SARS-CoV-2-Induced Vasculitic Skin Lesions Are Associated with Massive Spike Protein Depositions in Autophagosomes

Article Article scientifique Article SARS-CoV-2-Induced Vasculitic Skin Lesions Are Associated with Massive Spike Protein Depositions in Autophagosomes eng 2023-08-12 2024-02 author Gawaz Andrea Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. author Schindler Hendrik Michael Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany. 42311 author Hagelauer Elena Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany. author Blanchard Gabriela Department of Dermatology, Lausanne University Hospital (CHUV), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. author Riel Simon Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. author Vollert Anneli Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. author Gilliet Michel Department of Dermatology, Lausanne University Hospital (CHUV), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. author Unterluggauer Luisa Department of Dermatology, Medical University of Vienna, Vienna, Austria. author Stary Georg Department of Dermatology, Medical University of Vienna, Vienna, Austria. author Pospischil Isabella Department of Dermatology, Kepler University Hospital, Johannes Kepler University, Linz, Austria. author Hoetzenecker Wolfram Department of Dermatology, Kepler University Hospital, Johannes Kepler University, Linz, Austria. author Fehrenbacher Birgit Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. author Schaller Martine Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. 28805 author Guenova Emmanuella Department of Dermatology, Lausanne University Hospital (CHUV), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; Department of Dermatology, Hospital 12 de Octubre, Medical school, University Complutense, Madrid, Spain. Electronic address: emmanuella.guenova@unil.ch. author Forchhammer Stephan Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. 369-377.e4 10.1016/j.jid.2023.07.018 37580012 0022-202X https://www.sciencedirect.com/science/article/pii/S0022202X23025010 In patients infected with severe acute respiratory syndrome coronavirus 2, vasculopathic changes of the skin are associated with a severe prognosis. However, the pathogenesis of this vasculopathy is not conclusively clarified. In this study, 25 prospectively collected skin samples from patients with COVID-19-related skin lesions were examined for vasculopathic changes and, in case of vasculitis, were further analyzed with electron microscopy and immunohistochemistry. Vasculopathy was observed in 76% of all COVID-19-related inflammatory skin lesions. Visual endothelial changes without manifest leukocytoclastic vasculitis were found in 60% of the COVID-19-related skin lesions, whereas leukocytoclastic vasculitis was diagnosed in 16%. In the cases of vasculitis, there were extensive spike protein depositions in microvascular endothelial cells that colocalized with the autophagosome proteins LC3B and LC3C. The autophagy protein complex LC3-associated endocytosis in microvascular endothelial cells seems to be an important pathogenic factor for severe acute respiratory syndrome coronavirus 2-related vasculitis in the skin. On ultrastructural morphology, the vasculitic process was dominated by intracellular vesicle formation and endothelial cell disruption. Direct presence of severe acute respiratory syndrome coronavirus 2 particles in the skin was not observed. Therefore, our results suggest that instead of direct viral infection, dermal vasculitic lesions in COVID-19 are caused by severe acute respiratory syndrome coronavirus 2 spike protein deposition followed by endothelial damage with activation of autophagy. Humans SARS-CoV-2 COVID-19 / metabolism Spike Glycoprotein, Coronavirus / metabolism Endothelial Cells / metabolism Autophagosomes Vasculitis Vasculitis, Leukocytoclastic, Cutaneous true 576 Inflammation cutanée 919 Journal of investigative dermatology 144 2 c57e41db-8f96-4a10-bd25-04b1cbdb3d41 Article (Published version) Public SARS-COV-2.pdf 6744411 application/pdf CC BY-NC-ND-4.0 194e3434694fc60a8b076f8a07aa1c5b99f647c2d9e8fef78cc32e7497b52728 openAccess

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SARS-CoV-2-Induced Vasculitic Skin Lesions Are Associated with Massive Spike Protein Depositions in Autophagosomes	Journal of investigative dermatology			2024	41	42

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Schindler, Hendrik Michael