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The majority of severe COVID-19 patients develop anti-cardiac autoantibodies
GeroScience ( IF 5.3 ) Pub Date : 2022-09-16 , DOI: 10.1007/s11357-022-00649-6
Miklós Fagyas 1, 2, 3, 4 , Béla Nagy 5 , Arnold Péter Ráduly 1, 2, 6 , Ivetta Siket Mányiné 1 , Lilla Mártha 1 , Gábor Erdősi 1 , Sándor Sipka 2 , Enikő Enyedi 1, 6 , Attila Ádám Szabó 1, 6 , Zsófia Pólik 1 , János Kappelmayer 5 , Zoltán Papp 1, 3, 4 , Attila Borbély 2 , Tamás Szabó 7 , József Balla 3, 8 , György Balla 3, 7 , Péter Bai 4, 9, 10, 11 , Attila Bácsi 12, 13 , Attila Tóth 1, 3, 4
Affiliation  

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment. Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).



中文翻译:


大多数重症 COVID-19 患者会产生抗心脏自身抗体



COVID-19 重症病例的特点是炎症爆发,并伴有多器官衰竭。老年人群因 COVID-19 出现严重或致命后果的风险较高。炎症介质通过产生针对病毒抗原的抗体来促进免疫系统对抗病毒感染。多项研究报告称,COVID-19 中的促炎症状态和组织损伤也会通过自身抗体的产生促进自身免疫。我们假设这些自身抗体的一部分针对心脏抗原。在这里,我们的目的是检测重症 COVID-19 患者住院期间的抗心脏自身抗体。为此,招募了 104 名 COVID-19 患者,同时 40 名患有扩张型心肌病的心力衰竭患者和 20 名患有严重主动脉瓣狭窄的患者作为对照。使用人心脏匀浆作为诱饵,对患者进行抗心脏自身抗体测试。 29 名 COVID-19 患者获得了后续样本。 68%(104 名重症患者中的 71 名)检测到抗心脏自身抗体。总体而言,39% 的 COVID-19 患者具有抗心脏 IgG 自身抗体,而 51% 具有 IgM 同型抗心脏自身抗体。在 22% 的病例中观察到 IgG 和 IgM 抗心脏自身抗体,在 38% 的 COVID-19 患者中观察到多种心脏抗原。这些抗心脏自身抗体针对多种心肌蛋白,没有明显的选择性。作为对照,心力衰竭患者(扩张型心肌病)的 IgG 自身抗体发生率相似(45%, p = 0.57),而 IgM 自身抗体的发生率显着较低(30%, p = 0.03)。晚期主动脉瓣狭窄患者的两种 IgG 数量均显着较低(11%, p = 0.03) 和 IgM (10%, p < 0.01) 型抗心脏自身抗体高于 COVID-19 患者。此外,我们检测到 7 名 COVID-19 患者在住院治疗期间抗心脏自身抗体谱发生变化。令人惊讶的是,这些抗心脏自身抗体的存在并不影响临床结果,并且老年人(65 岁以上)和 65 岁以下患者之间自身抗体的患病率没有差异。我们的结果表明,大多数住院的 COVID-19 患者产生新型抗心脏 IgM 自身抗体。 COVID-19 还会重新激活常驻 IgG 自身抗体。这些自身抗体可能会促进自身免疫反应,从而使新冠肺炎后的恢复变得复杂,从而导致新冠肺炎(长期新冠肺炎)的急性后遗症。

更新日期:2022-09-16
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