• Christine J Ko, Malini Harigopal, Jeff R Gehlhausen, Marcus Bosenberg, Jennifer M McNiff, and William Damsky.
• Department of Dermatology, Yale Medical School, New Haven, Connecticut, USA.
• J. Cutan. Pathol. 2021 Jan 1; 48 (1): 47-52.

BackgroundPrior 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.ObjectiveIn 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.ResultsThree 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.ConclusionWhile 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.© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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