Dynamic and spatial transcriptional responses in COVID-19-related chilblains

"COVID-toes" are chilblains that occurred in patients who may have been exposed to SARS-CoV-2, but without COVID-19 symptoms and/or with negative PCR or serology. The literature suggests that chilblains are an unexpected consequence of a strong interferon-mediated antiviral response, but the underlying molecular mechanisms remain poorly understood. We thus sought to explore the physiopathology of COVID-related chilblains by using spatially and temporally resolved transcriptomics. We included 19 patients with COVID-toes, and performed a complete virological assessment to exclude SARS-CoV-2 infection including skin viral metagenomics. Some patients had clinical symptoms evoking viral infection, but none had COVID-19. Apart from low levels of non-conventional antiphospholipid antibodies, biological tests were unremarkable. We performed spatially resolved transcriptomics (Visium, 10X Genomics) in 3 patients at different timepoints and compared them with 1 vaccination-related chilblain. We observed a different transcriptional profile in COVID-toes compared with COVID-19 vaccine-related chilblains. IRF1, CXCL10, ISG15 and STAT1 were highly expressed in COVID-toes and their expression decreased over time, confirming an activation of interferon and JAK/STAT pathways that was absent in vaccine-related chilblains. The proportion of inflammatory cell types obtained by spatial deconvolution varied over time in COVID-toes. Migratory dendritic cells were present at early stages, while T lymphocytes populations increased later. Overall, this work explores the mechanisms of COVID-19-related chilblains using spatially and temporally resolved transcriptomics.Copyright © 2023

Clinicopathological features of cutaneous reactions after mRNA-based COVID-19 vaccines.

BACKGROUND: Cutaneous reactions, mostly on injection site after mRNA-based COVID-19 vaccines, have been reported but not with detailed histopathological characterization. OBJECTIVES: Characterization and classification of these reactions in a clinical and pathological point of view. METHODS: Monocentric case series of 11 patients with cutaneous manifestations, clinically and histologically characterized after COVID-19 vaccination. RESULTS: From January to June 2021, we recorded 11 cutaneous reactions to mRNA COVID-19 vaccines from BNT162b2 (n = 8) and mRNA-1273 (n = 3). Generalized reactions showing erythematous rash or purpura were the most common clinical presentation, and drug-reaction-like pattern was the most common histological finding. CONCLUSIONS: A proper clinicopathological classification will be helpful in the early diagnosis and management of the cutaneous reactions to mRNA COVID-19 vaccines.