key: cord-0911643-svtz8jyi authors: Ionescu, Marius‐Anton title: COVID‐19 skin lesions are rarely positive at RT‐PCR test: the macrophage activation with vascular impact and SARS‐CoV‐2‐induced cytokine storm date: 2021-07-02 journal: Int J Dermatol DOI: 10.1111/ijd.15749 sha: ec88ddec3cd16453104350466ceca937dd0a0804 doc_id: 911643 cord_uid: svtz8jyi 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. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the epidemic of coronavirus disease- , which began at the end of 2019 in Wuhan, China, declared a pandemic by the World Health Organization on March 11, 2020. An important part of patients positive at the RT-PCR nasal test for SARS-CoV-2 is being asymptomatic. 1 Symptomatic COVID-19 patients most frequently present general symptoms (fever, fatigue, and anorexia), dysgeusia, anosmia, and respiratory signs (cough, dyspnea, pneumonia, and in the most severe cases, a severe acute respiratory syndrome). Dermatological manifestations of COVID-19 described in case-series published over the past 12 months were most often (according to the prevalence of these manifestations 1-11 ): chilblains-like lesions (toes 88%, fingers 24% 11 ), diffuse erythematous rash, erythema multiforme-like, punctiform purpura lesions, urticarialike, varicella-like, and ischemic acrosyndromes. 11 In a large series of chilblains observed in France during the COVID-19 pandemic, most cases of skin lesions were negative to RT-PCR and serological tests. 11 Skin RT-PCR tests were made in most reports some days after their onset, which was the reason for consulting a dermatologist, with or without other symptoms. 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