biostudies-literatureUnknown603(7899)Domizio JDCOVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications^1,2. Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs ^3-5). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome^5-17. Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. ¹⁸). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature thNature145-151https://www.ebi.ac.uk/biostudies/studies/S-EPMC8891013biostudies-literatureThe cGAS-STING pathway drives type I IFN immunopathology in COVID-19.PMC8891013de Leval LNass TGarnier CVThacker VVBerezowska SDomizio JDSchaller MGuenova EGulen MFSharma KAblasser AYatim ADubois AGoepfert CSaidoune FGilliet MConrad CfalseThe cGAS-STING pathway drives type I IFN immunopathology in COVID-19.COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications^1,2. Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs ^3-5). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome^5-17. Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. ¹⁸). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature th2022-01-01T00:00:00Z2022 Mar2025-04-04T19:58:12.332Z2025-04-04T19:58:12.332ZS-EPMC88910133504556510.1038/s41586-022-04421-w