Delayed reemergence of consciousness in survivors of severe COVID-19

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Delayed reemergence of consciousness in survivors of severe COVID‑19 Brian L. Edlow1, Jan Claassen2, Jonathan D. Victor3, Emery N. Brown4,5 and Nicholas D. Schiff3* © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society

Survivors of coronavirus disease 2019 (COVID-19) around the world are coming off ventilators every day, having overcome multi-organ system failure and weeks sedated, paralyzed, and isolated from family in the intensive care unit (ICU). The triumph of survival, for those who recover consciousness, is celebrated with nurses, physicians, respiratory therapists and the multitudes of hospital staff who care for patients with COVID-19. The long journey to inpatient rehabilitation, and ultimately home, begins. Yet many COVID-19 survivors have not recovered consciousness. They remain unresponsive and bedbound, persistently disconnected from their environment. As each day passes after removing the endotracheal tube and weaning sedation, a patient’s inability to regain consciousness becomes more disconcerting to families and clinicians. Prolonged alterations of consciousness ranging from coma to delirium have consistently been reported in patients with severe COVID-19 [1–4], but epidemiological estimates of incidence and prevalence are not yet available. Altered consciousness in patients with severe COVID-19 was the most common reason for neurological consultation at our medical centers in New York and Boston during the COVID-19 surge in the Spring of 2020 [5]. Although we tried to use every diagnostic and prognostic tool at our disposal—the neurological exam, electroencephalography (EEG), computed tomography (CT), and magnetic resonance imaging (MRI)—resource limitations and concerns about the exposure to health care workers and other patients constrained our ability to use these tools. Nearly every question about how severe

*Correspondence: [email protected] 3 Feil Family Brain and Mind Research Institute, Weill Cornell Medical Center, New York, NY, USA Full list of author information is available at the end of the article

COVID-19 affects the brain thus remains incompletely answered [6]. Sedation likely contributes to prolonged unconsciousness, given that sustained, high levels of sedation are often needed to ensure ventilator synchrony in COVID19 patients with acute respiratory distress syndrome (ARDS) [7, 8]. The adverse effects of sedatives on higherorder cognition are well established [9, 10], but how sustained, high doses of sedatives affect the reemergence of consciousness itself is unknown. Moreover, some sedative agents may predispose to more enduring depression of consciousness [11]. After unprecedented drug combinations, dosing regimes, and durations of sedation, often in the setting of hypoxia, metabolic derangements, and impaired drug clearance due to renal or liver failure, the human brain’s ability to reintegrate its neural networks is now being tested in ICUs around the world. Addressing the new challenges posed by the COVID19