Clinicopathologic correlations of COVID-19–related cutaneous manifestations with special emphasis on histopathologic patterns

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.