Orholm Nielsen Anne, Brændholt Rasmussen Kirsten, Toft Frederikke Bay, Nielsen Henning Bay, Hildebrandt Thomas, Sloth Carsten, Mayorca-Guiliani Alejandro E, Karsdal Morten, Leeming Diana Julie, Borg Rikke
Department of Medicine, Zealand University Hospital, Roskilde, Denmark.
Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Eur Clin Respir J. 2025 May 29;12(1):2510032. doi: 10.1080/20018525.2025.2510032. eCollection 2025.
Impaired lung function and fibrotic scarring of the lungs following severe COVID-19 infection are well-known manifestations. However, the risk factors and predisposing factors are still unknown. This study explored whether serological biomarkers for collagen synthesis associate with impaired lung function and fibrotic scarring after COVID-19 infection.
In a prospective, observational cohort study involving patients hospitalized with COVID-19 requiring intensive care from June 2020 to December 2021, patients were followed up at 1, 3, 6, and 12 months after discharge. Lung function, diffusion capacity, and a panel of serological biomarkers for collagen-based fibrogenesis (PRO-C3, PRO-C6, and PRO-FIB) were measured. Additionally, a high-resolution CT scan of the lungs was performed at 3 and 12 months.
Thirty-four patients were included in the study. Twenty-seven (80%) were men (mean age 61 years). Most patients were former or active smokers (56%), while 44% were never smokers. Levels of both PRO-C3, PRO-C6, and PRO-FIB were higher 3 months after discharge compared to the normal range. The highest levels were measured 1 month after discharge, with PRO-C3 23.2 ng/ml, PRO-C6 15.9 ng/ml, and PRO-FIB 29.3 ng/ml. The levels of PRO-C3 declined up to 6 months after discharge and were hereafter stabilized, whereas the levels of PRO-C6 declined for the entire follow up period. Lung function improved during the first 6 months and then stabilized. Comparing lung function with PRO-C3 and PRO-C6 showed a positive correlation with lung function improving, while levels of the biomarkers declined. However, only PRO-C3 was found to be significantly associated with improvement in lung function 1 month after discharge.
This study found that PRO-C3 and PRO-C6 are associated with changes in lung function after severe COVID-19 infection. High levels of both PRO-C6 and PRO-C3 were found up to 6 months after discharge in patients with impaired lung function, however, the values declined towards reference levels after 12 months.
严重新型冠状病毒肺炎（COVID-19）感染后肺功能受损和肺部纤维化瘢痕形成是众所周知的表现。然而，其危险因素和易感因素仍不清楚。本研究探讨了胶原蛋白合成的血清生物标志物是否与COVID-19感染后的肺功能受损和纤维化瘢痕形成相关。
在一项前瞻性观察性队列研究中，纳入了2020年6月至2021年12月因COVID-19住院并需要重症监护的患者，在出院后1、3、6和12个月对患者进行随访。测量肺功能、弥散能力以及一组基于胶原蛋白的纤维生成的血清生物标志物（PRO-C3、PRO-C6和PRO-FIB）。此外，在3个月和12个月时进行肺部高分辨率CT扫描。
本研究共纳入34例患者。27例（80%）为男性（平均年龄61岁）。大多数患者为既往吸烟者或现吸烟者（56%），而44%为从不吸烟者。出院后3个月时，PRO-C3、PRO-C6和PRO-FIB的水平均高于正常范围。出院后1个月时测量到最高水平，PRO-C3为23.2 ng/ml，PRO-C6为15.9 ng/ml，PRO-FIB为29.3 ng/ml。PRO-C3的水平在出院后6个月内下降，此后趋于稳定，而PRO-C6的水平在整个随访期内均下降。肺功能在最初6个月内改善，然后趋于稳定。将肺功能与PRO-C3和PRO-C6进行比较，结果显示随着肺功能改善，生物标志物水平下降，二者呈正相关。然而，仅发现PRO-C3与出院后1个月时的肺功能改善显著相关。
本研究发现PRO-C3和PRO-C6与严重COVID-19感染后的肺功能变化相关。肺功能受损患者出院后6个月内PRO-C6和PRO-C3水平均较高，但12个月后这些值向参考水平下降。
