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<p>The mechanisms driving immune dysregulation in long COVID disease remain elusive. Here we integrated single-cell multiome data, immunological profiling and functional assays to investigate immune alterations across multiple cohorts. A transcriptional state in circulating monocytes (LC-Mo) was enriched in individuals with mild–moderate acute infection and accompanied by persistent elevations of plasma CCL2, CXCL11 and TNF. LC-Mo showed TGFβ and WNT–β-catenin signaling and correlated with fatigue severity. Protein markers of LC-Mo were increased in individuals with pronounced fatigue or dyspnea, and those with severe respiratory symptoms showed higher LC-Mo expression. Epigenetically, LC-Mo exhibited AP-1- and NF-κB1-driven profibrotic programs. LC-Mo-like macrophages in bronchoalveolar lavage samples from individuals with severe respiratory symptoms displayed a profibrotic profile, and individuals with a high LC-Mo transcriptional state showed impaired interferon responses after stimulation. Collectively, our findings define a pathogenic monocyte transcriptional state linking systemic immune dysfunction to persistent long COVID disease, providing mechanistic insights and potential therapeutic targets.</p>

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A distinct monocyte transcriptional state links systemic immune dysregulation to pulmonary impairment in long COVID

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Saumya Kumar,
  • Chaofan Li,
  • Liang Zhou,
  • Qiuyao Zhan,
  • Ahmed Alaswad,
  • Sonja Volland,
  • Bibiana Costa,
  • Simon Alexander Krooss,
  • Isabel Klefenz,
  • Hagen Schmaus,
  • Antonia Zeuzem,
  • Dorothee von Witzendorff,
  • Helena Lickei,
  • Lea Pueschel,
  • Anke R. M. Kraft,
  • Markus Cornberg,
  • Andreas Rembert Koczulla,
  • Isabell Pink,
  • Marius M. Hoeper,
  • Cheng-Jian Xu,
  • Susanne Häussler,
  • Miriam Wiestler,
  • Mihai G. Netea,
  • Thomas Illig,
  • Jie Sun,
  • Yang Li

摘要

The mechanisms driving immune dysregulation in long COVID disease remain elusive. Here we integrated single-cell multiome data, immunological profiling and functional assays to investigate immune alterations across multiple cohorts. A transcriptional state in circulating monocytes (LC-Mo) was enriched in individuals with mild–moderate acute infection and accompanied by persistent elevations of plasma CCL2, CXCL11 and TNF. LC-Mo showed TGFβ and WNT–β-catenin signaling and correlated with fatigue severity. Protein markers of LC-Mo were increased in individuals with pronounced fatigue or dyspnea, and those with severe respiratory symptoms showed higher LC-Mo expression. Epigenetically, LC-Mo exhibited AP-1- and NF-κB1-driven profibrotic programs. LC-Mo-like macrophages in bronchoalveolar lavage samples from individuals with severe respiratory symptoms displayed a profibrotic profile, and individuals with a high LC-Mo transcriptional state showed impaired interferon responses after stimulation. Collectively, our findings define a pathogenic monocyte transcriptional state linking systemic immune dysfunction to persistent long COVID disease, providing mechanistic insights and potential therapeutic targets.