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Identification of prognostic markers for development of chronic lung fibrosis in COVID-19 patients

Foto på Gunilla Westergren-Thorsson
Gunilla Westergren-Thorsson wants to establish methods to identify risk groups at an early stage. Photo Agata Garpenlind.

Pulmonary fibrosis is a severe and life shortening chronic condition. Although most people experience mild symptoms of COVID-19, some patients develop serious and life-threatening conditions with severe lung damage. In order to influence the outcome of the disease, lung researchers in Lund are currently establishing methods to identify risk groups at an early stage.

A significantly altered lung structure with an overproduction of connective tissue, so-called pulmonary fibrosis, is a chronic condition with profound suffering and impaired quality of life. In its most severe form, the lungs stop working with a premature death as a result.

In severe COVID-19 infection the lung tissue composition become seriously affected with massive inflammation and fibrosis.

"We need methods for early diagnosis of patients likely to develop fibrotic changes. Being able to identify risk groups will help us to start treating these patients at an early stage" says Gunilla Westergren-Thorsson, professor in Lung Biology at the Department of Experimental Medical Science at Lund University, who is leading the study.

Unique proteins

When studying fibrotic lung tissue in the lab, researchers have found proteins, unique markers, reflecting the clinical course seen in patients with pulmonary fibrosis. These potential biomarkers will be further studied in blood samples from patients with pulmonary fibrosis and patients who have had a COVID-19 infection, in order to characterize COVID-19 patients at risk of developing pulmonary fibrosis.

"We will link our results to clinical parameters such as age, sex and underlying diseases, which are known risk factors for developing a more severe disease outcome, to identify patients with COVID-19 infection who are at risk of developing chronic pulmonary fibrosis”.

Studying the mechanisms

The researchers will investigate the previously identified biomarkers in patients in risk for developing severe COVID-19 including smokers, to understand whether these proteins link to the development of pulmonary fibrosis. In addition, the disease mechanisms will be studied in detail; the protein- and carbohydrate composition within the tissue (in lung biopsies taken at controls), the signaling pathways for development of fibrosis and how the virus is established in the lung.

"Early diagnosis of patients likely to develop pulmonary fibrosis would allow for preventative actions to be taken, for example to reduce fibrotic changes and thus reduce patient mortality. An increased knowledge of what mechanisms confer the risk factors such as comorbidity and gender differences, and how they impact disease progression is of great importance. So far, for example, it appears that most patients with COVID-19 are men with underlying diseases, but the exact mechanisms behind are still elusive”.

 Pulmonary fibrosis is recognized by an extensive remodelling of the tissue surrounding the bronchi- and alveolar region, resulting in stiff scar tissue, so called fibrosis. As a result, the exchange of oxygen and carbon dioxide between the lungs and the

Pulmonary fibrosis is recognized by an extensive remodelling of the tissue surrounding the bronchi- and alveolar region, resulting in stiff scar tissue, so called fibrosis. As a result, the exchange of oxygen and carbon dioxide between the lungs and the nearby blood vessels is hampered, which causes breathlessness and eventually dyspnea. The more fibrosis, the harder it gets to breathe. Illustration: Lisa Karlsson

Impaired lung function

Gunilla Westergren-Thorsson and her team have an extensive experience (25 years) and knowledge in pathobiological turnover of the connective tissue in various lung diseases, lung tissue composition at a molecular level as well as the structural heterogeneity in different parts of the lung. The hope is to transfer this knowledge to COVID-19, focusing on the composition and turnover of connective tissue and the connection to lung function and the ability of oxygenation.

"Our research focus is on the distal part of the lung, where the oxygen exchange occurs. Getting an infection or inflammation in the lower respiratory tract is not good. However, this is seen in some inflammatory lung diseases and it can also occur during COVID-19 infection. We believe that it is possible to affect the structural changes at an early stage, however, in later disease stages damages of the lung tissue becomes irreversible resulting in impaired lung function.

The study at Lund University is conducted in collaboration with researchers at the Karolinska Institute and the first results regarding patients with severe pulmonary fibrosis is expected by the end of autumn 2020. These results will pave the way for how to proceed with the COVID-19 samples.





Facts about the study

Name: "Identifying early signs of permanent lung damage in COVID-19 patients”

Started 2020-05-07

The Lung biology teamconsists of about 20 people led by professor Gunilla Westergren-Thorsson. The group aims to contribute to a better understanding of the mechanisms behind chronic inflammatory lung diseases. The aim is also to identify biomarkers for early diagnosis and new targets for treatment of these diseases.

The researchers involved in this project:

  • Gunilla Westergren-Thorsson, Professor in Lung Biology, Director the of Wallenberg Center for Molecular Medicine (WCMM) and Lund University Bioimaging Center (LBIC)
  • Anna Löfdahl, post-doc
  • Linda Elowsson Rendin, post-doc
  • Emil Tykesson, post-doc
  • Dimitrios Kalafatis, PhD student
  • Barbora Michaliková, PhD student
  • Collaborator in the project is Magnus Sköld, professor Pulmonary Medicine at Karolinska Institute

Links to relevant related previous research: