COVID-19 Neuroscience/ Translational neurology

COVID Breaking news: CNS injury biomarkers elevated in COVID patients

Kanberg et al., 2020: Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.

In this paper, the authors investigated the level of neuronal injury and glial activation in patients affected by COVID-19 by measuring the plasma level of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp). GFAp is a marker of axonal injury and NfL of axonal lesion; both biomarkers measured in plasma and CSF can reliably detect CNS injury and correlate with prognosis in a variety of neuropathological conditions.

Overall, 47 patients with molecularly confirmed COVID-19 diagnosis were enrolled in the study. They were divided into three groups depending on the severity of infection: 20 with a mild form (hospitalization was not necessary), 9 with moderate disease (hospitalized and on oxygen supplementation), and 18 with severe infection (17 hospitalized on the ICU and on mechanical ventilation and 1 with fatal outcome). The individuals with psychiatric, neurological, or previous MRI abnormalities were excluded. The biomarkers levels were compared to the age-matched healthy controls. The collection of samples took place at the mean of 13 days after admission and at the follow-up at the mean of 11,4 days after first sample collection.  Patients with a severe COVID-19 infection had higher plasma concentrations of GFAp (p=0.001) and NfL (p<0.001) compared to age -matched control groups. In patients with a severe COVID form GFAp in plasma decreased significantly upon follow-up (p<0,01) while NfL increased between two sampling periods (p<0.01). These results could not be reproduced in a moderate and mildly affected sub-groups.

The authors show evidence of neuronal injury and glial activation and elevation of NfL and GFAp serum biomarkers in severely affected COVID-19 patients. Moreover, it is hypothesised that early GFAp decrease and late NfL increase in a severely affected group may reflect early glial activation and delayed axonal damage in the disease course.

The authors highlight that a direct CNS infection seems to be unlikely, and the biomarkers change is probably caused by hypoxia secondary to respiratory failure, microembolism or strong inflammatory response. Besides, the number of participants was small, a thorough cognitive and neurological physical examination not possible due to restrictions implied and data regarding comorbidity are lacking. Although the study had several limitations, and further studies are warranted to clarify the nature of CNS involvement in COVID-19 patients, such novel findings may pave the way for validating the prognostic utility of these two biomarkers.

Full text: https://n.neurology.org/content/early/2020/06/16/WNL.0000000000010111