Publication date: Sep 11, 2025
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.
| Concepts | Keywords |
|---|---|
| Airways | Cov |
| Late | Ifn |
| Pathogenic | Infection |
| Plasmacytoid | Inflammation |
| Vaccines | Interferon |
| Lesions | |
| Manifestations | |
| Necrotic | |
| Pdcs | |
| Rashes | |
| Sars | |
| Skin | |
| Vaccination | |
| Vaccines | |
| Viral |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | SARS-CoV-2 infection |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | MESH | urticaria |
| disease | IDO | production |
| pathway | KEGG | Viral replication |
| disease | MESH | infection |
| disease | MESH | inflammation |
| pathway | REACTOME | Release |
| disease | IDO | nucleic acid |
| drug | DRUGBANK | Isoxaflutole |