Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant, 2026, Kawaguchi et al.

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Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant

Spoiler: Authors

Kawaguchi, Marina; Sakurada, Yasue; Tokumasu, Kazuki; Otsuka, Yuki; Nakano, Yasuhiro; Matsuda, Yui; Honda, Hiroyuki; Omura, Daisuke; Matsuki, Nobuyoshi; Furukawa, Masanori; Higashikage, Akihito; Otsuka, Fumio

Abstract​

Background: Long COVID (LC) presents persistent symptoms that pose a major clinical challenge. Identification of reliable biomarkers to evaluate LC pathophysiology is needed.

Objectives: To investigate whether serum S- and N-antibody titers against SARS-CoV-2 spike and nucleocapsid proteins reflect the clinical features of LC.

Methods: This retrospective observational study included patients diagnosed with Omicron variant-related LC who attended a post-COVID-19 outpatient clinic between July 2023 and November 2024 and provided informed consent for antibody testing.

Results: Among 275 patients (129 men and 146 women), 57 (21%) were unvaccinated. Median S- and N-antibody titers in vaccinated versus unvaccinated patients were 20,963 U/mL and 24.8 cut-off index (COI) versus 24 U/mL and 44.5 COI, respectively.
S-antibody titers were associated with the number of vaccine doses received, whereas N-antibody titers correlated with disease severity during the acute phase of COVID-19 infection, with females having higher titers by multivariable analysis.
N-antibody titers in unvaccinated patients with LC were negatively correlated with time interval from infection to clinic visit, with an estimated daily decline of 0.34% in measured N-antibody levels.
Patients with LC having memory impairment had low S-antibody titers by multivariable logistic regression analysis, and low S-antibody levels were associated with reduced quality of life (QOL).
Additionally, N-antibody titers positively correlated with lymphocyte counts and immunoglobulin levels.

Conclusion: Serum N-antibody titers reflect immune responses to COVID-19, although they are affected by gender differences and interval between infection and evaluation.
Lower S-antibody titers were associated with brain fog symptoms and reduced QOL in patients with LC.

Web | DOI | PMC | PDF | British Journal of Biomedical Science

 

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Antibody clues could improve long COVID care and prognosis

Long COVID (LC), characterized by onset of symptoms within 3 months of COVID-19, poses a major clinical challenge. This highlights the need for biomarkers to evaluate the pathophysiology of LC. In this context, researchers have analyzed the antibody titers against SARS-CoV-2 spike (S) and...

www.eurekalert.org

News Release 12-Jun-2026

Antibody clues could improve long COVID care and prognosis​

Researchers found that SARS-CoV-2 antibody patterns may help assess infection history, symptom severity, and cognitive complications in long COVID

Peer-Reviewed Publication
Okayama University


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Researchers analyzed spike and nucleocapsid antibody levels in patients with long COVID and found that antibody patterns may help identify prior infection severity, cognitive symptoms such as brain fog and quality of life outcomes during the Omicron era.

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Credit: Trinity Care Foundation from Openverse Source link: https://openverse.org/image/37aed479-aae9-439f-a384-2e6a3b6b2a92?q=COVID+19+VIRUS&p=1

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.



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Reference
DOI: 10.3389/bjbs.2026.16255



About Okayama University, Japan
As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of the integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience.
Website: https://www.okayama-u.ac.jp/index_e.html



About Professor Fumio Otsuka from Okayama University, Japan
Dr. Fumio Otsuka is a Professor at the Department of General Medicine, Okayama University Graduate School of Medicine, Japan. He earned his M.D. and Ph.D. from Okayama University. His research focuses on internal medicine, general practice, endocrinology and metabolism, rheumatology, and laboratory medicine.

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Journal​

British Journal of Biomedical Science

DOI​

10.3389/bjbs.2026.16255

Method of Research​

Observational study

Subject of Research​

People

Article Title​

Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant

Article Publication Date​

22-Apr-2026

COI Statement​

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.