Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up.

BACKGROUND AND OBJECTIVES: Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION: There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.

Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization.

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.

Post-acute sequelae of COVID-19 symptom phenotypes and therapeutic strategies: A prospective, observational study.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC) includes a heterogeneous group of patients with variable symptomatology, who may respond to different therapeutic interventions. Identifying phenotypes of PASC and therapeutic strategies for different subgroups would be a major step forward in management. METHODS: In a prospective cohort study of patients hospitalized with COVID-19, 12-month symptoms and quantitative outcome metrics were collected. Unsupervised hierarchical cluster analyses were performed to identify patients with: (1) similar symptoms lasting ≥4 weeks after acute SARS-CoV-2 infection, and (2) similar therapeutic interventions. Logistic regression analyses were used to evaluate the association of these symptom and therapy clusters with quantitative 12-month outcome metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). RESULTS: Among 242 patients, 122 (50%) reported ≥1 PASC symptom (median 3, IQR 1-5) lasting a median of 12-months (range 1-15) post-COVID diagnosis. Cluster analysis generated three symptom groups: Cluster1 had few symptoms (most commonly headache); Cluster2 had many symptoms including high levels of anxiety and depression; and Cluster3 primarily included shortness of breath, headache and cognitive symptoms. Cluster1 received few therapeutic interventions (OR 2.6, 95% CI 1.1-5.9), Cluster2 received several interventions, including antidepressants, anti-anxiety medications and psychological therapy (OR 15.7, 95% CI 4.1-59.7) and Cluster3 primarily received physical and occupational therapy (OR 3.1, 95%CI 1.3-7.1). The most severely affected patients (Symptom Cluster 2) had higher rates of disability (worse modified Rankin scores), worse NeuroQoL measures of anxiety, depression, fatigue and sleep disorder, and a higher number of stressors (all P<0.05). 100% of those who received a treatment strategy that included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical/occupational therapy, and 83% who received few interventions (P = 0.042). CONCLUSIONS: We identified three clinically relevant PASC symptom-based phenotypes, which received different therapeutic interventions with varying response rates. These data may be helpful in tailoring individual treatment programs.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study.

BACKGROUND AND OBJECTIVE: Little is known about trajectories of recovery 12 months after hospitalization for severe COVID-19. METHODS: We conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test. RESULTS: Twelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index <100 (64%), t-MoCA ≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%), or poor sleep (10%). Twelve-month mRS scores did not differ significantly among those with (n = 113) or without (n = 129) neurologic complications during hospitalization after adjusting for age, sex, race, pre-COVID-19 mRS, and intubation status (adjusted OR 1.4, 95% CI 0.8-2.5), although those with neurologic 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). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients. DISCUSSION: At 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic 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 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

Prior Stroke and Age Predict Acute Ischemic Stroke Among Hospitalized COVID-19 Patients: A Derivation and Validation Study.

Objectives: Our objective was to identify characteristics associated with having an acute ischemic stroke (AIS) among hospitalized COVID-19 patients and the subset of these patients with a neurologic symptom. Materials and Methods: Our derivation cohort consisted of COVID-19 patients admitted to Yale-New Haven Health between January 3, 2020 and August 28, 2020 with and without AIS. We also studied a sub-cohort of hospitalized COVID-19 patients demonstrating a neurologic symptom with and without an AIS. Demographic, clinical, and laboratory results were compared between AIS and non-AIS patients in the full COVID-19 cohort and in the sub-cohort of COVID-19 patients with a neurologic symptom. Multivariable logistic regression models were built to predict ischemic stroke risk in these two COVID-19 cohorts. These 2 models were externally validated in COVID-19 patients hospitalized at a major health system in New York. We then compared the distribution of the resulting predictors in a non-COVID ischemic stroke control cohort. Results: A total of 1,827 patients were included in the derivation cohort (AIS N = 44; no AIS N = 1,783). Among all hospitalized COVID-19 patients, history of prior stroke and platelet count ≥ 200 × 1,000/µL at hospital presentation were independent predictors of AIS (derivation AUC 0.89, validation AUC 0.82), irrespective of COVID-19 severity. Among hospitalized COVID-19 patients with a neurologic symptom (N = 827), the risk of AIS was significantly higher among patients with a history of prior stroke and age <60 (derivation AUC 0.83, validation AUC 0.81). Notably, in a non-COVID ischemic stroke control cohort (N = 168), AIS patients were significantly older and less likely to have had a prior stroke, demonstrating the uniqueness of AIS patients with COVID-19. Conclusions: Hospitalized COVID-19 patients who demonstrate a neurologic symptom and have either a history of prior stroke or are of younger age are at higher risk of ischemic stroke.

Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

[Figure: see text].

Prevalence and Predictors of Prolonged Cognitive and Psychological Symptoms Following COVID-19 in the United States.

BACKGROUND/OBJECTIVES: Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. METHODS: We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. RESULTS: Among 999 respondents, the average age was 45 years (range 18-84), 49% were male, 76 (7.6%) had a history of COVID-19 and 19/76 (25%) COVID-19 positive participants reported prolonged symptoms lasting a median of 4 months (range 1-13). Prolonged COVID-19 participants were more often younger, female, Hispanic, and had a history of depression/mood/thought disorder (all P < 0.05). They experienced significantly higher rates of unemployment and financial insecurity, and their symptoms created greater interference with work and household activities compared to other COVID-19 status groups (all P < 0.05). After adjusting for demographics, past medical history and stressor covariates in multivariable logistic regression analysis, COVID-19 status was independently predictive of worse Neuro-QoL cognitive dysfunction scores (adjusted OR 11.52, 95% CI 1.01-2.28, P = 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. CONCLUSION: Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

Changes in Stroke Hospital Care During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

[Figure: see text].

Cerebral Vein Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia.

In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.

COVID-19 and ischemic stroke.

Since the onset of the COVID-19 pandemic, a substantial proportion of COVID-19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune-mediated thrombosis, the renin angiotensin system and the effect of SARS-CoV-2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID-19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID-19 particularly challenging. In this review, we summarize the current knowledge on epidemiology, clinical manifestation, and pathophysiology of ischemic stroke in patients with COVID-19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Characteristics and Outcomes Among US Patients Hospitalized for Ischemic Stroke Before vs During the COVID-19 Pandemic.

Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19. Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if they were admitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 discharged between January and March 2020 were excluded from the analysis because they had unreliable data on COVID-19 status, leaving 282 847 patients for the study. Exposure: Ischemic stroke and laboratory-confirmed COVID-19. Main Outcomes and Measures: Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were discharged in 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non-COVID-19 groups, respectively) who were discharged between April and December 2020. Results: Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non-COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13 846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10 846 patients in April 2020 before returning to a prepandemic level of 13 639 patients by July 2020. A mean (SD) of 13 492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non-COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05). Conclusions and Relevance: In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbidity was high.

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States.

OBJECTIVE: To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort. METHODS: We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes. RESULTS: There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge. CONCLUSIONS: Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.

Global impact of COVID-19 on stroke care.

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

BACKGROUND: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. METHODS: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. RESULTS: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001). CONCLUSIONS: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

OBJECTIVE: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes. METHODS: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders. RESULTS: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, p < 0.001). CONCLUSIONS: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.