Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke.

Background and purpose: Prevalence of acute ische-mic stroke (AIS) is increased in patients with coronavirus disease 2019 (COVID-19). A proposed hypothesis is increased virus-induced propensity to hypercoagulation resulting in arterial thrombosis. Our aim was to provide evidence regarding the involvement of neutrophil extracellular trap (NET) formation (NETosis) in COVID-19 related AIS. Methods: Twenty-six consecutively enrolled COVID-19+ pneumonia patients with AIS, 32 COVID-19+ pneumonia patients without AIS and 24 AIS patients without COVID-19 infection were included to the study. Clinical characteristics of recruited patients were collected. Serum levels of citrullinated histone H3 (H3Cit; a factor of NETosis), IL-8 and C5a (mediators associated with NETosis) were measured by ELISA (enzyme-linked immunosorbent assay). Results: H3Cit levels were significantly higher in COVID-19+ AIS patients, whereas all study groups showed comparable IL-8 and C5a levels. There were no significant differences among etiological subgroups of AIS patients with or without COVID-19. AIS patients with COVID-19 showed relatively increased white blood cell, lymphocyte, neutrophil, D-dimer, C-reactive protein and procalcitonin levels than control groups. H3Cit levels did not correlate with clinical/prognostic features and inflammation parameters. H3Cit and IL-8 levels were correlated in COVID-19 patients without stroke but not in COVID-19 positive or negative AIS patients. Conclusion: Increased levels of inflammation parameters and H3Cit in COVID-19 related AIS suggest that NETosis may cause susceptibility to arterial thrombosis. However, H3Cit levels do not correlate with clinical severity measures and inflammation parameters diminishing the prognostic biomarker value of NETosis factors. Moreover, the link between IL-8 and NETosis appears to be abolished in AIS.

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

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.

A Case of HaNDL with Low Cerebrospinal Fluid Level of Neurofilament Light Chain.

Diagnosis of the syndrome of headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is based on clinical features, and no diagnostic biomarkers are available. We present a case presenting with characteristic features of HaNDL and an MRI lesion in the splenium of corpus callosum. CSF neurofilament light chain (NFL) levels were assessed in this patient together with 7 additional HaNDL patients, 18 multiple sclerosis (MS) patients, and 15 primary headache patients. Both HaNDL and primary headache patients showed significantly lower NFL levels than MS patients. Our results suggest that increased CSF levels of NFL and neuroaxonal loss are not characteristic features of HaNDL. Neurological disorders mimicking HaNDL often present with increased levels of NFL, and thus CSF measurement of NFL might be useful in differential diagnosis of HaNDL.