Blood neurofilament light chain and S100B as biomarkers of neurological involvement and functional prognosis in COVID-19: a multicenter study

Background and aim: COVID-19 is associated with neurological complications, termed neuro-COVID, affecting patient outcomes. We aimed to evaluate the association between serum neurofilament light chain (NfL) and S100B biomarkers with the presence of neurological manifestations and functional prognosis in COVID-19 patients. Methods: A multicenter prospective cohort study was conducted in three hospitals in the Emilia-Romagna region, Italy, from March 2020 to April 2022. Hospitalized patients with PCR-confirmed COVID-19 were enrolled. Serum S100B and NfL levels were measured in the acute or subacute phase after admission. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analyses. Statistical analyses were performed to evaluate the association between biomarkers, clinical/laboratory variables, and prognosis, specifically focusing on worsening of the modified Rankin Scale (mRS) from admission to discharge. Results: A total of 279 patients (153 males, median age 76.7 years) were included. Among them, 69 (24.7%) developed neuro-COVID. Serum NfL levels were significantly higher in the neuro-COVID group (median 110 vs 68.3; p = 0.035) and correlated with severe encephalopathy and extracranial neurologic manifestations. The ROC analysis showed low accuracy in the discrimination between the two groups for both NfL and S100B. Key predictors of worsening mRS included mechanical ventilation (OR = 9.56, 95% CI = 1.67–54.75; p = 0.011), severe encephalopathy (OR = 5.10, 95% CI = 1.58–16.19; p = 0.006), and elevated S100B levels (OR = 2.62, 95% CI = 1.10–6.46; p = 0.037). Conclusions: Serum NfL and S100B biomarkers were not accurate in discriminating neuro-COVID patients, however NfL levels were associated with severe and extracranial neuro-COVID, while S100B with functional outcomes, potentially informing clinical management.