Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes
Ross W Paterson, Laura A Benjamin, Puja R Mehta, Rachel L Brown, Dilan Athauda, Nicholas J Ashton, Claire A Leckey, Oliver J Ziff, Judith Heaney, Amanda J Heslegrave, Andrea L Benedet, Kaj Blennow, Anna M Checkley, Catherine F Houlihan, Catherine J Mummery, Michael P Lunn, Hadi Manji, Michael S Zandi, Stephen Keddie, Michael Chou, Deepthi Vinayan Changaradil, Tom Solomon, Ashvini Keshavan, Suzanne Barker, Hans Rolf Jäger, Francesco Carletti, Robert Simister, David J Werring, Moira J Spyer, Eleni Nastouli, Serge Gauthier, Pedro Rosa-Neto, Henrik Zetterberg, Jonathan M Schott
Abstract Graphical 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. Paterson, Benjamin et al. report elevation of CSF neurofilament light (NfL), reflecting CNS damage, in some but not all SARS-CoV-2 associated neurological syndromes. Increased NfL concentration was a common finding in hospitalized patients with COVID-19, likely predominantly reflecting peripheral neuronal damage. Non-hospitalized individuals did not have elevated NfL. Graphical Abstract
Artikel, 2021