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Background <p>Long COVID is a complex multisystem disorder affecting approximately 65&#xa0;million individuals worldwide, with autoimmune mechanisms implicated in its pathogenesis. This study aimed to elucidate the role of SARS-CoV-2-induced autoantibodies and immune dysregulation in the development of Long COVID, focusing specifically on autoimmunity and aberrant immune activation. The investigation sought to explore the underlying mechanisms through serological and peptide-based analyses.</p> Methods <p>Serum samples from 315 healthcare workers, serving as a control cohort, were analyzed for the presence of SARS-CoV-2 IgM, IgG, and Neutralizing Antibodies (NAbs), with stratification based on age, gender, vaccination timing, and symptom clusters. Bioinformatic approaches were employed to identify SARS-CoV-2 epitopes with homology to human proteins, screening for epitopes of the SARS-CoV-2 Spike (S) and Nucleocapsid (N) proteins and their human homologous peptides through analyses of hydrophilicity, antigenicity, and homology prediction. An ELISA-based method was utilized to detect antibody responses to these peptides in both COVID-19 infected groups (categorized as mild, moderate, or severe) and an uninfected group.</p> Results <p>The primary findings indicated a high seropositivity rate for IgG (97%) and Neutralizing Antibodies (94%) among the control group, with notable age-related trends: IgM levels increased with age, whereas IgG and Neutralizing Antibodies showed a decline. Female participants demonstrated higher IgG levels compared to their male counterparts. Antibody levels did not exhibit significant differences across acute or persistent symptom clusters (≥ 6 months post-infection). However, neurological symptoms, whether acute or chronic, were associated with elevated IgG and Neutralizing Antibody titers, suggesting that neurotropic infections may elicit a more robust humoral immune response. Bioinformatic analyses identified 29 potential epitopes within the S protein and 10 within the N protein, with 91 and 24 human homologous peptides, respectively. The detection of peptide-specific antibodies in the serum of the COVID-19 infected group revealed that antibodies against eight peptides displayed a greater than 2.5-fold difference between the COVID-19-infected and uninfected groups.</p> Conclusion <p>These findings underscore age- and gender-related variations in antibody responses, identify immunodominant peptides with potential implications for COVID-19 symptoms, and suggest that cross-reactive antibodies targeting viral-human homologous peptides (e.g., S68-CHL1) may play a role in autoimmune mechanisms associated with COVID-19.</p> Trial registration <p>Clinical trial number: Not applicable.</p>

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Expression levels of SARS-CoV-2 IgM, IgG, and neutralizing antibodies in a Chinese cohort and detection of peptide-specific antibodies in COVID-19 patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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  • Suli Yang,
  • Xiaosha Wen,
  • Yi Lin,
  • Ranrong Zhang,
  • Dixian Luo

摘要

Background

Long COVID is a complex multisystem disorder affecting approximately 65 million individuals worldwide, with autoimmune mechanisms implicated in its pathogenesis. This study aimed to elucidate the role of SARS-CoV-2-induced autoantibodies and immune dysregulation in the development of Long COVID, focusing specifically on autoimmunity and aberrant immune activation. The investigation sought to explore the underlying mechanisms through serological and peptide-based analyses.

Methods

Serum samples from 315 healthcare workers, serving as a control cohort, were analyzed for the presence of SARS-CoV-2 IgM, IgG, and Neutralizing Antibodies (NAbs), with stratification based on age, gender, vaccination timing, and symptom clusters. Bioinformatic approaches were employed to identify SARS-CoV-2 epitopes with homology to human proteins, screening for epitopes of the SARS-CoV-2 Spike (S) and Nucleocapsid (N) proteins and their human homologous peptides through analyses of hydrophilicity, antigenicity, and homology prediction. An ELISA-based method was utilized to detect antibody responses to these peptides in both COVID-19 infected groups (categorized as mild, moderate, or severe) and an uninfected group.

Results

The primary findings indicated a high seropositivity rate for IgG (97%) and Neutralizing Antibodies (94%) among the control group, with notable age-related trends: IgM levels increased with age, whereas IgG and Neutralizing Antibodies showed a decline. Female participants demonstrated higher IgG levels compared to their male counterparts. Antibody levels did not exhibit significant differences across acute or persistent symptom clusters (≥ 6 months post-infection). However, neurological symptoms, whether acute or chronic, were associated with elevated IgG and Neutralizing Antibody titers, suggesting that neurotropic infections may elicit a more robust humoral immune response. Bioinformatic analyses identified 29 potential epitopes within the S protein and 10 within the N protein, with 91 and 24 human homologous peptides, respectively. The detection of peptide-specific antibodies in the serum of the COVID-19 infected group revealed that antibodies against eight peptides displayed a greater than 2.5-fold difference between the COVID-19-infected and uninfected groups.

Conclusion

These findings underscore age- and gender-related variations in antibody responses, identify immunodominant peptides with potential implications for COVID-19 symptoms, and suggest that cross-reactive antibodies targeting viral-human homologous peptides (e.g., S68-CHL1) may play a role in autoimmune mechanisms associated with COVID-19.

Trial registration

Clinical trial number: Not applicable.