Since March 2020, Europe has been facing the outbreak of the new coronavirus disease 2019 (COVID-19). This highly contagious infectious disease is a viral zoonosis caused by a virus SARS-CoV-2 from the coronavirus family that emerged in Wuhan in Chine in November 2019, causing first an epidemic that escalated to a pandemic in March 2020. The virus is highly virulent and is spread mainly through droplets from the mouth or nose of the infected person to the person in proximity or in close contact.
In the vast majority the SARS-CoV-2 infection is non symptomatic, however, a minority of cases may evolve towards severe forms. The population most at risk of unfavourable outcome are the elderly, people suffering from chronic diseases such as diabetes, obesity or cancer, as well as patients receiving immunosuppressive treatment. In spite of these known risk factors, little is known about why some infected patients may progress to severe disease forms while others remain asymptomatic, and the immune response in the context of COVID-19 remains largely unexplored.
Analysis of cellular immune response after non-specific stimulation of T lymphocytes has proven to be useful in predicting the risk of infection in different contexts, including in patients with end-stage kidney disease waiting for a graft in which a lower interferon gamma (IFN-?) level was associated with a higher risk of infection in the year following kidney transplantation.
A study on 41 patients infected with SARS-CoV-2 in Huanan seafood market (first identified cases) has demonstrated that while all patients presented with the same symptoms (cough in 76% of cases, fever in 98% of cases), some patients rapidly required mechanical ventilation. These patients in an urgent need of intensive care also presented with a higher level of inflammatory cytokines: IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFa.
The aim of our study is to determine the cytokine profile of subjects exposed to or infected with SARS-CoV-2 in order to find biomarkers of developing a mild or a severe form of infection at the moment of their exposure to the virus, and to find biomarkers of developing a mild or a severe form in the course of infection after being diagnosed positive. We believe that the immune system of the infected person plays a major role in determining the evolution of the infection: from the asymptomatic development to mild flu-like symptoms or to acute respiratory distress syndrome (ARDS). By identifying these immune system risk factors we hope to better stratify patients infected with SARS-CoV-2 in order to optimise their medical care and to personalise their treatment: corticoids, immunomodulators or antiviral therapies.
Our study concerns two primary research areas: clinical (i) and cellular in vitro (ii) studies.
In the clinical part we will quantify the immune response in two populations of patients:
- Subjects exposed to a risk of infection with SARS-CoV-2. We will enrol medical personnel in charge of testing, care and treatment of SARS-CoV-2-infected patients at the moment of their first exposure to the virus in their professional environment. We will quantify their Th1 immune response by measuring the level of IFN? in their serum after non-specific stimulation of T lymphocytes. Our hypothesis is that the medical workers with a lower level of IFN? at the moment of exposure are more likely to develop a severe form of the disease once infected.
- Patients hospitalized for a SARS-CoV-2 infection. We will correlate the evolution of their inflammatory cytokine profile at D1, D5 and D10 with a risk of developing ARDS.
We will then test in vitro (ii) the capability of different therapeutics, such as non-steroidal anti-inflammatory drugs, corticoids, anti-IL6 and chloroquine, to induce the secretion of anti-viral cytokines such as IFN? in the cells of healthy subjects as well as in patients infected with SARS-CoV-2 with different either a mild or a severe form of disease.
Madame Barbara SEITZ-POLSKI (Délégation à la Recherche Clinique et à l'Innovation CHU de Nice)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
DRCI Délégation à la Recherche Clinique et à l'Innovation CHU de Nice
Help of the ANR 92,202 euros
Beginning and duration of the scientific project: June 2020 - 6 Months