Brain-binding auto-antibodies in subjects with and without post-COVID-syndrome after SARS-CoV-2 infection

Various pathomechanisms are discussed as possible causes of Post-COVID syndrome (PCS). Immune system dysfunction with increase of autoimmune responses is one of them. Whether the observed increase of autoantibody prevalence after COVID-19 is of any significance for the well-being of affected subjects in the long-term is controversial. We assessed the seroprevalence of 44 autoantibodies against brain epitopes in 703 subjects a few months after a proven SARS-CoV-2 infection, and compared the results between 455 patients with Post-COVID syndrome and 248 subjects who had completely recovered. In addition, we looked for relationships between N-Methyl-D-Aspartate-Receptor-1 (NMDAR1)-autoantibody presence and symptoms during COVID-19 as well as Post-COVID symptoms in median 15.4 months after the infection, and we analyzed the occurrence of NMDAR1-autoantibodies regarding the severity of the PCS. We observed a slight increase in serum autoantibody prevalence in our cohort compared to published data for healthy controls from the pre-pandemic time. Interestingly, NMDAR1 autoantibodies were by far the most frequent, with an occurrence twice as much as reported in the pre-pandemic literature. The increase in occurrence was predominantly based on an increase of NMDAR1-IgM antibodies. We did not find differences in prevalence and features of auto-antibodies between patients with PCS and recovered individuals. Nor did we observe a relationship between the symptoms during COVID-19 or with PCS and the presence of serum autoantibodies. Our data further support the conjecture of a dysregulated immune system after COVID-19, and endorse former observations that there is no direct link between autoantibody prevalence and clinical symptoms of Post-COVID syndrome.