Autoimmunity is a hallmark of post-COVID syndrome

Abstract

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

Keywords: Antigen array; Autoantibodies; Autoimmunity; COVID-19; Latent autoimmunity; Long COVID; Post-COVID; Post-COVID syndrome; Post-acute COVID-19.

Fig. 1

Autoimmune assessment of post-COVID syndrome. A Positivity of autoantibodies in patients with PCS. Antibodies were considered “positive” if NFI was > 2 SD above the average NFI for pre-pandemic controls for that antigen. B Positivity for antibodies against coronaviruses, influenza, Epstein-Barr, cytomegalovirus, and the respiratory syncytial virus. C Correlation matrix between IgG anti-SARS-CoV-2 antibodies and the rest of IgG autoantibodies included in the microarray. Blue color represents negative correlation, whereas red color represents positive correlation. Only those significant correlations by spearman tests are colored (i.e., P < 0.0500). D Correlation matrix between age, sex, and the IgG autoantibodies. Blue color represents negative correlation, whereas red color represents positive correlation. Only those significant correlations by spearman tests are colored (i.e., P < 0.0500). NFI: normalized fluorescence intensity