Long COVID biomarkers found – associated with respiratory problems

Long COVID, also known as Post COVID, is a condition characterised by persistent symptoms of previous COVID-19. A new study from Karolinska Institutet and Cardiff University, UK, led by Marcus Buggert, docent at the Department of Medicine, Karolinska Institutet (Huddinge), has identified a set of proteins in the blood of people with Long COVID.

 “The proteins were mainly found in patients with Long COVID and severe respiratory problems,” says Dr Buggert. “This is a biomarker pattern that we know to be linked to inflammatory signal pathways involved in cell death and lung damage and that has also been observed in other patient groups with severe pulmonary disorders.”

Detailed analysis of blood samples

Severe and permanent symptoms of acute breathlessness is one of the most common and most typical symptoms of Long COVID. The researchers also studied samples from a group of patients that had recovered from their previous COVID-19 and who had, interestingly, none of these proteins in their blood.

The finding was based on a detailed analysis of blood samples from independent patient groups in Sweden and the UK, something that had not been done before.

All 265 patients who participated in the study had contracted COVID-19 during the early days of the pandemic when no vaccine was yet available. Using advanced techniques, the researchers measured thousands of proteins in the blood plasma, which they related to the patients’ symptoms. They also used flow cytometry to conduct immunological analyses.

“By identifying the proteins that are elevated in affected patients, we’re creating a platform from which to develop diagnostic tools and new targeted therapies,” Dr Buggert says. “This is especially important since there are no specific biomarkers and treatments for Long COVID.”

Symptom biology

The results of the study expose the underlying biological processes that can cause certain patients to experience severe symptoms long after previous COVID-19.

The next step in the research is to understand what underpins this pattern by studying lung and gastrointestinal tissue. In doing so, the researchers hope to locate the source of the identified proteins and find if there is any remaining inflammation or tissue damage in specific organs of patients with Long COVID.

The study was funded by the PolyBio Research Foundation, the Swedish Research Council, SciLifeLab/KAW National COVID-19 Research Program, the Knut and Alice Wallenberg Foundation and Karolinska Institutet. Some of the co-authors receive consultancy and lecture fees from pharmaceutical companies, but they are unconnected to this study.

Publication

“Identification of soluble biomarkers that associate with distinct manifestations of long COVID”, Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S. Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A. Jones, Per Julin, Christer Lidman, Richard J. Stanton, Paul A. Goepfert, Michael J. Peluso, Steven G. Deeks, Helen E. Davies, Soo Aleman, Marcus Buggert & David A. Price, Nature Immunology, online 30 April 2025.