Scientists Identify Biomarkers Driving Long COVID Breathlessness and Fatigue Symptoms
Nikhil Prasad Fact checked by:Thailand Medical News Team May 01, 2025 11 hours, 48 minutes ago
Medical News: Groundbreaking Research from International Collaboration
In a major scientific breakthrough, researchers from Karolinska Institutet in Sweden and Cardiff University in the United Kingdom—along with collaborators from several other institutions—have identified critical blood-based biomarkers that shed light on why some individuals develop long COVID. Their study reveals that persistent symptoms like breathlessness, fatigue, and chronic pain may be linked to specific protein imbalances and subtle immune system abnormalities in the blood.
Scientists Identify Biomarkers Driving Long COVID Breathlessness and Fatigue Symptoms
What Is Long COVID and Why Is It So Mysterious
Long COVID, also known as post-acute sequelae of COVID-19, affects millions of people globally. Even after recovering from the initial infection, many continue to experience long-lasting symptoms that affect daily life. These range from difficulty breathing and overwhelming fatigue to brain fog, joint pain, and chest discomfort. The underlying causes have been poorly understood—until now.
This
Medical News report explains how new research has uncovered distinct biological signatures in the blood that are tied to long COVID symptoms, offering hope for improved diagnosis and treatment.
Study Design and Participant Analysis
The researchers studied blood samples from two groups of individuals: one group had fully recovered from COVID-19, while the other was still experiencing long COVID symptoms. Participants were recruited from hospitals in both the United Kingdom and Sweden, ensuring the data had global relevance. Both groups had similar age, sex, vaccination status, and virus exposure histories.
Importantly, the analysis found that despite having similar amounts of antibodies targeting the SARS-CoV-2 spike protein, individuals with long COVID had significantly lower levels of neutralizing antibodies. These are the antibodies that actually block the virus from infecting cells. This suggests that long COVID may be partly driven by a less effective immune memory.
Immune Exhaustion Markers Signal Dysfunction
Another key discovery was the higher expression of PD-1 and TIM-3 markers on CD8+ T cells in long COVID patients. These proteins are associated with T cell exhaustion—a state in which immune cells are less responsive and less effective. This immune fatigue could be one reason why some people struggle to fully recover from COVID-19.
A Unique Protein Signature Linked to Breathlessness
One of the most striking findings was the discovery of a unique set of blood proteins linked to breathlessness, one of the most common and distressing symptoms of long COVID. Proteins such as CCL3, CD40, IL-18, IKBKG, and IRAK1 were elevated in those with severe breathing issues. These proteins are involved in inflammatory responses, programmed cell death, lung tissue damage, and blood clotting.
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Advanced statistical tools showed that individuals who reported more severe breathlessness had elevated levels of these proteins in their blood. These molecular patterns resembled those seen in conditions like lung collapse (atelectasis) and rapid breathing (tachypnea), suggesting a direct physiological connection between these blood changes and the experience of breathlessness.
Findings Validated Across Two Countries
To ensure their results were robust, the team analyzed samples from both UK and Swedish patients and found consistent protein expression patterns. This strengthens the evidence that long COVID has a recognizable and reproducible biological basis, independent of geography or healthcare system.
The study also found smaller changes in other immune cells. For instance, patients with long COVID had more plasmacytoid dendritic cells and basophils—cells involved in immune regulation and allergic reactions. However, these shifts were less pronounced than the dramatic differences observed in plasma protein profiles.
Potential for Future Blood Tests and Treatments
This study not only enhances our understanding of long COVID but also lays the groundwork for developing clinical tools. In the future, doctors might be able to use blood tests to predict who is at risk of long COVID or to confirm the diagnosis in patients with persistent symptoms. Even more promising is the potential to target specific molecules like IL-18 or CD40 for drug development, offering new hope for treatment.
Conclusion
This study represents a pivotal step forward in unraveling the complex puzzle of long COVID. It confirms that persistent symptoms are driven by real and measurable biological processes—particularly immune dysregulation and chronic inflammation. The discovery of unique protein networks in the blood points to the potential for new diagnostic and therapeutic approaches. While more research is needed to fully translate these findings into medical practice, this work paves a clearer path toward understanding and managing long COVID. With continued scientific investigation, there is hope for millions who are still suffering.
The study findings were published in the peer reviewed journal: Nature Immunology.
https://www.nature.com/articles/s41590-025-02135-5
For the latest on Long COVID, keep on logging to Thailand
Medical News.
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https://www.thailandmedical.news/articles/long-covid
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