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长新冠住院后患者的大规模表型分析揭示了疾病的机制亚型。

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

机构信息

National Heart and Lung Institute, Imperial College London, London, UK.

Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK.

出版信息

Nat Immunol. 2024 Apr;25(4):607-621. doi: 10.1038/s41590-024-01778-0. Epub 2024 Apr 8.

DOI:10.1038/s41590-024-01778-0
PMID:38589621
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11003868/
Abstract

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

摘要

每 10 例严重急性呼吸综合征冠状病毒 2 感染中就有 1 例导致长期症状，称为长冠状病毒病（COVID），但疾病表型和机制仍不清楚。在这里，我们对 657 名住院后至少 3 个月的患者的 368 种血浆蛋白进行了分析。其中，426 人至少有一个长期 COVID 症状，233 人已完全康复。髓样炎症和补体激活的升高标志物与长期 COVID 有关。IL-1R2、MATN2 和 COLEC12 与心肺症状、疲劳和焦虑/抑郁有关；MATN2、CSF3 和 C1QA 在胃肠道症状中升高，C1QA 在认知障碍中升高。神经组织修复中其他标志物的改变（SPON-1 和 NFASC）在认知障碍患者中升高，而胃肠道症状中升高的 SCG3 提示脑-肠轴紊乱。一些长期 COVID 患者的严重急性呼吸综合征冠状病毒 2 特异性免疫球蛋白 G（IgG）持续升高，但痰液中未检测到病毒。对鼻液中炎症标志物的分析表明，其与症状无关联。我们的研究旨在了解长期 COVID 背后的炎症过程，并非旨在发现生物标志物。我们的研究结果表明，与组织损伤相关的特定炎症途径与长期 COVID 的亚型有关，这可能是未来治疗试验的目标。

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J Clin Med. 2025-7-29

[5]
From Stagnation to Strategy: Challenges in Advancing Long COVID Research.

J Eval Clin Pract. 2025-8

[6]
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本文引用的文献

[1]
Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Science. 2024-1-19

[2]
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Front Immunol. 2023

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