Neurochemical biomarkers to study CNS effects of COVID-19: A narrative review and synthesis

J Neurochem. 2021 Oct;159(1):61-77. doi: 10.1111/jnc.15459. Epub 2021 Aug 20.


Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with the detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood-brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare and often of uncertain significance. In this review, we provide an overview of the neurological impact that occurs in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well-characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19.

Keywords: COVID-19; SARS-CoV-2; biomarker; central nervous system; cerebrospinal fluid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier
  • COVID-19 / cerebrospinal fluid
  • COVID-19 / complications*
  • COVID-19 / diagnosis
  • Humans
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / etiology*


  • Biomarkers