Abstract
Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n = 34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n = 94) and without (n = 24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14 800 pg/ml (400, 32 400)], compared to those with encephalopathy [1410 pg/ml (756, 1446)], peripheral syndromes (Guillain–Barré syndrome) [740 pg/ml (507, 881)] and controls [872 pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.
Highlights
SARS-CoV-2, causing COVID-19, may damage the nervous system
Following an initial report,[1] several case series have reported neurological and neuropsychiatric syndromes associated with SARS-CoV-2.2,3 Neuroimaging and neuropathological studies have demonstrated a range of abnormalities,[4] including multi-territory infarcts, CSF and serum biomarkers in acute COVID-19 cerebral microbleeds and white matter lesions.[5]
We prospectively recruited patients presenting to our hospitals between March and June 2020 with probable/confirmed COVID-19.11,12 Confirmed cases were diagnosed by polymerase chain reaction (PCR) test for SARS-CoV-2 on nasopharyngeal swab or positive IgG SARS-CoV-2
Summary
SARS-CoV-2, causing COVID-19, may damage the nervous system. Following an initial report,[1] several case series have reported neurological and neuropsychiatric syndromes associated with SARS-CoV-2.2,3 Neuroimaging and neuropathological studies have demonstrated a range of abnormalities,[4] including multi-territory infarcts, CSF and serum biomarkers in acute COVID-19 cerebral microbleeds and white matter lesions.[5] The pathogenic mechanisms are unclear but may include direct viral CNS infection, para- and post-infectious inflammation, hypercoagulability and the consequences of critical illness.[3]. Biomarkers of infection, neuronal injury and astrocytic activation are a means of understanding brain pathobiology in vivo. Neurofilament light chain protein (NfL) is a dynamic marker of active neuronal damage.[6,7] Glial fibrillary acidic protein (GFAp), highly expressed in astrocytes, is a biomarker of astrocytic activation/injury[8] and Neopterin is a marker of immune activation with prognostic value.[9] Sampling biomarkers in different biological compartments (CSF and blood) permit further anatomical localization
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