Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;268(12):4436-4442.
doi: 10.1007/s00415-021-10595-6. Epub 2021 May 10.

Blood neurofilament light chain and total tau levels at admission predict death in COVID-19 patients

Rebecca De Lorenzo #  1   2 , Nicola I Loré #  1   2 , Annamaria Finardi  3 , Alessandra Mandelli  3 , Daniela M Cirillo  4 , Cristina Tresoldi  5 , Francesco Benedetti  2   6 , Fabio Ciceri  2   5 , Patrizia Rovere-Querini  1   2 , Giancarlo Comi  2   3 , Massimo Filippi  2   7 , Angelo A Manfredi  1   2 , Roberto Furlan  8
Affiliations

Blood neurofilament light chain and total tau levels at admission predict death in COVID-19 patients

Rebecca De Lorenzo et al. J Neurol. 2021 Dec.

Abstract

Background and aims: Patients infected with SARS-CoV-2 range from asymptomatic, to mild, moderate or severe disease evolution including fatal outcome. Thus, early predictors of clinical outcome are highly needed. We investigated markers of neural tissue damage as a possible early sign of multisystem involvement to assess their clinical prognostic value on survival or transfer to intensive care unit (ICU).

Methods: We collected blood from 104 patients infected with SARS-CoV-2 the day of admission to the emergency room and measured blood neurofilament light chair (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and total tau protein levels.

Results: We found that NfL, GFAP, and tau were significantly increased in patients with fatal outcome, while NfL and UCH-L1 in those needing ICU transfer. ROC and Kaplan-Meier curves indicated that total tau levels at admission accurately predict mortality.

Conclusions: Blood neural markers may provide additional prognostic value to conventional biomarkers used to predict COVID-19 outcome.

Keywords: COVID-19; GFAP; Neurofilament light chain; SARS-CoV-2; Tau; UCH-L1.

PubMed Disclaimer

Conflict of interest statement

No conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Biomarkers of neural damage are increased at admission in patients that will decrease from COVID-19. NfL (A), GFAP (B), and tau (D), but not UCH-L1 (C), plasmatic levels are significantly increased at admission in the ER in patients with fatal outcome (dead) of COVID-19 as compared to survivor (alive). Only NfL (E) and UCH-L1 (G), are significantly increased in patients that were transferred to ICU (ICU) as compared to those that were not (non ICU), while GFAP (F), and tau (H) are unchanged. Boxes and whiskers represent median and 95% confidence interval values. * ≤ 0.05, ** ≤ 0.01, *** ≤ 0.001 (Mann–Whitney)
Fig. 2
Fig. 2
Biomarkers of neural damage predict fatal outcome of COVID-19. (ROC curves for NfL (A), GFAP (B), UCH-L1 (C), tau (D), the combination of the four biomarkers (E), and without UCH-L1 (F). Area under the curve (AUC) is indicated for each ROC curve
Fig. 3
Fig. 3
Kaplan–Meier survival curves in patients with different tau levels. We divided patients according to blood tau levels at admission in those being above (red line), or below (black line) median values and performed Kaplan–Meier overall survival and log-rank test, finding that those with high values had a significantly higher risk of fatal outcome
See this image and copyright information in PMC

References

    1. Song E, Zhang C, Israelow B, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021;218:389–425. doi: 10.1084/jem.20202135. - DOI - PMC - PubMed
    1. Solomon T. Neurological infection with SARS-CoV-2—the story so far. Nat Rev Neurol. 2021;17:65–66. doi: 10.1038/s41582-020-00453-w. - DOI - PMC - PubMed
    1. Egervari K, Thomas C, Lobrinus JA, et al. Neuropathology associated with SARS-CoV-2 infection. Lancet. 2021;397:276–277. doi: 10.1016/S0140-6736(21)00095-7. - DOI - PMC - PubMed
    1. von Weyhern CH, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. Lancet. 2020;395:e109. doi: 10.1016/S0140-6736(20)31282-4. - DOI - PMC - PubMed
    1. Bienvenu OJ, Friedman LA, Colantuoni E, et al. Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study. Intensive Care Med. 2018;44:38–47. doi: 10.1007/s00134-017-5009-4. - DOI - PMC - PubMed