<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/NCT04442789</url>
  </required_header>
  <id_info>
    <org_study_id>SECOV</org_study_id>
    <nct_id>NCT04442789</nct_id>
  </id_info>
  <brief_title>Sequelae of Sars-CoV-2 Infections</brief_title>
  <official_title>Long-term Sequelae of Severe Sars-CoV-2 Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Giessen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Giessen</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>
      By the end of 2019 a new coronavirus, named SARS-CoV-2, was discovered in patients with&#xD;
      pneumonia in Wuhan, China. In the following weeks and months the virus spread globally,&#xD;
      having a tremendous impact on global health and economy. To date, no vaccine or therapy is&#xD;
      available. Severe courses of the infection not only affect the lungs, but also other organs&#xD;
      like the heart, kidney, or liver. The lack of preexisting immunity might at least partially&#xD;
      explain the affection of extra pulmonary organs not yet seen in infections due to other&#xD;
      respiratory viruses. In this observational investigation the study group will follow up on&#xD;
      patients that have been hospitalized due to a SARS-CoV-2 infection, and monitor sequelae in&#xD;
      various organs, with an emphasis on the pulmo-cardiovascular system. Our that in some&#xD;
      patients, organ damage will persist and require long-term medical care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 requires hospitalization in a&#xD;
      significant amount of patients. The hospitalization rate and disease severity increases in&#xD;
      the elderly and patients with comorbidities such as diabetes, arterial hypertension, lung&#xD;
      pathologies and obesity (Garg et al.). Patients with severe infections have pneumonia,&#xD;
      requiring prolonged invasive ventilation. Sequelae of longer periods of mechanical&#xD;
      ventilation and reduction of quality of life after acute respiratory distress syndrome (ARDS)&#xD;
      are described (Herridge et al., 2 references). Besides, SARS-CoV-2 can induce - without&#xD;
      preexisting immunity - strong inflammatory reactions, which can affect various organs.&#xD;
      COVID-19 specific complications like thromboembolic events, neurologic events, myocardial&#xD;
      involvement, or liver damage are reported during the acute stage of the infection. The lung&#xD;
      is affected even during less severe infections, and ground glass opacities can result in&#xD;
      consolidations (Shi et al.). These changes were reported to persist after discharge (Mo et&#xD;
      al.). Acute kidney failure occurs in critically ill patients in 20-40% (Richardson et al.),&#xD;
      and 40% of patients admitted to the hospital had proteinuria (Cheng et al.). Myocardial&#xD;
      damage is reported, and some patients even presented initially with chest tightness and&#xD;
      palpitations before having fever or cough (Zheng et al.). Moreover, patients with COVID-19&#xD;
      have a higher risk of thromboembolic events (Klok et al., Llitjos et al). Typically these&#xD;
      patients have a prolonged activated partial thromboplastin time (aPTT), and often&#xD;
      antiphospholipid antibodies (Bowles et al.). The long-term consequences of the strong&#xD;
      inflammatory response affecting various organs are currently unknown. We hypothesize that&#xD;
      some patients will have transient or persistent sequelae requiring medical care. The study&#xD;
      group will therefore clinically examine patients that were hospitalized due to COVID-19, and&#xD;
      monitor pulmonary, and other organ functions for at least one year after symptom onset. The&#xD;
      study group will thereby perform lung and cardial examinations, monitor nephrologic&#xD;
      parameters and perform radiology. Pneumologic tests will include a lung function test, a&#xD;
      spiroergometry, a 6-minute walking test, and a grip-force test. Cardiac examination will&#xD;
      include an echocardiography, and an electrocardiogram. In case of of severe pneumonia, or&#xD;
      deterioration in lung function, computer tomography of the lungs will be performed. Blood&#xD;
      (and urine) tests will include kidney parameters, inflammatory markers, liver values, and&#xD;
      coagulation tests. Additional examinations will be done on an individual basis if clinically&#xD;
      indicated, e.g. lung biopsies in case of suspected interstitial fibrosis. Additionally&#xD;
      patient samples, which were taken for diagnostic purposes (serum, PBMCs, biopsies) will be&#xD;
      stored in the biobank of the German center for lung research (DZL). Clinical evaluation and&#xD;
      testing will start 2 months after symptom onset and the last visit is scheduled 10 months&#xD;
      later. Depending on the results and the needs of the individual patient additional testing&#xD;
      will be conducted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Sequelae after COVID-19</measure>
    <time_frame>12 months, extension if required</time_frame>
    <description>Identify organ dysfunction after SARS-CoV-2 infections</description>
  </primary_outcome>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Lung Diseases</condition>
  <condition>Cardiac Disease</condition>
  <condition>Inflammatory Reaction</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      PBMCs&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients that have been hospitalized due to Covid 19&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  hospitalization due to Sars-CoV-2 infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  under 18 years of age&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Ulrich Matt, MD, PhD</last_name>
    <phone>0049-(0)641-985-58773</phone>
    <email>ulrich.matt@innere.med.uni-giessen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Khodr Tello, MD</last_name>
    <email>khodr.tello@innere.med.uni-giessen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University</name>
      <address>
        <city>Giessen</city>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ulrich Matt, MD, PhD</last_name>
      <phone>0049064198558773</phone>
      <email>ulrich.matt@innere.med.uni-giessen.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Garg S, Kim L, Whitaker M, O'Halloran A, Cummings C, Holstein R, Prill M, Chai SJ, Kirley PD, Alden NB, Kawasaki B, Yousey-Hindes K, Niccolai L, Anderson EJ, Openo KP, Weigel A, Monroe ML, Ryan P, Henderson J, Kim S, Como-Sabetti K, Lynfield R, Sosin D, Torres S, Muse A, Bennett NM, Billing L, Sutton M, West N, Schaffner W, Talbot HK, Aquino C, George A, Budd A, Brammer L, Langley G, Hall AJ, Fry A. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):458-464. doi: 10.15585/mmwr.mm6915e3.</citation>
    <PMID>32298251</PMID>
  </reference>
  <reference>
    <citation>Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003 Feb 20;348(8):683-93. doi: 10.1056/NEJMoa022450.</citation>
    <PMID>12594312</PMID>
  </reference>
  <reference>
    <citation>Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.</citation>
    <PMID>21470008</PMID>
  </reference>
  <reference>
    <citation>Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.</citation>
    <PMID>32105637</PMID>
  </reference>
  <reference>
    <citation>Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, Xiong Y, Cheng Z, Gao S, Liang K, Luo M, Chen T, Song S, Ma Z, Chen X, Zheng R, Cao Q, Wang F, Zhang Y. Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2021 Dec 6;73(11):e4208-e4213. doi: 10.1093/cid/ciaa270.</citation>
    <PMID>32173725</PMID>
  </reference>
  <reference>
    <citation>Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum In: JAMA. 2020 May 26;323(20):2098.</citation>
    <PMID>32320003</PMID>
  </reference>
  <reference>
    <citation>Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829-838. doi: 10.1016/j.kint.2020.03.005. Epub 2020 Mar 20.</citation>
    <PMID>32247631</PMID>
  </reference>
  <reference>
    <citation>Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5.</citation>
    <PMID>32139904</PMID>
  </reference>
  <reference>
    <citation>Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10.</citation>
    <PMID>32291094</PMID>
  </reference>
  <reference>
    <citation>Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, MacDonald V, Green L, Sivapalaratnam S, Pasi KJ, MacCallum P. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020 Jul 16;383(3):288-290. doi: 10.1056/NEJMc2013656. Epub 2020 May 5. No abstract available.</citation>
    <PMID>32369280</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</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>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Inflammation</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/NCT04442789
org study id: SECOV
nct id: NCT04442789
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
By the end of 2019 a new coronavirus, named SARS-CoV-2, was discovered in patients with
      pneumonia in Wuhan, China. In the following weeks and months the virus spread globally,
      having a tremendous impact on global health and economy. To date, no vaccine or therapy is
      available. Severe courses of the infection not only affect the lungs, but also other organs
      like the heart, kidney, or liver. The lack of preexisting immunity might at least partially
      explain the affection of extra pulmonary organs not yet seen in infections due to other
      respiratory viruses. In this observational investigation the study group will follow up on
      patients that have been hospitalized due to a SARS-CoV-2 infection, and monitor sequelae in
      various organs, with an emphasis on the pulmo-cardiovascular system. Our that in some
      patients, organ damage will persist and require long-term medical care.
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 requires hospitalization in a
      significant amount of patients. The hospitalization rate and disease severity increases in
      the elderly and patients with comorbidities such as diabetes, arterial hypertension, lung
      pathologies and obesity (Garg et al.). Patients with severe infections have pneumonia,
      requiring prolonged invasive ventilation. Sequelae of longer periods of mechanical
      ventilation and reduction of quality of life after acute respiratory distress syndrome (ARDS)
      are described (Herridge et al., 2 references). Besides, SARS-CoV-2 can induce - without
      preexisting immunity - strong inflammatory reactions, which can affect various organs.
      COVID-19 specific complications like thromboembolic events, neurologic events, myocardial
      involvement, or liver damage are reported during the acute stage of the infection. The lung
      is affected even during less severe infections, and ground glass opacities can result in
      consolidations (Shi et al.). These changes were reported to persist after discharge (Mo et
      al.). Acute kidney failure occurs in critically ill patients in 20-40% (Richardson et al.),
      and 40% of patients admitted to the hospital had proteinuria (Cheng et al.). Myocardial
      damage is reported, and some patients even presented initially with chest tightness and
      palpitations before having fever or cough (Zheng et al.). Moreover, patients with COVID-19
      have a higher risk of thromboembolic events (Klok et al., Llitjos et al). Typically these
      patients have a prolonged activated partial thromboplastin time (aPTT), and often
      antiphospholipid antibodies (Bowles et al.). The long-term consequences of the strong
      inflammatory response affecting various organs are currently unknown. We hypothesize that
      some patients will have transient or persistent sequelae requiring medical care. The study
      group will therefore clinically examine patients that were hospitalized due to COVID-19, and
      monitor pulmonary, and other organ functions for at least one year after symptom onset. The
      study group will thereby perform lung and cardial examinations, monitor nephrologic
      parameters and perform radiology. Pneumologic tests will include a lung function test, a
      spiroergometry, a 6-minute walking test, and a grip-force test. Cardiac examination will
      include an echocardiography, and an electrocardiogram. In case of of severe pneumonia, or
      deterioration in lung function, computer tomography of the lungs will be performed. Blood
      (and urine) tests will include kidney parameters, inflammatory markers, liver values, and
      coagulation tests. Additional examinations will be done on an individual basis if clinically
      indicated, e.g. lung biopsies in case of suspected interstitial fibrosis. Additionally
      patient samples, which were taken for diagnostic purposes (serum, PBMCs, biopsies) will be
      stored in the biobank of the German center for lung research (DZL). Clinical evaluation and
      testing will start 2 months after symptom onset and the last visit is scheduled 10 months
      later. Depending on the results and the needs of the individual patient additional testing
      will be conducted.
observational model: Cohort
time perspective: Prospective
measure: Sequelae after COVID-19
time frame: 12 months, extension if required
description: Identify organ dysfunction after SARS-CoV-2 infections
PBMCs
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Ulrich Matt, MD, PhD
phone: 0049-(0)641-985-58773
email: ulrich.matt@innere.med.uni-giessen.de
last name: Khodr Tello, MD
email: khodr.tello@innere.med.uni-giessen.de
facility: 
status: Recruiting
contact: 
country: Germany
citation: Garg S, Kim L, Whitaker M, O'Halloran A, Cummings C, Holstein R, Prill M, Chai SJ, Kirley PD, Alden NB, Kawasaki B, Yousey-Hindes K, Niccolai L, Anderson EJ, Openo KP, Weigel A, Monroe ML, Ryan P, Henderson J, Kim S, Como-Sabetti K, Lynfield R, Sosin D, Torres S, Muse A, Bennett NM, Billing L, Sutton M, West N, Schaffner W, Talbot HK, Aquino C, George A, Budd A, Brammer L, Langley G, Hall AJ, Fry A. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):458-464. doi: 10.15585/mmwr.mm6915e3.
PMID: 32298251
citation: Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003 Feb 20;348(8):683-93. doi: 10.1056/NEJMoa022450.
PMID: 12594312
citation: Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
PMID: 21470008
citation: Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.
PMID: 32105637
citation: Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, Xiong Y, Cheng Z, Gao S, Liang K, Luo M, Chen T, Song S, Ma Z, Chen X, Zheng R, Cao Q, Wang F, Zhang Y. Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2021 Dec 6;73(11):e4208-e4213. doi: 10.1093/cid/ciaa270.
PMID: 32173725
citation: Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum In: JAMA. 2020 May 26;323(20):2098.
PMID: 32320003
citation: Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829-838. doi: 10.1016/j.kint.2020.03.005. Epub 2020 Mar 20.
PMID: 32247631
citation: Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5.
PMID: 32139904
citation: Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10.
PMID: 32291094
citation: Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, MacDonald V, Green L, Sivapalaratnam S, Pasi KJ, MacCallum P. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020 Jul 16;383(3):288-290. doi: 10.1056/NEJMc2013656. Epub 2020 May 5. No abstract available.
PMID: 32369280
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Lung Diseases
mesh term: Heart Diseases
mesh term: Inflammation
sharing ipd: No