Gualtierotti Roberta, Fox Sharon E, Da Silva Lameira Fernanda, Giachi Andrea, Valenti Luca, Borghi Maria Orietta, Meroni Pier Luigi, Cugno Massimo, Peyvandi Flora
S.C. Medicina-Emostasi e Trombosi, Centro Emofilia e Trombosi Angelo Bianchi Bonomi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy.
Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, 20122 Milan, Italy.
J Clin Med. 2023 May 28;12(11):3727. doi: 10.3390/jcm12113727.
Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States. All COVID-19 patients studied with videocapillaroscopy showed alterations rarely seen in healthy individuals consistent with microangiopathy, such as hemosiderin deposits (sign of microthrombosis and microhemorrhages) and enlarged loops (sign of endotheliopathy). The number of hemosiderin deposits correlated both with ferritin and CRP levels (r = 0.67, = 0.008 for both) and the number of enlarged loops significantly correlated with the levels of VWF (r = 0.67, = 0.006). Ferritin levels were higher in non-O groups, determined by the rs657152 C > A cluster, (median 619, min-max 551-3266 mg/dL) than in the O group (373, 44-581 mg/dL, = 0.006). Nailfold histology revealed microvascular damage, i.e., mild perivascular lymphocyte and macrophage infiltration and microvascular ectasia in the dermal vessels of all cases, and microthrombi within vessels in five cases. Alterations in nailfold videocapillaroscopy and elevated biomarkers of endothelial perturbation that match histopathologic findings open new perspectives in the possibility of non-invasively demonstrating microangiopathy in COVID-19.
已有研究描述了新型冠状病毒肺炎（COVID-19）患者甲襞毛细血管镜检查的改变，但其与炎症、凝血和内皮功能紊乱生物标志物之间的相关性仍不明确，且目前尚无关于甲襞组织病理学的信息。在意大利米兰，对15例COVID-19患者进行了甲襞毛细血管镜检查，并将微血管病变的体征与炎症（C反应蛋白[CRP]、铁蛋白）、凝血（D-二聚体、纤维蛋白原）、内皮功能紊乱（血管性血友病因子[VWF]）和血管生成（血管内皮生长因子[VEGF]）的血浆生物标志物以及COVID-19易感性的基因驱动因素进行了关联分析。在美国新奥尔良，对15例因COVID-19死亡的患者进行了甲襞切除组织病理学分析。所有接受毛细血管镜检查的COVID-19患者均表现出与微血管病变一致的、在健康个体中很少见的改变，如含铁血黄素沉积（微血栓形成和微出血的体征）和袢扩大（内皮病变的体征）。含铁血黄素沉积的数量与铁蛋白和CRP水平均相关（两者r = 0.67，P = 0.008），袢扩大的数量与VWF水平显著相关（r = 0.67，P = 0.006）。由rs657152 C>A簇确定的非O组铁蛋白水平（中位数619，最小-最大551-3266 mg/dL）高于O组（373，44-581 mg/dL，P = 0.006）。甲襞组织学显示所有病例的真皮血管均有微血管损伤，即轻度血管周围淋巴细胞和巨噬细胞浸润及微血管扩张，5例血管内有微血栓形成。甲襞毛细血管镜检查的改变以及与组织病理学结果相符的内皮功能紊乱生物标志物升高，为无创性证明COVID-19微血管病变的可能性开辟了新的前景。
