Pandemic-associated pernio harbors footprints of an abortive SARS-CoV-2 infection

• Published in: iScience Vol. 27; no. 8; p. 110525
• Main Authors: Arkin, Lisa M., Costa-da-Silva, Ana C., Frere, Justin, Ng, Ashley, Sharma, Rubina, Moon, John J., Bussan, Hailey E., Kim, Clara H., Javaid, Ayesha, Steidl, Olivia R., Yatim, Ahmad, Saidoune, Fanny, Gilliet, Michel, Nguyen, Joe T., Nihal, Aman, Luong, George, Kenfield, Meaghan, Carrau, Lucia, Tran, Jennifer M., Hinshaw, Molly A., Brooks, Erin G., Ayuso, Jose M., O'Connor, David H., Casanova, Jean-Laurent, Cowen, Edward W., Drolet, Beth A., Singh, Anne Marie, tenOever, Benjamin, Mays, Jacqueline W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.08.2024; Elsevier
• Subjects: Adaptive immunology; Cell biology; Dermatology; Emerging diseases; Human health and pathology; Immune response; Immunology; Infectious diseases; Innate immunity; Life Sciences; Cell biology; Immunology; Immune response
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110525

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion. [Display omitted] •Pernio skin may contain SARS-CoV-2 viral material, even without seroconversion•Across two pernio cohorts, sparse SARS-CoV-2 RNA was detected in ∼25% of biopsies•The local immune profile had plasmacytoid dendritic cells and interferon activity•A golden hamster model replicated disseminated viral RNA without replicating virus Immunology; Immune response; Cell biology