<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/NCT04444310</url>
  </required_header>
  <id_info>
    <org_study_id>Assiut13</org_study_id>
    <nct_id>NCT04444310</nct_id>
  </id_info>
  <brief_title>Antibody Responses in Contacts of COVID-19 Patients</brief_title>
  <official_title>Antibody Responses in Asymptomatic Close Contacts of COVID-19 Patients and Their Implications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut 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>
      After several cases of pneumonia with an unfamiliar etiology were observed at the end of&#xD;
      2019, the National Health Commission of China released more details about the epidemic in&#xD;
      early 2020. The pathogen was identified as a novel coronavirus and named severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2), as it has a phylogenetic similarity to&#xD;
      SARS-CoV. Since then, SARS-CoV-2 has spread rapidly and the resulting coronavirus disease&#xD;
      2019 (COVID-19) has been declared a public health emergency of international concern (PHEIC)&#xD;
      by the World Health Organization (WHO).&#xD;
&#xD;
      SARS-CoV-2 is highly contagious, and there has not yet been any vaccine or effective&#xD;
      treatment that has received approval. So, the best solution for controlling the pandemic will&#xD;
      be the simultaneous application of preventive methods, sensitive diagnostic approaches, and&#xD;
      using current available drugs, while still developing novel treatments.&#xD;
&#xD;
      Coronaviruses are enveloped, non-segmented, single positive-stranded RNA viruses with round&#xD;
      or oval particles and a diameter of 50-200 nm. Coronavirus subfamily is divided into four&#xD;
      genera: α, β, γ and δ according to serotype and genomic characteristics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The SARS-CoV-2 belongs to the genus β which has been confirmed to be highly infectious by&#xD;
      research. (https://www.who.int/emergencies/&#xD;
      diseases/novel-coronavirus-2019/situation-reports).&#xD;
&#xD;
      The four major structural proteins of coronavirus are the spike surface glycoprotein (S),&#xD;
      small envelope protein (E), matrix protein (M), and nucleocapsid protein (N). The spike&#xD;
      protein (S) of coronavirus is a type I transmembrane glycoprotein and mediates the entrance&#xD;
      to human respiratory epithelial cells by interacting with cell surface receptor&#xD;
      angiotensin-converting enzyme 2 (ACE2) , the S protein contains distinct functional domains&#xD;
      near the amino (S1) and carboxy (S2) termini, the peripheral S1 portion can independently&#xD;
      bind cellular receptors while the integral membrane S2 portion is required to mediate fusion&#xD;
      of viral and cellular membranes . The nucleocapsid protein (N) forms complexes with genomic&#xD;
      RNA, interacts with the viral membrane protein during virion assembly and plays a critical&#xD;
      role in enhancing the efficiency of virus transcription and assembly .&#xD;
&#xD;
      The diagnosis of COVID-19 is dependent mainly on clinical characteristics, CT imaging and a&#xD;
      few laboratory tests. Although some symptoms and laboratory parameters have indicative values&#xD;
      in confirmed patients, they are not unique to SARSCoV-2 infection. The most used and reliable&#xD;
      test for diagnosis of COVID-19 has been the RT-PCR test performed using nasopharyngeal swabs.&#xD;
      A variety of RNA gene targets are used by different manufacturers, with most tests targeting&#xD;
      1 or more of the envelope (env), nucleocapsid (N), spike (S), RNA-dependent RNA polymerase&#xD;
      (RdRp), and ORF1 genes .&#xD;
&#xD;
      Spread of the COVID-19 global pandemic highlights the urgent need to develop effective&#xD;
      treatments or vaccines against SARS-CoV-2 infection. The identification of novel antibodies&#xD;
      to neutralize the virus is one of the approaches to fight COVID-19 . In particular, detect an&#xD;
      antibody against the SARS-CoV-2 spike protein by building on knowledge about the existing&#xD;
      structure of SARS-CoV-2 and learnings from previous SARS antibody generations. Potent&#xD;
      neutralizing antibodies often target the receptor interaction site in S1, disabling receptor&#xD;
      interactions. The so-called spike protein of 2019-nCoV is used by the virus to dock to human&#xD;
      cells. By targeting the protein, to prevent the infection.&#xD;
&#xD;
      COVID-19 patients developed SARS-CoV-2-specific NAbs at the convalescent phase of infection&#xD;
      (SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus). SARS-CoV -2 specific&#xD;
      NAbs reached their peak in patients from day 10-15 after the onset of the disease and&#xD;
      remained stable thereafter in the patients. Antibodies targeting on different domains of S&#xD;
      protein, including S1, RBD, and S2, may all contribute to the neutralization.&#xD;
&#xD;
      Neutralizing antibodies (NAbs) play important roles in virus clearance and have been&#xD;
      considered as a key immune product for protection or treatment against viral diseases.&#xD;
      Virus-specific NAbs, induced through either infection or vaccination, can block viral&#xD;
      infection . NAbs confer immunity by deactivate viruses by block access to receptors used by&#xD;
      the virus to enter host cells and bind to viral capsid and block uncoating of the viral&#xD;
      genome .&#xD;
&#xD;
      The level of NAbs has been used as a gold standard to evaluate the efficacy of vaccines&#xD;
      against smallpox, polio and influenza viruses . Passive antibody therapy, such as plasma&#xD;
      fusion, was successfully used to treat infectious viral diseases, including SARS-CoV virus,&#xD;
      influenza viruses, and Ebola virus. The efficacy of passive antibody therapy was associated&#xD;
      with the concentration of NAbs in plasma or antibodies of recovered donors. As the global&#xD;
      pandemic of COVID-19 proceeds, transfusion of convalescent plasma or serum from recovered&#xD;
      patients was also considered as a promising therapy for prophylaxis of infection or treatment&#xD;
      of disease. highly variable levels of NAbs in the patients of COVID-19 indicated that&#xD;
      convalescent plasma and serum from recovered donors should be titrated before use in passive&#xD;
      antibody therapy, an easy task that can be performed using the PsV neutralization assay. The&#xD;
      titers of NAbs were variable in different patients. Elderly patients (60-80 ys) were more&#xD;
      likely to induce higher titers of NAbs than younger patients. A moderate positive correlation&#xD;
      was also observed between age and Nab titers confirming the important role of age in the&#xD;
      generation of Nabs. The correlation of NAbs titers with age, lymphocyte counts, and blood CRP&#xD;
      levels suggested that the interplay between virus and host immune response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 18, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>14 Days</target_duration>
  <primary_outcome>
    <measure>Measure level of Abs in asymptomatic close contacts of COVID 19 patients.</measure>
    <time_frame>one day</time_frame>
    <description>serum level of antiSARS-CoV-2 IgG, IgM</description>
  </primary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>COVID-19</condition>
  <eligibility>
    <study_pop>
      <textblock>
        asymptomatic close contacts of confirmed COVID-19 patients, not complaining&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  close contacts of confirmed COVID-19 patients, apparently healthy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  symptomatic close contacts, any close contacts with malignant tumor, stroke, cardiac,&#xD;
             respiratory, Gastrointestinal, and renal diseases or any organ dysfunction.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>AssiutU</name>
      <address>
        <city>Assiut</city>
        <zip>71111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 21, 2020</last_update_submitted>
  <last_update_submitted_qc>June 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Aliae AR Mohamed Hussein</investigator_full_name>
    <investigator_title>Professor of Pulmonology</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>antibodies</keyword>
  <keyword>IgG</keyword>
  <keyword>IgM</keyword>
  <keyword>SARs-CoV-2</keyword>
  <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>Undecided</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/NCT04444310
org study id: Assiut13
nct id: NCT04444310
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
After several cases of pneumonia with an unfamiliar etiology were observed at the end of
      2019, the National Health Commission of China released more details about the epidemic in
      early 2020. The pathogen was identified as a novel coronavirus and named severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2), as it has a phylogenetic similarity to
      SARS-CoV. Since then, SARS-CoV-2 has spread rapidly and the resulting coronavirus disease
      2019 (COVID-19) has been declared a public health emergency of international concern (PHEIC)
      by the World Health Organization (WHO).

      SARS-CoV-2 is highly contagious, and there has not yet been any vaccine or effective
      treatment that has received approval. So, the best solution for controlling the pandemic will
      be the simultaneous application of preventive methods, sensitive diagnostic approaches, and
      using current available drugs, while still developing novel treatments.

      Coronaviruses are enveloped, non-segmented, single positive-stranded RNA viruses with round
      or oval particles and a diameter of 50-200 nm. Coronavirus subfamily is divided into four
      genera: α, β, γ and δ according to serotype and genomic characteristics.
The SARS-CoV-2 belongs to the genus β which has been confirmed to be highly infectious by
      research. (https://www.who.int/emergencies/
      diseases/novel-coronavirus-2019/situation-reports).

      The four major structural proteins of coronavirus are the spike surface glycoprotein (S),
      small envelope protein (E), matrix protein (M), and nucleocapsid protein (N). The spike
      protein (S) of coronavirus is a type I transmembrane glycoprotein and mediates the entrance
      to human respiratory epithelial cells by interacting with cell surface receptor
      angiotensin-converting enzyme 2 (ACE2) , the S protein contains distinct functional domains
      near the amino (S1) and carboxy (S2) termini, the peripheral S1 portion can independently
      bind cellular receptors while the integral membrane S2 portion is required to mediate fusion
      of viral and cellular membranes . The nucleocapsid protein (N) forms complexes with genomic
      RNA, interacts with the viral membrane protein during virion assembly and plays a critical
      role in enhancing the efficiency of virus transcription and assembly .

      The diagnosis of COVID-19 is dependent mainly on clinical characteristics, CT imaging and a
      few laboratory tests. Although some symptoms and laboratory parameters have indicative values
      in confirmed patients, they are not unique to SARSCoV-2 infection. The most used and reliable
      test for diagnosis of COVID-19 has been the RT-PCR test performed using nasopharyngeal swabs.
      A variety of RNA gene targets are used by different manufacturers, with most tests targeting
      1 or more of the envelope (env), nucleocapsid (N), spike (S), RNA-dependent RNA polymerase
      (RdRp), and ORF1 genes .

      Spread of the COVID-19 global pandemic highlights the urgent need to develop effective
      treatments or vaccines against SARS-CoV-2 infection. The identification of novel antibodies
      to neutralize the virus is one of the approaches to fight COVID-19 . In particular, detect an
      antibody against the SARS-CoV-2 spike protein by building on knowledge about the existing
      structure of SARS-CoV-2 and learnings from previous SARS antibody generations. Potent
      neutralizing antibodies often target the receptor interaction site in S1, disabling receptor
      interactions. The so-called spike protein of 2019-nCoV is used by the virus to dock to human
      cells. By targeting the protein, to prevent the infection.

      COVID-19 patients developed SARS-CoV-2-specific NAbs at the convalescent phase of infection
      (SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus). SARS-CoV -2 specific
      NAbs reached their peak in patients from day 10-15 after the onset of the disease and
      remained stable thereafter in the patients. Antibodies targeting on different domains of S
      protein, including S1, RBD, and S2, may all contribute to the neutralization.

      Neutralizing antibodies (NAbs) play important roles in virus clearance and have been
      considered as a key immune product for protection or treatment against viral diseases.
      Virus-specific NAbs, induced through either infection or vaccination, can block viral
      infection . NAbs confer immunity by deactivate viruses by block access to receptors used by
      the virus to enter host cells and bind to viral capsid and block uncoating of the viral
      genome .

      The level of NAbs has been used as a gold standard to evaluate the efficacy of vaccines
      against smallpox, polio and influenza viruses . Passive antibody therapy, such as plasma
      fusion, was successfully used to treat infectious viral diseases, including SARS-CoV virus,
      influenza viruses, and Ebola virus. The efficacy of passive antibody therapy was associated
      with the concentration of NAbs in plasma or antibodies of recovered donors. As the global
      pandemic of COVID-19 proceeds, transfusion of convalescent plasma or serum from recovered
      patients was also considered as a promising therapy for prophylaxis of infection or treatment
      of disease. highly variable levels of NAbs in the patients of COVID-19 indicated that
      convalescent plasma and serum from recovered donors should be titrated before use in passive
      antibody therapy, an easy task that can be performed using the PsV neutralization assay. The
      titers of NAbs were variable in different patients. Elderly patients (60-80 ys) were more
      likely to induce higher titers of NAbs than younger patients. A moderate positive correlation
      was also observed between age and Nab titers confirming the important role of age in the
      generation of Nabs. The correlation of NAbs titers with age, lymphocyte counts, and blood CRP
      levels suggested that the interplay between virus and host immune response.
observational model: Cohort
time perspective: Prospective
measure: Measure level of Abs in asymptomatic close contacts of COVID 19 patients.
time frame: one day
description: serum level of antiSARS-CoV-2 IgG, IgM
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Aliae AR Mohamed Hussein
investigator title: Professor of Pulmonology
mesh term: COVID-19
sharing ipd: Undecided