Long COVID impacts ~10% of people diagnosed with coronavirus disease 2019 (COVID-19), yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that ¹²⁹Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID. Therefore, we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes.

COVID-negative controls and participants who previously tested positive for COVID-19 underwent ¹²⁹Xe MRI ~14 months post-acute infection across three centres. Long COVID was defined as persistent dyspnoea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully recovered. ¹²⁹Xe MRI ventilation defect percent (VDP) and membrane-to-gas (Mem/Gas), red blood cell-to-membrane (RBC/Mem) and red blood cell-to-gas (RBC/Gas) ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction.

We evaluated 135 participants across three centres: 28 COVID-negative (mean±sd age 40±16 years), 34 fully recovered (42±14 years) and 73 long COVID (49±13 years). RBC/Mem (p=0.03) and forced expiratory volume in 1 s (FEV₁) (p=0.04) were different between long COVID and COVID-negative; FEV₁ and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster 1 was the youngest with normal MRI and mild gas trapping; Cluster 2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster 3 had mildly increased Mem/Gas with normal PFTs; and Cluster 4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern.

We identified four ¹²⁹Xe MRI long COVID phenotypes with distinct characteristics. ¹²⁹Xe MRI can dissect pathophysiological heterogeneity of long COVID to enable personalised patient care.

大约 10% 的 2019 年冠状病毒病 (COVID-19) 患者受到新冠病毒长期影响，但导致持续症状的病理生理学却知之甚少。我们假设¹²⁹ Xe 磁共振成像 (MRI) 可以识别长期 COVID 的独特肺部表型亚组。因此，我们通过聚类分析评估通气和气体交换测量，以生成基于成像的表型。

在三个中心的急性感染后约 14 个月，COVID 阴性对照和之前 COVID-19 检测呈阳性的参与者接受了¹²⁹ Xe MRI。长期新冠肺炎定义为 MRI 上显示的持续性呼吸困难、胸闷、咳嗽、疲劳、恶心和/或味觉/嗅觉丧失；报告没有症状的参与者被认为已完全康复。¹²⁹ Xe MRI 通气缺陷百分比 (VDP) 和膜与气体 (Mem/Gas)、红细胞与膜 (RBC/Mem) 和红细胞与气体 (RBC/Gas) 比率用于对长期 COVID 进行 k 均值聚类，并使用方差分析和事后 Bonferroni 校正对测量结果进行比较。

我们评估了三个中心的 135 名参与者：28 名新冠病毒呈阴性（平均值±标准差年龄 40±16 岁），34 名完全康复者（42±14 岁）和 73 名长期感染新冠患者（49±13 岁）。长期新冠病毒和新冠病毒阴性之间的RBC/Mem (p=0.03) 和 1 秒用力呼气量 (FEV ₁ ) (p=0.04) 不同； FEV ₁和所有其他肺功能测试 (PFT) 均在正常范围内。与康复者和新冠病毒阴性者相比，确定了四个独特的长新冠病毒簇。簇 1 是最年轻的，具有正常 MRI 和轻度气体滞留；簇 2 是最古老的，其特征是 RBC/Mem 减少，但 PFT 正常；簇 3 的 Mem/Gas 略有增加，PFT 正常；簇 4 的 Mem/Gas 显着增加，同时 RBC/Mem 减少，PFT 模式受限。

我们确定了四种具有不同特征的^{129 Xe MRI 长 COVID 表型。 129} Xe MRI 可以剖析长期新冠病毒的病理生理异质性，以实现个性化的患者护理。