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; UCLH Queen Square COVID-19 Biomarker Study Group; Henrik Zetterberg; Jonathan M Schott

doi:10.1093/braincomms/fcab099

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

Brain Commun. 2021 May 12;3(3):fcab099. doi: 10.1093/braincomms/fcab099. eCollection 2021.

Authors

Ross W Paterson^{1

2

3}, Laura A Benjamin^{2

4

5

6}, Puja R Mehta², Rachel L Brown^{2

7}, Dilan Athauda^{2

8}, Nicholas J Ashton^{9

10}, Claire A Leckey^{1

2}, Oliver J Ziff⁸, Judith Heaney^{2

11}, Amanda J Heslegrave^{1

2

12}, Andrea L Benedet⁹, Kaj Blennow⁹, Anna M Checkley^{13

14}, Catherine F Houlihan^{13

15}, Catherine J Mummery^{1

2}, Michael P Lunn^{1

2}, Hadi Manji², Michael S Zandi^{1

2}, Stephen Keddie^{1

2}, Michael Chou^{1

2}, Deepthi Vinayan Changaradil³, Tom Solomon^{16

17}, Ashvini Keshavan^{1

2}, Suzanne Barker^{1

2}, Hans Rolf Jäger^{1

2}, Francesco Carletti^{1

2}, Robert Simister^{1

2}, David J Werring^{2

4}, Moira J Spyer¹¹, Eleni Nastouli^{11

15}, Serge Gauthier^{18

19

20}, Pedro Rosa-Neto^{18

19

20}; UCLH Queen Square COVID-19 Biomarker Study Group; Henrik Zetterberg^{1

9

12}, Jonathan M Schott^{1

2}

Affiliations

¹ University College London, Queen Square Institute of Neurology, London WC1N 3BG, UK.
² National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
³ Darent Valley Hospital, Dartford, Kent DA2 8DA, UK.
⁴ UCL Institute of Neurology, Stroke Research Centre, Russell Square House, London WC1B 5EH, UK.
⁵ University of Liverpool, Brain Infections Group, Liverpool, Merseyside L69 3GA, UK.
⁶ Laboratory of Molecular and Cell Biology, UCL, London WC1E 6BT, UK.
⁷ University College London Institute of Immunity and Transplantation, London NW3 2QG, UK.
⁸ Francis Crick Institute, London NW1 1AT, UK.
⁹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal 431 41, Sweden.
¹⁰ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London SE5 9RT, UK.
¹¹ Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London WC1H 8NJ, UK.
¹² UK Dementia Research Institute, London WC1E 6BT, UK.
¹³ Department of Infection and Immunity, University College London, London WC1E 6BT, UK.
¹⁴ Hospital for Tropical Diseases, University College Hospitals London, London WC1E 6BT, UK.
¹⁵ Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London WC1H 8NJ, UK.
¹⁶ National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK.
¹⁷ Walton Centre NHS Foundation Trust, Liverpool L9 7LJ, UK.
¹⁸ Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Montreal H4H 1R3, Canada.
¹⁹ Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal H4H 1R3, Canada.
²⁰ Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal H4H 1R3, Canada.

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.

Keywords: ADEM; COVID-19; NfL; encephalitis.

Abstract

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