ABSTRACT
Objective: Early neurorehabilitation improves outcomes in patients with disorders of consciousness after brain injury, but its applicability in COVID-19 is unknown. We demonstrate the feasibility of an early neurorehabilitation protocol for patients with COVID-19-associated disorders of consciousness in the intensive care unit (ICU) and evaluate factors associated with recovery. Methods: Between March 10 and May 20, 2020, we prospectively enrolled 21 ICU patients with delayed recovery of consciousness after severe COVID-19 in a pilot early neurorehabilitation protocol including serial Coma Recovery Scale - Revised (CRS-R) assessments and multimodal treatment. We retrospectively compared clinical features of patients who did and did not achieve a CRS-R total score (TS) ≥8, consistent with minimally conscious state, before discharge. We additionally present preliminary 6-month follow-up data for 8 patients who survived to discharge. Results: Patients underwent CRS-R a median of 6 (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients achieved at least one CRS-R TS ≥8, after a median of 8 days (IQR 2-14) off continuous sedation;they had lower body mass index (p = 0.009), lower peak serum C-reactive protein (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028) and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time and best CRS-R TS was significantly higher than last CRS-R TS (median 8 [IQR 5- 23] vs 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with higher last CRS-R TS. Six-month follow-up data was obtained for 8 of 12 patients who survived to hospital discharge: of these, one patient (13%) had expired;3 (38%) remained in a disorder of consciousness;one (13%) was conscious but moderately disabled;and 3 (38%) achieved functional independence. Conclusion: It is feasible to provide early neurorehabilitation to patients with impaired consciousness after severe COVID-19 in the ICU. These patients can recover, but hypoxia, systemic inflammation, sedation and neuromuscular blockade may impact CRS-R scores and short-term outcomes. Return to functional independence is possible for some patients. Further research should evaluate factors influencing longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.