ABSTRACT
Objective: Evaluate the use of neurological biomarkers to predict discharge outcomes in COVID-19 patients. Background: Altered levels of brain-derived molecular biomarkers in patients with nonneurological critical illness associates with worse outcomes following these systemic insults. We hypothesized that COVID-19 critical illness would increase expression of brain-derived biomarkers and portend worse outcomes. Design/Methods: 38 adults admitted for COVID-19 at a single tertiary care medical center were prospectively enrolled (M = 63.63 ±19.51, 53% female, 71% requiring ICU admission) and clinical information collected including discharge disposition to home/rehabilitation (n=18) or expired/skilled nursing facility (SNF;n=20). Plasma GFAP, Tau, NfL, and UCHL1 were measured by digital ELISA. Results: COVID-19 patients admitted to the ICU exhibited significantly higher levels of NfL (p=0.003, d=1.25) and GFAP (p=0.03, d=0.88). We used binary logistic regression to determine if biomarkers predicted discharge outcome. Models were examined for best fit using biomarker level, age, ICU status, and history of prior neurological disease. A model including NfL level (Wald's χ =6.614, p=0.010, OR=1.043, 95%CI (1.010, 1.076)) predicting disposition was significant (χ = 22.247, p<0.001, Nagelkerke R = .591). The model's prediction success was 84.2% (90.0% for home/rehab and 77.8% for SNF/expired) A model including GFAP level (Wald's χ =3.055, p=0.080, OR=1.003, 95%CI (1.000, 1.007)) and ICU status (Wald's χ =4.073, p=0.044, OR=0.096, 95%CI (0.010, 0.935)) on disposition was also significant (χ = 17.377, p<0.01, Nagelkerke R = .490). The model successfully predicted disposition status at 78.9% (85% for home/rehab and 72.2% for SNF/expired). Adding age, ICU status, or prior neurological history did not improve outcome prediction. Conclusions: COVID-19 patients requiring ICU admission exhibit increases in circulating brainderived proteins. Higher levels of GFAP and NfL is associated with worse discharge outcomes, even after controlling for age, ICU status and prior neurological disease. Future work examining COVID-19 recovery will help determine if these biomarkers are predictive of long-term neurological consequences.