Cell Adhesion Department, National Medical Research Center of Cardiology, Moscow, Russia.
Department of Physics of Living Systems, Institute of Physics and Technology, Moscow, Russia.
Thromb Haemost. 2022 Jan;122(1):123-130. doi: 10.1055/a-1551-9911. Epub 2021 Sep 5.
Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient.
We analyzed erythrocytes, circulating endothelial cells, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 ( = 31) and matched healthy controls ( = 32) on admission and at hospital discharge.
All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endothelial cells was significantly (40-100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. COVID-19 also provoked formation of stacked aggregated erythrocytes capable of clogging microvascular bed and of diminishing oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining intracellular penetration of SARS-CoV-2 where it may be replicated and returned to circulation.
These observational and descriptive data suggest that persistent viral cell injury may cause blood vessel damage; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. There is a residual blood cell damage following the acute phase in some COVID-19 survivors. Controlled outcome-driven trials are urgently needed for exploring optimal use of long-term antithrombotics and vascular protection strategies even after mild COVID-19.
当前的 2019 年冠状病毒病（COVID-19）大流行在疾病高峰期揭示了血栓形成、血管和内皮功能障碍。然而，抗血栓形成策略的持续时间、损害程度和适当的长期应用尚不清楚。大多数 COVID 数据来自于随机临床观察或尸检后的样本，而幸存者中精确的血细胞数据不足。
我们通过电子显微镜和流式细胞术分析了确诊 COVID-19（n=31）患者和匹配的健康对照者（n=32）入院时和出院时的红细胞、循环内皮细胞和棘形红细胞。
所有患者均患有轻度疾病，无需肺部支持，且均存活。循环内皮细胞的入院数量在 COVID-19 患者中显著增加（40-100 倍）。细胞膜上有大量的孔，直径与 SARS-CoV-2（严重急性呼吸综合征冠状病毒 2）病毒的超级衣壳相当，导致细胞受到严重损伤。COVID-19 还引发了堆叠聚集的红细胞形成，这些红细胞能够堵塞微血管床并减少氧气供应。在一些患者中，这些异常情况在出院时仍然存在，表明 SARS-CoV-2 仍在细胞内穿透，可能在那里复制并重新进入循环。
这些观察性和描述性数据表明，持续的病毒细胞损伤可能导致血管损伤；其增加的通透性导致组织水肿、炎症、血小板激活和血栓形成增加。在一些 COVID-19 幸存者中，急性阶段后仍存在残余的血细胞损伤。迫切需要进行以结果为导向的对照试验，以探索即使在轻度 COVID-19 后，长期使用抗血栓形成和血管保护策略的最佳方法。
