Faculty Bibliography

BACKGROUND:Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19. METHODS:We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression. RESULTS:Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms). CONCLUSIONS:Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.

OBJECTIVES/OBJECTIVE:To evaluate the safety of immune checkpoint inhibitor use in patients with pre-existing neurological autoimmune diseases. METHODS:In this retrospective case-series, we examined exacerbations of underlying disease and the occurrence of immune-related adverse events in 5 patients who had been diagnosed with a neurological autoimmune disease prior to receiving immune checkpoint inhibitor therapy for advanced malignancy. RESULTS:Two patients had a prior diagnosis of myasthenia gravis, two had Guillain-Barré syndrome, and one had chronic idiopathic demyelinating polyneuropathy. Only one patient experienced a flare of neurological autoimmune disease. Four of the five patients experienced immune-related adverse events unrelated to their neurological disease. CONCLUSIONS:In this case-series, exacerbations of neurological autoimmune disease were less common and less severe than expected. Further research is needed to determine which individuals are at greatest risk of neurological autoimmune disease complication while receiving immune checkpoint inhibitor therapy.

BACKGROUND/OBJECTIVES/OBJECTIVE:Little is known about trajectories of recovery 12-months after hospitalization for severe COVID. METHODS:We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test. RESULTS:Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients. DISCUSSION/CONCLUSIONS:At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

Background/UNASSIGNED:Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). With the increased utilization of telehealth services, we sought to determine whether patients also increased their use of virtual CITs. Methods/UNASSIGNED:We examined datasets from two separate cross-sectional surveys that included cohorts of patients with neurological disorders. One was a dataset from a study that examined patient and provider experiences with teleneurology visits; the other was a study that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation. We assessed and reported the use of virtual (and non-virtual) CITs using descriptive statistics, and determined whether there were clinical characteristics that predicted the use of CITs using logistic regression analyses. Findings/UNASSIGNED:Patients who postponed medical treatment for non-COVID-19-related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy, and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/virtual CIT usage. Interpretations/UNASSIGNED:Our investigation demonstrates that virtual CIT-related technologies were utilized in the treatment of neurologic conditions during the pandemic, particularly by those patients who deferred non-COVID-related care.

One sentence summary: The purpose of this investigation was to expand the evidence base on CITs delivered by telehealth by evaluating CIT use in patients who presented to a large urban tertiary care neurology practice and to examine predictors of CIT use during the pandemic.
Background(s): Patients with neurological disorders may seek treatment options in addition to those recommended by their providers. Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). Given the reductions in in-person visits and the increases in teleneurology visits, we sought to determine whether patients increased their use of virtual complementary and integrative therapies.
Method(s): By examining two separate datasets that included cohorts of patients with neurological disorders, we assessed patients' use of virtual (and non-virtual) CITs and determined whether there were clinical characteristics that predicted their use. The two studies that comprised this report included one that examined patient and provider experiences with teleneurology visits, and another that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation.
Result(s): Patients who postponed medical treatment for non-COVID- 19- related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/ virtual CIT usage.
Conclusion(s): Data from our investigations demonstrated that, in addition to its other roles in teleneurology, CIT-related technologies might be utilized in the treatment of neurologic conditions