Autophagy during Severe Acute Respiratory Syndrome Coronavirus 2 Induced Leukocytoclastic Vasculitis: New Insights

• DOI: 10.1016/j.jid.2024.01.002
• Publication Date: 2024-02-21T09:30:43Z
• Authors: Nesrine Brahimi; Vincent Piguet
• Keywords: Leukocytoclastic vasculitis; Coronavirus; 2019-20 coronavirus outbreak

View Large Image Figure ViewerDownload Hi-res image Download (PPT) The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 and its devastating consequences. Research studies report frequent dermatological manifestations, with at least 20% of patients having cutaneous lesions (Magro et al., 2021Magro C. Nuovo G. Mulvey J.J. Laurence J. Harp Crowson A.N. skin as a critical window in unveiling the pathophysiologic principles COVID-19.Clin Dermatol. 2021; 39: 934-965Abstract Full Text PDF PubMed Scopus (22) Google Scholar). Reports this population note wide range vasculitis, including small vessel also known leukocytoclastic vasculitis (LCV)."The implication LC3B, LC3C, LL-37 COVID-19-associated vasculopathies could open novel avenues therapeutic targets." "The Gawaz 2024Gawaz A. Schindler M. Hagelauer E. Blanchard Riel S. Vollert al.SARS-CoV-2-induced vasculitic are associated massive spike protein depositions autophagosomes.J Invest 2024; 144: 369-377.e4Abstract (0) Scholar recently reported new data investigating mechanisms vascular injury potential causality SARS-CoV-2 lesions. From cohort 4 positive for LCV, compared 3 controls without disease, investigators characterized microvascular changes samples COVID-19–induced vasculitis. To explore mechanism investigate direct viral presence skin, they performed histological analyses ultrastructural characterization endothelial cells. Interestingly, found extensive deposition cells that colocalized autophagosome proteins LC3B LC3C—markers autophagy. researchers concluded autophagosomes occurs during SARS-CoV-2–associated vasculitis.Clinical Implications•This study provides insight into connection between lesions.•It spells out evidence relating virus manifestations.•It demonstrates COVID-19–associated targets. •This 1.8% all findings (Kaya 2020Kaya Kaya Saurat J.H. Clinical histopathological features pathological COVID-19: review literature.Dermatopathology (Basel). 2020; 7: 3-16Crossref Scholar), is type small-vessel by inflammation blood vessels. Often an immune response, various factors can trigger it, infections drugs. Immune complex aggregates postcapillary venules, infiltration polymorphonuclear cells, fibrinoid necrosis, leukocytoclasis histologically characterize LCV. vasculopathy true on histology develops minority cases, mostly or (Maronese 2022Maronese C.A. Zelin Avallone Moltrasio Romagnuolo Ribero al.Cutaneous era pandemic.Front Med (Lausanne). 2022; 9996288Google pathogenic not fully elucidated. Although role hyperactive complement activation, question, it appears result from due pauci-immune thromboembolic mechanisms. Previous beliefs attributed damage infection. However, recent research suggests indirect may be involved pathogenesis vasculopathy, low cell expression angiotensin-converting enzyme (ACE2) resistance SARS CoV-2 analysis electron microscopy capillaries. They inflammatory pattern were similar closely simulated pathology classical observed vasocentric lymphohistiocytic neutrophilic infiltrates, nuclear dust, erythrocyte extravasation, capillary wall degeneration fibrin deposition. surface (S) mediates entry fulfill function, S binds receptor ACE2 through binding domain activated human proteases, allowing infect cell. have detection particles sweat glands (Cazzato 2022Cazzato Cascardi Colagrande Foti Stellacci Marrone al.SARS-CoV-2 skin: insights perspectives.Biomolecules. 12: 1212Crossref (9) still uncertain whether attributable consequence circulating other organs leading Magro glycoproteins interalveolar septa 5 cases. microvasculature suggesting both eccrine authors (Gawaz Scholar) did detect microscopy. observe abundant cytoplasm in/around nucleus dermal date, there no real active replication most endothelium, despite localization capsid protein, specifically vessels Neutrophils one effective defense against external pathogens; play important pathogen clearance specific antiviral NETosis, form death primarily caused neutrophils, creation extracellular neutrophil traps (NETs). NETs composed DNA fibers chromatin encapsulate cytosolic granule histones depolymerized reticulated trap eliminate pathogens (Zhang 2023Zhang R. Sun Han Y. Huang L. Sheng H. Wang al.Neutrophil autophagy NETosis perspectives.Autophagy. 2023; 19: 758-767Crossref (3) Autophagy—the conserved autodegradation process neutrophils—plays phagocytosis pathogens. Autophagy catabolic isolates damaged cellular components well invasive microbes, isolating them rest cell, forming autophagosomes, delivering lysosomes degradation. This eukaryotic essential survival, homeostasis, immunity (Resnik 2023Resnik Lopez Mingorance F. Rivera Mitchell Gonzalez C.D. Vaccaro M.I. response SARS-CoV-2.Int J Mol Sci. 24: 4928Crossref viruses affect metabolism pathways. leads accumulation metabolites infected marker microtubule-associated (LC3B). LC3 plays crucial overall process. acts RNA-binding causes mRNA interference Different tissues types ubiquitously express LC3B. Researchers implicated which expressed lower levels, virus-induced formation (Delorme-Axford Klionsky, 2020Delorme-Axford Klionsky D.J. Highlights fight does infection?.Autophagy. 16: 2123-2127Crossref (24) focused LC3C—protein markers autophagy—to determine LC3-associated setting was more prominent areas vascular-associated whereas LC3C evident directly than healthy where neither nor detectable any perivascular structures. cathelicidin antimicrobial peptide belongs family host peptides. Neutrophilic granulocytes release LL-37, innate activity. Some elevated plasma levels cases clinical hypercoagulation manifestations (Duan 2022Duan Z. Zhang Chen X. Liu Zhao Jin al.Role thrombotic complications COVID-19.Cell Life 79: 309Crossref (10) predominantly present rather nonrelated therefore SARS-CoV-2–related might endothelia. In Aloul 2022Aloul K.M. Nielsen J.E. Defensor E.B. Lin J.S. Fortkort J.A. Shamloo al.Upregulating prevent responses reduce microthrombosis.Front Immunol. 13880961Crossref (14) Scholar, highlighted helps vitro endocytosis dendritic aggregation. Furthermore, suggested enhancing potentially mitigate reactions related decrease incidence microthrombosis. previous virus-dependent immune-mediated COVID-19–related yet clearly identified molecular pathways responsible COVID-19. concept autophagosome-associated SARS-CoV2 proteins. These contribute better understanding virus-associated vasculopathy. targets (Figure 1). should exercise caution owing sample size studied timing investigations, late course disease. We need further prospective larger cohorts confirm these findings. Nesrine Brahimi: http://orcid.org/0009-0007-0799-852X Vincent Piguet: http://orcid.org/0000-0001-6079-4517 VP personal financial ties pharmaceutical company. He undertakes advisory work Pfizer, AbbVie, Janssen, UCB, Novartis, Almirall, Celgene. received honoraria Kyowa Kirin. his Department Division Director Dermatology University Toronto, departmental support Bausch Health, Celgene, LEO Pharma, Lilly, NAOS, Pierre-Fabre, Sanofi past 36 months. NB fellowship funding AbbVie Canada Grants. No preparation commentary. SARS-CoV-2–Induced Vasculitic Skin Lesions Are Associated Massive Spike Protein Depositions AutophagosomesJournal Investigative DermatologyVol. 144Issue 2PreviewIn 2, vasculopathic prognosis. conclusively clarified. study, 25 prospectively collected examined and, case analyzed immunohistochemistry. Vasculopathy 76% Full-Text Open Access