Recherche Fondamentale (basic research) - Marqueurs prognostiques muqueux et systémiques de la résistance versus la tolérance dans la pandémie COVID-19 Mucosal and systemic clinical prognosis markers of resistance and tolerance in COVID-19

Coronavirus disease 2019 (COVID-19) pandemic is due to infection with SARS-CoV2 coronavirus and represents a major public health threat, due to unusual rapidity of viral spreading in humans, severity of symptoms and mortality rate. Recent data reveals that the clinical outcome of SARS-CoV2 infection can vary greatly among individuals, from asymptomatic to mild symptoms, severe symptoms or critical conditions. The reasons underlying this variation in the clinical outcome remain unknown. There are two main ways a host deals with infection. One is through resistance, the ability to restrict or eliminate the infectious agent. This function is primarily performed by the immune system. The second, disease tolerance, is the capacity of the host to avoid or restrict the pathological consequences of an infection. The rate of contamination by virus spreading to highly exposed healthcare professionals has been dramatic. Through longitudinal multi-parametric and pathophysiological analysis, the study will provide directly in human, the proof of the concept that disease tolerance allows for homeostatic protection against an ongoing viral infection in such emerging pandemic infection. We speculate from past experience and know-how on mucosal regulatory pathways maintaining protection and homeostasis against viral infections, that IgA and Treg/Th17 division of labor is essential both for controlling virus and at the same time ensuring a safe host responsiveness, with minimal collateral damage, from onset to end of infection and resolution of disease. The clinical follow up of the individuals, from early onset mild clinical symptoms to more severe pathological signs (respiratory failure, morbidity, mortality), will allow to retrospectively identify severity and risk individuals associated to failure of disease tolerance mechanisms. This knowledge should help to better control COVID-19 pandemia and would provide a scientific basis, un-valuable for identifying individuals that should benefit from therapeutic intervention and/or vaccination strategies.