Risk Stratification Models for Stroke in Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To derive models that identify patients with COVID-19 at high risk for stroke. MATERIALS AND METHODS: We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates. RESULTS: Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69. CONCLUSIONS: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Clinical Characteristics and Outcomes of Adults With a History of Heart Failure Hospitalized for COVID-19.

BACKGROUND: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). METHODS: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association's COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. RESULTS: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03-1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10-1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65-1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84-1.33]). CONCLUSIONS: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

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

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Evaluation of Transient Ischemic Attack and Minor Stroke: A Rapid Outpatient Model for the COVID-19 Pandemic and Beyond.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients' care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Missed cerebrovascular events during prolonged sedation for COVID-19 pneumonia.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-Analysis.

OBJECTIVE: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations. METHODS: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I2 = 45%). INTERPRETATION: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388.

Posterior reversible encephalopathy syndrome in patients with COVID-19.

OBJECTIVE: To report four patients with coronavirus disease 2019 (COVID-19) who developed posterior reversible encephalopathy syndrome (PRES). METHODS: Patient data was abstracted from medical records at Weill Cornell Medical Center. RESULTS: Four patients with SARS-CoV-2 infection and PRES were identified. The patients' ages ranged from 64 to 74 years, and two were women. All four patients were admitted to the hospital with acute respiratory distress syndrome requiring intensive care unit admission and mechanical ventilation. PRES was diagnosed after persistent confusion, lethargy, new focal neurological deficits, or seizures were noted, with evidence of seizures on electroencephalogram for two of the patients. Imaging confirmed the presence of cerebral vasogenic edema. All four patients had elevated blood pressure and renal injury in the days preceding PRES diagnosis, as well as evidence of systemic inflammation and systemic hypercoagulability. Symptoms of PRES improved with blood pressure control. CONCLUSIONS: Our four cases demonstrate the occurrence of PRES in critically-ill patients with COVID-19. PRES should be considered in the differential for acute neurological deficits and seizures in this setting.

Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza.

IMPORTANCE: It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. OBJECTIVE: To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). EXPOSURES: COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. RESULTS: Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.