Covid-19 Sentry

Contents

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

From Preprints

• Angiotensin Receptor Blockers Might be Preferred Over Angiotensin Converting Enzyme Inhibitors in COVID-19 Management -
  A meta-analysis published at BJCP has suggested that angiotensin converting enzyme inhibitors might possess more benefit over angiotensin receptor blockers regarding the likelihood of COVID-19 infection and non-COVID pneumonia induced mortality. We present a clinical and pharmacological COVID-19 contradictory point of view, and we also recommend extreme caution when similar clinical recommendations are considered.
  🖺 Full Text HTML: Angiotensin Receptor Blockers Might be Preferred Over Angiotensin Converting Enzyme Inhibitors in COVID-19 Management
• Cellular and Antibody Immunity after COVID-19 Vaccination at >4-Month Follow Up in Immunocompetent and Immunocompromised Subjects -

  We evaluated post-vaccination immunity after COVID-19 vaccination with serial changes in cellular and antibody responses to the spike protein S, its S2 component which is conserved between SARS-CoV-2 and human coronaviruses, and the S1 component, which is specific to SARS-CoV-2 and also contains its receptor binding domain (RBD). In 21 healthy immunocompetent subjects all of whom demonstrated circulating IgG antibodies 4 months after mRNA1273 or BNT162b vaccination, a) the strength of S-IgG was stable while RBD-IgG declined, b) S2-reactive B-cell frequencies increased progressively (p=0.002) c) S1-reactive CD8+T-cells and CD19+B-cells were undetectable after a transient increase, and d) monocytic and polymorphonuclear myeloid-derived suppressor cells (M-MDSC, PMN-MDSC) increased after the first vaccine dose. Compared with 4-month measurements from immunocompetent subjects, single samples from 20 vaccinated immunocompromised (IC) subjects revealed a) circulating S-IgG and RBD-IgG in 13 (65%) and 9 (45%) subjects, respectively, b) no differences in S2-reactive T- and B-cells, c) undetectable S1-reactive T- and B-cells, and d) fewer S-reactive CD8+T-cells and CD19+B-cells (p<0.05). Among 11 IC recipients who failed to make RBD-IgG, frequencies of PMN-MDSC were significantly higher (p<0.0004) compared with IC or immunocompetent subjects with RBD- IgG. COVID-19 vaccination induces stable antibodies to the spike protein and expands circulating B-cells reactive to the conserved spike protein sequence in immunocompetent subjects. MDSC which are known to suppress T- and B-cells, and which increase after vaccination, may limit post-vaccination responses especially among immunocompromised subjects. Antibody and cellular responses to SARS-CoV-2-specific spike antigenic sequences appear to be less durable.

• DECREASED BREADTH OF THE ANTIBODY RESPONSE TO THE SPIKE PROTEIN OF SARS-CoV-2 AFTER REPEATED VACCINATION -

  The rapid development of vaccines to prevent infection by SARS-CoV-2 virus causing COVID-19 makes necessary to compare the capacity of the different vaccines in terms of development of a protective humoral response. Here, we have used a highly sensitive and reliable flow cytometry method to measure the titers of antibodies of the IgG1 isotype in blood of healthy volunteers after receiving one or two doses of the vaccines being administered in Spain. We took advantage of the multiplexed capacity of the method to measure simultaneously the reactivity of antibodies with the S protein of the original strain Wuhan and the variants B.1.1.7 (Alpha), B.1.617.2 (Delta) and B.1.617.1 (Kappa). We found significant differences in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech and Ad26.COV.S/Janssen. Most important, we found a relative reduction in the reactivity of the sera with the Alpha, Delta and Kappa variants, versus the Wuhan one, after the second boosting immunization. These data allow to make a comparison of different vaccines in terms of anti-S antibody generation and cast doubts about the convenience of repeatedly immunizing with the same S protein sequence.

  🖺 Full Text HTML: DECREASED BREADTH OF THE ANTIBODY RESPONSE TO THE SPIKE PROTEIN OF SARS-CoV-2 AFTER REPEATED VACCINATION
• ‘When will this end? Will it end?’ The impact of the March-June 2020 UK Covid-19 lockdown response on mental health: a longitudinal survey of mothers in the Born in Bradford study. -

  Objectives To explore clinically important increases in depression/anxiety from before to during the first UK Covid-19 lockdown and factors related to this change, with a particular focus on ethnic differences. Design Pre-Covid-19 and lockdown surveys nested within two longitudinal Born in Bradford cohort studies. Participants 1,860 mothers with a child aged 0-5 or 9-13, 48% Pakistani heritage Main outcome measures Odds ratios (OR) for a clinically important increase (5 points or more) in depression (PHQ-8) and anxiety (GAD-7) in unadjusted regression analyses, repeated with exposures of interest separated by ethnicity to look for differences in magnitude of associations, and lived experience of mothers captured in open text questions. Results The number of women reporting clinically important depression/anxiety increased from 11% to 20% [10-13%;18-22%] and 10% to 16% [8-11%; 15-18%]) respectively. Increases in depression/anxiety were associated with: loneliness (OR: 8.37, [5.70-12.27]; 8.50, [5.71-12.65] respectively); financial (6.23, [3.96-9.80]; 6.03, [3.82-9.51]); food (3.33 [2.09-5.28]; 3.46 [2.15-5.58]); and housing insecurity (3.29 [2.36-4.58]; 3.0 [2.11-4.25]); a lack of physical activity (3.13 [2.15-4.56]; 2.55 [1.72-3.78]); and a poor partner relationship (3.6 [2.44-5.43]; 5.1 [3.37-7.62]. The magnitude of associations between key exposures and worsening mental health varied between ethnic groups. Responses to open text questions illustrated a complex inter-play of challenges contributing to mental ill health including: acute health anxieties; the mental load of managing multiple responsibilities; loss of social support and coping strategies; pressures of financial and employment insecurity; and being unable to switch off from the pandemic. Conclusions Mental ill health has worsened for many during the Covid-19 lockdown, particularly in those who are lonely and economically insecure. The magnitude of associations between key exposures and worsening mental health varied between ethnic groups. Mental health problems may have longer term consequences for public health and interventions that address the potential causes are needed.

  🖺 Full Text HTML: ‘When will this end? Will it end?’ The impact of the March-June 2020 UK Covid-19 lockdown response on mental health: a longitudinal survey of mothers in the Born in Bradford study.
• Quantifying meaningful usage of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona -

  Objective. To measure meaningful, local exposure notification usage without in-app analytics. Methods. We surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases. Results. Forty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of “push” notifications, in the context of a marketing campaign that leveraged social influencers. Conclusions. Usage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.

  🖺 Full Text HTML: Quantifying meaningful usage of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona
• Context Culture in CDC’s Health Alert: For All Travelers -
  The high number of covid-19 cases and the US’s mortality rate encourage The Centers for Disease Control and Prevention (CDC) to socialize and promote prevention guidance to stop the spreading. One of the preventive measures is by issuing travel warnings. Scholars have noted that the linguistic and cultural concept conveys norms of behavior and values in society at a particular stage of its development. In brief, advertisements messages are influenced by communicators’ cultural backgrounds and references. It means the signs in the CDC poster can show American values. To examine and explore those cultural values in CDC publication materials, the authors conducted a semiotic analysis on a poster entitled Health Alert: For All Travelers. The method used is Ferdinand de Saussure’s semiotic model. The study shows that the signs presented on the CDC poster are simple, use direct communication structures, and are equipped with universal meaning to understand the message conveyed easily. It indicates a representation of the dominant culture in the United States, the low-context culture with a high level of individualism values. Multidisciplinary research is needed to help create a universal communication model so that messages conveyed in advertisements can reach a wider audience.
  🖺 Full Text HTML: Context Culture in CDC’s Health Alert: For All Travelers
• Equal Opportunities in Learning in Diverse Groups in Nepal in the Pre-COVID Realm: Socioeconomic Status, Mathematics Learning, and the Diverse Groups -
  The article discusses the diversity and equity issues behind the learning outcomes of mathematics in the pre-COVID context in Nepal. The article intends to give a baseline for the further studies on the effect of COVID-19 pandemic in the educational realm. Datasets from the national assessment of student achievement in Nepal at grades 3 and 5 and grade 8 are reanalyzed based on socioeconomic status (SES), gender, caste-ethnicity, language, and geographical variables. In Nepal, where the society is customarily highly structured, gender-biased, and poverty-driven, SES influences remarkably in mathematics achievement. The datasets show notable relationships between SES and mathematics achievement (r = 0.35, 0.27 and 0.30 in grade 3, 5 and 8, respectively). In lower grades, the difference between the highest and lowest SES in the achievement of girls is wider than boys and it is reverse in grade 8. Nepali speakers had high scores when they had high SES but, when SES was very low, the non-Nepali speakers performed better in all grades. The advantageous castes tended to always perform higher irrespective of their level of SES. Nevertheless, it is difficult to know with certainty when average and marginalized caste/ethnic groups perform better.
  🖺 Full Text HTML: Equal Opportunities in Learning in Diverse Groups in Nepal in the Pre-COVID Realm: Socioeconomic Status, Mathematics Learning, and the Diverse Groups
• Impact of Macroeconomic Variables, American Stock Market Index and Covid-19 Pandemic on Indonesia Capital Market Development (Time Series Study 1990-2020) -
  The purpose of this study is 1.) To analyze the influence of foreign investment on the development of the Indonesian capital market. 2).To analyze the influence of the Exchange Rate on the Development of the Indonesian Capital Market. 3).To analyze the influence of the Interest Rate on the Development of the Indonesian Capital Market. 4).To analyze the influence of the Dow Jones Stock Market Index on the Development of the Indonesian Capital Market. 5).To analyze the influence of the Covid-19 Pandemic (dummy variable) on the Development of the Indonesian Capital Market.6). In this study, secondary data and library research were used as a technique for collecting data, using semi-annual data for the period 1990-2020. The research was processed using the EViews 11 program with the multiple linear regression method. The results of the research are known if 1.) Foreign Direct Investment has a significant and positive effect on Capital Market Development. 2.) Exchange Rates have a significant and positive influence on the Development of the Indonesian Capital Market. 3.) Interest Rates have a significant and negative effect on the Development of the Indonesian Capital Market. 4.) The Dow Jones Stock Market Index has a significant and positive effect on the Development of the Indonesian Capital Market. 5.) The Covid-19 pandemic had a significant and negative effect on the Development of the Indonesian Capital Market in the period 1990 to 2020. The results of this study are expected to contribute to policy holders regarding the role of macroeconomic variables on the development of the capital market, so that in the future it can be one of the references in conducting the policy mix so as to improve the development of the Indonesian capital market.
  🖺 Full Text HTML: Impact of Macroeconomic Variables, American Stock Market Index and Covid-19 Pandemic on Indonesia Capital Market Development (Time Series Study 1990-2020)
• 2-Deoxy-D-Glucose as an Adjunct to Standard of Care in the Medical Management of COVID-19: A Proof-of-Concept & Dose-Ranging Randomised Clinical Trial -

  ABSTRACT Objective: To evaluate the efficacy and safety of 2-deoxy-D-glucose (2-DG) in the treatment of COVID-19. Participants: 110 adults aged 18 to 65 years with moderate to severe COVID-19. Interventions: 63, 90, and 126 mg/kg/day 2-DG plus standard of care (SOC) versus SOC only. Main Outcome Measures: Times to maintaining SpO2 ≥94% on room air discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO 10-point ordinal scale, negative conversion on RT-PCR, intensive care, and mortality. Results: Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs 5 days, Hazard ratio [95% confidence interval]=2.3 [1.14, 4.64], p=0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalisation were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild. Conclusion: 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefits over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase-II study encourage confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase-III trial.

  🖺 Full Text HTML: 2-Deoxy-D-Glucose as an Adjunct to Standard of Care in the Medical Management of COVID-19: A Proof-of- Concept &amp; Dose-Ranging Randomised Clinical Trial
• Clinical Benefits and Budget Impact of Lenzilumab plus Standard of Care Compared with Standard of Care Alone for the Treatment of Hospitalized Patients with COVID-19 in the United States from the Hospital Perspective -

  Aims: The study estimated the clinical benefits and budget impact of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of hospitalized COVID-19 patients from the United States hospital perspective. Materials and Methods: An economic model was developed to estimate the clinical benefits and costs for an average newly hospitalized COVID-19 patient, with a 28-day time horizon for the index hospitalization. Clinical outcomes from the LIVE-AIR trial included failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included drug acquisition and administration for lenzilumab and hospital resource costs based on the level of care required. The inclusion of 1-year rehospitalization costs was examined in a scenario analysis. Results: In the base case and all scenarios, treatment with lenzilumab plus SOC improved all specified clinical outcomes over SOC alone. Adding lenzilumab to SOC was also estimated to result in cost savings of $3,190 per patient in a population aged <85 years with CRP <150 mg/L and receiving remdesivir (base case). Per-patient cost savings were also estimated in the following scenarios: 1) aged <85 years with CRP <150 mg/L, with or without remdesivir ($1,858); 2) Black and African American patients with CRP <150 mg/L ($13,154); and 3) Black and African American patients from the full population ($2,763). In the full mITT population, a budget impact of $4,952 was estimated. When adding rehospitalization costs to the index hospitalization, a total per-patient cost savings of $5,154 was estimated. Conclusions: The results highlight the clinical benefits for SWOV, ventilator use, time to recovery, mortality, time in ICU, and time on IMV, in addition to a favorable budget impact from the United States hospital perspective associated with adding lenzilumab to SOC for patients with COVID-19 pneumonia.

  🖺 Full Text HTML: Clinical Benefits and Budget Impact of Lenzilumab plus Standard of Care Compared with Standard of Care Alone for the Treatment of Hospitalized Patients with COVID-19 in the United States from the Hospital Perspective
• SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia -
  In addition to respiratory complications produced by SARS-CoV-2, accumulating evidence suggests that neurological symptoms are associated with the disease caused by the coronavirus. In this study, we investigated the effects of the SARS-CoV-2 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF, IL 6, IL-1{beta} and iNOS/NO. S1 also increased protein levels of phospho-p65 and phospho-I{kappa}B, as well as enhancing DNA binding and transcriptional activity of NF-{kappa}B. These effects of the protein were blocked in the presence of BAY11-7082 (1 M). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/mL), an action that was reduced in the presence of SKF 86002 (1 M). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 M) and transfection with TLR4 siRNA resulted in significant reduction in TNF and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-{kappa}B and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.
  🖺 Full Text HTML: SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia
• Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder -
  Animal models are essential to understand COVID-19 pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. This was confirmed by immunohistochemistry, with cells positive for SARS-CoV-2 nucleoprotein observed in the swim bladder. Several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. Mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.
  🖺 Full Text HTML: Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder
• High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape -
  Understanding the mechanisms of immune evasion is critical for formulating an effective response to global threats like SARS-CoV2. We have fully decoded the immune synapses for multiple TCRs from acute patients, including cognate peptides and the presenting HLA alleles. Furthermore, using a newly developed mammalian epitope display platform (MEDi), we determined that several mutations present in viral isolates currently expanding across the globe, resulted in reduced presentation by multiple HLA class II alleles, while some increased presentation, suggesting immune evasion based on shifting MHC-II peptide presentation landscapes. In support, we found that one of the mutations present in B1.1.7 viral strain could cause escape from CD4 T cell recognition in this way. Given the importance of understanding such mechanisms more broadly, we used MEDi to generate a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of multiple common HLA class II molecules. Unlike other strategies, our approach is sensitive and scalable, providing an unbiased and affordable high-resolution map of peptide presentation capacity for any MHC-II allele. Such information is essential to provide insight into T cell immunity across distinct HLA haplotypes across geographic and ethnic populations. This knowledge is critical for the development of effective T cell therapeutics not just against COVID-19, but any disease.
  🖺 Full Text HTML: High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape
• Higher education responses to COVID-19 in the United States: Evidence for the impacts of university policy -

  With a dataset of testing and case counts from over 1,400 institutions of higher education (IHEs) in the United States, we analyze the number of infections and deaths from SARS-CoV-2 in the counties surrounding these IHEs during the Fall 2020 semester (August to December, 2020). We used a matching procedure designed to create groups of counties that are aligned along age, race, income, population, and urban/rural categories—socio-demographic variables that have been shown to be correlated with COVID-19 outcomes. We find that counties with IHEs that remained primarily online experienced fewer cases and deaths during the Fall 2020 semester; whereas before and after the semester, these two groups had almost identical COVID-19 incidence. Additionally, we see fewer deaths in counties with IHEs that reported conducting any on-campus testing compared to those that reported none. We complement the statistical analysis with a case study of IHEs in Massachusetts—a rich data state in our dataset—which further highlights the importance of IHE- affiliated testing for the broader community. The results in this work suggest that campus testing can itself be thought of as a mitigation policy and that allocating additional resources to IHEs to support efforts to regularly test students and staff would be beneficial to mitigating the spread of COVID-19 in the general population.

  🖺 Full Text HTML: Higher education responses to COVID-19 in the United States: Evidence for the impacts of university policy
• Immunogenicity of the Ad26.CoV2.S vaccine in people living with HIV -

  Background People living with HIV (PLWH) have been reported to have an increased risk of more severe Covid-19 disease outcome and an increased risk of death relative to HIV-uninfected individuals. Here we assessed the ability of the Johnson and Johnson Ad26.CoV2.S vaccine to elicit neutralizing antibodies to the Delta variant in PLWH relative to HIV-uninfected individuals. Methods We enrolled 26 PLWH and 73 HIV-uninfected participants from the SISONKE phase 3b open label South African clinical trial of the Ad26.CoV2.S vaccine in health care workers (HCW) in a prospective observational cohort study. Enrollment was a median 56 days (range 19-98 days) post-vaccination. HCW PLWH had well suppressed HIV viremia. As a comparison, we also enrolled unvaccinated participants previously infected with SARS-CoV-2. This group consisted of 34 PLWH and 28 HIV-uninfected individuals. We used the presence of SARS-CoV-2 nucleocapsid antibodies and any previous record of SARS-CoV-2 infection to differentiate the vaccinated participants into participants who were previously infected with SARS-CoV-2 and those not previously infected. Neutralization capacity was assessed using participant plasma in a live virus neutralization assay of the Delta SARS-CoV-2 variant currently dominating infections in South Africa. This study was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001275/2020). Findings Unvaccinated PLWH showed 6-fold reduced neutralization of the Delta variant relative to HIV-uninfected participants (GMT=105 for HIV-uninfected, 15 for PLWH, p=0.001). The majority (68%) of Ad26.CoV2.S vaccinated HCW were found to be previously infected with SARS- CoV-2. In this group, Delta variant neutralization was 9-fold higher compared to the infected only group (GMT of 306 versus 36) and 26-fold higher relative to the vaccinated only group (GMT=12). There was no significant difference in Delta variant neutralization in vaccinated and previously SARS-CoV-2 infected PLWH relative to vaccinated and previously SARS-CoV-2 infected, HIV-uninfected participants (GMT of 300 for PLWH versus 307 for HIV-uninfected). Vaccinated only participants showed a low neutralization of the Delta variant, with a stronger response in PLWH (GMT=73, for PLWH, 6 for HIV-uninfected, p=0.02). Interpretation While PLWH showed reduced neutralization of the Delta variant following SARS-CoV-2 infection, the neutralization response following Ad26.CoV2.S vaccination was not inferior to HIV-uninfected study participants. Funding South African Medical Research Council, The Bill & Melinda Gates Foundation.

  🖺 Full Text HTML: Immunogenicity of the Ad26.CoV2.S vaccine in people living with HIV

From Clinical Trials

• Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition:   COVID-19
  Interventions:   Other: Lymphatic OMM;   Other: Light Touch
  Sponsor:   Rowan University
  Not yet recruiting

• SARS-CoV-2 Infection in COVID-19 Vaccinated Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 vaccinated people
  Sponsor:   Hospices Civils de Lyon
  Recruiting

• The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsor:   DreamTec Research Limited
  Recruiting

• A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults - Condition:   COVID-19, SARS-CoV-2
  Intervention:   Biological: AZD1222
  Sponsor:  
  AstraZeneca
  Not yet recruiting

• A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Drug: VXA-CoV2-1.1-S;   Other: Placebo Tablets
  Sponsor:   Vaxart
  Recruiting

• Randomized Trial of COVID-19 Booster Vaccinations (Cobovax Study) - Condition:   COVID-19 Vaccination
  Interventions:   Biological: BNT162b2;   Biological: CoronaVac
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• RCT on the Efficacy of Dexamethasone Versus Methyl Prednisolone in Covid-19 Infected Patients With High Oxygen Flow - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Dexamethasone;   Drug: Methylprednisolone
  Sponsor:   Cairo University
  Recruiting

• Prophylaxis of COVID-19 Disease With Ivermectin in COVID-19 Contact Persons [German: Prophylaxe Der COVID-19-Erkrankung Mit Ivermectin Bei COVID-19 Kontaktpersonen] - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsors:  
  Infectopharm Arzneimittel GmbH;   GKM Gesellschaft für Therapieforschung mbH
  Not yet recruiting

• Safety, Tolerability and Efficacy of Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Uproleselan
  Sponsors:  
  Lena Napolitano, MD;   GlycoMimetics Incorporated
  Not yet recruiting

• Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: AD17002;   Biological: Placebo (Formulation buffer)
  Sponsor:   Advagene Biopharma Co. Ltd.
  Not yet recruiting

• “Efesovir” (FS-1) for COVID-19, Phase 2 - Condition:   Covid19
  Intervention:   Drug: Efesovir
  Sponsor:   Scientific Center for Anti-infectious Drugs, Kazakhstan
  Not yet recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08);   Biological: COVID-19 vaccine (Vero cells);   Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine;   Biological: SARS-CoV-2 Inactivated Vaccine
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Not yet recruiting

• Pulmonary Rehabilitation After Pregnancy in COVID-19 Infection: A Case Report - Conditions:   COVID-19 Pneumonia;   Pulmonary Rehabilitation;   Pregnancy
  Intervention:  
  Other: pulmonary rehabilitation
  Sponsor:   Dr. Lutfi Kirdar Kartal Training and Research Hospital
  Not yet recruiting

• Acetylsalicylic Acid in COVID-19 (ASA-SARS) - Conditions:   SARS-CoV2 Infection;   Covid19
  Interventions:   Drug: Low-dose acetylsalicylic acid;   Drug: Placebo
  Sponsors:   Barcelona Institute for Global Health;   Hospital Universitario de Torrejón,Madrid;   Hospital Universitario Infanta Leonor;   Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau;   Hospital del Mar;   Hopsital Central de Maputo, Mozambique
  Not yet recruiting

From PubMed

• Prompt Reduction in CRP, IL-6, IFN-gamma, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19 - Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy…

• Regulatory T cells in COVID-19 - The outbreak of coronavirus disease 2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to the disruption of immune system, exacerbated inflammation, and even multiple organ dysfunction syndrome. Regulatory T cells (Tregs) are an important subpopulation of T cells that exert immunosuppressive effects. Recent studies have demonstrated that the number of Tregs is significantly reduced in COVID-19 patients, and this reduction may…

• Fighting coronaviruses with natural polyphenols - Few licensed drugs and vaccines are available concerning COVID-19, a disease caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Furthermore, numerous recent SARS-COV-2 variants of have arisen globally, demonstrating the need to develop broadly protective interventions for different coronavirus strains. Polyphenols are the largest class of natural bioactive compounds, categorized as flavonoids (catechins, quercetin and kaempferol) and non-flavonoids (gallic acid and…

• Will Auranofin Become a Golden New Treatment Against COVID-19? - Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression via inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that…

• Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease - BACKGROUND: Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture.

• Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico - The ongoing pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV 2) has led to more than 168 million confirmed cases with 3.5 million deaths as at 28th May, 2021 across 218 countries. The virus has a cysteine protease called main protease (Mpro) which is significant to it life cycle, tagged as a suitable target for novel antivirals. In this computer-assisted study, we designed 100 novel molecules through an artificial neural network-driven platform called LigDream…

• Differential roles of interferons in innate responses to mucosal viral infections - Interferons (IFNs) are among the first vertebrate immune pathways activated upon viral infection and are crucial for control of viral replication and dissemination, especially at mucosal surfaces as key locations for host exposure to pathogens. Inhibition of viral establishment and spread at and from these mucosal sites is paramount for preventing severe disease, while concomitantly limiting putative detrimental effects of inflammation. Here, we compare the roles of type I, II, and III IFNs in…

• Screening S protein - ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19 - The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination…

• Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential - The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to…

• A cell-free high throughput assay for assessment of SARS-CoV-2 neutralizing antibodies - Highly accurate serological tests are key to assessing the prevalence of SARS-CoV-2 antibodies and the level of immunity in the population. This is important to predict the current and future status of the pandemic. With the recent emergence of new and more infectious SARS-CoV-2 variants, assays allowing for high throughput analysis of antibodies able to neutralize SARS-CoV-2 become even more important. Here, we report the development and validation of a robust, high throughput method, which…

• A fluorescence-based, gain-of-signal, live cell system to evaluate SARS-CoV-2 main protease inhibition - The likelihood of continued circulation of COVID-19 and its variants, and novel coronaviruses due to future zoonotic transmissions, combined with the current paucity of coronavirus antivirals, emphasize the need for improved screening in developing effective antivirals for the treatment of infection by SARS-CoV-2 (CoV2) and other coronaviruses. Here we report the development of a live-cell based assay for evaluating the intracellular function of the critical, highly- conserved CoV2 target, the…

• The multifaceted biology of PCSK9 - This article reviews the discovery of PCSK9, its structure-function characteristics, and its presently known and proposed novel biological functions. The major critical function of PCSK9 deduced from human and mouse studies, as well as cellular and structural analyses, is its role in increasing the levels of circulating LDL-cholesterol (LDLc), via its ability to enhance the sorting and escort of the cell surface LDL receptor (LDLR) to lysosomes. This implicates the binding of the catalytic…

• Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity - Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to…

• SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray - There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that…

• Early IgG / IgA response in hospitalized COVID-19 patients is associated with a less severe disease - We determined the kinetics of anti-SARS-CoV-2 antibody response in fifteen hospitalized COVID-19 patients. Patients were divided into mild/moderate (mild, n = 1; moderate, n = 4) or severe (n = 10) and virus-specific anti-Nucleocapsid IgM, anti-Spike IgG and anti-Spike IgA were measured in serial serum samples collected 0 to 15 days after hospital admission. Surrogate neutralization assays were performed by testing inhibition of ACE-2 binding to Spike. In 3 patients (2 severe and 1 moderate…

From Patent Search

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• 健康智能检测方法、装置、电子设备及可读存储介质 - 本申请公开了一种健康智能检测方法、装置、电子设备及可读存储介质，其方法包括获取音频信号，并对所述音频信号进行预处理，得到检测信号；将所述检测信号转化为矩阵数字矩阵；将得到的矩阵数字矩阵作为检测样本，输入健康智能检测模型中，以获取检测结果；其中，所述健康智能检测模型是采用迁移学习和卷积神经网络对训练样本进行训练得到的。本申请由于卷积神经网络各组件或部分组件基于迁移学习进行了重新训练，显著提升了对人们健康检测的准确度；且本申请中的健康智能检测模型为分类模型，计算量小，可将其部署于人们的移动终端中，使用方便，极大程度上提升了用户的使用感受。 - link

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• 单克隆抗体32C7及其制备方法和用途 - 本发明公开了单克隆抗体32C7及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体32C7，在体外通过表面等离子共振检测抗体32C7可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体32C7的中和能力，测定了中和抗体32C7对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体32C7抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• 单克隆抗体35B5及其制备方法和用途 - 本发明公开了单克隆抗体35B5及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体35B5，在体外通过表面等离子共振检测抗体35B5可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体35B5的中和能力，测定了中和抗体35B5对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体35B5抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - link

• 一种抗病毒化合物及其制备方法 - 本发明公开了一种抗病毒的化合物及其制备方法。该化合物的结构式如式I所示，式(Ⅰ)中，R1选自：单取代或多取代的H、F、甲基、三氟甲基；R2选自：H、直链或取代烷烃(C1‑C6)；R3选自：单取代或多取代的H、Cl、Br、F。本发明中所述化合物经过实验证实，不仅对于H1N1甲型流感病毒具有较好的抑制作用，并且对于冠状病毒也具有较好的抑制作用，没有观察到对于人正常细胞的毒性，且能够在抗病毒的同时抑制炎症反应的程度。 - link

• 以痘苗病毒为载体的新冠疫苗 - 本申请涉及一种基于经过基因工程改造的痘苗病毒为载体的新型冠状病毒南非突变株疫苗。所述疫苗以A46R缺陷的痘苗病毒为载体携带新冠病毒南非突变株S基因核酸序列，所述痘苗病毒载体还可以携带IL‑21，该疫苗在免疫小鼠后可以产生针对新冠病毒南非突变株的抗体。 - link

• 氧化钛负载银单原子的材料在病毒消杀中的应用 - 本发明属于生物医药领域，尤其涉及一种负载银单原子的材料在病毒消杀中的应用，所述氧化钛负载银单原子材料具有以下的结构：银单原子以单分散的形式，稳定地锚定于氧化钛的表面和/或骨架中，键合方式为Ti‑O‑Ag；银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙范围为2.9‑3.2

eV；氧化钛负载银单原子材料具有较银纳米颗粒更加优异的催化活性，具有过氧化物酶活性，利用羟基自由基可高效破坏核酸和蛋白质的原理来实现广谱消杀病毒，银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙变小，对可见光的敏感性更强，可将光照射下的光催化诱导光动力杀伤病毒。 - link