Comparison of SARS-CoV-2, Adenovirus and Rhinovirus infection of the respiratory epithelium in chilldren vs. the elderly – VIRCHILLD

The objective of the VIRCHILLD project is to identify age-related modifications of the bronchial epithelium physiology able to explain differences in the response to respiratory viruses’ infection. Several epidemiological and cell-based data have demonstrated that respiratory virus infections differentially affect children, adults or the elderly populations. Perhaps, this difference has been put most notably into the spotlight by the current worldwide pandemic of SARS-CoV-2 (COVID-19) with a large part of deaths occurring in the elderly population whereas very few deaths amongst children have been recorded. According to some studies, this could be linked to a decreased transmission and/or viral load with SARS-CoV-2 in children compared to adults and elderly. What is less in the public eye is the observation that other major respiratory virus targeting the bronchial epithelium such as rhinovirus (RV) and adenovirus (AdV) cause important clinical feature in children and have a much lower incidence in adults and elderly populations, which is the opposite to the situation with SARS-CoV-2. Based on this remarkable discrepancy between respiratory viruses we hypothesize that intrinsic age-controlled properties of the respiratory epithelium under resting physiological conditions determines virus susceptibility and virus propagation. Such hypothesis is supported by the literature and our own strong preliminary data already showing that such a discrepancy between viruses and age-related epithelium can be observed in our in vitro model. Indeed, we have developed an in vitro model of bronchial epithelium. Using bronchial tissue from human donors, we are able to obtain a reconstituted fully functional respiratory epithelium. Thus, using donor’s tissue from children, adults and elderly we propose a project based on two connected work packages. The first one will compare the characteristics on bronchial epithelium from children, adults and elderly subjects under resting physiological conditions. The second will compare how the bronchial epithelium from children, adult and elderly patients react to viral infection with RV, AdV and SARS-CoV-2. The consortium brought together for the VIRCHILLD project is highly complemented and composed of experts in lung physiology, pulmonary transcriptomic (Single-cell RNA-seq), respiratory viruses and ultrastructure analysis by electronic microscopy. The uniqueness of the VIRCHILLD project will identify age related differences in epithelium and virus susceptibility which potentially will highlight novel and age-related points of therapeutic intervention to better manage respiratory viral infections.