Antibodies from Long COVID patients may directly cause persistent symptoms, according to a new study – giving scientists a new area of research for developing potential targeted treatments.
A new study led by researchers at UMC Utrecht and Amsterdam UMC has found that antibodies from patients with Long COVID can trigger lasting pain-like symptoms in mice. The findings suggest that autoantibodies may play a direct role in driving the condition, which could hopefully lead to future targeted treatments.
Long COVID, also known as post-COVID syndrome, is estimated to affect more than 10 percent of people following infection with SARS-CoV-2. The condition presents a wide range of symptoms, including extreme fatigue, post-exertional malaise and pain and cognitive difficulties often described as ‘brain fog’. Despite its prevalence, the biological mechanisms behind Long COVID have been poorly understood for some time.
Antibodies that transfer symptoms
In the study, researchers focused on immunoglobulin G, or IgG, a major class of antibodies found in the blood. They extracted IgG from 34 Long COVID patients and injected it into mice. Subsequently, the animals developed persistent pain-like hypersensitivity that lasted for at least two weeks.
In the study, researchers focused on immunoglobulin G, or IgG, a major class of antibodies found in the blood
More notably, IgG collected from the same patients two years later produced the same effect when introduced into mice.
“This finding suggests that the underlying disease mechanism may persist long after the initial infection, potentially explaining why many patients experience long-term symptoms,” said co-study lead Professor Niels Eijkelkamp.
Distinct biological subgroups
To further investigate, the researchers analysed blood samples from Long COVID patients and identified distinct subgroups based on markers linked to brain injury and immune system activity. These included GFAP, NFL and interferon-β. Each subgroup showed unique molecular patterns in large-scale protein analyses.
This finding supports the idea that Long COVID is not a single condition
When autoantibodies from these different groups were tested in mice, they produced varying symptom patterns.
“This finding supports the idea that Long COVID is not a single condition but a heterogeneous disease with different biological drivers,” said co-study lead and Principal Investigator at Amsterdam UMC, Jeroen den Dunnen.
A landscape of autoimmunity
The study also revealed that Long COVID patients have elevated levels of autoantibodies targeting a wide range of the body’s own proteins. These include proteins involved in immune regulation, nerve signalling and metabolism. Many of these autoantibodies were found to persist for years and differed across patient subgroups.
The researchers noted similarities with other conditions such as fibromyalgia, where patient-derived antibodies can also induce symptoms in animal models, suggesting shared immune pathways.
Towards targeted treatments
While the study has limitations, including its relatively small size, single-centre design and use of pooled samples, it provides strong evidence that IgG autoantibodies may actively contribute to Long COVID symptoms.
The findings also point towards new treatment approaches that could be designed to remove or neutralise harmful antibodies, such as immunoadsorption, plasmapheresis or targeted immunotherapy. All of these could offer relief to patients, particularly if tailored to specific biological subtypes.
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