Abstract
INTRODUCTION: Dysregulation of autoimmune responses and the presence of autoantibodies (AA), particularly those related to the renin-angiotensin system (RAS), have been implicated in the acute phase of COVID-19, and persistent dysregulation of brain RAS by RAS-related autoantibodies may also contribute to neurological symptoms of post-COVID. METHODS: We analyzed levels of serum and CSF RAS AA in post-COVID patients with neurological symptoms, individuals who have fully recovered from COVID-19 (after-COVID controls), and uninfected individuals, and their possible correlations with the serum marker of neuroaxonal damage neurofilament light chain (NfL) and the degrees of cognitive deficit. RESULTS: Both in serum and CSF, levels of AA agonists of the pro-inflammatory angiotensin II type 1 receptors (AT1-AA) were significantly elevated in this cohort of neurological post-COVID patients compared to both uninfected and after-COVID controls and correlated with serum levels of NfL. Changes in serum and CSF levels of AA promoting the RAS anti-inflammatory axis (upregulation of AA agonists of AT2 and Mas receptors, downregulation of AA antagonists of ACE2) suggest upregulation of the RAS compensatory response in this cohort of neurological post-COVID patients. Post-COVID patients with more pronounced cognitive impairment exhibited significantly higher CSF levels of MasR-AA and a trend toward elevated AT2-AA. Persistent brain RAS dysregulation, particularly persistent increase in AT1-AA, and its correlation with neuroaxonal damage markers and cognitive impairment, may play a significant role in neurological symptoms associated with post-COVID. Serum levels of NfL and AT1-AA may be interesting biomarkers for the early identification of CNS involvement in patients with neurological symptoms and a history of COVID-19. However, post-COVID is a highly heterogeneous entity and may result from various underlying mechanisms. The present study includes a cohort, which may differ from other cohorts with different clinical profiles, which may show different results on NfLs and CSF RAS autoantibodies, particularly AT1-AA. CONCLUSION: These findings highlight the potential of targeting AT1 receptors as a therapeutic strategy for mitigating cognitive deficits in post-COVID patients showing upregulated AT1-AA levels.