Neurological Biomarkers for COVID-19: NfL and GFAP 
Dear Researcher,

As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing and range from ageusia and anosmia to encephalitis and stroke. Blood-based biomarkers for brain damage such as Neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) could help in the monitoring of patients and in reducing the risk of severe brain injury. 

NfL is part of the axonal cytoskeleton and is released into cerebrospinal fluid and eventually into the blood compartment. GFAP is a protein expressed by astrocytes in the CNS and has been shown to be up regulated in blood as a result of CNS injury markers. Both biomarkers have been implicated in traumatic brain injury (TBI) and stroke among other conditions.

Plasma GFAP and NfL levels increase in moderate and severe COVID-19
A study from Gothenburg, Sweden by Kanberg et al. (2020) showed that patients with severe COVID-19 (i.e. patients requiring ventilator support) had higher plasma concentrations of GFAP and NfL than healthy controls (Table 1).

While levels of both biomarkers were initially elevated in patients with severe COVID-19; GFAP levels subsequently declined and NfL levels continued to increase in subsequent follow up. Further, a direct correlation between rise in plasma NfL levels and disease severity was observed.

Patients with moderate disease (that is patients who were admitted to hospital but not in need of ventilator support) also had raised plasma GFAP levels.The authors indicate that these rises have been greater than those seen in pre COVID Intensive Care studies and suggest that COVID-19 is causing brain injury.

Serum NfL levels as a predictor of disease severity
A study from Verona, Italy by Mariotto et al., (2020)  found that 57% of the patient group had increased levels of serum NfL compared with the control group. Only patients without antecedent comorbidities, which could independently alter NfL levels, were included in this study.

Also, increased NfL serum levels were significantly associated with longer and more severe disease with patients being more likely to be admitted to Intensive Care Units and to undergo orotracheal intubation (p<0.01). However, the study was unable to find any statistically relevant association between neurological symptoms and serum NfL levels.

In conclusion, the papers identify NfL and GFAP as potential biomarkers for neurological damage in COVID-19. While larger studies with long term follow up are required, both biomarkers could be very useful in proving the effectiveness of therapeutics in COVID-19 clinical trials.


Best wishes and stay safe,

The Biosensis Team
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Biosensis Pty Ltd

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