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Nervous system: subclinical target of SARS-CoV-2 infection
  1. Sara Mariotto1,
  2. Alessia Savoldi2,
  3. Katia Donadello3,
  4. Serena Zanzoni4,
  5. Silvia Bozzetti1,
  6. Sara Carta1,
  7. Cecilia Zivelonghi1,
  8. Daniela Alberti1,
  9. Francesco Piraino5,
  10. Pietro Minuz6,
  11. Domenico Girelli7,
  12. Ernesto Crisafulli7,
  13. Simone Romano6,
  14. Denise Marcon6,
  15. Giacomo Marchi7,
  16. Leonardo Gottin8,
  17. Enrico Polati3,
  18. Paolo Zanatta9,
  19. Salvatore Monaco1,
  20. Evelina Tacconelli2,
  21. Sergio Ferrari1
  1. 1 Neurology Unit, Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
  2. 2 Infectious Disease Section, Department of Diagnostic and Public Health, University of Verona, Verona, Italy
  3. 3 Department of Anesthesia and Intensive Care B, University of Verona, Verona, Italy
  4. 4 Centro Piattaforme Tecnologiche, University of Verona, Verona, Italy
  5. 5 Quanterix Corporation, Billerica, Massachusetts, USA
  6. 6 Department of Medicine, Section of General Medicine and Hypertension, University of Verona, Verona, Italy
  7. 7 Department of Medicine, Internal Medicine Section D, University of Verona, Verona, Italy
  8. 8 Department of Cardiothoracic Anesthesia and Intensive Care Unit, University of Verona, Verona, Italy
  9. 9 Department of Anesthesia and Intensive Care A, University of Verona, Verona, Italy
  1. Correspondence to Dr Sergio Ferrari, Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, 37134 Verona, Italy;{at}

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Neurofilament light chain (NfL) is the most abundant and soluble protein of the neuronal cytoskeleton and is released during axonal injury. An increase of cerebrospinal fluid (CSF) and serum levels of NfL has been demonstrated in patients with several inflammatory and degenerative neurological disorders of the nervous system, in correlation with clinical and radiological activity.1 Several clinical reports showed that patients with COVID-19 suffer from neurological symptoms including non-specific manifestations as headache, hyposmia, dysgeusia and altered consciousness.2 To date, the pathogenesis of the aforementioned symptoms and the role of inflammatory factors in the context of this severe systemic condition have not been elucidated. Different possible mechanisms of neuronal damage have been hypothesised, including direct viral nervous system invasion through hematogenous dissemination or neuronal retrograde dissemination and indirect injury mediated by inflammatory processes due to the cytokine storm.2 The aim of this study was to explore the nervous system involvement in patients with COVID-19 by evaluating the presence of neurological symptoms and measuring serum NfL levels as biomarker of axonal damage.

Patients and methods

We performed a 1-week point prevalence survey and evaluated all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted at the COVID-19 medical and intensive care unit (ICU) areas of the University Hospital of Verona, Italy. Exclusion criteria were neurological comorbidities, which could be independently associated with neuroaxonal damage.

Clinical data and testing

The diagnosis of COVID-19 was based on the presence of SARS-CoV-2 confirmed by positive assay of nasopharyngeal samples on reverse transcriptase PCR. Demographic, anamnestic and clinical data, including presence of comorbidities, symptom onset, antecedent/current treatments, symptoms of respiratory/intestinal involvement, symptoms possibly suggesting nervous system involvement (ie, presence of altered consciousness, myalgia, fatigue, headache, vertigo, hypogeusia and hyposmia), were prospectively analysed in each included case and collected in a standardised form.

NfL analysis

Investigators blinded to …

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