Ko Christine J, Harigopal Malini, Gehlhausen Jeff R, Bosenberg Marcus, McNiff Jennifer M, Damsky William
Department of Dermatology, Yale Medical School, New Haven, Connecticut, USA.
Department of Pathology, Yale Medical School, New Haven, Connecticut, USA.
J Cutan Pathol. 2021 Jan;48(1):47-52. doi: 10.1111/cup.13866. Epub 2020 Oct 1.
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.
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.
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.
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.
先前的研究表明，在被归类为“新冠脚趾”的冻疮样病变的内皮细胞和小汗腺上皮中存在针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白（SP）的免疫组织化学染色。然而，其他研究通过逆转录聚合酶链反应检测，未能在“新冠脚趾”的皮肤活检组织中检测到SARS-CoV-2 RNA。
为了解决这些明显相互矛盾的发现，我们比较了在2019冠状病毒病大流行期间出现的冻疮样病变的皮肤活检组织中，通过RNA原位杂交（ISH）与免疫组织化学（IHC）检测SARS-CoV-2 SP的情况。
6例中有3例显示内皮细胞免疫组织化学染色呈阳性，使用抗SARS-CoV-2刺突蛋白抗体检测，3例中有1例深度足够的病例小汗腺也有染色。这3例免疫组织化学阳性的病例，RNA原位杂交检测刺突蛋白呈阴性。
虽然组织切片中检测SARS-CoV-2的金标准尚未确定，但仅检测到SARS-CoV-2刺突蛋白而无刺突RNA，提示切割后的刺突蛋白可能存在于皮肤内皮细胞和小汗腺上皮中，这为新冠病毒内皮炎提供了一种潜在的发病机制。
