Antibody profiles offer insights into long Covid cognitive symptoms

Persistent symptoms after COVID-19 infection continue to affect millions of people worldwide, even as the number of acute infections has declined. Long COVID (LC) can cause fatigue, headaches, sleep disturbances, breathing difficulties, and cognitive problems commonly described as "brain fog." Despite the growing burden of these lingering symptoms, clinicians still lack reliable biological markers that can objectively assess disease severity, predict prognosis, or guide patient management. This challenge is especially important because many LC symptoms are subjective and difficult to quantify using conventional medical tests.

To address this, a research team led by Professor Fumio Otsuka from the Department of General Medicine, Okayama University Graduate School of Medicine, Japan, along with Assistant Professor Marina Kawaguchi and Dr. Yasue Sakurada from the Department of General Medicine, Okayama University Graduate School of Medicine, Japan, investigated whether blood levels of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins could provide clinically meaningful information for understanding LC during the Omicron era. They analyzed data of 275 patients diagnosed with Omicron variant-related LC who attended a specialized post-COVID outpatient clinic between July 2023 and November 2024. Their findings were published in Volume 83 of British Journal of Biomedical Science on April 22, 2026.

The team measured antibody levels and compared them with vaccination history, disease severity during acute infection, symptom profiles, laboratory findings, and quality of life assessments. Their analysis revealed that S-antibody levels were strongly associated with the number of vaccine doses received, whereas N-antibody levels reflected infection-related factors such as disease severity and the time elapsed since infection. Among unvaccinated patients, N-antibody levels steadily declined over time, decreasing by approximately 0.34% per day after infection. The findings also showed that women tended to have higher N-antibody levels than men.

Perhaps the most clinically significant observation involved cognitive symptoms. Patients experiencing memory impairment-a common manifestation of brain fog-had significantly lower S-antibody levels than those without memory problems. Higher S-antibody levels were also associated with better self-reported quality of life. Although antibody measurements alone were insufficient to fully predict cognitive symptoms, the results suggest that declining S-antibody levels may indicate a greater risk of neurological complications in LC.

"Objective biomarkers for LC remain limited, making patient evaluation particularly challenging. In the treatment of post-COVID-19 symptoms, viral antibody titers may help predict the history of COVID-19 infection during the Omicron phase and may aid in the prognosis of post-COVID-19 symptoms, which are difficult to objectively determine," says Prof. Otsuka.

The study also demonstrated that N-antibody levels correlated positively with lymphocyte counts and immunoglobulin levels, further supporting their role as indicators of immune activity following infection. These insights may help clinicians interpret antibody test results more effectively in patients whose acute infection history is incomplete or poorly documented.

"Our findings suggest that antibody profiles may provide useful information about infection history, immune responses, and symptom patterns, especially in patients experiencing cognitive difficulties. In future, we hope to combine viral antibody titers with clinical symptoms and other laboratory data to improve diagnosis and treatment strategies for LC," says Prof. Otsuka.

Overall, the findings indicate that SARS-CoV-2 antibody profiles may offer a practical tool for understanding LC during the Omicron era. By providing objective information about prior infection, immune responses, and cognitive symptoms, antibody testing could contribute to more personalized care for patients living with persistent post-COVID conditions and support future efforts to develop evidence-based management strategies.