TY - JOUR T1 - Mitophagy, at the crossroads of genetic pathways involved in sarcoidosis and host-pathogen interactions with SARS-COV2 proteins JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA699 VL - 58 IS - suppl 65 SP - PA699 AU - Alain Calender AU - Dominique Valeyre AU - Jérome Lamartine AU - Fabien Chevalier AU - Dominique Sigaudo Roussel AU - Yves Pacheco Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA699.abstract N2 - Introduction: Recent genetic studies by Whole Exome Sequencing (WES) in familial forms of sarcoidosis allowed the characterization of genes encoding factors involved in innate immunity and autophagy, mainly around mTOR and Rac1 hubs. The pandemic generated by the SARS CoV2 virus raises the question of the susceptibility of sarcoidosis patients with genetic defects to COVID-19.Aims and Objectives: We compared a panel of genes (named SARC-COV) mutated in familial forms of sarcoidosis to the 332 genes published in SARS-CoV2 interactome analysis (Gordon et al., Nature 2020; 583: 459-468), highlighting host-cell proteins which are targets of the structural and non-structural (NSP) proteins during the process of viral infection.Methods: WES was performed in 13 families with at least two first-degree related affected individuals. Selection of genes sharing pathogenic variants was done by various softwares (POLYPHENv2, ALAMUT VISUAL) and the functional evaluation established by ENRICH.R.Results: We have identified 30 SARC-COV genes common to the list of mutated genes in sarcoidosis families and those of the Gordon SARS CoV2 interactome. Gene-set enrichment analysis of the SARC-COV gene panel identified 4 over-represented signaling pathways mediated by 1) retinoic acid-inducible gene 1 (RIG1) like receptor; 2) Toll-like Receptor (TLR3); 3) Interferon Regulatory Factors (IRF3/7) and 4) mitochondrial complex I assembly model OXPHOS system, all closely related to the mitophagy pathway.Conclusion: Our study is the first one searching genetic factors which could be related to the susceptibility of sarcoidosis patients to SARS-CoV2 infection and mainly severe forms of COVID-19FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA699.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -