Millions of people worldwide are affected by Long COVID. Yet the underlying causes are still not fully understood. A research group at Helsinki University Hospital therefore investigated whether so-called antineuronal antibodies (antibodies directed against nerve cells) might play a role in Long COVID.
Study overview
A total of 314 patients with Long COVID participated in the study between 2021 and 2023. All had a confirmed COVID-19 infection at least three months prior. Each underwent a comprehensive medical examination, laboratory tests, and questionnaires. In addition, a control group of 35 individuals who had experienced COVID-19 but did not develop Long COVID symptoms was examined.
The findings: Antineuronal antibodies were detected in 12.1% of Long COVID patients. Most frequently, these antibodies targeted the neuronal proteins CASPR-2, neurofascin-186, and a glycine receptor.
Only prior intensive care was identified as a clear risk factor for the presence of antineuronal antibodies in the blood.
The analysis showed that the sole significant association was with intensive care treatment during the acute phase of COVID-19. Patients who had required intensive care were more than three times as likely to test positive for these antibodies later on.
Significance of the findings
Interestingly, the frequency of antineuronal antibodies did not differ significantly between Long COVID patients and the control group. Two individuals without Long COVID also tested positive for such antibodies. Moreover, there was no evidence of a classic autoimmune disease such as autoimmune encephalitis (a severe inflammation of the brain caused by misdirected antibodies).
Antineuronal antibodies alone do not explain the symptoms of Long COVID.
This suggests that the presence of these antibodies is more likely a consequence of severe illness and the associated strong immune activation, rather than the direct cause of Long COVID-specific symptoms. In neuropsychological testing, antibody-positive participants more often showed cognitive problems such as attention deficits. However, similar impairments were also observed in other patients who had been severely ill with COVID-19—regardless of antibody status.
The results call for caution in the interpretation of blood tests.
The researchers emphasize that the detection of antineuronal antibodies should not automatically lead to additional or potentially burdensome treatments. Instead, the findings seem to reflect a broader immune response following critical illness.
Conclusion
The study demonstrates that while Long COVID may be associated with measurable changes in the immune system, antibodies against nerve cells do not appear to play a central role. Rather, the severity of the initial illness—particularly the need for intensive care—seems to influence the likelihood of detecting such antibodies in blood samples. For both patients and researchers, this means: Long COVID remains a complex condition whose causes cannot yet be reduced to a single explanation.
