Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study.
Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study.
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DOI：
10.1016/j.eclinm.2021.101070
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发表时间：
2021-09
影响因子：
15.1
通讯作者：
UCLH Queen Square COVID-19 Biomarker Study group
中科院分区：
文献类型：
--
作者：
Benjamin LA;Paterson RW;Moll R;Pericleous C;Brown R;Mehta PR;Athauda D;Ziff OJ;Heaney J;Checkley AM;Houlihan CF;Chou M;Heslegrave AJ;Chandratheva A;Michael BD;Blennow K;Vivekanandam V;Foulkes A;Mummery CJ;Lunn MP;Keddie S;Spyer MJ;Mckinnon T;Hart M;Carletti F;Jäger HR;Manji H;Zandi MS;Werring DJ;Nastouli E;Simister R;Solomon T;Zetterberg H;Schott JM;Cohen H;Efthymiou M;UCLH Queen Square COVID-19 Biomarker Study group
据报道，在具有神经系统表现和 COVID-19 的病例系列中，抗磷脂抗体的患病率很高；然而，抗磷脂抗体在 COVID-19 神经病学中的致病性仍不清楚。这项单中心横断面研究纳入了 106 名成年患者：2020 年 3 月至 7 月期间招募的 30 名住院新冠肺炎神经病例、47 名非神经科新冠住院对照和 29 名新冠非住院对照。我们评估了 9 种抗磷脂抗体：抗心磷脂抗体 [aCL] IgA、IgM、IgG；抗心磷脂抗体 [aCL] IgA、IgM、IgG；抗 β2 糖蛋白 1 [aβ2GPI] IgA、IgM、IgG；抗磷脂酰丝氨酸/凝血酶原 [aPS/PT] IgM、IgG；和抗结构域 I β2GPI (aD1β2GPI) IgG。与新冠肺炎非住院对照 (48.2%) 相比，新冠神经病住院对照 (73.3%) 和非神经病新冠住院对照 (76.6%) 中抗磷脂抗体的患病率较高。与两个对照组相比，COVID 神经病学组的 aPS/PT IgG 滴度显着更高 (p < 0.001)。在 3 名急性播散性脑脊髓炎 [ADEM] 患者中，有 2 名 (67%) 发现了中高滴度的 aPS/PT IgG。 aPS/PT IgG 滴度与需氧量呈负相关 (FiO2R=-0.15 p = 0.040)，并与静脉血栓栓塞相关 (p = 0.043)。相比之下，与其他组相比，aCL IgA (p < 0.001) 和 IgG (p < 0.001) 与非神经科新冠肺炎住院对照组相关，并且与 D-二聚体和肌酐呈正相关，但与 FiO2 呈负相关。我们的研究结果表明，aPS/PT IgG 与 COVID-19 相关 ADEM 相关。相比之下，aCL IgA 和 IgG 在非神经系统住院的 COVID-19 患者中更为常见。需要抗磷脂抗体持久性和潜在的纵向临床影响的表征来指导适当的管理。这项工作得到伦敦大学学院皇后广场生物医学研究中心 (BRC) 和 Moorfields BRC 赠款（#560441 和 #557595）的支持。 LB 得到 Wellcome Trust Fellowship (222102/Z/20/Z) 的支持。 RWP 得到阿尔茨海默病协会临床科学家奖学金 (AACSF-20-685780) 和英国痴呆症研究所的支持。根据瑞典政府与郡议会之间的 ALF 协议 (#ALFGBG-715986)，KB 得到瑞典研究委员会 (#2017-00915) 和瑞典政府的支持。 HZ 是瓦伦堡学者，获得瑞典研究委员会 (#2018-02532)、欧洲研究委员会 (#681712)、瑞典国家临床研究支持 (#ALFGBG-720931)、美国阿尔茨海默病药物发现基金会 (ADDF) (#201809-2016862) 和伦敦大学学院英国痴呆症研究所的资助。 BDM 得到 MRC/UKRI (MR/V007181/1)、MRC (MR/T028750/1) 和 Wellcome (ISSF201902/3) 的资助。 MSZ、MH 和 RS 得到 UCL/UCLH NIHR 生物医学研究中心的支持，MSZ 得到 Queen Square National Brain Appeal 的支持。
A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [aβ2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I β2GPI (aD1β2GPI) IgG. There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO2R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with d-dimer and creatinine but negatively with FiO2. Our findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management. This work is supported by UCL Queen Square Biomedical Research Centre (BRC) and Moorfields BRC grants (#560441 and #557595). LB is supported by a Wellcome Trust Fellowship (222102/Z/20/Z). RWP is supported by an Alzheimer's Association Clinician Scientist Fellowship (AACSF-20-685780) and the UK Dementia Research Institute. KB is supported by the Swedish Research Council (#2017-00915) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and theUK Dementia Research Institute at UCL. BDM is supported by grants from the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). MSZ, MH and RS are supported by the UCL/UCLH NIHR Biomedical Research Centre and MSZ is supported by Queen Square National Brain Appeal.
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DOI：
10.1111/jth.14849
发表时间：
2020-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
通讯作者：
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影响因子：
3.7
作者：
Pericleous C;Ferreira I;Borghi O;Pregnolato F;McDonnell T;Garza-Garcia A;Driscoll P;Pierangeli S;Isenberg D;Ioannou Y;Giles I;Meroni PL;Rahman A
通讯作者：
Rahman A
影响因子：
56.3
作者：
Carsana, Luca;Sonzogni, Aurelio;Nebuloni, Manuela
通讯作者：
Nebuloni, Manuela
影响因子：
10.4
作者：
Tang, Ning;Li, Dengju;Sun, Ziyong
通讯作者：
Sun, Ziyong
影响因子：
3.1
作者：
Tung ML;Tan B;Cherian R;Chandra B
通讯作者：
Chandra B