<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04411563</url>
  </required_header>
  <id_info>
    <org_study_id>2020/143</org_study_id>
    <nct_id>NCT04411563</nct_id>
  </id_info>
  <brief_title>Epigenetic Tools as Prognostic Predictors in Covid19</brief_title>
  <official_title>The Effect of miRNA and Epigenetic Modifications on Prognosis in Covid-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Istanbul University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The necessity for early detection and hence improving the outcome of treatment of pneumonia&#xD;
      is critical especially SARS-CoV-2 induced cases. This work was designed to evaluate the&#xD;
      potential application of measuring circulating epigenetic markers namely, miR-744, miR-24,&#xD;
      miR-124, miR-155, miR-19a, miR-122, miR-21, miR-223, let-7f, miR-146, miR-196, miR-136,&#xD;
      P13-K, miR-9 expression, and DNA methylation profiling of the ACE2, TMPRSS2, PARP, HOX1 genes&#xD;
      in Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 with/without pneumonia and severe&#xD;
      acute respiratory syndrome (SARS) patients as an attempt to evaluate the potential benefits&#xD;
      of these new circulating, prognostic, epigenetic markers for Turkish patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objectives of this observational study are 1) To investigate why COVID-19 infection&#xD;
      causes different biological behavioral patterns in individuals, 2) To determine the role of&#xD;
      epigenetic mechanisms here to detect the difference between individuals, 3)To determine the&#xD;
      effectiveness of this behavior model and mechanisms on clinical treatment and to ensure that&#xD;
      the results obtained are a step for further treatment studies, 4) To evaluate whether the&#xD;
      data obtained in MicroRNA analysis is a predictive marker on prognosis. Material and methods&#xD;
      Study design This is an observational prospective cohort study. In the power analysis&#xD;
      performed with the G * power 3.1 programs related to our study, the effect size for the&#xD;
      lymphocyte percentage and C-reactive protein was found to be 0.57 (Effective Treatment of&#xD;
      Severe COVID-19 Patients with Tocilizumab) (alpha probability of error = 0.05); in the sample&#xD;
      width analysis, taking the power value 0.80, the total number of patients to be collected was&#xD;
      105 (105/3 = 35 for each group).&#xD;
&#xD;
      Patient's criteria This study was approved by the Clinical Research Ethics Committee (2011-&#xD;
      CREC-40) at Bakırköy Dr.Sadi Konuk Training and Research Hospital and informed consent will&#xD;
      be obtained from all patients according to the rules of the Declaration of Helsinki. Approval&#xD;
      of the local ethical committee number is 2020/143 (2011-CREC-40). Patients enrolled in this&#xD;
      study will be admitted to the Infectious Diseases and Clinical Microbiology Department and&#xD;
      the Intensive Care Department from May 2020 to September 2020. Diagnosis of COVID 19 will be&#xD;
      depending upon the presence of specific lesions in lungs confirmed by computed tomography&#xD;
      (CT), and/or laboratory findings according to the Republic of Turkey Ministry of Health&#xD;
      diagnostic criteria.&#xD;
&#xD;
      Inclusion criteria All patients between the ages of 18 and 65 included will suffer from COVID&#xD;
      19, and specific treatment should not yet be initiated. COVID 19 diagnosis of patients will&#xD;
      be based on full medical history, thorough clinical examination, radiological imaging,&#xD;
      laboratory assessment, and SARS-CoV-2 analysis by RT-PCR.&#xD;
&#xD;
      Exclusion criteria&#xD;
&#xD;
        1. People with chronic lung disease or previous AC surgery&#xD;
&#xD;
        2. People with immune deficiency or cancer patients&#xD;
&#xD;
        3. Patients receiving immunosuppressive therapy for autoimmune disease&#xD;
&#xD;
        4. People with neurological diseases affecting the respiratory muscles, such as hypotonia.&#xD;
&#xD;
      On the basis of the inclusion and exclusion criteria 105 patients subjects will be included&#xD;
      in this study, divided into three groups; group I (n = 35) patients are mild, group II (n =&#xD;
      35) patients are moderate, and group III (n = 35) patients are severe and critical. Mild and&#xD;
      moderate cases are usually defined as those without severe pneumonia or severe acute&#xD;
      respiratory syndrome. Mild symptoms are low-grade fever (not more than 38 degrees celsius),&#xD;
      dry cough, fatigue, sore throat, headache, the new loss of taste, and smell. Patients with&#xD;
      normal or mild pneumonia findings of radiological imaging and blood lymphocyte count ≥800 /&#xD;
      µl and serum CRP≤40 mg /l, ferritin ≤500ng/ml, D-Dimer ≤1000 ng/ml will be included in group&#xD;
      I. Moderate symptoms are fever of about 38,5-39 degrees celsius, chills, deep cough, fatigue&#xD;
      and body aches, muscle pain, the general feeling of being unwell. Patients with bilateral&#xD;
      diffuse pneumonia findings of radiological imaging or blood lymphocyte count &lt;800 / µl or&#xD;
      serum CRP&gt; 40 mg / l or ferritin&gt; 500ng / ml or D-Dimer&gt; 1000 ng / ml will be included in&#xD;
      group II. Severe symptoms are all the common symptoms mentioned above along with shortness of&#xD;
      breath, chest discomfort, confusion/unresponsiveness, bluish face/lips, possible&#xD;
      gastrointestinal issues, like diarrhea or nausea. Patients with ICU (intensive care unit)&#xD;
      admission criteria, such as confusion or tachycardia (&gt; 125 / min) or respiratory distress or&#xD;
      tachypnea (&gt; 22 / min) or hypotension &lt;90/60 mmHg or SPO2 &lt;93%will be included in group III.&#xD;
      Also, patients with the central nervous system and heart involvement will be directly&#xD;
      included in the severe case group.&#xD;
&#xD;
      Specimen collection and handling About 10 ml of peripheral venous blood will be collected&#xD;
      under strict aseptic conditions by clean venipuncture using vacuum blood collection tubes and&#xD;
      will be distributed as 3 ml in EDTA tubes for complete blood count and DNA extraction, 3 ml&#xD;
      in another sterile special RNA protective tube (stored at -80 °C) for miRNA extraction. In&#xD;
      addition, 4 ml in a plane tube will be allowed to clot at the room temperature and then will&#xD;
      be centrifuged at 3000 rpm for 10 minutes and the collected serum will be stored at -80°C to&#xD;
      be used for analyzing cytokine, and other specific tests.On the 7th day of treatment, second&#xD;
      samples will be taken under the same conditions and finally, on the 21st day, third samples&#xD;
      will be taken.&#xD;
&#xD;
      Laboratory investigations RNA Extraction was done according to the miRNeasy Serum/Plasma&#xD;
      Advanced Kit (cat. no. 217204) https:// www.qiagen.com/&#xD;
&#xD;
      The expressions of selected miRNAs and genes were analyzed using Real-Time PCR. The list of&#xD;
      required kits, chemicals and consumables is as follows:&#xD;
&#xD;
      miRCURY LNA RT Kit (Cat No: 339340) miRCURY LNA miRNA PCR Assay (200) (Cat No: 339306)&#xD;
      miRCURY LNA SYBR Green PCR Kit (600) (Cat No: 339346) miRCURY LNA SYBR Green PCR Kit (200)&#xD;
      (Cat No: 339345) PAXgene Blood miRNA Kit (50) (Cat No: 763134) miRNeasy Serum/Plasma Kit (50)&#xD;
      (Cat No: 217184) PCR Tubes 0.2 ml (1000) (Cat No: 981005) TF/10UL FILTER TIPS FOR P-10,RAC&#xD;
      (Cat No: TF-10-R-S) TF/100UL FILTER TIPS FOR (Cat No: TF-100-R-S) TF /1000UL UNIVERSAL FILTER&#xD;
      TIPS (Cat No: TF-1000-R-S)&#xD;
&#xD;
      Kit and consumables required for DNA methylation analysis:&#xD;
&#xD;
      ZymoResearch EZ DNA Methylation-Gold™ Kit 200 Preps (Cat no: D5006) ZymoResearch Human&#xD;
      Methylated &amp; Non-methylated DNA Set (DNA w/ primers) 1 set (Cat no: D5014) ZymoResearch&#xD;
      ZymoTaq qPCR Premix 200 Reactions (Cat no: E2055) Primary synthesis consumable for 1 gene&#xD;
      region AXYGEN 0.5ml Thin Wall PCR Tubes,Flat Cap. Clear1000 (Cat no: PCR-05-C) Capp 2.0ml&#xD;
      Boil-Proof Microtubes. Clear 1000 (Cat no: MCT-200-C) Capp 10 ul Dnase, Rnase Free Bulk Pipet&#xD;
      tips 10 rack (Cat no: 5.030.010) Capp 200 ul Dnase, Rnase Free Bulk Pipet ucu (Yellow Tips)&#xD;
      10 rack (Cat no: 4.130.075) Capp 1000 ul Dnase, Rnase Free Bulk Pipet ucu (Blue Tips) 10 rack&#xD;
      (Cat no: 4.130.135) Bio Molecular Systems Mic Tubes and Caps 1 Box: 20 racks of 48&#xD;
      tubes/rack, 960 Tubes in Strips of 4 with matching caps (Cat no: MIC-TUBES960).&#xD;
&#xD;
      The motivation element behind the choice of miRNAs in the current work is a product of the&#xD;
      following integrated online databases for miRNA target prediction and functional&#xD;
      analysis.http://microrna.osumc.edu, https://www.genecards.org. http://www.mirdb.org/miRDB/&#xD;
      Gene association networks with ACE2, TMPRSS2, PARP, HOX1 genes in COVID 19 cases were&#xD;
      analyzed using GeneMANIA (Multiple Association Network Integration Algorithm) for prediction&#xD;
      of possible functional interactions among them (http://www. genemania.org).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 21, 2020</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>7 Months</target_duration>
  <primary_outcome>
    <measure>Determination of the relationship between the severity of disease and epigenetic factors in COVID 19</measure>
    <time_frame>Seven months</time_frame>
    <description>Analysis of pathway-related micro RNAs in patients with mild, moderate and severe Covid 19 clinics</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">105</enrollment>
  <condition>Prognosis</condition>
  <arm_group>
    <arm_group_label>Group I-Mild</arm_group_label>
    <description>The patients who have these mild symptoms are low-grade fever (not more than 38 degrees celsius), dry cough, fatigue, sore throat, headache, the new loss of taste, and smell. Patients with normal or mild pneumonia findings of radiological imaging and blood lymphocyte count ≥800 / µl and serum CRP≤40 mg /l, ferritin ≤500ng/ml, D-Dimer ≤1000 ng/ml will be included in group I.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II-Moderate</arm_group_label>
    <description>The patients who have these moderate symptoms are fever of about 38,5-39 degrees celsius, chills, deep cough, fatigue and body aches, muscle pain, the general feeling of being unwell. Patients with bilateral diffuse pneumonia findings of radiological imaging or blood lymphocyte count &lt;800 / µl or serum CRP&gt; 40 mg / l or ferritin&gt; 500ng / ml or D-Dimer&gt; 1000 ng / ml will be included in group II.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group III-Severe</arm_group_label>
    <description>The patients who have these severe symptoms are all the common symptoms mentioned above along with shortness of breath, chest discomfort, confusion/unresponsiveness, bluish face/lips, possible gastrointestinal issues, like diarrhea or nausea. Patients with ICU (intensive care unit) admission criteria, such as confusion or tachycardia (&gt; 125 / min) or respiratory distress or tachypnea (&gt; 22 / min) or hypotension &lt;90/60 mmHg or SPO2 &lt;93%will be included in group III. Also, patients with the central nervous system and heart involvement will be directly included in the severe case group</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Taking biological samples</intervention_name>
    <description>Taking blood samples for biochemical and epigenetic analysis</description>
    <arm_group_label>Group I-Mild</arm_group_label>
    <arm_group_label>Group II-Moderate</arm_group_label>
    <arm_group_label>Group III-Severe</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Genomic material will be stored to continue prognostic biomarker studies.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        On the basis of the inclusion and exclusion criteria 105 patients subjects will be included&#xD;
        in this study, divided into three groups; group I (n = 35) patients are mild, group II (n =&#xD;
        35) patients are moderate, and group III (n = 35) patients are severe and critical. Mild&#xD;
        and moderate cases are usually defined as those without severe pneumonia or sever acute&#xD;
        respiratory syndrome.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients between the ages of 18 and 65 included will suffer from COVID 19, and&#xD;
             specific treatment should not yet be initiated.&#xD;
&#xD;
          -  COVID 19 diagnosis of patients will be based on full medical history, thorough&#xD;
             clinical examination, radiological imaging, laboratory assessment, and SARS-CoV-2&#xD;
             analysis by RT-PCR.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  People with chronic lung disease or previous AC surgery&#xD;
&#xD;
          -  People with immune deficiency or cancer patients&#xD;
&#xD;
          -  Patients receiving immunosuppressive therapy for autoimmune disease&#xD;
&#xD;
          -  People with neurological diseases affecting the respiratory muscles, such as&#xD;
             hypotonia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gokhan T. Adas, Prof</last_name>
    <role>Study Director</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Asuman Gedikbasi, Assoc.Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kadriye Yaşar, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nilgün Isiksacan, Assoc.Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zafer Çukurova, Assoc.Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Oya G. Hergünsel, MD, Intensivist</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sacide Pehlivan, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Istanbul University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Asuman Gedikbasi, Assoc.Prof.</last_name>
    <phone>00905327009660</phone>
    <email>asugedikbasi@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gokhan T Adas, Prof.</last_name>
    <phone>00905326155892</phone>
    <email>gokhantolgaadas@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34147</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gokhan T. Adas, Prof.</last_name>
      <phone>00905326155892</phone>
      <email>gokhantolgaadas@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Asuman Gedikbasi, Assoc.Prof.</last_name>
      <phone>00905327009660</phone>
      <email>asugedikbasi@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bakirkoy Dr. Sadi Konuk Research and Training Hospital</investigator_affiliation>
    <investigator_full_name>Gokhan Tolga Adas</investigator_full_name>
    <investigator_title>Faculty Member</investigator_title>
  </responsible_party>
  <keyword>COVID 19</keyword>
  <keyword>Prognostic Epigenetics</keyword>
  <keyword>miRNA</keyword>
  <keyword>DNA methylation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Since studies on COVID 19 in our country during this pandemic are subject to certain permissions, the decision will be made when the permit processes are completed.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04411563
org study id: 2020/143
nct id: NCT04411563
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The necessity for early detection and hence improving the outcome of treatment of pneumonia
      is critical especially SARS-CoV-2 induced cases. This work was designed to evaluate the
      potential application of measuring circulating epigenetic markers namely, miR-744, miR-24,
      miR-124, miR-155, miR-19a, miR-122, miR-21, miR-223, let-7f, miR-146, miR-196, miR-136,
      P13-K, miR-9 expression, and DNA methylation profiling of the ACE2, TMPRSS2, PARP, HOX1 genes
      in Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 with/without pneumonia and severe
      acute respiratory syndrome (SARS) patients as an attempt to evaluate the potential benefits
      of these new circulating, prognostic, epigenetic markers for Turkish patients.
The objectives of this observational study are 1) To investigate why COVID-19 infection
      causes different biological behavioral patterns in individuals, 2) To determine the role of
      epigenetic mechanisms here to detect the difference between individuals, 3)To determine the
      effectiveness of this behavior model and mechanisms on clinical treatment and to ensure that
      the results obtained are a step for further treatment studies, 4) To evaluate whether the
      data obtained in MicroRNA analysis is a predictive marker on prognosis. Material and methods
      Study design This is an observational prospective cohort study. In the power analysis
      performed with the G * power 3.1 programs related to our study, the effect size for the
      lymphocyte percentage and C-reactive protein was found to be 0.57 (Effective Treatment of
      Severe COVID-19 Patients with Tocilizumab) (alpha probability of error = 0.05); in the sample
      width analysis, taking the power value 0.80, the total number of patients to be collected was
      105 (105/3 = 35 for each group).

      Patient's criteria This study was approved by the Clinical Research Ethics Committee (2011-
      CREC-40) at Bakırköy Dr.Sadi Konuk Training and Research Hospital and informed consent will
      be obtained from all patients according to the rules of the Declaration of Helsinki. Approval
      of the local ethical committee number is 2020/143 (2011-CREC-40). Patients enrolled in this
      study will be admitted to the Infectious Diseases and Clinical Microbiology Department and
      the Intensive Care Department from May 2020 to September 2020. Diagnosis of COVID 19 will be
      depending upon the presence of specific lesions in lungs confirmed by computed tomography
      (CT), and/or laboratory findings according to the Republic of Turkey Ministry of Health
      diagnostic criteria.

      Inclusion criteria All patients between the ages of 18 and 65 included will suffer from COVID
      19, and specific treatment should not yet be initiated. COVID 19 diagnosis of patients will
      be based on full medical history, thorough clinical examination, radiological imaging,
      laboratory assessment, and SARS-CoV-2 analysis by RT-PCR.

      Exclusion criteria

        1. People with chronic lung disease or previous AC surgery

        2. People with immune deficiency or cancer patients

        3. Patients receiving immunosuppressive therapy for autoimmune disease

        4. People with neurological diseases affecting the respiratory muscles, such as hypotonia.

      On the basis of the inclusion and exclusion criteria 105 patients subjects will be included
      in this study, divided into three groups; group I (n = 35) patients are mild, group II (n =
      35) patients are moderate, and group III (n = 35) patients are severe and critical. Mild and
      moderate cases are usually defined as those without severe pneumonia or severe acute
      respiratory syndrome. Mild symptoms are low-grade fever (not more than 38 degrees celsius),
      dry cough, fatigue, sore throat, headache, the new loss of taste, and smell. Patients with
      normal or mild pneumonia findings of radiological imaging and blood lymphocyte count ≥800 /
      µl and serum CRP≤40 mg /l, ferritin ≤500ng/ml, D-Dimer ≤1000 ng/ml will be included in group
      I. Moderate symptoms are fever of about 38,5-39 degrees celsius, chills, deep cough, fatigue
      and body aches, muscle pain, the general feeling of being unwell. Patients with bilateral
      diffuse pneumonia findings of radiological imaging or blood lymphocyte count <800 / µl or
      serum CRP> 40 mg / l or ferritin> 500ng / ml or D-Dimer> 1000 ng / ml will be included in
      group II. Severe symptoms are all the common symptoms mentioned above along with shortness of
      breath, chest discomfort, confusion/unresponsiveness, bluish face/lips, possible
      gastrointestinal issues, like diarrhea or nausea. Patients with ICU (intensive care unit)
      admission criteria, such as confusion or tachycardia (> 125 / min) or respiratory distress or
      tachypnea (> 22 / min) or hypotension <90/60 mmHg or SPO2 <93%will be included in group III.
      Also, patients with the central nervous system and heart involvement will be directly
      included in the severe case group.

      Specimen collection and handling About 10 ml of peripheral venous blood will be collected
      under strict aseptic conditions by clean venipuncture using vacuum blood collection tubes and
      will be distributed as 3 ml in EDTA tubes for complete blood count and DNA extraction, 3 ml
      in another sterile special RNA protective tube (stored at -80 °C) for miRNA extraction. In
      addition, 4 ml in a plane tube will be allowed to clot at the room temperature and then will
      be centrifuged at 3000 rpm for 10 minutes and the collected serum will be stored at -80°C to
      be used for analyzing cytokine, and other specific tests.On the 7th day of treatment, second
      samples will be taken under the same conditions and finally, on the 21st day, third samples
      will be taken.

      Laboratory investigations RNA Extraction was done according to the miRNeasy Serum/Plasma
      Advanced Kit (cat. no. 217204) https:// www.qiagen.com/

      The expressions of selected miRNAs and genes were analyzed using Real-Time PCR. The list of
      required kits, chemicals and consumables is as follows:

      miRCURY LNA RT Kit (Cat No: 339340) miRCURY LNA miRNA PCR Assay (200) (Cat No: 339306)
      miRCURY LNA SYBR Green PCR Kit (600) (Cat No: 339346) miRCURY LNA SYBR Green PCR Kit (200)
      (Cat No: 339345) PAXgene Blood miRNA Kit (50) (Cat No: 763134) miRNeasy Serum/Plasma Kit (50)
      (Cat No: 217184) PCR Tubes 0.2 ml (1000) (Cat No: 981005) TF/10UL FILTER TIPS FOR P-10,RAC
      (Cat No: TF-10-R-S) TF/100UL FILTER TIPS FOR (Cat No: TF-100-R-S) TF /1000UL UNIVERSAL FILTER
      TIPS (Cat No: TF-1000-R-S)

      Kit and consumables required for DNA methylation analysis:

      ZymoResearch EZ DNA Methylation-Gold™ Kit 200 Preps (Cat no: D5006) ZymoResearch Human
      Methylated & Non-methylated DNA Set (DNA w/ primers) 1 set (Cat no: D5014) ZymoResearch
      ZymoTaq qPCR Premix 200 Reactions (Cat no: E2055) Primary synthesis consumable for 1 gene
      region AXYGEN 0.5ml Thin Wall PCR Tubes,Flat Cap. Clear1000 (Cat no: PCR-05-C) Capp 2.0ml
      Boil-Proof Microtubes. Clear 1000 (Cat no: MCT-200-C) Capp 10 ul Dnase, Rnase Free Bulk Pipet
      tips 10 rack (Cat no: 5.030.010) Capp 200 ul Dnase, Rnase Free Bulk Pipet ucu (Yellow Tips)
      10 rack (Cat no: 4.130.075) Capp 1000 ul Dnase, Rnase Free Bulk Pipet ucu (Blue Tips) 10 rack
      (Cat no: 4.130.135) Bio Molecular Systems Mic Tubes and Caps 1 Box: 20 racks of 48
      tubes/rack, 960 Tubes in Strips of 4 with matching caps (Cat no: MIC-TUBES960).

      The motivation element behind the choice of miRNAs in the current work is a product of the
      following integrated online databases for miRNA target prediction and functional
      analysis.http://microrna.osumc.edu, https://www.genecards.org. http://www.mirdb.org/miRDB/
      Gene association networks with ACE2, TMPRSS2, PARP, HOX1 genes in COVID 19 cases were
      analyzed using GeneMANIA (Multiple Association Network Integration Algorithm) for prediction
      of possible functional interactions among them (http://www. genemania.org).
observational model: Cohort
time perspective: Prospective
measure: Determination of the relationship between the severity of disease and epigenetic factors in COVID 19
time frame: Seven months
description: Analysis of pathway-related micro RNAs in patients with mild, moderate and severe Covid 19 clinics
arm group label: Group I-Mild
description: The patients who have these mild symptoms are low-grade fever (not more than 38 degrees celsius), dry cough, fatigue, sore throat, headache, the new loss of taste, and smell. Patients with normal or mild pneumonia findings of radiological imaging and blood lymphocyte count ≥800 / µl and serum CRP≤40 mg /l, ferritin ≤500ng/ml, D-Dimer ≤1000 ng/ml will be included in group I.
arm group label: Group II-Moderate
description: The patients who have these moderate symptoms are fever of about 38,5-39 degrees celsius, chills, deep cough, fatigue and body aches, muscle pain, the general feeling of being unwell. Patients with bilateral diffuse pneumonia findings of radiological imaging or blood lymphocyte count <800 / µl or serum CRP> 40 mg / l or ferritin> 500ng / ml or D-Dimer> 1000 ng / ml will be included in group II.
arm group label: Group III-Severe
description: The patients who have these severe symptoms are all the common symptoms mentioned above along with shortness of breath, chest discomfort, confusion/unresponsiveness, bluish face/lips, possible gastrointestinal issues, like diarrhea or nausea. Patients with ICU (intensive care unit) admission criteria, such as confusion or tachycardia (> 125 / min) or respiratory distress or tachypnea (> 22 / min) or hypotension <90/60 mmHg or SPO2 <93%will be included in group III. Also, patients with the central nervous system and heart involvement will be directly included in the severe case group
intervention type: Other
intervention name: Taking biological samples
description: Taking blood samples for biochemical and epigenetic analysis
arm group label: Group I-Mild
arm group label: Group II-Moderate
arm group label: Group III-Severe
Genomic material will be stored to continue prognostic biomarker studies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Gokhan T. Adas, Prof
role: Study Director
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Asuman Gedikbasi, Assoc.Prof.
role: Principal Investigator
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Kadriye Yaşar, Prof.
role: Principal Investigator
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Nilgün Isiksacan, Assoc.Prof.
role: Principal Investigator
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Zafer Çukurova, Assoc.Prof.
role: Principal Investigator
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Oya G. Hergünsel, MD, Intensivist
role: Principal Investigator
affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
last name: Sacide Pehlivan, Prof.
role: Principal Investigator
affiliation: Istanbul University
last name: Asuman Gedikbasi, Assoc.Prof.
phone: 00905327009660
email: asugedikbasi@yahoo.com
last name: Gokhan T Adas, Prof.
phone: 00905326155892
email: gokhantolgaadas@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
investigator full name: Gokhan Tolga Adas
investigator title: Faculty Member
mesh term: COVID-19
sharing ipd: Undecided
ipd description: Since studies on COVID 19 in our country during this pandemic are subject to certain permissions, the decision will be made when the permit processes are completed.