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CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series
Arvid Edén1, Nelly Kanberg1, Johanna Gostner1
1From the Department of Infectious Diseases (A.E., N.K., L.H., L.-M.A., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg; Region Västra Götaland (A.E., N.K., L.H., L.-M.A., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden; Institutes of Medical Biochemistry (J.G.) and Biological Chemistry (D.F.), Medical University of Innsbruck, Biocenter, Austria; Department of Neurology (R.W.P.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Objective:
To explore whether hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurologic symptoms have evidence of CNS infection, inflammation, and injury using CSF biomarker measurements.
Methods:
We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin, and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe coronavirus disease 2019 (COVID-19) and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4 of 6), suspected meningitis (1 of 6), and dysgeusia (1 of 6). SARS-CoV-2 infection was confirmed by real-time PCR analysis of nasopharyngeal swabs.
Results:
SARS-CoV-2 RNA was detected in the plasma of 2 patients (cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in 1 but not in a second real-time PCR assay. CSF neopterin (median 43.0 nmol/L) and β2-microglobulin (median 3.1 mg/L) were increased in all. Median immunoglobulin G index (0.39), albumin ratio (5.35), and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.
Conclusion:
Our results in patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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