COVID-19 - Coronavirus disease 2019

Acute Immune response and Omics analysis in Covid19 infection: molecular rationale for targeted therapies – AIROCovid19

Submission summary

As of March 23rd 2020, the COVID-19 outbreak is affecting > 340,000 people worldwide, carrying a mortality rate ranging from 1/1000 in some countries but reaching several % in others. This variability may result from the rate of detection which differs in these countries, but it also relies on the overload of Intensive Care Units (ICU) as some of the infected patients develop an acute respiratory distress syndrome (ARDS) requiring ICU hospitalization, whereas others require conventional care or even remain mildly symptomatic. Of note, severe secondary deterioration (between day 9 and 12 after the symptoms onset) has been reported in relatively young adults suggesting involvement of an immunopathological component. In the absence of efficient anti-viral therapy or vaccine, there is an immediate need to understand the underlying ARDS pathophysiological mechanisms in order to adapt efficient therapies to control these severe forms of SARS-CoV2 infections, and therefore to reduce the ICUs overload which will impact on the mortality rate. In parallel, there is the observation of the very limited number of severe cases of SARS-CoV2 infection in the pediatric population, raising the question of the immunological mechanisms at play in the SARS-CoV2 infection in children. The goal of the present project is to study the pathophysiology of the disease, to provide 1) cellular and molecular data in a very short time period to better characterize the acute immune response of SARS-CoV2 infected hosts who develop ARDS in order to support possible targeted therapies (and thus to reduce the duration of ICU need or even to avoid aggravation), and 2) a comparison of severe cases to milder cases and to the pediatric setting at the single cell level. This project gathered clinicians (Internal medicine and Pulmonology departments of the Cochin Hospital for adult patients, and Pediatricians from Jean Verdier and Necker Hospital) taking care of SARS-CoV2 infected patients, with research team of the Imagine Institute who developed cellular and molecular approaches to decipher the Human Immune responses in bulk as well as at the single cell level. The project, that relies on recent preliminary results, will benefit of the core facilities of the Imagine Institute (in particular the single cell RNAseq core facility), the Institut Pasteur (Simoa) and Pitié-Salpêtrière University Hospital (CytOF). It will provide unprecedented cellular and molecular information regarding the SARS-CoV2 infection in the adult and pediatric context that will help guiding the clinicians to choose adapted and specific targeted therapies to treat the most severe cases.

Project coordination

Frederic Rieux-Laucat (INSTITUT DES MALADIES GÉNÉTIQUES (IHU))

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.

Partner

IMAGINE INSTITUT DES MALADIES GÉNÉTIQUES (IHU)
IMAGINE INSTITUT DES MALADIES GÉNÉTIQUES (IHU)

Help of the ANR 199,692 euros
Beginning and duration of the scientific project: March 2020 - 12 Months

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