Clinical trial NCT04703114: Study of the Immunological and Virological Response of Patients With COVID-19 and Presenting an Asymptomatic or Pauci-symptomatic Form (AMBUCOV)
Official title: Study of the Immunological and Virological Response of Patients Infected With SARS-CoV-2 and Presenting an Asymptomatic or Pauci-symptomatic Form
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
SARS-CoV-2
Keywords: Covid19
SARS-CoV-2
Immunology
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fonds IMMUNOV
First posted: 2021-01-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Interferon response
timeFrame: Up to 90 days
Secondary outcomes:
measure: Immunology : cytokines
timeFrame: Up to 90 days
measure: Immunology : cell population
timeFrame: Up to 90 days
measure: Immunology : proteins
timeFrame: Up to 90 days
measure: Immunology : pathways
timeFrame: Up to 90 days
measure: Immunology : antibody response
timeFrame: Up to 90 days
measure: Virology : Nasopharyngeal Viral clearance kinetics
timeFrame: Up to 90 days
measure: Virology : Saliva Viral clearance kinetics
timeFrame: Up to 90 days
measure: Virology : faeces viral clearance kinetics
timeFrame: Up to 90 days
measure: Virology : peripheral blood viral clearance kinetics
timeFrame: Up to 90 days
measure: Virology : sequencing
timeFrame: Up to 90 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Cochin
state: Île-de-France
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Solen KERNEIS, Doctor
role: STUDY_DIRECTOR
References:
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citation: Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
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citation: Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A; Yale IMPACT Team; Herbst R, Shaw AC, Medzhitov R, Schulz WL, Grubaugh ND, Dela Cruz C, Farhadian S, Ko AI, Omer SB, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020 Aug;584(7821):463-469. doi: 10.1038/s41586-020-2588-y. Epub 2020 Jul 27.