Study of the Immunological and Virological Response of Patients With COVID-19 and Presenting an Asymptomatic or Pauci-symptomatic Form (AMBUCOV)

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Completed
CT.gov ID
NCT04703114
Collaborator
Fonds IMMUNOV (Other)
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Study Details

Study Description

Brief Summary

The purpose of this study is to describe the immunological and virological response of patients infected with CoV-2-SARS and presenting an asymptomatic or mildly symptomatic form, in particular the innate and adaptive response as well as the virological clearance kinetics.

The research hypothesis is that patients with an ambulatory form of SARS-CoV-2 infection, whether asymptomatic or mildly symptomatic, are able to mount an innate and adaptive immunological response capable of rapidly clearing the virus, in contrast to severe forms in which an early deficit of type 1 IFN response has been demonstrated, possibly responsible for a defect in the control of viral replication in the blood.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: Blood count
  • Diagnostic Test: Blood collection
  • Diagnostic Test: Nasopharyngeal swab
  • Diagnostic Test: Saliva samples
  • Diagnostic Test: Faeces samples
  • Genetic: Genetic blood collection
  • Other: Data collection
N/A

Detailed Description

A new coronavirus (SARS-CoV-2) was identified in December 2019 in the Wuhan region of China and is currently causing a global pandemic.

The disease, named COVID-19, causes an influenza syndrome associated with respiratory signs, but there are also asymptomatic and pauci-symptomatic forms. Approximately 2 to 3% of patients, primarily patients with pre-existing chronic diseases and the elderly, develop a very severe form responsible for an acute respiratory distress syndrome (ARDS) that can lead to death.

It has been shown that patients with a severe and critical form had an impaired type 1 interferon response, with decreased plasma levels of IFN-alpha2 in the most severe patients compared to hospitalized patients with a moderate form, and undetectable levels of IFN-beta. This lack of type 1 IFN response was associated with greater viral persistence in the blood and an exaggerated inflammatory response mediated primarily by the NF-kB pathway.

Almost all studies published to date on immune system disruption during CoV-2-SARS infection included mainly hospitalized patients requiring oxygen therapy due to their severity, assessed at the time of clinical worsening.

Thus, there is no or little data on immunological response profiles, particularly on type 1 IFN response but also on other aspects of the immunological response (adaptive cellular and humoral immunity), and its relationship with viral clearance kinetics during ambulatory forms of SARS-CoV-2 infection, whereas these forms represent more than 95% of the clinical forms.

The asymptomatic and pauci-symptomatic forms managed on an outpatient basis represent the most common form of CoV-2-SARS infection, with a favourable outcome in almost all cases.

A better description and understanding of the immunological profile, including type 1 IFN response and viral clearance kinetics in saliva, blood and feces, during asymptomatic and mild clinical forms will allow the identification of the major players in the immune response against SARS-CoV-2, and thus better define the responses that are lacking in severe patients.

Study Design

Study Type:
Interventional
Actual Enrollment :
57 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Study of the Immunological and Virological Response of Patients Infected With SARS-CoV-2 and Presenting an Asymptomatic or Pauci-symptomatic Form
Actual Study Start Date :
Feb 5, 2021
Actual Primary Completion Date :
Sep 15, 2021
Actual Study Completion Date :
Sep 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Symptomatic

40 symptomatic patients to COVID-19 infection

Diagnostic Test: Blood count
Blood count at each visit

Diagnostic Test: Blood collection
Blood collection to understanding of the immunological profile at each visit

Diagnostic Test: Nasopharyngeal swab
Research of SARS-CoV-2 infection in nasopharyngeal swab by RT-PCR at day 8 and day 15

Diagnostic Test: Saliva samples
Research of SARS-CoV-2 infection in saliva samples at each visit (excepted inclusion)

Diagnostic Test: Faeces samples
Research of SARS-CoV-2 infection in faeces samples at day 3, day 15 and day 90

Genetic: Genetic blood collection
Collection to further research at each visit

Other: Data collection
Demographics, symptoms, biological constants

Experimental: Asymptomatic

40 asymptomatic patients to COVID-19 infection

Diagnostic Test: Blood count
Blood count at each visit

Diagnostic Test: Blood collection
Blood collection to understanding of the immunological profile at each visit

Diagnostic Test: Nasopharyngeal swab
Research of SARS-CoV-2 infection in nasopharyngeal swab by RT-PCR at day 8 and day 15

Diagnostic Test: Saliva samples
Research of SARS-CoV-2 infection in saliva samples at each visit (excepted inclusion)

Diagnostic Test: Faeces samples
Research of SARS-CoV-2 infection in faeces samples at day 3, day 15 and day 90

Genetic: Genetic blood collection
Collection to further research at each visit

Other: Data collection
Demographics, symptoms, biological constants

Outcome Measures

Primary Outcome Measures

  1. Interferon response [Up to 90 days]

    Concentration of type I, type II and type III Interferon in peripheral blood

Secondary Outcome Measures

  1. Immunology : cytokines [Up to 90 days]

    Concentration of IL-6, TNF-alpha, IL-8, calprotectin in peripheral blood

  2. Immunology : cell population [Up to 90 days]

    Proportions of monocytes, B cells and T cells in peripheral blood

  3. Immunology : proteins [Up to 90 days]

    Concentration of anaphylatoxins C3a and C5a in peripheral blood

  4. Immunology : pathways [Up to 90 days]

    Screening for genetic mutations involved in the interferon pathway

  5. Immunology : antibody response [Up to 90 days]

    Concentration of antibodies directed against spike protein and nucleocapsids

  6. Virology : Nasopharyngeal Viral clearance kinetics [Up to 90 days]

    Viral clearance kinetics in nasopharyngeal samples

  7. Virology : Saliva Viral clearance kinetics [Up to 90 days]

    Viral clearance kinetics in saliva

  8. Virology : faeces viral clearance kinetics [Up to 90 days]

    Viral clearance kinetics in faeces

  9. Virology : peripheral blood viral clearance kinetics [Up to 90 days]

    Viral clearance kinetics in peripheral blood

  10. Virology : sequencing [Up to 90 days]

    Analysis of virus mutations, especially of the gene encoding spike protein

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Adult patients

  • Nasopharyngeal PCR positive for SARS-CoV-2 within 48 hours prior to inclusion in the study protocol, carried out in one of the participating outpatient screening centers

  • Symptomatic patients (nasopharyngeal screening positive due to suggestive symptoms) or asymptomatic (nasopharyngeal screening positive due to screening after contact with a positive subject)

  • Patients who have been informed and signed the consent

  • Pregnant and breastfeeding women who may be included in the study.

Exclusion Criteria:
  • Patients with criteria for hospitalization at the time of diagnosis (seriousness criteria, impossibility of staying at home)

  • Non-consent or inability to obtain consent,

  • Patient with dementia or not authorized, for psychiatric reasons or intellectual failure, to receive information on the protocol and to give informed consent,

  • Patient under guardianship / curatorship

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hôpital Cochin Paris Île-de-France France 75014

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris
  • Fonds IMMUNOV

Investigators

  • Study Director: Solen KERNEIS, Doctor, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT04703114
Other Study ID Numbers:
  • AMBUCOV
  • 2020-A03102-37
First Posted:
Jan 11, 2021
Last Update Posted:
Sep 28, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Assistance Publique - Hôpitaux de Paris
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 28, 2021