W90 - CSF Inflammatory and Neuroaxonal Damage Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis

The frequency and spectrum of neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described, but many questions remain regarding the underlying mechanisms related to central nervous system involvement.

Sixty patients with COVID-19 and new-onset neurological symptoms were included in the study. We measured 14-3-3 protein, IgG oligoclonal bands, intracellular and neuronal surface autoantibodies and a panel of chemokines, cytokines and other soluble factors in serum and CSF. We then compared the results obtained with age-matched healthy control subjects.

Compared to HC, in the COVID cohort, IL-18, IL-6, and IL-8 levels were elevated in both serum and CSF; IL-10, IL-1RA, IP-10, MIG and NfL were elevated in serum only, and MCP1 was elevated in CSF only. Antibodies against neural antigens were all negative. No differences were found in serum and CSF levels of cytokines, NfL or 14-3-3 protein when comparing patients according to their neurologic diagnosis. 14-3-3 and NfL CSF levels in addition to serum levels of IL-18, IL-1RA, IL-8 and NfL, were significantly associated with the severity of the acute COVID-19 systemic disease. Furthermore, 14-3-3 protein and NfL levels in CSF significantly correlated with the long-term functional outcome measured by the mRS.

Several proinflammatory cytokines are significantly associated with acute COVID-19 severity. Furthermore, levels of 14-3-3 and NfL in CSF could be useful as biomarker of long-term functional outcome.