Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1401015

TGF-β1 overexpression in severe COVID-19 survivors and its implications for early-phase fibrotic abnormalities and long-term functional impairment

Provisionally accepted
Enrique Alfaro Enrique Alfaro 1,2Raquel Casitas Raquel Casitas 1,2Elena Díaz-García Elena Díaz-García 1,2Sara García-Tovar Sara García-Tovar 1Raúl Galera Raúl Galera 1,2María Torres-Vargas María Torres-Vargas 1,2María Fernández-Velilla María Fernández-Velilla 3Cristina López-Fernández Cristina López-Fernández 1,2José M. Añón José M. Añón 3Manuel Quintana-Díaz Manuel Quintana-Díaz 3Francisco García-Río Francisco García-Río 1,2,4Carolina Cubillos-Zapata Carolina Cubillos-Zapata 1,2*
  • 1 University Hospital La Paz, La Paz, Asturias, Spain
  • 2 Network Biomedical Research Center for Respiratory Diseases, Carlos III Health Institute (ISCIII), Madrid, Spain
  • 3 Department of Intensive Medicine, University Hospital La Paz, Madrid, Spain
  • 4 Faculty of Medicine, Autonomous University of Madrid, Madrid, Madrid, Spain

The final, formatted version of the article will be published soon.

    In post-COVID survivors, transforming growth factor-beta-1 (TGF-β1) might mediate fibroblast activation, resulting in persistent fibrosis. In this study, 82 survivors of COVID-19-associated ARDS were examined at 6-and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-β1 was measured in blood and exhaled breath condensate (EBC). At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-β1. Plasma TGF-β1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-β receptordependent manner. Finally, at 6-months, plasma and EBC active TGF-β1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. TGF-β1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

    Keywords: post-COVID, Acute Respiratory Distress Syndrome, lung fibrosis, Transforming growth factor, gas transfer components

    Received: 14 Mar 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Alfaro, Casitas, Díaz-García, García-Tovar, Galera, Torres-Vargas, Fernández-Velilla, López-Fernández, Añón, Quintana-Díaz, García-Río and Cubillos-Zapata. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Carolina Cubillos-Zapata, University Hospital La Paz, La Paz, Asturias, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.