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

Overview

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.

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.