<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/NCT04423640</url>
  </required_header>
  <id_info>
    <org_study_id>R-2020, 3601-043</org_study_id>
    <nct_id>NCT04423640</nct_id>
  </id_info>
  <brief_title>Analysis of the Inflammatory Response and the Development of Humoral and Cellular Immunity in Patients With COVID-19</brief_title>
  <official_title>The Analysis of the Inflammatory Response and the Development of Humoral and Cellular Immunity in Patients With Coronavirus Disease 2019 (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Coordinación de Investigación en Salud, Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto Mexicano del Seguro Social</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Coordinación de Investigación en Salud, Mexico</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The SARS-CoV-2 infection in the airway epithelium induces cytopathic effects and the&#xD;
      cessation of ciliary movement. Increased cytokines and chemokines have been reported to be&#xD;
      associated with the severity of the disease. However, most of the molecular and cellular&#xD;
      aspects of the inflammatory response and the processes of development of humoral and cellular&#xD;
      immunity in these patients are unknown. The aim of this study is characterizing inflammatory&#xD;
      processes, seeking to expand the knowledge of the cellular and molecular pathophysiology of&#xD;
      COVID-19 that could help in the decision-making of treating health personnel. Mainly, the&#xD;
      study is focused on analyzing the inflammatory response by determining cytokines and&#xD;
      chemokines. Also, the viral load of the patients with COVID-19 will be determined and will be&#xD;
      correlated with the antibody titers. On the other hand, cells will be immunophenotyped to&#xD;
      search the cellular depletion profile. Finally, an epidemiological analysis of the patients&#xD;
      will be carried out.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 15, 2020</start_date>
  <completion_date type="Anticipated">August 15, 2020</completion_date>
  <primary_completion_date type="Actual">June 15, 2020</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Serum levels of cytokines and chemokines</measure>
    <time_frame>Day 0</time_frame>
    <description>Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum levels of cytokines and chemokines</measure>
    <time_frame>Day 3</time_frame>
    <description>Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum levels of cytokines and chemokines</measure>
    <time_frame>Day 7</time_frame>
    <description>Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Viral load</measure>
    <time_frame>Day 0</time_frame>
    <description>log10 U/ml</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Viral load</measure>
    <time_frame>Day 7</time_frame>
    <description>log10 U/ml</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunophenotype of myeloid cells</measure>
    <time_frame>Day 0</time_frame>
    <description>Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunophenotype of myeloid cells</measure>
    <time_frame>Day 3</time_frame>
    <description>Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunophenotype of myeloid cells</measure>
    <time_frame>Day 7</time_frame>
    <description>Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RBD-SARS-CoV Protein S- antibodies</measure>
    <time_frame>Day 0</time_frame>
    <description>relative absorbance units by ELISA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RBD-SARS-CoV Protein S- antibodies</measure>
    <time_frame>Day 3</time_frame>
    <description>relative absorbance units by ELISA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RBD-SARS-CoV Protein S- antibodies</measure>
    <time_frame>Day 7</time_frame>
    <description>relative absorbance units by ELISA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Analysis of cellular immune response</measure>
    <time_frame>Day 0</time_frame>
    <description>Cell count per area (/ mm2) of immune cell sub-populations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Analysis of cellular immune response</measure>
    <time_frame>Day 3</time_frame>
    <description>Cell count per area (/ mm2) of immune cell sub-populations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Analysis of cellular immune response</measure>
    <time_frame>Day 7</time_frame>
    <description>Cell count per area (/ mm2) of immune cell sub-populations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hematopoietic stem cells and progenitor cells populations in peripheral blood</measure>
    <time_frame>Day 0</time_frame>
    <description>Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hematopoietic stem cells and progenitor cells populations in peripheral blood</measure>
    <time_frame>Day 3</time_frame>
    <description>Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hematopoietic stem cells and progenitor cells populations in peripheral blood</measure>
    <time_frame>Day 7</time_frame>
    <description>Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Questionnaire of Sociodemographic, labor, pathological and personal characteristics</measure>
    <time_frame>Day 0</time_frame>
    <description>Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOFA (Secuential Organ Failure Assessment Score)</measure>
    <time_frame>Day 0</time_frame>
    <description>Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOFA (Secuential Organ Failure Assessment Score)</measure>
    <time_frame>Day 3</time_frame>
    <description>Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOFA (Secuential Organ Failure Assessment Score)</measure>
    <time_frame>Day 7</time_frame>
    <description>Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogen</measure>
    <time_frame>Day 0</time_frame>
    <description>mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogen</measure>
    <time_frame>Day 3</time_frame>
    <description>mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogen</measure>
    <time_frame>Day 7</time_frame>
    <description>mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive protein</measure>
    <time_frame>Day 0</time_frame>
    <description>mg/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive protein</measure>
    <time_frame>Day 3</time_frame>
    <description>mg/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive protein</measure>
    <time_frame>Day 7</time_frame>
    <description>mg/L</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>SARS-CoV-2</condition>
  <arm_group>
    <arm_group_label>COVID Patients</arm_group_label>
    <description>Diagnosed patients with COVID-19 by PCR</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Active COVID-19 disease</intervention_name>
    <description>Adult patients admitted to the UMAE Specialty Hospital of CMN SXXI with a diagnosis of COVID-19. The diagnosis must be corroborated by the RT-PCR test.</description>
    <arm_group_label>COVID Patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Mexicans, beneficiaries of the IMSS&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients over 16 years old with positive molecular diagnosis of Covid-19, in the&#xD;
             Laboratory of IMSS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with immunosuppressive diseases: HIV +, Hepatitis C virus, primary&#xD;
             immunodeficiencies, rheumatoid arthritis, lupus erythematosus and patients under&#xD;
             treatment with immunosuppressants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Constantino López Macías, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>UIMIQ Hospital de especialidades, CMN S.XXI</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Constantino López Macías, PhD</last_name>
    <phone>52 55 56276900</phone>
    <phone_ext>21476</phone_ext>
    <email>constantino.lopez@imss.gob.mx</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eduardo Ferat-Osorio, PhD</last_name>
    <phone>52 55 56276900</phone>
    <phone_ext>21476</phone_ext>
    <email>eduardoferat@me.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UMAE Hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS.</name>
      <address>
        <city>México</city>
        <state>Ciudad De México</state>
        <zip>06720</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suria Loza Jalil, MD</last_name>
      <phone>52 55 56276900</phone>
      <phone_ext>21547</phone_ext>
      <email>suria_loza@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>August 12, 2020</last_update_submitted>
  <last_update_submitted_qc>August 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data of outcomes for meta-analysis purposes</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>After publication for 6 months</ipd_time_frame>
    <ipd_access_criteria>Data for meta-analysis purposes, the review requests will be done by the responsible of the research.</ipd_access_criteria>
  </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/NCT04423640
org study id: R-2020, 3601-043
nct id: NCT04423640
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The SARS-CoV-2 infection in the airway epithelium induces cytopathic effects and the
      cessation of ciliary movement. Increased cytokines and chemokines have been reported to be
      associated with the severity of the disease. However, most of the molecular and cellular
      aspects of the inflammatory response and the processes of development of humoral and cellular
      immunity in these patients are unknown. The aim of this study is characterizing inflammatory
      processes, seeking to expand the knowledge of the cellular and molecular pathophysiology of
      COVID-19 that could help in the decision-making of treating health personnel. Mainly, the
      study is focused on analyzing the inflammatory response by determining cytokines and
      chemokines. Also, the viral load of the patients with COVID-19 will be determined and will be
      correlated with the antibody titers. On the other hand, cells will be immunophenotyped to
      search the cellular depletion profile. Finally, an epidemiological analysis of the patients
      will be carried out.
observational model: Cohort
time perspective: Prospective
measure: Serum levels of cytokines and chemokines
time frame: Day 0
description: Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.
measure: Serum levels of cytokines and chemokines
time frame: Day 3
description: Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.
measure: Serum levels of cytokines and chemokines
time frame: Day 7
description: Pg/ml of IL-2, CXCL8 / IL-8,IL-4, CCL5 / RANTES, IL-6, CXCL9 / MIG, IL-10, CCL2 / MCP-1, TNF-alfa, CXCL10 / IP-10, IFN-alfa, soluble receptor IL6, IFN-gamma.
measure: Viral load
time frame: Day 0
description: log10 U/ml
measure: Viral load
time frame: Day 7
description: log10 U/ml
measure: Immunophenotype of myeloid cells
time frame: Day 0
description: Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry
measure: Immunophenotype of myeloid cells
time frame: Day 3
description: Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry
measure: Immunophenotype of myeloid cells
time frame: Day 7
description: Immunophenotypic profile of myeloid cells in COVID by surface molecules CD45, CD14, CD16, mIL-6R, CD73 and CD3. reported in relative fluorescence units and relative percentage of cells analyzed by flow cytometry
measure: RBD-SARS-CoV Protein S- antibodies
time frame: Day 0
description: relative absorbance units by ELISA
measure: RBD-SARS-CoV Protein S- antibodies
time frame: Day 3
description: relative absorbance units by ELISA
measure: RBD-SARS-CoV Protein S- antibodies
time frame: Day 7
description: relative absorbance units by ELISA
measure: Analysis of cellular immune response
time frame: Day 0
description: Cell count per area (/ mm2) of immune cell sub-populations
measure: Analysis of cellular immune response
time frame: Day 3
description: Cell count per area (/ mm2) of immune cell sub-populations
measure: Analysis of cellular immune response
time frame: Day 7
description: Cell count per area (/ mm2) of immune cell sub-populations
measure: Hematopoietic stem cells and progenitor cells populations in peripheral blood
time frame: Day 0
description: Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry
measure: Hematopoietic stem cells and progenitor cells populations in peripheral blood
time frame: Day 3
description: Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry
measure: Hematopoietic stem cells and progenitor cells populations in peripheral blood
time frame: Day 7
description: Immunophenotypic profile of stem cells and progenitor cells populations COVID by surface molecules CD34, CD38, CD45RA, Lin, CD3, CD8, CD56, CD19, CD20, CD11b, CD235a andCD14. reported in relative fluorescence units and relative percentage of cells, analyzed by flow cytometry
measure: Questionnaire of Sociodemographic, labor, pathological and personal characteristics
time frame: Day 0
description: Questionnaire
measure: SOFA (Secuential Organ Failure Assessment Score)
time frame: Day 0
description: Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.
measure: SOFA (Secuential Organ Failure Assessment Score)
time frame: Day 3
description: Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.
measure: SOFA (Secuential Organ Failure Assessment Score)
time frame: Day 7
description: Is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.
measure: Fibrinogen
time frame: Day 0
description: mg/dL
measure: Fibrinogen
time frame: Day 3
description: mg/dL
measure: Fibrinogen
time frame: Day 7
description: mg/dL
measure: C-Reactive protein
time frame: Day 0
description: mg/L
measure: C-Reactive protein
time frame: Day 3
description: mg/L
measure: C-Reactive protein
time frame: Day 7
description: mg/L
arm group label: COVID Patients
description: Diagnosed patients with COVID-19 by PCR
intervention type: Other
intervention name: Active COVID-19 disease
description: Adult patients admitted to the UMAE Specialty Hospital of CMN SXXI with a diagnosis of COVID-19. The diagnosis must be corroborated by the RT-PCR test.
arm group label: COVID Patients
Whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Constantino López Macías, PhD
role: Study Chair
affiliation: UIMIQ Hospital de especialidades, CMN S.XXI
last name: Constantino López Macías, PhD
phone: 52 55 56276900
phone ext: 21476
email: constantino.lopez@imss.gob.mx
last name: Eduardo Ferat-Osorio, PhD
phone: 52 55 56276900
phone ext: 21476
email: eduardoferat@me.com
facility: 
status: Recruiting
contact: 
country: Mexico
responsible party type: Sponsor
sharing ipd: Yes
ipd description: Data of outcomes for meta-analysis purposes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After publication for 6 months
ipd access criteria: Data for meta-analysis purposes, the review requests will be done by the responsible of the research.