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

Covid19 Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04703114
• Other study ID #: AMBUCOV
• Secondary ID: 2020-A03102-37
• Status: Completed
• Phase: N/A
• Start date: February 5, 2021
• Est. completion date: September 15, 2021

Study information

• Verified date: September 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 15, 2021
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV-2

Intervention

Diagnostic Test:
• Blood count
Blood count at each visit
• Blood collection
Blood collection to understanding of the immunological profile at each visit
• Nasopharyngeal swab
Research of SARS-CoV-2 infection in nasopharyngeal swab by RT-PCR at day 8 and day 15
• Saliva samples
Research of SARS-CoV-2 infection in saliva samples at each visit (excepted inclusion)
• 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

Locations

Country	Name	City	State
France	Hôpital Cochin	Paris	Île-de-France

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fonds IMMUNOV

Country where clinical trial is conducted

France, 

References & Publications (4)

Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, Péré H, Charbit B, Bondet V, Chenevier-Gobeaux C, Breillat P, Carlier N, Gauzit R, Morbieu C, Pène F, Marin N, Roche N, Szwebel TA, Merkling SH, Treluyer JM, Veyer D, Mouthon L, Blanc C, Tharaux PL, Rozenberg F, Fischer A, Duffy D, Rieux-Laucat F, Kernéis S, Terrier B. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020 Aug 7;369(6504):718-724. doi: 10.1126/science.abc6027. Epub 2020 Jul 13. — View 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. — View 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. Erratum in: Lancet Respir Med. 2020 Apr;8(4):e26. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interferon response	Concentration of type I, type II and type III Interferon in peripheral blood	Up to 90 days
Secondary	Immunology : cytokines	Concentration of IL-6, TNF-alpha, IL-8, calprotectin in peripheral blood	Up to 90 days
Secondary	Immunology : cell population	Proportions of monocytes, B cells and T cells in peripheral blood	Up to 90 days
Secondary	Immunology : proteins	Concentration of anaphylatoxins C3a and C5a in peripheral blood	Up to 90 days
Secondary	Immunology : pathways	Screening for genetic mutations involved in the interferon pathway	Up to 90 days
Secondary	Immunology : antibody response	Concentration of antibodies directed against spike protein and nucleocapsids	Up to 90 days
Secondary	Virology : Nasopharyngeal Viral clearance kinetics	Viral clearance kinetics in nasopharyngeal samples	Up to 90 days
Secondary	Virology : Saliva Viral clearance kinetics	Viral clearance kinetics in saliva	Up to 90 days
Secondary	Virology : faeces viral clearance kinetics	Viral clearance kinetics in faeces	Up to 90 days
Secondary	Virology : peripheral blood viral clearance kinetics	Viral clearance kinetics in peripheral blood	Up to 90 days
Secondary	Virology : sequencing	Analysis of virus mutations, especially of the gene encoding spike protein	Up to 90 days