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Brain neuronal and glial damage during acute COVID-19 infection in absence of clinical neurological manifestations
  1. Domenico Plantone,
  2. Sara Locci,
  3. Laura Bergantini,
  4. Carlo Manco,
  5. Rosa Cortese,
  6. Martina Meocci,
  7. Dalila Cavallaro,
  8. Miriana d'Alessandro,
  9. Elena Bargagli,
  10. Nicola De Stefano
  1. Centre of Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
  1. Correspondence to Prof Nicola De Stefano, Centre of Precision and Translation Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, 53100, Italy; destefano{at}


Background To assess whether SARS-CoV-2 infection may affect the central nervous system, specifically neurons and glia cells, even without clinical neurological involvement.

Methods In this single centre prospective study, serum levels of neurofilament light chain (sNfL) and glial fibrillar acidic protein (sGFAp) were assessed using SimoaTM assay Neurology 2-Plex B Assay Kit, in 148 hospitalised patients with COVID-19 without clinical neurological manifestations and compared them to 53 patients with interstitial pulmonary fibrosis (IPF) and 108 healthy controls (HCs).

Results Age and sex-corrected sNfL levels were higher in patients with COVID-19 (median log10-sNfL 1.41; IQR 1.04–1.83) than patients with IPF (median log10-sNfL 1.18; IQR 0.98–1.38; p<0.001) and HCs (median log10-sNfL 0.89; IQR 0.72–1.14; p<0.001). Likewise, age and sex-corrected sGFAP levels were higher in patients with COVID-19 (median log10-sGFAP 2.26; IQR 2.02–2.53) in comparison with patients with IPF (median log10-sGFAP 2.15; IQR 1.94–2.30; p<0.001) and HCs (median log10-sGFAP 1.87; IQR 0.64–2.09; p<0.001). No significant difference was found between patients with HCs and IPF (p=0.388 for sNfL and p=0.251 for sGFAp). In patients with COVID-19, a prognostic model with mortality as dependent variable (26/148 patients died during hospitalisation) and sNfl, sGFAp and age as independent variables, showed an area under curve of 0.72 (95% CI 0.59 to 0.84; negative predictive value (NPV) (%):80,positive predictive value (PPV)(%): 84; p=0.0008).

Conclusion The results of our study suggest that neuronal and glial degeneration can occur in patients with COVID-19 regardless of overt clinical neurological manifestations. With age, levels of sNfl and GFAp can predict in-hospital COVID-19-associated mortality and might be useful to assess COVID-19 patient prognostic profile.

  • COVID-19

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Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors Conceptualisation and design: DP, SL, LB, EB, NDS. Data analysis: DP, SL, CM, LB, NDS. Methodology: DP, SL, Md’A. Interpretation: DP, SL, LB, CM, RC, MM, DC, Md’A, EB, NDS. Data collection: DP, SL, LB, CM, MM, DC. First draft: DP, SL, CM, LB, EB, NDS. Supervision: EB, NDS. Guarantor: NDS.

  • Funding This study was funded by the Centre of Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience of the University of Siena, Italy. Grant number: N/A.

  • Competing interests DP, SL, LB, CM: none declared. Unrelated to this work, RC received speaker honoraria from Roche and Merck. She was awarded a MAGNIMS-ECTRIMS fellowship in 2019. MM, DC, Md’A: none declared. Competing interests unrelated to this work, EB provides consultancy to GSK, BI and Chiesi. Unrelated to this work, NDS is a consultant for Biogen, Merck, Novartis, Sanofi-Genzyme, Roche, and Teva and is on the speakers’ bureaus of Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. He has received travel funds from Merck, Novartis, Roche, Sanofi-Genzyme, and Teva and has grants pending from FISM. He is co-founder of Siena-Imaging.

  • Provenance and peer review Not commissioned; externally peer reviewed.