Aims While acute cardiovascular complications of coronavirus disease 2019 (COVID-19) are well described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19. Methods and results Twenty-one participants {mean age 47 [standard deviation (SD) 13] years, 71% female} with long COVID-19 (n = 17), raised troponin (n = 2), or unexplained new-onset heart failure (n = 2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment, were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers were performed. Nine of the 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and two had severe left ventricular (LV) impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23, and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(−). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(−) patients, and functional studies of CD8 T αβ cells showed higher proportions of cytotoxic granzyme B+(GZB+)-secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a least absolute shrinkage and selection operator regression model (composite area under the curve 0.96, 95% confidence interval 0.88–1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r = 0.47, P = 0.04). Conclusion COVID-19-related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.

中文翻译：

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2019 冠状病毒病相关心肌损伤与心脏磁共振成像异常症状患者的免疫失调相关


目的 虽然 2019 冠状病毒病 （COVID-19） 的急性心血管并发症已得到充分描述，但对长期心脏后遗症知之甚少。对于许多在 COVID-19 感染后出现心脏体征或症状的个体，病因尚不清楚。我们检查了 COVID-19 后不明原因心脏损伤患者与磁共振成像 （MRI） 异常相关的免疫特征。方法和结果 21 名参与者 {平均年龄 47 [标准差 （SD） 13] 岁，71% 为女性}患有长期 COVID-19 （n = 17）、肌钙蛋白升高 （n = 2） 或不明原因的新发心力衰竭 （n = 2），他们没有预先存在的心脏病或最近的类固醇/免疫抑制治疗，在一项前瞻性观察性研究中，平均在 COVID-19 感染后 346 （SD 191） 天入组。使用质谱流式细胞术按飞行时间进行心脏 MRI 和血液采样以进行深度免疫表型分析，并测量蛋白质组学炎症标志物。21 名参与者中有 9 名 （43%） 患有 MRI 异常 （MRI（+）），包括 8 名参与者的晚期钆增强和/或视觉上明显的心肌水肿的非缺血模式。1 例患者双心室功能轻度受损，无纤维化或水肿，2 例有严重的左心室 （LV） 损害。MRI（+） 个体的血液 CCL3 、 CCL7 、 FGF-23 和 CD4 Th2 细胞高于 MRI （−），CD8 T 效应记忆 （TEM） 细胞较低。聚类分析显示，MRI （+） 患者的 CD8 TEM 细胞中抑制性受体 PD1 和 TIM3 的表达低于 MRI （-） 患者，CD8 T αβ 细胞的功能研究表明，刺激后细胞毒性颗粒酶 B + （GZB+） 分泌细胞的比例较高。 CD8 TEM 细胞和 CCL7 是最小绝对收缩和选择算子回归模型中 MRI 异常的最强预测因子 （曲线下复合面积 0.96,95% 置信区间 0.88-1.0）。CCL7 与定量 T1 标测检测到的弥漫性心肌纤维化/水肿相关 （r = 0.47，P = 0.04）。结论 非缺血性心肌炎样 MRI 异常症状患者 COVID-19 相关心脏损伤与免疫失调相关，包括外周 CD8 TEM 细胞减少和 CCL7 升高，在初始感染后持续很长时间。