID-19-guidelines: A Qualitative Study on Facilitators and Barriers
• COVID-19 and false dichotomies — A nuanced review of the evidence regarding public health, COVID-19 symptomatology, SARS-CoV-2 transmission, mask wearing, and reinfection -
  Background: Scientists across disciplines, policymakers, and journalists have voiced frustration at the polarization of opinions focusing on global and national responses to the coronavirus disease 2019 (COVID-19) pandemic. Herein, we address several false dichotomies that have emerged in public debates. Methods and main text: This narrative review endeavors to thoughtfully review the evidence and knowledge gaps about six COVID-19 topics commonly presented as false dichotomies: 1) Health and lives vs. economy and livelihoods, 2) Indefinite lockdown vs. unlimited reopening, 3) Symptomatic vs. asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 4) Droplet vs. aerosol transmission of SARS-CoV-2, 5) Masks for all vs. no masking, and 6) SARS-CoV-2 reinfection vs. no reinfection. Basic concepts, nuances, and debated issues are presented for each topic. We discuss the importance of multidisciplinary integration (health, social, and physical sciences), multilayered approaches to reducing risk, harm reduction, smart masking, and context-sensitive policymaking for COVID-19 response plans. We also address the challenges in understanding the broad clinical presentation of COVID-19, the transmission of SARS-CoV-2, and the occurrence of SARS-CoV-2 reinfection. Conclusions: Our review compiles and discusses evidence in the context of a complex policy landscape with many actors and competing priorities and risks. Science, public health, and several aspects of pathogen transmission, infection, and disease are fraught with uncertainty. They exist on a spectrum of gray shades between the extremes of black and white—they are hardly binary, simple, settled, or uniform, and should not be framed as such. In light of the challenges surrounding the science-policy interface for COVID-19, we caution against black-or-white messaging, all-or-nothing guidance, and one-size-fits-all approaches. We underscore the need for culturally appropriate public health communication, science-informed tailored policies, and health journalism that reckon with shades of gray, uncertainties, local contexts, and social determinants.
  🖺 Full Text HTML: COVID-19 and false dichotomies — A nuanced review of the evidence regarding public health, COVID-19 symptomatology, SARS-CoV-2 transmission, mask wearing, and reinfection
• Pan-ErbB inhibition protects from SARS-CoV-2 replication, inflammation, and injury -
  Effective therapies are needed to combat emerging viruses. Seventeen candidates that rescue cells from SARS-CoV-2-induced lethality and target diverse functions emerged in a screen of 4,413 compounds. Among the hits was lapatinib, an approved inhibitor of the ErbB family of receptor tyrosine kinases. Lapatinib and other pan-ErbB inhibitors suppress replication of SARS-CoV-2 and unrelated viruses with a high barrier to resistance. ErbB4, but not lapatinib’s cancer targets ErbB1 and ErbB2, is required for SARS-CoV-2 entry and Venezuelan equine encephalitis virus infection and is a molecular target mediating lapatinib’s antiviral effect. In human lung organoids, lapatinib protects from SARS-CoV-2-induced activation of pathways implicated in acute and chronic lung injury downstream of ErbBs (p38-MAPK, MEK/ERK, and AKT/mTOR), pro-inflammatory cytokine production, and epithelial barrier injury. These findings reveal regulation of viral infection, inflammation, and tissue injury via ErbBs and propose approved candidates to counteract these effects with implications for coronaviruses and unrelated viruses.
  🖺 Full Text HTML: Pan-ErbB inhibition protects from SARS-CoV-2 replication, inflammation, and injury
• Stabilization of the SARS-CoV-2 Spike receptor-binding domain using deep mutational scanning and structure-based design -
  The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40{degrees}C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.
  🖺 Full Text HTML: Stabilization of the SARS-CoV-2 Spike receptor-binding domain using deep mutational scanning and structure-based design
• Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome -
  The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is a major health burden. Volatile garlic organosulfur compounds, such as the thiol-reactive allicin (diallyl thiosulfinate) exert strong antimicrobial activity against various respiratory pathogens. Here, we investigated the antiviral activity of allicin against SARS-CoV-2 in infected Vero E6 and Calu-3 lung cells. Allicin efficiently inhibited viral replication and infectivity in both cell lines. Proteome analyses of infected Calu-3 cells revealed a strong induction of the antiviral interferon-stimulated gene (ISG) signature (e.g. cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, OAS and ISG15), pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTC1, ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin abrogated the ISG host response and reverted the host cellular pathways to levels of uninfected Calu-3 cells, confirming the antiviral and immunomodulatory activity of allicin in the host proteome. Thus, biocompatible doses of garlic could be promising for protection of lung cells against SARS-CoV-2.
  🖺 Full Text HTML: Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome
• Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition -
  The emergence of novel SARS-CoV-2 lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of COVID-19. Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the LIBRA-seq technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 showed potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryo-EM structure of 54042-4 in complex with the SARS-CoV-2 spike revealed an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses unique genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings motivate 54042-4 as a lead candidate for clinical development to counteract current and future SARS-CoV-2 VOCs.
  🖺 Full Text HTML: Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition
• The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies. -
  Highly transmissible SARS-CoV-2 variants recently identified in India designated B.1.617 and B.1.618 have mutations within the spike protein that may contribute to their increased transmissibility and that could potentially result in re-infection or resistance to vaccine-elicited antibody. B.1.617 encodes a spike protein with mutations L452R, E484Q, D614G and P681R while the B.1.618 spike has mutations {Delta}145-146, E484K and D614G. We generated lentiviruses pseudotyped by the variant proteins and determined their resistance to neutralization by convalescent sera, vaccine-elicited antibodies and therapeutic monoclonal antibodies. Viruses with B.1.617 and B.1.618 spike were neutralized with a 2-5-fold decrease in titer by convalescent sera and vaccine-elicited antibodies. The E484Q and E484K versions were neutralized with a 2-4-fold decrease in titer. Virus with the B.1.617 spike protein was neutralized with a 4.7-fold decrease in titer by the Regeneron monoclonal antibody cocktail as a result of the L452R mutation. The modest neutralization resistance of the variant spike proteins to vaccine elicited antibody suggests that current vaccines will remain protective against the B.1.617 and B.1.618 variants.
  🖺 Full Text HTML: The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies.
• CovidExpress: an interactive portal for intuitive investigation on SARS-CoV-2 related transcriptomes -
  Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans could cause coronavirus disease 2019 (COVID-19). Since its first discovery in Dec 2019, SARS-CoV-2 has become a global pandemic and caused 3.3 million direct/indirect deaths (2021 May). Amongst the scientific community’s response to COVID-19, data sharing has emerged as an essential aspect of the combat against SARS-CoV-2. Despite the ever-growing studies about SARS-CoV-2 and COVID-19, to date, only a few databases were curated to enable access to gene expression data. Furthermore, these databases curated only a small set of data and do not provide easy access for investigators without computational skills to perform analyses. To fill this gap and advance open-access to the growing gene expression data on this deadly virus, we collected about 1,500 bulk RNA-seq datasets from publicly available resources, developed a database and visualization tool, named CovidExpress (https://stjudecab.github.io/covidexpress). This open access database will allow research investigators to examine the gene expression in various tissues, cell lines, and their response to SARS-CoV-2 under different experimental conditions, accelerating the understanding of the etiology of this disease in order to inform the drug and vaccine development. Our integrative analysis of this big dataset highlights a set of commonly regulated genes in SARS-CoV-2 infected lung and nasal tissues, including OASL that were under-studied in COVID-19 related reports. Our results also suggested a potential FURIN positive feedback loop that might explain the evolutional advantage of SARS-CoV-2.
  🖺 Full Text HTML: CovidExpress: an interactive portal for intuitive investigation on SARS-CoV-2 related transcriptomes
• Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants -
  SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations.
  🖺 Full Text HTML: Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants
• The first patient with COVID-19: Notes from the Trenches -
  COVID-19 is a rapidly evolving situation and presently India has amongst the highest numbers of patients in the world. However, in the initial parts of the pandemic, the reaction of patients and clinicians to COVID-19 was one that was informed by being faced with a totally novel situation. This paper describes the personal experience of the first patient with COVID-19 admitted to a tertiary hospital in North India and the treating doctors. Implications of the experiences are discussed.
  🖺 Full Text HTML: The first patient with COVID-19: Notes from the Trenches
• Relative burdens of the COVID-19, malaria, tuberculosis and HIV/AIDS epidemics in sub-Saharan Africa -

  Objectives: COVID-19 has had considerable global impact, but in sub-Saharan Africa is one of several infectious disease priorities. Prioritization is normally guided by disease burden, but the highly age-dependent nature of COVID-19 and other infectious diseases makes comparisons challenging unless considered through metrics that incorporate life years lost and time lived in adverse health. We compared the burdens of COVID-19 and three major epidemic-causing pathogens; malaria, tuberculosis and HIV/AIDS. Design: We compared estimates of 12-month disease burdens in sub-Saharan African populations through mortality and Disability-Adjusted Life Years lost (DALYs) for COVID-19, malaria, tuberculosis and HIV/AIDS, applying known age-related mortality to UN estimates of age structure. We further compared exacerbations disease burden predicted from the COVID-19 public health response. Data was derived from public sources, predicted exacerbations from those published by international agencies. Main outcome measures: Mortality and DALYs lost Results: For sub-Saharan African populations north of South Africa, recorded COVID-19 DALYs lost in 2020 was 3.7%, 2.3% and 2.4% of those estimated for tuberculosis, HIV/AIDS and malaria respectively. The predicted exacerbations alone of these comparator diseases were greater than the estimated COVID-19 burden. Including South Africa and Lesotho, COVID-19 DALYs lost were <12% of those for comparator diseases and dominated by them in all age groups below 65 years. Conclusions: The analysis suggests a relatively low impact from COVID-19. While all four epidemics continue, concentration on COVID-19 runs a high risk of increasing the overall health burden, further increasing global inequities in health and life expectancy.

  🖺 Full Text HTML: Relative burdens of the COVID-19, malaria, tuberculosis and HIV/AIDS epidemics in sub-Saharan Africa
• Global seroprevalence of SARS-CoV-2 antibodies: a systematic review and meta-analysis -

  Background Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. Methods In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. Results We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6 % in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. Discussion Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

  🖺 Full Text HTML: Global seroprevalence of SARS-CoV-2 antibodies: a systematic review and meta-analysis
• Toxoplasmosis: An important risk factor for acquiring SARS-CoV-2 infection and a severe course of Covid-19 disease -

  Background Latent toxoplasmosis, i.e. a lifelong infection with the protozoan parasite Toxoplasma gondii, affects about a third of human population worldwide. In the past ten years, numerous studies had shown that infected subjects have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases. Methods A cross-sectional internet study was performed on a population of 4,499 Toxoplasma-free and 786 Toxoplasma-infected subjects and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of Covid-19. Findings Logistic regression and partial Kendall correlation controlled for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1.50) before sport (OR = 1.30), and borreliosis (1.27). It also had the strongest effect on the risk of severe course of infection (Tau = 0.146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat keeping (in the form of higher likelihood of Covid infection and higher severity of the course of infection), which was observed especially in a subset of Toxoplasma-infected subjects (Tau = 0.153). Effects of keeping a cat were detected only in subjects from multi-member families, suggesting that a cat could a vector for the transmission of SARS-CoV-2 within a family. Interpretations Toxoplasmosis is currently not considered a risk factor for Covid-19 and Toxoplasma-infected subjects are neither informed about their higher risks nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on Covid-19-associated effects on public health could be considerable.

  🖺 Full Text HTML: Toxoplasmosis: An important risk factor for acquiring SARS-CoV-2 infection and a severe course of Covid-19 disease
• Missing data matters in participatory syndromic surveillance systems: comparative evaluation of missing data methods when estimating disease burden -

  Introduction Traditional surveillance methods have been enhanced by the emergence of online participatory syndromic surveillance systems that collect health-related digital data. These systems have many applications including tracking weekly prevalence of Influenza-Like Illness (ILI), predicting probable infection of Coronavirus 2019 (COVID-19), and determining risk factors of ILI and COVID-19. However, not every volunteer consistently completes surveys. In this study, we assess how different missing data methods affect estimates of ILI burden using data from FluTracking, a participatory surveillance system in Australia. Methods We estimate the incidence rate, the incidence proportion, and weekly prevalence using five missing data methods: available case, complete case, assume missing is non-ILI, multiple imputation (MI), and delta (δ) MI, which is a flexible and transparent method to impute missing data under Missing Not at Random (MNAR) assumptions. We evaluate these methods using simulated and FluTracking data. Results Our simulations show that the optimal missing data method depends on the measure of ILI burden and the underlying missingness model. Of note, the δ-MI method provides estimates of ILI burden that are similar to the true parameter under MNAR models. When we apply these methods to FluTracking, we find that the δ-MI method accurately predicted complete, end of season weekly prevalence estimates from real-time data. Conclusion Missing data is an important problem in participatory surveillance systems. Here, we show that accounting for missingness using statistical approaches leads to different inferences from the data.

  🖺 Full Text HTML: Missing data matters in participatory syndromic surveillance systems: comparative evaluation of missing data methods when estimating disease burden

From Clinical Trials

• A Phase 3 Randomized, Double-Blind Placebo Controlled, Multi-regional Trial to Evaluate the Efficacy and Safety of GT0918 for the Treatment of Mild to Moderate COVID-19 Male Patients - Condition:   COVID-19
  Intervention:   Drug: GT0918 tablets or placebo
  Sponsor:   Suzhou Kintor Pharmaceutical Inc,
  Not yet recruiting

• Recombinant Hyperimmune Polyclonal Antibody (GIGA-2050) in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: GIGA-2050
  Sponsor:   GigaGen, Inc.
  Not yet recruiting

• The Role of High Dose Co-trimoxazole in Severe Covid-19 Patients - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Co-trimoxazole;   Drug: Placebo
  Sponsor:   Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  Not yet recruiting

• The Effect of Vitamin D Supplementation on COVID-19 Recovery - Condition:   Covid19
  Interventions:   Drug: Vit-D 0.2 MG/ML Oral Solution [Calcidol];   Drug: Physiological Irrigating Solution
  Sponsors:   University of Monastir;   Loussaief Chawki;   Nissaf Ben Alaya;   Cyrine Ben Nasrallah;   Manel Ben Belgacem;   Hela Abroug;   Imen Zemni;   Manel Ben fredj;   Wafa Dhouib
  Completed

• A Clinical Trial to Evaluate the Recombinant SARS-CoV-2 Vaccine (CHO Cell) for COVID-19 - Condition:   COVID-19
  Interventions:   Biological: low-dose Recombinant SARS-CoV-2 Vaccine (CHO cell);   Biological: high-dose Recombinant SARS-CoV-2 Vaccine (CHO cell);   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd.;   Zhengzhou University
  Recruiting

• A Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects With Severe Corona Virus Disease 2019（COVID-19）Pneumonia - Condition:   Severe COVID-19 Pneumonia
  Intervention:   Drug: STC3141
  Sponsors:   Grand Medical Pty Ltd.;   Trium Clinical Consulting
  Not yet recruiting

• tDCS for Post COVID-19 Fatigue - Condition:   Post Covid-19 Patients
  Intervention:   Device: Transcranial Direct Current Stimulation
  Sponsor:   Thorsten Rudroff
  Recruiting

• A Phase 2 Study of APX-115 in Hospitalized Patients With Confirmed Mild to Moderate COVID-19. - Condition:   COVID-19
  Interventions:   Drug: APX-115;   Drug: Placebo
  Sponsors:   Aptabio Therapeutics, Inc.;   Covance
  Not yet recruiting

• Leveraging CHWs to Improve COVID-19 Testing and Mitigation Among CJIs Accessing a Corrections-focused CBO - Condition:   Covid19
  Intervention:   Behavioral: Onsite Point-of-care
  Sponsors:   Montefiore Medical Center;   The Fortune Society;   University of Bristol
  Not yet recruiting

• Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus - Condition:   COVID-19 Pneumonia
  Intervention:   Device: Esophageal catheter
  Sponsor:   San Luigi Gonzaga Hospital
  Recruiting

• Convalescent Plasma as Adjunct Therapy for COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Convalescent plasma treatment
  Sponsors:   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   Indonesian Red Cross;   Eijkman Institute for Molecular Biology
  Recruiting

• Selenium as a Potential Treatment for Moderately-ill, Severely-ill, and Critically-ill COVID-19 Patients. - Condition:   Covid19
  Interventions:   Drug: Selenium (as Selenious Acid);   Other: Placebo
  Sponsors:   CHRISTUS Health;   Pharco Pharmaceuticals
  Not yet recruiting

• Safety, Tolerability and PK of Ensovibep (MP0420 - a New Candidate With Potential for Treatment of COVID-19) - Condition:   COVID-19
  Interventions:   Drug: Ensovibep;   Drug: Placebo
  Sponsor:   Molecular Partners AG
  Recruiting

• A Global Phase III Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Other: Placebo control
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   WestVac Biopharma Co., Ltd.;   West China Hospital
  Not yet recruiting

• #SafeHandsSafeHearts: An eHealth Intervention for COVID-19 Prevention and Support - Condition:   Covid19
  Intervention:   Behavioral: eHealth for Covid-19 prevention and support
  Sponsor:   University of Toronto
  Recruiting

From PubMed

• A SCID mouse-human lung xenograft model of SARS-CoV-2 infection - SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or…

• Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm - Cytokine storm (CS), an excessive release of proinflammatory cytokines upon overactivation of the innate immune system, came recently to the focus of interest because of its role in the life-threatening consequences of certain immune therapies and viral diseases, including CAR-T cell therapy and Covid-19. Because complement activation with subsequent anaphylatoxin release is in the core of innate immune stimulation, studying the relationship between complement activation and cytokine release in…

• Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration - The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how…

• Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro - Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we…

• Psychological Predictors of Precautionary Behaviors in Response to COVID-19: A Structural Model - The first lines of defense during an epidemic are behavioral interventions, including stay-at-home measures or precautionary health training, aimed at reducing contact and disease transmission. Examining the psychosocial variables that may lead to greater adoption of such precautionary behaviors is critical. The present study examines predictors of precautionary practices against coronavirus disease 2019 (COVID-19) in 709 Mexican participants from 24 states. The study was conducted via online…

• Profiling Ribonucleotide and Deoxyribonucleotide Pools Perturbed by Remdesivir in Human Bronchial Epithelial Cells - Remdesivir (RDV) has generated much anticipation for its moderate effect in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the unsatisfactory survival rates of hospitalized patients limit its application to the treatment of coronavirus disease 2019 (COVID-19). Therefore, improvement of antiviral efficacy of RDV is urgently needed. As a typical nucleotide analog, the activation of RDV to bioactive triphosphate will affect the biosynthesis of endogenous…

• An insight into the inhibitory mechanism of phytochemicals and FDA-approved drugs on the ACE2-Spike complex of SARS-CoV-2 using computational methods - The S-glycoprotein (Spike) of the SARS-CoV-2 forms a complex with the human transmembrane protein angiotensin-converting enzyme 2 (ACE2) during infection. It forms the first line of contact with the human cell. The FDA-approved drugs and phytochemicals from Indian medicinal plants were explored. Molecular docking and simulations of these molecules targeting the ACE2-Spike complex were performed. Rutin DAB10 and Swertiapuniside were obtained as the top-scored drugs as per the docking protocol….

• Inhibition of SARS-CoV-2 reproduction using Boswellia carterii: A theoretical study - This study investigated the possibility of inhibition of the SARS-CoV-2 virus using the compounds alpha-Boswellic acid (ABA) and beta-Boswellic acid (BBA) which are active components in the well-known natural product Boswellia carterii (BC). The SARS-CoV-2 virus reproduces in the body by linking its spike with the cell receptor. At the same time, a pH range (4.5-6) of the cell’s lysosomes is considered as a perfect environment to release RNA in the cell cytoplasm. In view of these, docking…

• Protein kinase CK2: a potential therapeutic target for diverse human diseases - CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic,…

• In vitro activity of human recombinant alpha-2b interferon against SARS-CoV-2 virus - CONCLUSION: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

• Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS CoV2 infection and long COVID - COVID-19 can present with lymphopenia and extraordinary complex multi-organ pathologies that can trigger long-term sequela. Given that inflammasome products, like caspase-1,play a role inthe pathophysiology of a number of co-morbid conditions,we investigated caspases across the spectrum of COVID-19 disease.We assessed transcriptional states of multiple caspases and using flow cytometry, theexpression ofactive caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of…

• Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice - BACKGROUND: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein .

• PdCl(2)-catalyzed synthesis of a new class of isocoumarin derivatives containing aminosulfonyl / aminocarboxamide moiety: First identification of a isocoumarin based PDE4 inhibitor - While anti-inflammatory properties of isocoumarins are known their PDE4 inhibitory potential was not explored previously. In our effort the non-PDE4 inhibitor isocoumarins were transformed into the promising inhibitors via introducing an aminosulfonyl/aminocarboxamide moiety to the C-3 benzene ring attached to the isocoumarin framework. This new class of isocoumarins were synthesized via a PdCl(2)-catalyzed construction of the 4-allyl substituted 3-aryl isocoumarin ring starting from the…

• A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19 - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three…

• Structural Basis for the Understanding of Entry Inhibitors Against SARS Viruses - Outbreaks due to Severe Acute Respiratory Syndrome-Corona virus 2 (SARS-CoV-2) initiated in Wuhan city, China, in December 2019 which continued to spread internationally, posing a pandemic threat as declared by WHO and as of March 10, 2021, confirmed cases reached 118 million along with 2.6 million deaths worldwide. In the absence of specific antiviral medication, symptomatic treatment and physical isolation remain the options to control the contagion. The recent clinical trials on antiviral…

From Patent Search

• IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link

• A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link

• UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19 - - link

• USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link

• 逆转录酶突变体及其应用 - 本发明提供一种MMLV逆转录酶突变体，在野生型MMLV逆转录酶氨基酸序列（如SEQ ID No.1序列所示）中进行七个氨基酸位点的突变，氨基酸突变位点为：R205H；V288T；L304K；G525D；S526D；E531G；E574G。该突变体可以降低MMLV逆转录酶对Taq DNA聚合酶的抑制作用，大大提高了一步法RT‑qPCR的灵敏度。 - link

• Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link

• 用于检测新型冠状病毒的试纸和试剂盒 - 本发明涉及生物技术和免疫检测技术领域，具体涉及一种用于检测新型冠状病毒的试纸和试剂盒。所述试纸或试剂盒含有抗体1和/或抗体2，所述抗体1的重、轻链可变区的氨基酸序列分别如SEQ ID NO:1‑2所示，所述抗体2的重、轻链可变区的氨基酸序列分别如SEQ ID NO:3‑4所示。本发明对于大批量的新型冠状病毒样本，包括新型冠状病毒突变（英国、南非）与非突变株的人血清、鼻咽拭子等样本的检测有普遍检测意义，避免突变株的漏检。 - link

• Fahrgastleitsystem und Verfahren zum Leiten von Fahrgästen -

  Die Erfindung betrifft ein Fahrgastleitsystem zum Leiten von mit einem Fahrzeug (1) mit wenigstens zwei Türen (2.L, 2.R) transportieren Fahrgästen (3), mit wenigstens einem Sensor (4) zur Überwachung der Fahrgäste (3), wenigstens einem Anzeigemittel (5) zur Ausgabe von Leitinformationen, wenigstens einem Aktor zum Öffnen oder Verriegeln einer Tür (2.L, 2.R) und wenigstens einer Recheneinheit (7). Das erfindungsgemäße Fahrgastleitsystem ist dadurch gekennzeichnet, dass die Recheneinheit (7) dazu eingerichtet ist durch Auswertung vom wenigstens einen Sensor (4) erzeugter Sensordaten zu erkennen an welcher Tür (2.L, 2.R) des Fahrzeugs (1) Fahrgäste (3) ein- und/oder aussteigen möchten und wenigstens eine Tür (2.L, 2.R) für einen Ausstieg festzulegen und/oder wenigstens eine Tür (2.L, 2.R) für einen Einstieg festzulegen, sodass eine Anzahl an Begegnungen von sich durch das Fahrzeug (1) bewegender Fahrgäste (3) und/oder aus dem Fahrzeug (1) aussteigenden und/oder in das Fahrzeug (1) einsteigenden Fahrgästen (3) minimiert wird.

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• Vorrichtung zum Desinfizieren, der Körperpflege oder dergleichen -

  Vorrichtung zum Desinfizieren, der Körperpflege oder dergleichen mittels einer flüssigen oder cremigen Substanz (20), dadurch gekennzeichnet, dass die Vorrichtung mit einem elektrisch betriebenen Erinnerungs-Modul und einem Vorratsbehälter (10) für die Substanz (20) versehen ist, die Substanz (20) in dosierter Menge zur Ausgabeöffnung (9) gefördert wird und die Vorrichtung dazu geeignet ist, am Körper oder der Kleidung einer Person getragen zu werden.

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• Gebrauchter Schnellteststreifen als Probenmaterial für eine Nachtestung -

  Die Erfindung betrifft ein Verfahren zur laborbasierten Überprüfung und/oder weiteren Ausdifferenzierung einer im Schnelltestverfahren erhaltenen Diagnose einer Infektionskrankheit, wobei im Rahmen des Schnelltestverfahrens eine flüssige Patientenprobe auf ein Objekt aus einem porösen Material aufgetragen wird und wobei dieses Objekt nach Trocknung der flüssigen Patientenprobe an das diagnostische Labor übermittelt wird. Im Labor werden dann die eingetrockneten Probenreste aus dem porösen Material ausgelöst und analysiert.

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