{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:06:16Z","timestamp":1790658376642,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The SARS-CoV-2 pandemic has disrupted global health systems and brought the entire globe to its knees. Although born as a disease of the respiratory system, COVID-19 can affect different parts of the body, including the skin. Reports of ongoing skin manifestations of COVID-19 have gradually multiplied, pushing researchers to investigate the etiopathogenic mechanisms underlying these phenomena in more depth. In an attempt to investigate the possible association between SARS-CoV-2, ACE2, TMPRSS2 and skin manifestations, we performed immunohistochemical investigations of the ACE2 receptor and TMPRSS2 in nine skin samples from SARS-CoV-2-positive patients compared to a cohort of healthy controls. Furthermore, after consulting public databases regarding ACE2 mRNA expression in various cell populations resident in the skin, we conducted a literature review aimed at outlining the current state of this topic. We did not find statistically different immuno-expression of ACE2 and TMPRSS2 between the group of SARS-CoV-2-positive patients (nine skin biopsies) and the control group. Regarding ACE2, major immunolabeling was present in the epidermal keratinocytes and, rarely, in the fibroblasts and in the adenomeres of the eccrine sweat glands. Regarding the immune expression of TMPRSS2, we found no significant differences between the two groups, with a weak immune staining only in some skin cytotypes. From the review of the literature, we isolated 35 relevant articles according to the inclusion criteria adopted. ACE2 appears to be a target of SARS-CoV-2, although, other receptor molecules may potentially be implicated, such as TMPRSS2. Future studies with large cases and different molecular investigative methods are needed to further elucidate the mechanisms underlying the skin manifestations of SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/biom12091212","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T23:53:21Z","timestamp":1661990001000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["SARS-CoV-2 and Skin: New Insights and Perspectives"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4316","authenticated-orcid":false,"given":"Gerardo","family":"Cazzato","sequence":"first","affiliation":[{"name":"Section of Molecular Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-4285","authenticated-orcid":false,"given":"Eliano","family":"Cascardi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"},{"name":"Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Str. Provinciale 142 lm 3.95, 10060 Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-0761","authenticated-orcid":false,"given":"Anna","family":"Colagrande","sequence":"additional","affiliation":[{"name":"Section of Molecular Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Foti","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Biomedical Sciences and Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-0097","authenticated-orcid":false,"given":"Alessandra","family":"Stellacci","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Interdisciplinary Medicine, Bari Policlinico Hospital, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-7269","authenticated-orcid":false,"given":"Maricla","family":"Marrone","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Interdisciplinary Medicine, Bari Policlinico Hospital, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-3545","authenticated-orcid":false,"given":"Giuseppe","family":"Ingravallo","sequence":"additional","affiliation":[{"name":"Section of Molecular Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Arezzo","sequence":"additional","affiliation":[{"name":"Section of Gynecology and Obstetrics, Department of Biomedical 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