Disorders of Consciousness Associated With COVID-19: A Prospective Multimodal Study of Recovery and Brain Connectivity.

BACKGROUND AND OBJECTIVES: In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile. METHODS: In a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC. RESULTS: After screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI. DISCUSSION: Patients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT04476589.

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia.

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following. METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6). RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following  was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

A low dose heparinized saline protocol is associated with improved duration of arterial line patency in critically ill COVID-19 patients.

PURPOSE: Critically ill patients with Coronavirus Disease 2019 (COVID-19) have high rates of line thrombosis. Our objective was to examine the safety and efficacy of a low dose heparinized saline (LDHS) arterial line (a-line) patency protocol in this population. MATERIALS AND METHODS: In this observational cohort study, patients ≥18 years with COVID-19 admitted to an ICU at one institution from March 20-May 25, 2020 were divided into two cohorts. Pre-LDHS patients had an episode of a-line thrombosis between March 20-April 19. Post-LDHS patients had an episode of a-line thrombosis between April 20-May 25 and received an LDHS solution (10 units/h) through their a-line pressure bag. RESULTS: Forty-one patients (pre-LDHS) and 30 patients (post-LDHS) were identified. Baseline characteristics were similar between groups, including age (61 versus 54 years; p = 0.24), median Sequential Organ Failure Assessment score (6 versus 7; p = 0.67) and systemic anticoagulation (47% versus 32%; p = 0.32). Median duration of a-line patency was significantly longer in post-LDHS versus pre-LDHS patients (8.5 versus 2.9 days; p < 0.001). The incidence of bleeding complications was similar between cohorts (13% vs. 10%; p = 0.71). CONCLUSIONS: A LDHS protocol was associated with a clinically significant improvement in a-line patency duration in COVID-19 patients, without increased bleeding risk.