Nelly Kanberg1, Nicholas J Ashton1, Lars-Magnus Andersson1, Aylin Yilmaz1, Magnus Lindh1, Staffan Nilsson1, Richard W Price1, Kaj Blennow1, Henrik Zetterberg1, Magnus Gisslén2. 1. From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco. 2. From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco. magnus.gisslen@infect.gu.se.
Abstract
OBJECTIVE: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort. RESULTS: The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
OBJECTIVE: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort. RESULTS: The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
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Authors: N J Ashton; A Leuzy; T K Karikari; N Mattsson-Carlgren; A Dodich; M Boccardi; J Corre; A Drzezga; A Nordberg; R Ossenkoppele; H Zetterberg; K Blennow; G B Frisoni; V Garibotto; O Hansson Journal: Eur J Nucl Med Mol Imaging Date: 2021-03-06 Impact factor: 9.236
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