Zuo Yu, Estes Shanea K, Ali Ramadan A, Gandhi Alex A, Yalavarthi Srilakshmi, Shi Hui, Sule Gautam, Gockman Kelsey, Madison Jacqueline A, Zuo Melanie, Yadav Vinita, Wang Jintao, Woodard Wrenn, Lezak Sean P, Lugogo Njira L, Smith Stephanie A, Morrissey James H, Kanthi Yogendra, Knight Jason S
medRxiv. 2020 Sep 15:2020.06.15.20131607. doi: 10.1101/2020.06.15.20131607.
Patients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. At the same time, lung histopathology often reveals fibrin-based occlusion in the small vessels of patients who succumb to the disease. Antiphospholipid syndrome (APS) is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies (aPL) targeting phospholipids and phospholipid-binding proteins. Case series have recently detected aPL in patients with COVID-19. Here, we measured eight types of aPL [anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti- phosphatidylserine/prothrombin (aPS/PT) IgG/IgM] in the sera of 172 patients hospitalized with COVID-19. We detected aPS/PT IgG in 24%, anticardiolipin IgM in 23%, and aPS/PT IgM in 18%. Any aPL was present in 52% of patients using the manufacturer's threshold and in 30% using a more stringent cutoff (≥40 units). Higher levels of aPL were associated with neutrophil hyperactivity (including the release of neutrophil extracellular traps/NETs), higher platelet count, more severe respiratory disease, and lower glomerular filtration rate. Similar to patients with longstanding APS, IgG fractions isolated from patients with COVID-19 promoted NET release from control neutrophils. Furthermore, injection of these COVID-19 IgG fractions into mice accelerated venous thrombosis. Taken together, these studies suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic.
新型冠状病毒肺炎（COVID-19）患者发生动脉和静脉血栓性闭塞的风险很高。与此同时，肺组织病理学检查常显示，死于该疾病的患者小血管中存在基于纤维蛋白的闭塞。抗磷脂综合征（APS）是一种后天获得性且可能危及生命的易栓症，患者会产生针对磷脂和磷脂结合蛋白的致病性自身抗体（aPL）。近期的病例系列研究在COVID-19患者中检测到了aPL。在此，我们检测了172例因COVID-19住院患者血清中的8种aPL[抗心磷脂IgG/IgM/IgA、抗β2糖蛋白I IgG/IgM/IgA以及抗磷脂酰丝氨酸/凝血酶原（aPS/PT）IgG/IgM]。我们检测到24%的患者存在aPS/PT IgG、23%的患者存在抗心磷脂IgM以及18%的患者存在aPS/PT IgM。按照制造商的阈值，52%的患者存在任何一种aPL；若采用更严格的临界值（≥40单位），则30%的患者存在。较高水平的aPL与中性粒细胞活性亢进（包括中性粒细胞胞外诱捕网/NETs的释放）、较高的血小板计数、更严重的呼吸系统疾病以及较低的肾小球滤过率相关。与长期患有APS的患者相似，从COVID-19患者中分离出的IgG组分可促进对照中性粒细胞释放NETs。此外，将这些COVID-19 IgG组分注射到小鼠体内可加速静脉血栓形成。综上所述，这些研究表明，相当比例的COVID-19患者至少会出现aPL短暂阳性，并且这些aPL可能具有致病性。
