COVID-19 skin lesions are rarely positive at RT-PCR test: the macrophage activation with vascular impact and SARS-CoV-2-induced cytokine storm.

BACKGROUND: Several skin manifestations have been reported since the start of the COVID-19 pandemic: chilblains-like, livedoid lesions, urticaria-like, pseudo-Kawasaki disease, and others. Histopathologic images of these lesions most often show aspects of endothelitis, images similar to autoimmune vasculitis. Cutaneous lesions are often negative at RT-PCR for SARS-CoV-2 virus.

METHOD AND RESULTS: We reviewed recent articles on the mechanisms of COVID-19 and we synthesized main pathways of inflammatory cascade. After the penetration into the cells of the respiratory epithelium, SARS-CoV-2 virus initiates a "cytokine storm" well described in previous publications: the expression of interferon type I (IFN-I) is one of the key elements of the antiviral response in COVID-19 patients, IFN-I expression seems to play an important role in the induction of interleukin 6 (IL-6), chemotactic factors such as Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and the consequent activation of monocyte-macrophage system followed by the expression of TNF-alpha, and finally by the induction of coagulation factors by both extrinsic and intrinsic pathways.

CONCLUSIONS: The simplified synthesis of the main pathophysiological mechanisms of COVID-19 could help us to understand at least partially the importance of macrophage activation and its vascular involvement in many skin lesions that remain often negative at in situ tests for SARS-CoV-2.