BACKGROUND: Prior studies have shown the presence of immunohistochemical staining for the SARS-CoV-2 spike protein (SP) in endothelial cells and eccrine epithelium of acral perniosis classified as "COVID toes." Yet, other studies have been unable to detect SARS-CoV-2 RNA in skin biopsies of "COVID toes" by reverse-transcriptase polymerase chain reaction testing. OBJECTIVE: In order to address these apparently conflicting findings, we compared detection of SARS-CoV-2 SP, through RNA in situ hybridization (ISH) vs immunohistochemistry (IHC), in skin biopsies of acral perniotic lesions presenting during the COVID-19 pandemic. RESULTS: Three of six cases showed positive immunohistochemical labeling of endothelial cells, with one of three cases with sufficient depth also having labeling of eccrine glands, using an anti-SP SARS-CoV-2 antibody. These three cases positive with IHC were negative for SP by RNA ISH. CONCLUSION: While the gold standard for detection of SARS-CoV-2 in tissue sections has yet to be determined, the detection of SARS-CoV-2 SP alone without spike RNA suggests that cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis.
BACKGROUND: Prior studies have shown the presence of immunohistochemical staining for the SARS-CoV-2spike protein (SP) in endothelial cells and eccrine epithelium of acral perniosis classified as "COVID toes." Yet, other studies have been unable to detect SARS-CoV-2 RNA in skin biopsies of "COVID toes" by reverse-transcriptase polymerase chain reaction testing. OBJECTIVE: In order to address these apparently conflicting findings, we compared detection of SARS-CoV-2 SP, through RNA in situ hybridization (ISH) vs immunohistochemistry (IHC), in skin biopsies of acral perniotic lesions presenting during the COVID-19 pandemic. RESULTS: Three of six cases showed positive immunohistochemical labeling of endothelial cells, with one of three cases with sufficient depth also having labeling of eccrine glands, using an anti-SP SARS-CoV-2 antibody. These three cases positive with IHC were negative for SP by RNA ISH. CONCLUSION: While the gold standard for detection of SARS-CoV-2 in tissue sections has yet to be determined, the detection of SARS-CoV-2 SP alone without spike RNA suggests that cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis.
Authors: Miguel Fernando García-Gil; Juan Monte-Serrano; Alejandro Lapeña-Casado; Pablo Villagrasa-Boli; Mar Ramírez-Lluch; Isabel Martínez-Pallás; Aura Bularca; Beatriz Aldea-Manrique; Rafael Benito-Ruesca; María Purificación Ventura-Faci; Mariano Ara-Martín Journal: Dermatol Ther Date: 2021-10-08 Impact factor: 3.858
Authors: M F García-Gil; J Monte-Serrano; M García García; L Prieto-Torres; A J Pascual-Del-Riquelme; I Casas Flecha; M Ara-Martín Journal: J Eur Acad Dermatol Venereol Date: 2021-03-02 Impact factor: 9.228
Authors: Lilian Schimmel; Keng Yih Chew; Claudia J Stocks; Teodor E Yordanov; Patricia Essebier; Arutha Kulasinghe; James Monkman; Anna Flavia Ribeiro Dos Santos Miggiolaro; Caroline Cooper; Lucia de Noronha; Kate Schroder; Anne Karine Lagendijk; Larisa I Labzin; Kirsty R Short; Emma J Gordon Journal: Clin Transl Immunology Date: 2021-10-24
Authors: I Colmenero; C Santonja; M Alonso-Riaño; D Andina; J L Rodríguez Peralto; L Requena; A Torrelo Journal: Br J Dermatol Date: 2020-12-16 Impact factor: 11.113
Authors: Tsuguhisa Nakayama; Ivan T Lee; Sizun Jiang; Matthias S Matter; Carol H Yan; Jonathan B Overdevest; Chien-Ting Wu; Yury Goltsev; Liang-Chun Shih; Chun-Kang Liao; Bokai Zhu; Yunhao Bai; Peter Lidsky; Yinghong Xiao; David Zarabanda; Angela Yang; Meena Easwaran; Christian M Schürch; Pauline Chu; Han Chen; Anna K Stalder; David R McIlwain; Nicole A Borchard; Phillip A Gall; Sachi S Dholakia; Wei Le; Le Xu; Chih-Jaan Tai; Te-Huei Yeh; Elizabeth Erickson-Direnzo; Jason M Duran; Kirsten D Mertz; Peter H Hwang; Jasmin D Haslbauer; Peter K Jackson; Thomas Menter; Raul Andino; Peter D Canoll; Adam S DeConde; Zara M Patel; Alexandar Tzankov; Garry P Nolan; Jayakar V Nayak Journal: Cell Rep Med Date: 2021-09-28
Authors: Federica Zito Marino; Tiziana De Cristofaro; Massimo Varriale; Giuseppa Zannini; Andrea Ronchi; Elvira La Mantia; Carlo Pietro Campobasso; Francesco De Micco; Pasquale Mascolo; Maurizio Municinò; Emilia Municinò; Francesco Vestini; Omero Pinto; Marta Moccia; Noè De Stefano; Oscar Nappi; Carmen Sementa; Giovanni Zotti; Lamberto Pianese; Carmela Giordano; Renato Franco Journal: Virchows Arch Date: 2022-02-01 Impact factor: 4.535