Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes

Paterson, Ross W; Benjamin, Laura A; Mehta, Puja R; Brown, Rachel L; Athauda, Dilan; Ashton, Nicholas J; Leckey, Claire A; Ziff, Oliver J; Heaney, Judith; Heslegrave, Amanda J; Benedet, Andrea L; Blennow, Kaj; Checkley, Anna M; Houlihan, Catherine F; Mummery, Catherine J; Lunn, Michael P; Manji, Hadi; Zandi, Michael S; Keddie, Stephen; Chou, Michael; Changaradil, Deepthi Vinayan; Solomon, Tom; Keshavan, Ashvini; Barker, Suzanne; Jäger, Hans Rolf; Carletti, Francesco; Simister, Robert; Werring, David J; Spyer, Moira J; Nastouli, Eleni; Gauthier, Serge; Rosa-Neto, Pedro; Zetterberg, Henrik; Schott, Jonathan M

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 characterised neurological syndromes involving the peripheral and central nervous system (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 central nervous system inflammation (encephalitis and acute disseminated encephalomyelitis) (14800pg/mL [400, 32400]), compared to those with encephalopathy (1410pg/mL [756, 1446], peripheral syndromes (GBS) (740pg/mL [507, 881]) and controls (872pg/mL [654,1200]). Serum neurofilament light levels were elevated across patients hospitalised 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.