Increased neuropil antibody prevalence in COVID-19 patients with acute ischemic stroke.

ABSTRACT

OBJECTIVES: COVID-19 infection is associated with an increased risk of acute ischemic stroke (AIS). Although the underlying mechanisms are largely unknown, autoimmunity has been implicated as a potential role player. METHODS: To investigate the presence and clinical impact of neuronal cell surface antibodies in COVID-19 associated AIS, patients with COVID-19 pneumonia and AIS (n = 30), COVID-19 pneumonia without AIS (n = 32) and AIS without COVID-19 infection (n = 27) were recruited. Serum anti-neuronal antibodies directed against well-characterized and novel cell surface antibodies were evaluated by cell-based assays and indirect immunohistochemistry, respectively. RESULTS: None of the recruited patients displayed well-characterized neuronal cell surface antibodies. Ten patients in the COVID-19 pneumonia with AIS group and three patients in the COVID-19 pneumonia without AIS group exhibited antibodies to neuropil of hippocampus and cerebellum. Neuropil-antibody positive patients showed trends towards milder clinical severity and reduced blood levels of inflammation factors. CONCLUSION: Our results confirm the presence of neuropil antibodies in patients with COVID-19 infection and identify a putative antibody-driven association between AIS and COVID-19. The antigenic targets and potential pathogenic action of these antibodies need to be further explored.