<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/NCT04401436</url>
  </required_header>
  <id_info>
    <org_study_id>200111</org_study_id>
    <secondary_id>20-I-0111</secondary_id>
    <nct_id>NCT04401436</nct_id>
  </id_info>
  <brief_title>COVID-19 Associated Lymphopenia Pathogenesis Study in Blood</brief_title>
  <official_title>COVID-19-associated Lymphopenia Pathogenesis Study in Blood</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</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>
      Background:&#xD;
&#xD;
      COVID-19 is an acute respiratory syndrome. One symptom of COVID-19 is a reduction in the&#xD;
      number of cells called lymphocytes in the blood. Lymphocytes are a type of white blood cell&#xD;
      that fights infections. With fewer lymphocytes, the body cannot effectively fight back&#xD;
      against SARS CoV-2, the virus that causes COVID-19. Researchers want to better understand how&#xD;
      SARS-CoV-2 affects these blood cells. This information may give them ideas for new&#xD;
      treatments.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To learn more about how SARS-CoV-2 affects lymphocytes, the immune, and the blood clotting&#xD;
      system.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults age 18 and older who either currently have COVID-19 or have recently recovered from it&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will give a blood sample. For this, a needle is used to collect blood from an&#xD;
      arm vein. For participants who have a central line, blood will be collected through that&#xD;
      instead.&#xD;
&#xD;
      Participants medical records related to COVID-19 will be reviewed.&#xD;
&#xD;
      Participants who have recovered from COVID-19 will be asked to undergo leukapheresis to&#xD;
      collect white blood cells. For this, blood is taken from a needle placed in one arm. A&#xD;
      machine separates out the white blood cells. The rest of the blood is returned to the&#xD;
      participant through a needle placed in the other arm. This takes about 2-3 hours.&#xD;
&#xD;
      Recovered participants may have material collected from inside the nostrils and/or rectum.&#xD;
      This is done by gently rubbing the area with a sterile cotton swab.&#xD;
&#xD;
      Recovered participants may have an echocardiogram to look at their heart. For this, a small&#xD;
      probe is held against the chest to get pictures of the heart from different angles. This&#xD;
      takes less than 30 minutes.&#xD;
&#xD;
      Participation lasts 1-2 days on most cases and may be split in a few visits for recovered&#xD;
      patients if leukapheresis and echocardiogram are done.&#xD;
&#xD;
      ...&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel&#xD;
      coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The emergence of&#xD;
      SARS-CoV-2 has led to a pandemic with a wide range of manifestations. One of the hallmarks of&#xD;
      severe illness is the presence of elevated levels of inflammatory biomarkers, coagulopathy,&#xD;
      and lymphopenia. Lymphopenia is a robust and consistent predictor of mortality in COVID-19.&#xD;
      Understanding the intersection of inflammation, complement activation, endothelial damage,&#xD;
      and coagulation is critical to a better understanding of COVID-19 pathogenesis.&#xD;
&#xD;
      This is a multisite study that will conducted at the National Institutes of Health Clinical&#xD;
      Center and other local hospitals. We will recruit patients with mild to severe COVID-19, as&#xD;
      well as patients who have recently recovered from the disease. Participants will have blood&#xD;
      drawn via venipuncture or available venous access and optional nasal and/or rectal swabs,&#xD;
      with optional leukapheresis and echocardiogram for recovered patients. Leftover clinical&#xD;
      specimens may also be used for research. Blood will be used for genetic testing, lymphocyte&#xD;
      phenotyping, soluble biomarker analysis, and other research tests. Clinical and laboratory&#xD;
      data from routine care&#xD;
&#xD;
      (eg, basic demographic information, vital signs, medications, clinical labs, and radiologic&#xD;
      imaging) will also be collected and up to two follow up visits may be done for clinical&#xD;
      purposes. Participants may re-enroll in the study after recovery from infection as recovered&#xD;
      participants or if they experience a new infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Evaluation of lymphocyte subsets in patients with COVID-19 at various stages of disease, including recovery.</measure>
    <time_frame>Throughout the study</time_frame>
    <description>To characterize lymphopenia and immunologic phenotypes and inflammatory responses including inflammasome responses and coagulopathy in patients with COVID-19.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of inflammatory pathways that may contribute to COVID-19 disease pathogenesis.</measure>
    <time_frame>Throughout the study</time_frame>
    <description>1. Correlation of lymphopenia, immunologic phenotypes, and inflammatory responses with clinical outcomes. 2. Characterization of complement activation in patients with COVID-19. 3. Evaluation of activation-induced cell death and activated T cell autonomous death through measurement of intracellular reactive oxygen species in monocyte, natural killer (NK), and T cell subsets in peripheral blood and correlation with double stranded (ds)-DNA damage (gamma-H2AX), FAS/FasL, BCL-2, caspase-1 activation, and activation-induced proliferation. 4. Evaluation of homing receptors to lymphoid, skin, and mucosal surfaces on B and T cells and correlate with ACE2, bradykinin, and homing chemokine levels.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">625</enrollment>
  <condition>Coronavirus Disease 2019</condition>
  <arm_group>
    <arm_group_label>COVID 19 patients</arm_group_label>
    <description>Study participants will be adults who either have COVID-19 or who have recently recovered from the disease(recovered per Centers for Disease Control and Prevention guidelines).</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        COVID 19 positive and recovered patients from inpatient settings at the NIH CC and&#xD;
        Georgetown University Medical Center, and the local community for COVID 19 recovered&#xD;
        patients.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Aged &gt;=18 years.&#xD;
&#xD;
               2. Diagnosis of COVID-19 via molecular assay or other commercial or public health&#xD;
                  assay.&#xD;
&#xD;
               3. Meets one of the following criteria for COVID-19:&#xD;
&#xD;
                    1. Group A, mild clinical presentation: asymptomatic to oxygen requirements&#xD;
                       &lt;-4L nasal cannula (NC).&#xD;
&#xD;
                    2. Group B, moderate clinical presentation: oxygen requirements &gt;4L NC to &lt;=50%&#xD;
                       fraction of inspired oxygen (FiO2) on high-flow oxygen devices.&#xD;
&#xD;
                    3. Group C, severe clinical presentation: non-invasive ventilation with oxygen&#xD;
                       requirements &gt;50% FiO2 on high-flow oxygen devices, any other modality of&#xD;
                       non-invasive ventilation, or mechanical ventilation.&#xD;
&#xD;
                    4. Group D, recovered: meets CDC criteria for discontinuation of&#xD;
                       transmission-based precautions and disposition of patients with COVID-19 in&#xD;
                       healthcare settings. Enrollment will occur at least 30 days after the above&#xD;
                       criteria were met.&#xD;
&#xD;
               4. Able to provide informed consent.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Individuals meeting any of the following criteria will be excluded from study&#xD;
        participation:&#xD;
&#xD;
          1. Documented history of hemoglobin from most recent blood draw &lt;7g/dL if known.&#xD;
&#xD;
          2. Any condition that, in the opinion of the investigator, contraindicates participation&#xD;
             in this study.&#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_official>
    <last_name>Irini Sereti, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elizabeth Laidlaw, P.A.-C</last_name>
    <phone>(301) 827-9717</phone>
    <email>elizabeth.laidlaw@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Irini Sereti, M.D.</last_name>
    <phone>(301) 496-5533</phone>
    <email>isereti@niaid.nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Princy Kumar, M.D.</last_name>
      <phone>202-444-0086</phone>
      <email>kumarp@gunet.georgetown.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>MedStar Health Research Institute: Washington Hospital Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Glenn Wortmann, MD</last_name>
      <phone>208-877-0333</phone>
      <email>Glenn.W.Wortmann@medstar.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-I-0111.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.</citation>
    <PMID>32217835</PMID>
  </reference>
  <reference>
    <citation>Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.</citation>
    <PMID>32171076</PMID>
  </reference>
  <reference>
    <citation>Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.</citation>
    <PMID>31978945</PMID>
  </reference>
  <verification_date>December 23, 2022</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>December 28, 2022</last_update_submitted>
  <last_update_submitted_qc>December 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Lymphopenia</keyword>
  <keyword>Coagulopathy</keyword>
  <keyword>Cytokines</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Lymphopenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>.No plans at this time.</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/NCT04401436
org study id: 200111
secondary id: 20-I-0111
nct id: NCT04401436
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      COVID-19 is an acute respiratory syndrome. One symptom of COVID-19 is a reduction in the
      number of cells called lymphocytes in the blood. Lymphocytes are a type of white blood cell
      that fights infections. With fewer lymphocytes, the body cannot effectively fight back
      against SARS CoV-2, the virus that causes COVID-19. Researchers want to better understand how
      SARS-CoV-2 affects these blood cells. This information may give them ideas for new
      treatments.

      Objective:

      To learn more about how SARS-CoV-2 affects lymphocytes, the immune, and the blood clotting
      system.

      Eligibility:

      Adults age 18 and older who either currently have COVID-19 or have recently recovered from it

      Design:

      Participants will give a blood sample. For this, a needle is used to collect blood from an
      arm vein. For participants who have a central line, blood will be collected through that
      instead.

      Participants medical records related to COVID-19 will be reviewed.

      Participants who have recovered from COVID-19 will be asked to undergo leukapheresis to
      collect white blood cells. For this, blood is taken from a needle placed in one arm. A
      machine separates out the white blood cells. The rest of the blood is returned to the
      participant through a needle placed in the other arm. This takes about 2-3 hours.

      Recovered participants may have material collected from inside the nostrils and/or rectum.
      This is done by gently rubbing the area with a sterile cotton swab.

      Recovered participants may have an echocardiogram to look at their heart. For this, a small
      probe is held against the chest to get pictures of the heart from different angles. This
      takes less than 30 minutes.

      Participation lasts 1-2 days on most cases and may be split in a few visits for recovered
      patients if leukapheresis and echocardiogram are done.

      ...
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel
      coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The emergence of
      SARS-CoV-2 has led to a pandemic with a wide range of manifestations. One of the hallmarks of
      severe illness is the presence of elevated levels of inflammatory biomarkers, coagulopathy,
      and lymphopenia. Lymphopenia is a robust and consistent predictor of mortality in COVID-19.
      Understanding the intersection of inflammation, complement activation, endothelial damage,
      and coagulation is critical to a better understanding of COVID-19 pathogenesis.

      This is a multisite study that will conducted at the National Institutes of Health Clinical
      Center and other local hospitals. We will recruit patients with mild to severe COVID-19, as
      well as patients who have recently recovered from the disease. Participants will have blood
      drawn via venipuncture or available venous access and optional nasal and/or rectal swabs,
      with optional leukapheresis and echocardiogram for recovered patients. Leftover clinical
      specimens may also be used for research. Blood will be used for genetic testing, lymphocyte
      phenotyping, soluble biomarker analysis, and other research tests. Clinical and laboratory
      data from routine care

      (eg, basic demographic information, vital signs, medications, clinical labs, and radiologic
      imaging) will also be collected and up to two follow up visits may be done for clinical
      purposes. Participants may re-enroll in the study after recovery from infection as recovered
      participants or if they experience a new infection.
observational model: Cohort
time perspective: Prospective
measure: Evaluation of lymphocyte subsets in patients with COVID-19 at various stages of disease, including recovery.
time frame: Throughout the study
description: To characterize lymphopenia and immunologic phenotypes and inflammatory responses including inflammasome responses and coagulopathy in patients with COVID-19.
measure: Evaluation of inflammatory pathways that may contribute to COVID-19 disease pathogenesis.
time frame: Throughout the study
description: 1. Correlation of lymphopenia, immunologic phenotypes, and inflammatory responses with clinical outcomes. 2. Characterization of complement activation in patients with COVID-19. 3. Evaluation of activation-induced cell death and activated T cell autonomous death through measurement of intracellular reactive oxygen species in monocyte, natural killer (NK), and T cell subsets in peripheral blood and correlation with double stranded (ds)-DNA damage (gamma-H2AX), FAS/FasL, BCL-2, caspase-1 activation, and activation-induced proliferation. 4. Evaluation of homing receptors to lymphoid, skin, and mucosal surfaces on B and T cells and correlate with ACE2, bradykinin, and homing chemokine levels.
arm group label: COVID 19 patients
description: Study participants will be adults who either have COVID-19 or who have recently recovered from the disease(recovered per Centers for Disease Control and Prevention guidelines).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Irini Sereti, M.D.
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
last name: Elizabeth Laidlaw, P.A.-C
phone: (301) 827-9717
email: elizabeth.laidlaw@nih.gov
last name: Irini Sereti, M.D.
phone: (301) 496-5533
email: isereti@niaid.nih.gov
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-I-0111.html
description: NIH Clinical Center Detailed Web Page
citation: Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PMID: 32217835
citation: Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.
PMID: 32171076
citation: Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
PMID: 31978945
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Lymphopenia
sharing ipd: No
ipd description: .No plans at this time.