Discordant anti-SARS-CoV-2 spike protein and RNA staining in cutaneous perniotic lesions suggests endothelial deposition of cleaved spike protein.

Ko, Christine J; Harigopal, Malini; Gehlhausen, Jeff R; Bosenberg, Marcus; McNiff, Jennifer M; Damsky, William

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 1 of 3 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 cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis. This article is protected by copyright. All rights reserved.