Vogelgesang et al. (2025)
- Authors: Antje Vogelgesang, Anke Steinmetz, Angela Stufano, Valentina Schino, Domenico Plantone, Agnes Flöel, Guglielmo Lucchese.
- Institutes: Department of Neurology, Universitätsmedizin Greifswald, Greifswald, Germany; Physical and Rehabilitation Medicine, Center for Orthopedics, Trauma Surgery and Rehabilitation Medicine, Universitätsmedizin Greifswald, Greifswald, Germany; Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy; German Centre for Neurodegenerative Diseases (DZNE) Standort Greifswald, Greifswald, Germany; Department of Experimental Medicine, University of Salento, Lecce, Italy.
- Publisher: Frontiers in Immunology
- Link: DOI
Summary
This research identifies a specific autoimmune reaction that may explain some of the most debilitating symptoms of Post-COVID Syndrome. It shows that people with PCS have higher levels of antibodies that attack their own nerve cells in the brainstem and mitochondria, which are the powerhouses of all cells. The presence of these autoantibodies was directly linked to worse physical function and more severe respiratory problems, providing a tangible biological basis for these symptoms. This discovery is a step towards developing an objective biomarker to identify a subset of patients and could open new avenues for treatments that target this specific autoimmune process, although further research is needed to confirm these findings.
What was researched?
This study investigated whether specific IgG autoantibodies that target neuronal (DAB1) and mitochondrial (AIFM1, SURF1) proteins in the brainstem are present in patients with Post COVID Syndrome (PCS). The researchers aimed to determine if these antibodies are associated with the clinical symptoms of PCS, such as reduced functional status, respiratory issues, fatigue, and cognitive problems.
Why was it researched?
The same research group had previously identified these specific autoantibodies as markers of severe acute COVID-19. They hypothesized that a persistent, ongoing autoimmune response against these same neuronal and mitochondrial proteins might contribute to the long-term symptoms seen in PCS, particularly those affecting respiratory and functional capacity.
How was it researched?
This was a patient data analysis study that measured IgG antibody levels in serum samples from 45 patients with PCS and 30 control individuals who had recovered from COVID-19 without long-term symptoms. Using a multiplexed bead-based immunoassay, they tested for antibodies against 18 synthetic peptides derived from the DAB1, AIFM1, and SURF1 proteins. The researchers then used advanced statistical models to analyze the relationship between antibody levels and a wide range of clinical data, including functional status (PCFS scale), fatigue, and cognitive scores (MoCA), collected at 3 and 6 months post-infection.
What has been found?
Higher levels of autoantibodies against the three target proteins (DAB1, AIFM1, SURF1) were found to be a significant predictor of having PCS three months after infection. Statistical analysis revealed that these elevated antibody levels were specifically associated with a combination of more severe respiratory symptoms and a lower functional status (worse disability). Interestingly, no correlation was found between these autoantibody levels and cognitive performance as measured by the MoCA test.
Discussion
The authors note that the study’s findings are consistent with the known biological functions of the autoantigen targets, which are involved in brainstem respiratory control and mitochondrial energy production. They acknowledge several limitations, including the correlational nature of the study (it shows an association, not a cause), the relatively small sample size, and differences between the patient and control groups regarding sex and vaccination status. The lack of correlation with cognitive test scores may be due to the insensitivity of the MoCA tool in the PCS population.
Conclusion & Future Work
The study concludes that a sustained autoimmune response targeting specific neuronal and mitochondrial proteins is likely involved in PCS, contributing to respiratory dysfunction and reduced functional capacity. These autoantibodies could potentially serve as biomarkers for disability in PCS. The authors call for future research to replicate these findings in larger patient groups, establish a causal link, and explore these autoantibodies as potential targets for immunomodulatory therapies.