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Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity.
Virhammar, Johan; Nääs, Anja; Fällmar, David; Cunningham, Janet L; Klang, Andrea; Ashton, Nicholas J; Jackmann, Sven; Westman, Gabriel; Frithiof, Robert; Blennow, Kaj; Zetterberg, Henrik; Kumlien, Eva; Rostami, Elham.
  • Virhammar J; Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
  • Nääs A; Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
  • Fällmar D; Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
  • Cunningham JL; Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
  • Klang A; Department of Neuroscience, Rehabilitation Medicine, Uppsala University, Uppsala, Sweden.
  • Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
  • Jackmann S; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
  • Westman G; Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute, Clinical Neuroscience Institute, King's College London, London, UK.
  • Frithiof R; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Blennow K; Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
  • Zetterberg H; Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
  • Kumlien E; Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
  • Rostami E; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Eur J Neurol ; 28(10): 3324-3331, 2021 10.
Article in English | MEDLINE | ID: covidwho-1035403
Semantic information from SemMedBD (by NLM)
1. Injury of central nervous system COEXISTS_WITH COVID-19
Subject
Injury of central nervous system
Predicate
COEXISTS_WITH
Object
COVID-19
2. Biological Markers ASSOCIATED_WITH Neurologic Symptoms
Subject
Biological Markers
Predicate
ASSOCIATED_WITH
Object
Neurologic Symptoms
3. Neurologic Symptoms PROCESS_OF hospitalized patients
Subject
Neurologic Symptoms
Predicate
PROCESS_OF
Object
hospitalized patients
4. COVID-19 PROCESS_OF hospitalized patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
hospitalized patients
5. Circumferential Supracrestal Fiberotomy TREATS Neurologic Manifestations
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
Neurologic Manifestations
6. Neurologic Manifestations PROCESS_OF Patients
Subject
Neurologic Manifestations
Predicate
PROCESS_OF
Object
Patients
7. Circumferential Supracrestal Fiberotomy TREATS Patients
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
Patients
8. Neurologic Symptoms PROCESS_OF Patients
Subject
Neurologic Symptoms
Predicate
PROCESS_OF
Object
Patients
9. Epidermal cGVHD Score 2 PROCESS_OF Patients
Subject
Epidermal cGVHD Score 2
Predicate
PROCESS_OF
Object
Patients
10. Elevated immunoglobulin levels PROCESS_OF Patients
Subject
Elevated immunoglobulin levels
Predicate
PROCESS_OF
Object
Patients
11. Negative PROCESS_OF Patients
Subject
Negative
Predicate
PROCESS_OF
Object
Patients
12. Circumferential Supracrestal Fiberotomy TREATS CNS symptom
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
CNS symptom
13. CNS symptom PROCESS_OF Patients
Subject
CNS symptom
Predicate
PROCESS_OF
Object
Patients
14. Circumferential Supracrestal Fiberotomy TREATS COVID-19
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
COVID-19
15. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
16. NEFL gene|NEFL ASSOCIATED_WITH CNS symptom
Subject
NEFL gene|NEFL
Predicate
ASSOCIATED_WITH
Object
CNS symptom
17. Injury of central nervous system COEXISTS_WITH COVID-19
Subject
Injury of central nervous system
Predicate
COEXISTS_WITH
Object
COVID-19
18. Biological Markers ASSOCIATED_WITH Neurologic Symptoms
Subject
Biological Markers
Predicate
ASSOCIATED_WITH
Object
Neurologic Symptoms
19. Neurologic Symptoms PROCESS_OF hospitalized patients
Subject
Neurologic Symptoms
Predicate
PROCESS_OF
Object
hospitalized patients
20. COVID-19 PROCESS_OF hospitalized patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
hospitalized patients
21. Circumferential Supracrestal Fiberotomy TREATS Neurologic Manifestations
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
Neurologic Manifestations
22. Neurologic Manifestations PROCESS_OF Patients
Subject
Neurologic Manifestations
Predicate
PROCESS_OF
Object
Patients
23. Circumferential Supracrestal Fiberotomy TREATS Patients
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
Patients
24. Neurologic Symptoms PROCESS_OF Patients
Subject
Neurologic Symptoms
Predicate
PROCESS_OF
Object
Patients
25. Epidermal cGVHD Score 2 PROCESS_OF Patients
Subject
Epidermal cGVHD Score 2
Predicate
PROCESS_OF
Object
Patients
26. Elevated immunoglobulin levels PROCESS_OF Patients
Subject
Elevated immunoglobulin levels
Predicate
PROCESS_OF
Object
Patients
27. Negative PROCESS_OF Patients
Subject
Negative
Predicate
PROCESS_OF
Object
Patients
28. Circumferential Supracrestal Fiberotomy TREATS CNS symptom
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
CNS symptom
29. CNS symptom PROCESS_OF Patients
Subject
CNS symptom
Predicate
PROCESS_OF
Object
Patients
30. Circumferential Supracrestal Fiberotomy TREATS COVID-19
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
COVID-19
31. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
32. NEFL gene|NEFL ASSOCIATED_WITH CNS symptom
Subject
NEFL gene|NEFL
Predicate
ASSOCIATED_WITH
Object
CNS symptom
ABSTRACT
BACKGROUND AND

PURPOSE:

Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19.

METHODS:

Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity.

RESULTS:

Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms.

CONCLUSIONS:

Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Neurofilament Proteins / COVID-19 Type of study: Diagnostic study / Risk factors Limits: Humans Language: English Journal: Eur J Neurol Journal subject: Neurology Year: 2021 Document Type: Article Affiliation country: Ene.14703

Full text: Available Collection: International databases Database: MEDLINE Main subject: Neurofilament Proteins / COVID-19 Type of study: Diagnostic study / Risk factors Limits: Humans Language: English Journal: Eur J Neurol Journal subject: Neurology Year: 2021 Document Type: Article Affiliation country: Ene.14703