SARS-CoV-2 and Skin: The Pathologist's Point of View

Abstract

The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real "sentinel" of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.

Keywords: COVID-19; SARS-CoV-2; eruption; skin.

Figure 1

(A) Examples of an erythema multiforme-like lesion in the first group of patients. Note the detail of the violaceous erythematous well-defined border lesions with a typical targetoid aspects; (B) “Targetoid” type lesions with initial desquamation at the level of the periauricular area.

Figure 2

(A) Example of an erythema-multiforme like lesion of the first group of patients. In (A), we note the presence of modest ortho-parakeratosis (sampling from the pre-auricular area), with acanthosis and a mild inflammatory lymphomonocytic infiltrate (Hematoxylin-Eosin, Original Magnification: 4×. (B) Histological examination revealed a modest inflammatory infiltrate mainly peri-vasally, in the superficial and middle dermis (sample taken from the back) (Hematoxylin-Eosin, Original Magnification: 10×); (C) Histological details of the dermal edema and mucinosis of the hair appendages (Hematoxylin-Eosin, Original Magnification: 20×).

Figure 3

(A,B) Histological preparation for immunostaining with Anti-SARS-CoV-2 monoclonal antibody. Note the granular, cytoplasmic positivity at the level of the cells constituting the eccrine sweat glands. Involvement of the vascular endothelium is rarely described (IHC, Original Magnification: 10×).

Figure 4

Cytoplasm of eccrine sweat glands. Among the cellular organelles (mitochondria and endoplasmic reticulum) the presence of two virions is observed, indicated by arrows (Electron microscopy, Original Magnification: 44,000×).

Figure 5

Clinical appearance of the lesions in the second group of patients studied, showing a nodular appearance and overlying erythematous skin.

Figure 6

(A) Histological preparation demonstrating mild ortho-parakeratosis, focal vacuolation of the keratinocytes of the basal layer and mild inflammatory infiltration of the superficial dermis (Hematoxylin-Eosin, 4×); (B,C) Histological details of the superficial capillary plexus vessels characterized by swollen endothelial cells, of the “hobnail” type, with a narrow lumen and focal thrombotic phenomena (Hematoxylin-Eosin, 10× and 40×); (D) Masson’s trichrome stain which highlights the preservation of collagen fibers in the superficial dermis and their fragmentation at the level of the medial/deep dermis (Masson’s Trichrome stain, Original Magnification: 10×, box: 20×).

Figure 7

(A,B) Preparations for immunostaining with anti-SARS-CoV-2 antibody, showing positivity in the eccrine sweat glands cells, but also in the vascular endothelium (B).

Figure 8

The photomicrograph shows the endothelial cell cytoplasm, with numerous vacuoles within which viral particles are observed (14,000 x and 71,000 box).