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    ACE2

    This report considers only clinical trials that are associated with COVID-19 vaccines.

    Developed by Shray Alag, The Harker School
    Sections: Correlations, Clinical Trials, and HPO

    Correlations computed by analyzing all clinical trials.

    Navigate: Clinical Trials and HPO


    Correlated Drug Terms (5)


    Name (Synonyms) Correlation
    drug177 Aerosolized 13 cis retinoic acid Wiki 1.00
    drug180 Aerosolized All trans retinoic acid Wiki 1.00
    drug1592 INO-4800 Wiki 0.58
    Name (Synonyms) Correlation
    drug557 CELLECTRA® 2000 Wiki 0.50
    drug2490 Placebo Wiki 0.13

    Correlated MeSH Terms (2)


    Name (Synonyms) Correlation
    D045169 Severe Acute Respiratory Syndrome NIH 0.20
    D018352 Coronavirus Infections NIH 0.16

    Correlated HPO Terms (0)


    Name (Synonyms) Correlation

    Clinical Trials

    Navigate: Correlations   HPO

    There is one clinical trial.


    1 Aerosol Combination Therapy of All-trans Retinoic Acid and Isotretinoin as A Novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients Better Than Vaccine : An Innovative Treatment

    Aerosol Combination therapy of All-trans retinoic acid and Isotretinoin as A novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients better than vaccine : An innovative Treatment Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Ahmed M. Kabel(4), Abedelaziz Elsayed(5) ,Yousry Abo-amer(6) ,Hesham Attia(7) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University,Egypt. 2. Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt 4. Department of Clinical Pharmacy, Faculty of Medicine , Tanta University,Egypt. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy,Tanta University,Egypt. 6. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital,Egypt 7. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. - Study Chair ((( Dr.Tamer Hydara))), Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt Contact: Dr.Tamer Hydara-Tel: 00201142233340 Mail: tamerhydara@yahoo.com - Principal Investigator ((( Mahmoud Elkazzaz))), Faculty of Science, Damietta University,GOEIC,Egypt Contact:Tel: 00201090302015 Mail: mahmoudramadan2051@yahoo.com - Study coordinator ((Prof/Dr Mohamed Abdelaal)), Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt Contact:Tel: 00201001422577 Mail: Malaal2@hotmail.com Abstract The pandemic of COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has infected over 20,000,000 people causing over 700,000 deaths .It has no currently approved treatments. In this clinical study we confirm that combination of isotretinoin and All trans retinoic acid can be used in the treatment of SARS-COV-2 better than vaccine according to the findings of previous studies and researches. Retenoic acid can induce neutralizing antibodies in case of corona virus (COVID-19) by restoring inhebited and exhausted T cells via inhebiting both CD13 and Angiotensin-converting enzyme-2 (ACE2). CD13 amyloid receptor which abundantly overexpressed on cell surface of lymphocyte, Dentritic cell, Macrophage, granulocytes and monocytes and is ubiquitous in respiratory tract epithelial cells, smooth muscle cells, fibroblasts, epithelial cells in the kidneys and small intestine, activated endothelial cells, and platelets In addition inhibing of Angiotensin-converting enzyme-2 (ACE2) , Angiotensin T1 protein and Angiotensin II-mediated intracellular calcium release pathway which is responsible for COVID-19 cell fusion and entry.ACE2-expressing cells are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. A study demonestrated that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression.Butisotretinoin was found to be the strongest down-regulator of ACE 2 receptors.and this will give hope for diabetic patients or patients with hypertension infected with COVID-19.Therefore we suggest that Retinoic Acid will help in inhabiting factors which may enhance antibody dependent enhancement (ADE), A phenomenon caused by covid-19 which expected to lead to failure of vaccination specially in case of corona virus (covid-19) as a hyper mutatated COVID-19 antigens can lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like Dentric cells, macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. In this clinical study we suggest that Hyper mutated spike protein ,lymphopenia, and impaired dentreic cells all these factors can help in and lead to delayed antibodies response and appearing after a period of covid -19 symptoms onset and this may be responsible for antibody dependent enhancement (ADE) Keywords: COVID 2019 , Retinoic acid, Lymphopenia ,T Cells, Dentric cells , ADE, Vaccine

    NCT04396067
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Aerosolized 13 cis retinoic acid
    2. Drug: Aerosolized All trans retinoic acid
    3. Other: Placebo

    Primary Outcomes

    Description: Proportion of lung injury score decreased or increased after treatment

    Measure: lung injury score

    Time: at 7 days

    Secondary Outcomes

    Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Time: at day 7 and 14 after randimization

    Description: Serum level of COVID19 RNA

    Measure: Serum level of COVID19 RNA

    Time: at day 7 and 14

    Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample

    Measure: d-dimers

    Time: within 14 days

    Description: lymphocyte counts

    Measure: Absolute lymphocyte counts

    Time: at day 7 and 14 after randimization

    Description: To determine the immune correlates of viral clearance (Antibody Titres sufficient for viral clearance and neutralizing ) against future exposure to SARS-CoV-2

    Measure: The immune correlates of protection against future exposure to SARS-CoV-2

    Time: within 14 days

    Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

    Measure: Immunological profile

    Time: within 14 days

    Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

    Time: at day 7 and 14

    Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    Measure: Occurrence of adverse event related to immunoglobulins

    Time: at day 14

    Description: serum levels of IgG and IgM against COVID-19

    Measure: IgG, IgA and IgM against COVID-19

    Time: at day 7 and 14

    Description: ACE2 expression in patients with COVID-19 infection

    Measure: ACE2 expression in patients with COVID-19 infection

    Time: at day 7 and 14

    Measure: All cause mortality rate [

    Time: at day 7 and 14

    Measure: Ventilation free days

    Time: at 14 days

    Measure: ICU free days

    Time: at 14 days

    No related HPO nodes (Using clinical trials)


    HPO

    Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


    No related HPO nodes (Using clinical trials)


    Reports

    Data processed on January 01, 2021.

    An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

    Drug Reports   MeSH Reports   HPO Reports  

    Interventions

    4,818 reports on interventions/drugs

    MeSH

    706 reports on MeSH terms

    HPO

    306 reports on HPO terms

    All Terms

    Alphabetical index of all Terms

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