SARS-CoV-2 viral RNA disseminates to hamster toes and associates with localized IFN-I production: mechanistic footprints of an abortive COVID-19 infection in pandemic-associated pernio

SARS-CoV-2 infection generates a systemic immune response mediated by type I interferons. Pernio is a rare cutaneous manifestation of disorders characterized by excessive IFN-I signaling. Pernio increased in incidence during the pandemic but lacks direct evidence of SARS-CoV-2. We characterized clinical pernio samples and mechanistic feasibility in a rodent model which phenocopies human SARS-CoV-2 infection. Golden hamsters infected with SARS-CoV-2 experienced rapid dissemination of viral RNA to both lungs and toes. Interferon responses at both sites coincided with detection of viral RNA, which cleared within 10 days post-infection. Live virus could not be detected at acral sites. In two cohorts of clinical biopsies of affected skin, we detected SARS-CoV-2 RNA in 20-30% of cases, plasmacytoid dendritic cell activation, and a robust IFN-I response across all samples. Our data suggest footprints from SARS-CoV-2 exposure in a subset of cases that can produce a sustained localized IFN-I response-- even in the absence of serconversion.