<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/NCT04473365</url>
  </required_header>
  <id_info>
    <org_study_id>RIA2020EF-2905</org_study_id>
    <nct_id>NCT04473365</nct_id>
  </id_info>
  <brief_title>Rapid Diagnostic Profiling of SARS-CoV-2 (COVID-19)</brief_title>
  <acronym>Profile-Cov</acronym>
  <official_title>Rapid Diagnostic Profiling of SARS-CoV-2 in the Context of Persistent Immune Activation in Sub-Saharan Africa (Profile-Cov)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mekelle University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ethiopian Public Health Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Liverpool School of Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mekelle University</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 investigators will evaluate the profile of the immune response of Ethiopian population&#xD;
      and examine its relationship with the noted low CD4+ T-cell count and underlying immune&#xD;
      activation status among participants with COVID-19 and will compare results with those&#xD;
      residing in Europe. In addition, this project will evaluate the performance of various rapid&#xD;
      diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune&#xD;
      system characteristics. We will also evaluate the effect of co-infection with parasites on&#xD;
      COVID-19 severity&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In December 2019, a cluster of patients with pneumonia of unknown aetiology was linked to an&#xD;
      infection with a novel coronavirus - the SARS-CoV-2. Since then, the infection has become&#xD;
      pandemic and spread affecting almost every country in the world. Knowledge of virus dynamics&#xD;
      and the host's immune response to it is essential to understanding the pathogenesis as well&#xD;
      as in formulating diagnostic, therapeutic and preventive strategies. There are no studies,&#xD;
      however, related to these issues, particularly in Sub-Saharan Africa (SSA) context. Previous&#xD;
      studies by the investigators have shown that the immune profile of healthy Ethiopians shows&#xD;
      evidence of chronic immune activation with significant low naïve cells but high activated&#xD;
      memory cells, of both CD4+ and CD8+ T-cell sub populations. The above immune system&#xD;
      characteristics of Ethiopians as compared to Europeans led the investigators to the&#xD;
      assumption that these could contribute to the pathogenesis of and severity of clinical&#xD;
      presentation of COVID-19. Persistent immune activation due to continuous infections with&#xD;
      helminths is common in the entire SSA region. Such activation usually skewes the immune&#xD;
      system towards T helper (Th)-2-type responses. The immune response against SARS-CoV-2 is&#xD;
      typically of so called &quot;cytokine storm&quot;. Here, the investigators hypothesize that SARS-CoV-2&#xD;
      infection induced immune activation as observed in patients in the industrialized world (with&#xD;
      concomitant cytokine storms and extensive non-specific CD8 T-cell cytotoxicity) might be more&#xD;
      prominent than in people from SSA, due to the Th2 profile of their immune system.&#xD;
&#xD;
      The investigators propose to study the profile of the immune response of Ethiopian population&#xD;
      and will examine its relationship with the noted low CD4+ T-cell count and underlying immune&#xD;
      activation status among patients with COVID-19 and will compare results with those residing&#xD;
      in Europe. In addition, this project will evaluate the performance of various rapid&#xD;
      diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune&#xD;
      system characteristics. In addition, the investigators will evaluate the RDTs for use in the&#xD;
      screening of infected patients who are asymptomatic, in particular in health-care settings,&#xD;
      as well as for monitoring recovery or clearance of virus shedding for use in&#xD;
      resource-constrained setting. Such comparative studies will help identify immune factors that&#xD;
      could play a role in attenuating the disrupted immune responses caused by SARS-CoV-2&#xD;
      infection and thus contribute to the design and development of effective diagnostic,&#xD;
      therapeutic or vaccine.&#xD;
&#xD;
      The pathogenesis of severe COVID-19 is related to hyper-inflammation. However, COVID-19&#xD;
      symptomatology in SSA appears significantly less serious than in industrialized world. We&#xD;
      postulate that individuals residing in SSA and co-infected with intestinal parasites down&#xD;
      regulate immune to SARS-CoV-2 and mute COVID-19 severity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</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>Proportion of patients identified as Covid-19 by and monitoring virus clearance with COVID-19 using algorithm of RDTs.</measure>
    <time_frame>Up to 30 days after onset of infection</time_frame>
    <description>RT-PCR confirmed Covid-19 patients identified by rapid antibody- and antigen-based assays</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of non-Covid-19 cases identified as negative by antibody assay</measure>
    <time_frame>Up to 30 days after onset of infection other than SARS-CoV-2</time_frame>
    <description>Healthy controls on samples collected pre-Covid-19 pandemic period tested by rapid antibody-based assays</description>
  </primary_outcome>
  <other_outcome>
    <measure>Proportion of Ethiopian vs. European COVID-19 patients with predominant Th1 type immune responses.</measure>
    <time_frame>Up to 30 days after onset of infection</time_frame>
    <description>Different immune biomarkers measured in Covid-19 patients presenting with different disease severity stage/spectrum</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of severe COVID-19 patients with or without parasite co-infection</measure>
    <time_frame>Up to 45 days after onset of infection/during hospitalization)</time_frame>
    <description>Stool exam undertaken among COVID-19 patients presenting with different clinical status at time of admission or isolation</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of patients with SARS-CoV-2 neutralizing antibody titer</measure>
    <time_frame>Up to 45 days of follow-up after symptom onset</time_frame>
    <description>Measurement of neutralizing antibody titers</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">838</enrollment>
  <condition>SARS-CoV-2</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Without parasite</arm_group_label>
    <description>For secondary outcome: effect of co-infection with parasite on COVID-19 severity Group 1 will constitute those without parasite co-infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>With parasite</arm_group_label>
    <description>For secondary outcome: effect of co-infection with parasite on COVID-19 severity Group 2 will constitute those with parasite co-infection</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intestinal parasite</intervention_name>
    <description>Pre-existing intestinal parasite infection present or absent at time of admission</description>
    <arm_group_label>With parasite</arm_group_label>
    <other_name>Without intestinal parasite</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma samples and PBMC biobanking for further analysis&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients suspected of having SARS-CoV-2 infection and admitted to Covid-19 isolation and&#xD;
        treatment centers.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical case-definition confirmed by RT-PCR.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent history of COVID-19&#xD;
&#xD;
          -  Not capable of understanding or complying with the study protocol&#xD;
&#xD;
          -  Anticipated transfer to another hospital which is not a study site within 72 hours&#xD;
&#xD;
          -  Refusal to consent and participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dawit Wolday, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mekelle University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mekelle University College of Health Sciences</name>
      <address>
        <city>Mekelle</city>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 11, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>March 31, 2023</last_update_submitted>
  <last_update_submitted_qc>March 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mekelle University</investigator_affiliation>
    <investigator_full_name>Prof. Dawit Wolday</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Immune profile</keyword>
  <keyword>Serology</keyword>
  <keyword>Antibody test</keyword>
  <keyword>Antigen test</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Immune response</keyword>
  <keyword>Severity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <!-- 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/NCT04473365
org study id: RIA2020EF-2905
nct id: NCT04473365
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators will evaluate the profile of the immune response of Ethiopian population
      and examine its relationship with the noted low CD4+ T-cell count and underlying immune
      activation status among participants with COVID-19 and will compare results with those
      residing in Europe. In addition, this project will evaluate the performance of various rapid
      diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune
      system characteristics. We will also evaluate the effect of co-infection with parasites on
      COVID-19 severity
In December 2019, a cluster of patients with pneumonia of unknown aetiology was linked to an
      infection with a novel coronavirus - the SARS-CoV-2. Since then, the infection has become
      pandemic and spread affecting almost every country in the world. Knowledge of virus dynamics
      and the host's immune response to it is essential to understanding the pathogenesis as well
      as in formulating diagnostic, therapeutic and preventive strategies. There are no studies,
      however, related to these issues, particularly in Sub-Saharan Africa (SSA) context. Previous
      studies by the investigators have shown that the immune profile of healthy Ethiopians shows
      evidence of chronic immune activation with significant low naïve cells but high activated
      memory cells, of both CD4+ and CD8+ T-cell sub populations. The above immune system
      characteristics of Ethiopians as compared to Europeans led the investigators to the
      assumption that these could contribute to the pathogenesis of and severity of clinical
      presentation of COVID-19. Persistent immune activation due to continuous infections with
      helminths is common in the entire SSA region. Such activation usually skewes the immune
      system towards T helper (Th)-2-type responses. The immune response against SARS-CoV-2 is
      typically of so called "cytokine storm". Here, the investigators hypothesize that SARS-CoV-2
      infection induced immune activation as observed in patients in the industrialized world (with
      concomitant cytokine storms and extensive non-specific CD8 T-cell cytotoxicity) might be more
      prominent than in people from SSA, due to the Th2 profile of their immune system.

      The investigators propose to study the profile of the immune response of Ethiopian population
      and will examine its relationship with the noted low CD4+ T-cell count and underlying immune
      activation status among patients with COVID-19 and will compare results with those residing
      in Europe. In addition, this project will evaluate the performance of various rapid
      diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune
      system characteristics. In addition, the investigators will evaluate the RDTs for use in the
      screening of infected patients who are asymptomatic, in particular in health-care settings,
      as well as for monitoring recovery or clearance of virus shedding for use in
      resource-constrained setting. Such comparative studies will help identify immune factors that
      could play a role in attenuating the disrupted immune responses caused by SARS-CoV-2
      infection and thus contribute to the design and development of effective diagnostic,
      therapeutic or vaccine.

      The pathogenesis of severe COVID-19 is related to hyper-inflammation. However, COVID-19
      symptomatology in SSA appears significantly less serious than in industrialized world. We
      postulate that individuals residing in SSA and co-infected with intestinal parasites down
      regulate immune to SARS-CoV-2 and mute COVID-19 severity.
observational model: Cohort
time perspective: Prospective
measure: Proportion of patients identified as Covid-19 by and monitoring virus clearance with COVID-19 using algorithm of RDTs.
time frame: Up to 30 days after onset of infection
description: RT-PCR confirmed Covid-19 patients identified by rapid antibody- and antigen-based assays
measure: Proportion of non-Covid-19 cases identified as negative by antibody assay
time frame: Up to 30 days after onset of infection other than SARS-CoV-2
description: Healthy controls on samples collected pre-Covid-19 pandemic period tested by rapid antibody-based assays
measure: Proportion of Ethiopian vs. European COVID-19 patients with predominant Th1 type immune responses.
time frame: Up to 30 days after onset of infection
description: Different immune biomarkers measured in Covid-19 patients presenting with different disease severity stage/spectrum
measure: Proportion of severe COVID-19 patients with or without parasite co-infection
time frame: Up to 45 days after onset of infection/during hospitalization)
description: Stool exam undertaken among COVID-19 patients presenting with different clinical status at time of admission or isolation
measure: Proportion of patients with SARS-CoV-2 neutralizing antibody titer
time frame: Up to 45 days of follow-up after symptom onset
description: Measurement of neutralizing antibody titers
arm group label: Without parasite
description: For secondary outcome: effect of co-infection with parasite on COVID-19 severity Group 1 will constitute those without parasite co-infection
arm group label: With parasite
description: For secondary outcome: effect of co-infection with parasite on COVID-19 severity Group 2 will constitute those with parasite co-infection
intervention type: Other
intervention name: Intestinal parasite
description: Pre-existing intestinal parasite infection present or absent at time of admission
arm group label: With parasite
other name: Without intestinal parasite
Plasma samples and PBMC biobanking for further analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dawit Wolday, MD, PhD
role: Principal Investigator
affiliation: Mekelle University
facility: 
country: Ethiopia
responsible party type: Principal Investigator
investigator affiliation: Mekelle University
investigator full name: Prof. Dawit Wolday
investigator title: Associate Professor of Medicine
mesh term: COVID-19