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
School of Medicine and Public Health, University of Wisconsin-Madison, Department of Dermatology, Madison, WI 53726, USA.
Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
iScience. 2024 Jul 17;27(8):110525. doi: 10.1016/j.isci.2024.110525. eCollection 2024 Aug 16.
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.
在新冠疫情期间观察到冻疮发病率升高。这项前瞻性研究招募了威斯康星州和瑞士患有与疫情相关冻疮的受试者。由于冻疮是干扰素病的一种皮肤表现，且I型干扰素（IFN-I）免疫对新冠康复至关重要，我们检验了以下假设：严重急性呼吸综合征冠状病毒2（SARS-CoV-2）介导的IFN-I信号传导可能是某些冻疮病例的基础。在威斯康星州的所有病例中均证实了组织水平的IFN-I活性和浆细胞样树突状细胞浸润。在两个队列中，25%（6/22）的活检样本中检测到少量SARS-CoV-2 RNA，所有样本均有高度炎症。受影响的患者缺乏对SARS-CoV-2的适应性免疫。鼻内感染SARS-CoV-2的仓鼠模型用作原理验证实验：在肺部和脚趾均检测到RNA且有IFN-I活性，而仅在肺部发现了正在复制的病毒。这些数据支持某些冻疮病例存在病毒触发因素，即在未发生血清转化的情况下可触发持续的局部IFN-I活性。
