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Purpose <p>Post-acute sequelae of COVID-19 (PASC) has emerged as a major healthcare problem. A comprehensive mechanism of disease remains to be elucidated. In this study we aimed to explore pulmonary and muscle fibroblast activation protein (FAP) activity in former critical COVID-19 patients with persistent dyspnea, using [<sup>68</sup>Ga]FAPI-46 PET/CT.</p> Methods <p>In this single center prospective observational study we included former critical COVID-19 patients reporting complaints of dyspnea &gt; 3&#xa0;months after hospital discharge. A [<sup>68</sup>Ga]FAPI PET/CT scan was performed including a high-resolution CT scan, lung function test, EQ-5D questionnaire, 6 min walking test and inflammatory markers. Age and sex-matched subjects, without pulmonary pathology, served as controls. The [<sup>68</sup>Ga]FAPI uptake was corrected for lean body mass and the target-to-background ratio (TBR) was calculated.</p> Results <p>Eighteen PASC patients and 15 controls (median age 59 and 63 years and BMI of 34.6 and 25.2 kg/m<sup>2</sup>) were included. The interval between hospital discharge and study visit was 30 months. Increased pulmonary FAP expression was observed in PASC, (TBR 0.79 ± 0.23) compared to controls (TBR 0.40 ± 0.13, <i>P</i> &lt; 0.001). Increased FAP expression was also observed in the paravertebral muscles (PASC: TBR 1.17 and controls TBR 1.00, <i>P</i> = 0.03). Forced expiratory volume and forced vital capacity showed moderate negative correlation with the pulmonary TBR, while the percentage of ground glass opacities showed a moderate positive correlation.</p> Conclusion <p>[<sup>68</sup>Ga]FAPI PET/CT demonstrated elevated FAP expression in PASC. These findings provide insight into possible pathophysiological mechanisms of PASC and a potential new diagnostic modality.</p>

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[68Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月21日

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  • B. van Leer,
  • M. Londema,
  • Ö. Kasalak,
  • J. H. van Snick,
  • M. L. Duiverman,
  • J. C. Kuijvenhoven,
  • M. D. de Kruif,
  • D. E. Oprea-Lager,
  • K. Pabst,
  • M. E. Hellemons,
  • H. H. Boersma,
  • M. Prokop,
  • M. W. Nijsten,
  • A. W. J. M. Glaudemans,
  • J. Pillay,
  • R. H. J. A. Slart,
  • R. J. H. C. G. Beijers,
  • S. M. J. van Kuijk,
  • D. Gach,
  • S. Schalekamp,
  • B. van den Borst,
  • L. M. Bek,
  • J. L. Stöger,
  • L. F. M. Beenen,
  • A. A. Lammertsma,
  • D. F. Postma,
  • F. A. A. Mohamed Hoesein,
  • H. A. Gietema,
  • A. Schols

摘要

Purpose

Post-acute sequelae of COVID-19 (PASC) has emerged as a major healthcare problem. A comprehensive mechanism of disease remains to be elucidated. In this study we aimed to explore pulmonary and muscle fibroblast activation protein (FAP) activity in former critical COVID-19 patients with persistent dyspnea, using [68Ga]FAPI-46 PET/CT.

Methods

In this single center prospective observational study we included former critical COVID-19 patients reporting complaints of dyspnea > 3 months after hospital discharge. A [68Ga]FAPI PET/CT scan was performed including a high-resolution CT scan, lung function test, EQ-5D questionnaire, 6 min walking test and inflammatory markers. Age and sex-matched subjects, without pulmonary pathology, served as controls. The [68Ga]FAPI uptake was corrected for lean body mass and the target-to-background ratio (TBR) was calculated.

Results

Eighteen PASC patients and 15 controls (median age 59 and 63 years and BMI of 34.6 and 25.2 kg/m2) were included. The interval between hospital discharge and study visit was 30 months. Increased pulmonary FAP expression was observed in PASC, (TBR 0.79 ± 0.23) compared to controls (TBR 0.40 ± 0.13, P < 0.001). Increased FAP expression was also observed in the paravertebral muscles (PASC: TBR 1.17 and controls TBR 1.00, P = 0.03). Forced expiratory volume and forced vital capacity showed moderate negative correlation with the pulmonary TBR, while the percentage of ground glass opacities showed a moderate positive correlation.

Conclusion

[68Ga]FAPI PET/CT demonstrated elevated FAP expression in PASC. These findings provide insight into possible pathophysiological mechanisms of PASC and a potential new diagnostic modality.