<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/NCT04451577</url>
  </required_header>
  <id_info>
    <org_study_id>UNICODE</org_study_id>
    <nct_id>NCT04451577</nct_id>
  </id_info>
  <brief_title>Epidemiologic, Clinical, Molecular Characteristics of Hospital Employees With or Without Covid-19 Infection</brief_title>
  <acronym>UNICODE</acronym>
  <official_title>Epidemiologic, Clinical, Molecular Characteristics of Hospital Employees With or Without Covid-19 Infection: a Retrospective-prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Clinico Humanitas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Clinico Humanitas</source>
  <oversight_info>
    <has_dmc>No</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 study cohort will be enrolled among all Humanitas group employees (including ICH,&#xD;
      Humanitas University and Gavazzeni), and two validation cohorts. Participants will be asked&#xD;
      consent for the research use of blood, pharyngeal swab, and for those hospitalized for&#xD;
      COVID-19, also for the bronchoalveolar lavage and fecal samples. Biological samples will be&#xD;
      used to perform cellular, microbial and molecular analyses aimed at better understanding the&#xD;
      disease pathogenesis and the individual differences in susceptibility to the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The analysis will include:&#xD;
&#xD;
        -  study the expression levels of molecules known to mediated viral infection, like the&#xD;
           Angiotensin converting enzyme 2 (ACE2) and genetic variants in these genes, which could&#xD;
           be related to susceptibility to the viral infection and/or to the severity of the&#xD;
           clinical course of the disease&#xD;
&#xD;
        -  compare the frequency of genetic variants potentially related with COVID-19&#xD;
           susceptibility/severity in different subgroups of patients, ranging from individuals&#xD;
           positive for the virus but asymptomatic to individuals affected by COVID-19 with ARDS&#xD;
           requiring admission to ICU&#xD;
&#xD;
        -  germline DNA analysis to search for genetic factors predisposing or protecting against&#xD;
           severe pulmonary affection in COVID-19 infected participants. To this aim DNA will be&#xD;
           analyzed by a GWAS (Genome Wide Association Study) approach by using the GSA Illumina&#xD;
           chip. The obtained data will also be used to try to develop a polygenic risk score to&#xD;
           stratify individuals with a particularly high or low risk for severe disease course&#xD;
&#xD;
        -  explore the contribution of rare variants by studying the exome&#xD;
&#xD;
        -  sepsis and ARDS biomarkers developed at ICH (e.g. PTX3, sIL-1R2, MSF) analysis to&#xD;
           address their prognostic potential in Covid-19 patients&#xD;
&#xD;
        -  PBMC analysis by FACS to investigate the immunophenotype and correlate it to the&#xD;
           clinical outcome&#xD;
&#xD;
        -  microbiota analysis of residual BAL and pharyngeal swab to evaluate whether different&#xD;
           microbial or metabolome profiles are associated to worsen disease or to protection&#xD;
&#xD;
        -  plasma and saliva/sputum test for anti-SARS-Cov-2 antibodies (IgM, IgG, IgE and IgA) and&#xD;
           for microbiota analysis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response to COVID-19</measure>
    <time_frame>36 months</time_frame>
    <description>COVID-19 infection will be assessed by serological analysis of the presence of IgG anti-Covid-19 antibodies, an a subsequent pharyngeal swab. Symphtoms and possible hospitalization will be considered in clinical response.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunological response to COVID-19</measure>
    <time_frame>36 months</time_frame>
    <description>PBMC analysis by FACS to investigate the immunophenotype and correlate it to the clinical outcome (symptoms aggressiveness).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Genetic predisposition to COVID-19</measure>
    <time_frame>36 months</time_frame>
    <description>Genetic variants analysis potentially related with COVID-19 susceptibility/severity in different subgroups of patients, ranging from individuals positive for the virus but asymptomatic to individuals affected by COVID-19 with ARDS requiring admission to ICU</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Microbiome-related response to COVID-19</measure>
    <time_frame>36 months</time_frame>
    <description>Microbiota analysis (using 16S rDNA sequencing technology) of residual BAL, pharyngeal swab, plasma and saliva/sputum to evaluate whether different microbial or metabolome profiles are associated to worsen disease or to protection</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">5000</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>EMPLOYEES WITHOUT COVID-19 INFECTION</arm_group_label>
    <description>Humanitas group employees (including ICH, Humanitas University and Gavazzeni), and two validation cohorts.&#xD;
Negativity to COVOD-19 will be tested by peripheral blood samples every month for 6 months (or until seroconversion). If they are positive for anti- covid 19 antibodies, a test for positivity of the virus will be carried out. T</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EMPLOYEES WITH COVID-19 INFECTION</arm_group_label>
    <description>Humanitas group employees (including ICH, Humanitas University and Gavazzeni), and two validation cohorts.&#xD;
employees that are Sars-Cov-2 positive both symptomatic and asymptomatic, there will be at least 2 peripheral blood samples (5 and 3 ml) at every control visit until ascertained negativity. They will also undergo a pharyngeal swab for viral titers and microbiota analysis at enrollment and at negativity. In addition, a sample of saliva/sputum will be collected for most of the employees at positivity and at every control visit.&#xD;
For employees hospitalized but not requiring intensive care the following samples will be collected:&#xD;
an aliquot of samples from the respiratory tract (e.g., bronchial aspirate, bronchoalveolar lavage) residual from the normal clinical practice&#xD;
saliva/sputum&#xD;
pharyngeal swab not used for diagnosis both at admission and at the first check up&#xD;
blood sample in EDTA for plasma and peripheral blood mononuclear cell (PBMC)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No intervention, analysis of biological samples</description>
    <arm_group_label>EMPLOYEES WITH COVID-19 INFECTION</arm_group_label>
    <arm_group_label>EMPLOYEES WITHOUT COVID-19 INFECTION</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, pharyngeal swab, and for those hospitalized for COVID-19, also for the bronchoalveolar&#xD;
      lavage and fecal samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study cohort will be enrolled among all Humanitas group employees (including ICH,&#xD;
        Humanitas University and Gavazzeni), and two validation cohorts&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Individuals aged ≥ 18 years;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Lack of informed consent according to local procedure per critically ill patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Maria Rescigno, PhD</last_name>
    <phone>00390282245431</phone>
    <email>maria.rescigno@hunimed.eu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Humanitas reseach hospital (ICH)</name>
      <address>
        <city>Rozzano</city>
        <state>Milan</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Rescigno, PhD</last_name>
      <phone>+390282245431</phone>
      <email>maria.rescigno@hunimed.eu</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>June 27, 2020</last_update_submitted>
  <last_update_submitted_qc>June 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>No</sharing_ipd>
  </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/NCT04451577
org study id: UNICODE
nct id: NCT04451577
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study cohort will be enrolled among all Humanitas group employees (including ICH,
      Humanitas University and Gavazzeni), and two validation cohorts. Participants will be asked
      consent for the research use of blood, pharyngeal swab, and for those hospitalized for
      COVID-19, also for the bronchoalveolar lavage and fecal samples. Biological samples will be
      used to perform cellular, microbial and molecular analyses aimed at better understanding the
      disease pathogenesis and the individual differences in susceptibility to the disease.
The analysis will include:

        -  study the expression levels of molecules known to mediated viral infection, like the
           Angiotensin converting enzyme 2 (ACE2) and genetic variants in these genes, which could
           be related to susceptibility to the viral infection and/or to the severity of the
           clinical course of the disease

        -  compare the frequency of genetic variants potentially related with COVID-19
           susceptibility/severity in different subgroups of patients, ranging from individuals
           positive for the virus but asymptomatic to individuals affected by COVID-19 with ARDS
           requiring admission to ICU

        -  germline DNA analysis to search for genetic factors predisposing or protecting against
           severe pulmonary affection in COVID-19 infected participants. To this aim DNA will be
           analyzed by a GWAS (Genome Wide Association Study) approach by using the GSA Illumina
           chip. The obtained data will also be used to try to develop a polygenic risk score to
           stratify individuals with a particularly high or low risk for severe disease course

        -  explore the contribution of rare variants by studying the exome

        -  sepsis and ARDS biomarkers developed at ICH (e.g. PTX3, sIL-1R2, MSF) analysis to
           address their prognostic potential in Covid-19 patients

        -  PBMC analysis by FACS to investigate the immunophenotype and correlate it to the
           clinical outcome

        -  microbiota analysis of residual BAL and pharyngeal swab to evaluate whether different
           microbial or metabolome profiles are associated to worsen disease or to protection

        -  plasma and saliva/sputum test for anti-SARS-Cov-2 antibodies (IgM, IgG, IgE and IgA) and
           for microbiota analysis
observational model: Case-Control
time perspective: Other
measure: Clinical response to COVID-19
time frame: 36 months
description: COVID-19 infection will be assessed by serological analysis of the presence of IgG anti-Covid-19 antibodies, an a subsequent pharyngeal swab. Symphtoms and possible hospitalization will be considered in clinical response.
measure: Immunological response to COVID-19
time frame: 36 months
description: PBMC analysis by FACS to investigate the immunophenotype and correlate it to the clinical outcome (symptoms aggressiveness).
measure: Genetic predisposition to COVID-19
time frame: 36 months
description: Genetic variants analysis potentially related with COVID-19 susceptibility/severity in different subgroups of patients, ranging from individuals positive for the virus but asymptomatic to individuals affected by COVID-19 with ARDS requiring admission to ICU
measure: Microbiome-related response to COVID-19
time frame: 36 months
description: Microbiota analysis (using 16S rDNA sequencing technology) of residual BAL, pharyngeal swab, plasma and saliva/sputum to evaluate whether different microbial or metabolome profiles are associated to worsen disease or to protection
arm group label: EMPLOYEES WITHOUT COVID-19 INFECTION
description: Humanitas group employees (including ICH, Humanitas University and Gavazzeni), and two validation cohorts.
Negativity to COVOD-19 will be tested by peripheral blood samples every month for 6 months (or until seroconversion). If they are positive for anti- covid 19 antibodies, a test for positivity of the virus will be carried out. T
arm group label: EMPLOYEES WITH COVID-19 INFECTION
description: Humanitas group employees (including ICH, Humanitas University and Gavazzeni), and two validation cohorts.
employees that are Sars-Cov-2 positive both symptomatic and asymptomatic, there will be at least 2 peripheral blood samples (5 and 3 ml) at every control visit until ascertained negativity. They will also undergo a pharyngeal swab for viral titers and microbiota analysis at enrollment and at negativity. In addition, a sample of saliva/sputum will be collected for most of the employees at positivity and at every control visit.
For employees hospitalized but not requiring intensive care the following samples will be collected:
an aliquot of samples from the respiratory tract (e.g., bronchial aspirate, bronchoalveolar lavage) residual from the normal clinical practice
saliva/sputum
pharyngeal swab not used for diagnosis both at admission and at the first check up
blood sample in EDTA for plasma and peripheral blood mononuclear cell (PBMC)
intervention type: Other
intervention name: No intervention
description: No intervention, analysis of biological samples
arm group label: EMPLOYEES WITH COVID-19 INFECTION
arm group label: EMPLOYEES WITHOUT COVID-19 INFECTION
blood, pharyngeal swab, and for those hospitalized for COVID-19, also for the bronchoalveolar
      lavage and fecal samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria Rescigno, PhD
phone: 00390282245431
email: maria.rescigno@hunimed.eu
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No