Curr Opin Immunol. 2025 Sep 11;97:102656. doi: 10.1016/j.coi.2025.102656. Online ahead of print.
ABSTRACT
SARS-CoV-2 infection and vaccination are associated with a broad range of skin manifestations, including chilblains, urticaria, morbilliform and papulovesicular rashes, purpuric-necrotic lesions, and autoimmune flares. These patterns reflect differences in the timing and nature of type I interferon (IFN-I) responses. Rapid TLR7-mediated IFN-I production by plasmacytoid dendritic cells (pDCs) in the upper airways restricts viral replication; hyperresponsive pDCs protect from severe infection but may cause chilblain-like lesions through exaggerated local inflammation. When early IFN-I responses are weak, viral spread to the lungs triggers endothelial cell death, mitochondrial DNA release, and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation, producing a late IFN-I surge that amplifies inflammation, mirrored by morbilliform, vesicular, or necrotic skin lesions. mRNA and viral vector vaccines can similarly activate nucleic acid sensors, inducing IFN-I-driven rashes, and promote spike-specific T cells that cross-react with skin antigens. Recognizing these cutaneous signs offers insight into the balance between protective and pathogenic immunity in COVID-19.
PMID:40939529 | DOI:10.1016/j.coi.2025.102656