ABSTRACT
Background and Purpose: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. Method(s): We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). Result(s): During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. Conclusion(s): We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.
ABSTRACT
Aims This study aimed to investigate the potential of tocilizumab therapy in minimizing mortality and mechanical ventilation (MV) requirements among hospitalized COVID-19 patients. Methods A single-center, retrospective, observational cohort study of 375 patients with severe COVID-19 (from March 1 to April 22, 2020) included 150 patients treated with tocilizumab and 225 consecutive control patients adjusted for age and sex. Both groups received concomitant standard of care treatments in addition to tocilizumab. The statistical methods relied on survival analyses, conditional logistic regression models, and contingency analyses. The outcomes included in-hospital mortality and the MV requirement. Results Tocilizumab associated with improved in-hospital mortality (34.7% vs 46.7%, P = 0.0136) and lower requirement for MV on days 1, 3, and 5 after treatment (P = 0.005, P < 0.0001, and P = 0.0021, respectively). Lower mortality was observed if tocilizumab was administered within 48 hours after admission (P = 0.0226). Older age and low blood oxygen saturation on admission decreased the odds of survival (P < 0.005). Conclusions Our study demonstrates a significant reduction in mortality and decreased requirement of MV with tocilizumab treatment in addition to the standard of care. Early administration of tocilizumab within 48 hours reduces the risk of mortality.
ABSTRACT
Background: Although hospital admissions for stroke declined in 2020 during the COVID-19 pandemic, patients with comorbid COVID-19 and stroke had increased mortality. We explored stroke mortality in 2020 and its association with COVID-19 prevalence and state-level hospital capacities. Methods: We analyzed CDC National Vital Statistics System and COVID Data Tracker data from 2017-2020. The primary outcome was age-adjusted stroke (ischemic and hemorrhagic) mortality rate per 100,000. The secondary outcome was % change in state-level stroke mortality rates in 2020 (vs. 2017-19);we report its correlation with state-level 1) prevalence of confirmed COVID-19 infections by 12/31/2021, 2) total COVID mortality by 12/31/20, and the 2020 average state-level % of 3) hospital and 4) ICU beds occupied by COVID-19 patients. Results: Figure 1A shows the typical seasonal decline in stroke mortality in quarters 2/3 was attenuated in 2020. The % change in state-level stroke mortality in 2020 (Figure 1B) was not correlated with prevalence of COVID-19 infection (rho=0.05, p=0.74), mortality (rho=0.10, p=0.49), or the % of ICU beds occupied by COVID-19 patients (rho=0.24, p=0.09). There was a correlation with % of hospital beds occupied by COVID-19 patients (rho=0.35, p=0.01) (Figure 2) Conclusion: Overall stroke mortality increased in 2020, particularly in Q2/3, the early-to-mid phase of the COVID-19 pandemic. At the state level, the average % of all hospital beds occupied by COVID-19 patients in 2020 was the only COVID-19 metric associated with change in stroke mortality. Future work should determine if this association was due to decreased hospital capacity to deliver standard stroke care.
ABSTRACT
Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods. Background: The COVID-19 pandemic led to widespread repercussions on the delivery of health care worldwide. Design/Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by ICD-10 codes and/or classifications in stroke center 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%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). There were greater declines in primary compared to comprehensive stroke centers (CSC) for stroke hospitalizations (-17.3% vs-10.3%, p<0.0001) and IVT (-15.5% vs-12.6%, p=0.0001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) months of the pandemic, with greater recovery in hospitals with lower COVID-19 hospitalization volume, high volume stroke center, and CSC. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. 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 COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months, with greater recovery in hospitals with lower COVID-19 hospitalizations, high volume stroke centers, and CSCs.
ABSTRACT
Introduction: While the thrombotic complications of COVID-19 have been described, there are limited data on its implications in hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this group of patients are especially salient as empiric therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both nontraumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between 3/1/20-5/15/20 at a NYC hospital system, during the coronavirus pandemic. We compared the demographic and clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital between 3/1/20-5/15/20 (contemporary controls) and 3/1/19-5/15/19 (historical controls), using Fischer's exact test and nonparametric testing. We adjusted for multiple comparisons using the Bonferroni method. Results: During the study period, 19 out of 4071 (0.5%) patients who were hospitalized with COVID-19 had hemorrhagic stroke on imaging. Of all COVID-19 with hemorrhagic stroke, only 3 had non-aneurysmal SAH without intraparenchymal hemorrhage. Among hemorrhagic stroke and COVID-19 patients, coagulopathy was the most common etiology (73.7%);empiric anticoagulation was started in 89.5% vs 4.2% of contemporary and 10.0% of historical controls (both with p = <0.001). Compared to contemporary and historical controls, COVID-19 patients had higher initial NIHSS scores, INR, PTT and fibrinogen levels. These patients also had higher rates of in-hospital mortality [84.6% vs. 4.6%, p =<0.001]. Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in COVID-19 patients occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in COVID-19 patients.
ABSTRACT
Background: Because COVID-19 is thought to be pro-thrombotic and could theoretically increase the severity of cerebral venous sinus thrombosis (CVST), we sought to examine the outcomes of CVST patients with comorbid COVID-19 infection. Methods: We performed a retrospective analysis using the Vizient Clinical Data Base (CDB), a healthcare analytics platform employed by participating US hospitals. We identified CVST with the ICD-10 codes I63.6, I67.6, G08.x, O22.5, and O87.3. We created three cohorts of patients: CVST with confirmed or suspected COVID-19 in April, May or June 2020, CVST with influenza-like illness (ILI) in 2019, and CVST without ILI in 2019. The outcomes are 1) in-hospital death and 2) favorable discharge (discharge destination home or acute rehabilitation). We fit logistic regression models to our outcomes and adjusted for patient age, sex, race/ethnicity, Elixhauser comorbidity score, acute respiratory failure requiring intubation, and hospital length of stay. Results: We identified 73 patients with CVST and COVID-19, 159 with CVST and ILI, and 4,146 with CVST and no COVID-19 or ILI. The patient death rates were 20.6%, 8.8%, and 5.1%, respectively, and favorable discharge rates were 58.9%, 52.8%, and 77.3%, respectively. Compared to CVST patients with ILI, those with COVID-19 were not significantly more likely to die in-hospital (adjusted OR 1.43, 95% CI 0.44-4.66, p=0.557) or to have favorable discharge (adjusted OR 1.75, 95% CI 0.58-5.25, p=0.321). Compared to CVST patients without ILI or COVID-19, those with COVID-19 were also not significantly more likely to die in-hospital (adjusted OR 0.87, 95% CI 0.35- 2.12, p=0.751) or to have favorable discharge (adjusted OR 1.52, 95% CI 0.62-3.69, p=0.358). Conclusion: Although CVST patients with COVID-19 had a higher in-hospital death rate and lower favorable discharge rates, after adjusting for potential confounders there was no association between worse outcomes in CVST patients with COVID-19. This suggests that while CVST may complicate COVID-19, it does not portend a worse prognosis than CVST in patients with either ILI or no ILI or COVID-19.
ABSTRACT
Introduction: While coronavirus disease 2019 (COVID-19) has been associated with acute ischemic stroke (AIS), the causal relationship has yet to be elucidated. Factors that likely confer increased stroke risk are COVID-19-associated coagulopathy and hyperinflammatory response. Studying clinical features of patients with otherwise undetermined cause of AIS could help better define COVID-19-associated stroke. Methods: We performed a multicenter cross-sectional study of consecutive patients presenting with AIS and COVID-19 to one of two large healthcare systems in New York City during the local COVID- 19 surge from March 1, 2020 to May 31, 2020. In-hospital stroke cases were excluded. We compared demographic and clinical features of patients with COVID-19 and a cryptogenic AIS subtype to patients with COVID-19 and a determined subtype. Baseline characteristics and clinical variables were compared using chi-squared and Fisher exact tests. Results: A total of 62 patients with AIS and COVID-19 at the time of hospital arrival were identified. Of these, 30 were classified as having a cryptogenic subtype (80% after complete diagnotics evaluation), and 32 had an identifiable stroke mechanism. Patients with cryptogenic AIS were significantly younger (p=0.011) and less likely to have co-morbid hypertension (p=0.019), coronary artery disease (p=0.024), heart failure (p=0.039), atrial fibrillation (<0.0001), and prior stroke or TIA (p=0.033) compared to those with defined mechanisms. Further, d-dimer, but not C-reactive protein, was significantly higher in patients with cryptogenic stroke compared to those with defined causes (p=0.009). Conclusion: Patients with AIS in the setting of COVID-19 and no other determined stroke mechanism were younger, less likely to have classic risk factors, and had higher d-dimer levels when compared to those with a determined mechanism. Further study of COVID-19-associated hypercoagulability as a mechanism of stroke is warranted.
ABSTRACT
Background: Emerging data indicates an increased risk for cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and highlights 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 SARSCoV- 2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (95%CI). Results: We identified 16 cohort studies including 44,004 patients. Among patients with SARS-CoV- 2, 1.3% (95%CI: 0.9-1.8%;I =88%) were hospitalized for cerebrovascular events, 1.2% (95%CI: 0.8-1.5%;I =85%) for ischemic stroke, and 0.2% (95%CI: 0.1-0.4%;I =69%) for hemorrhagic stroke. Compared to non-infected 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;I =43%) and cryptogenic stroke (OR=3.98, 95%CI: 1.62-9.77;I =0%). Odds for in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical stroke patients (OR=5.60, 95%CI: 3.19-9.80;I =45%). SARS-CoV-2 infection status was not associated to the likelihood of receiving intravenous thrombolysis (OR=1.42, 95%CI: 0.65-3.10;I =0%) or endovascular thrombectomy (OR=0.78, 95%CI: 0.35-1.74;I =0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls(OR=1.39, 95%CI: 1.04-1.86;I =0%). Conclusion: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke,particularly the cryptogenic subtype. SARS-CoV-2 infection in stroke substantially increases themortality risk.
ABSTRACT
Introduction: COVID-19 is associated with incident cerebrovascular disease (CVD). We evaluated the association between preexisting CVD and COVID-19 mortality. Methods: Utilizing deidentified pooled data from 40 healthcare organizations, adult (≥ 18 years) COVID-19 patients were identified based on ICD-10 diagnostic codes and documentation of laboratory positivity for SARS-CoV-2 RNA or antibodies. Among COVID-19 patients, those with documented ICD-10 diagnoses for cerebral infarction / ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA) at least 30- days before the index COVID-19 event were classified as the CVD group. The CVD and non-CVD groups were propensity score (PS) matched on demographic and comorbidity variables. Pre and post-match risk ratios (RR) and 95% confidence intervals (CI) for 30 and 90-day mortality were calculated. Mortality rates for CVD subgroups (ICH, SAH, AIS, TIA) are also reported. Results: Among a total of 140,034 COVID-19 cases, 4,614 (3.3%) had prevalent CVD. CVD patients were significantly older and were predominantly males of either white or black race (vs. other). CVD patients also had a higher comorbidity burden (vs. non-CVD patients) (graphic). A 1:1 PS algorithm yielded an optimally matched sample of 8,218 COVID-19 patients (4,109 CVD and non-CVD patients each). In the matched sample, 30-day mortality was 8.4% among CVD patients and 7.0% among non-CVD patients RR (CI): 1.20 (1.03 - 1.39). 90-day mortality among CVD patients (vs. Non-CVD patients) remained significantly elevated (9.7% vs. 8.2%), RR (CI): 1.20 (1.04 - 1.37). Among CVD subgroups, 30 and 90-day mortality was higher for patients with preexisting ICH (11.8% and 13.7%, respectively) compared to IS (8.7% and 10.2%, respectively). Conclusion: Preexisting CVD significantly increases the mortality risk in COVID-19 patients. Mechanisms for poor COVID-19 outcomes among CVD patients need to be evaluated.
ABSTRACT
OBJECTIVES: Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN: Retrospective, multicenter, observational cohort study. SETTING: Four New York City hospitals that are part of the same health network. PATIENTS: Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: <= 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43;95% CI, 1.08-1.88;p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS: Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.
ABSTRACT
BACKGROUND: Studies have shown worse outcomes in patients with comorbid ischemic stroke (IS) and coronavirus disease 2019 (COVID-19), but have had small sample sizes. METHODS: We retrospectively identified patients in the Vizient Clinical Data Base R with IS as a discharge diagnosis. The study outcomes were in-hospital death and favorable discharge (home or acute rehabilitation). In the primary analysis, we compared IS patients with laboratory-confirmed COVID-19 (IS-COVID) discharged April 1-July 31, 2020 to pre-COVID IS patients discharged in 2019 (IS controls). In a secondary analysis, we compared a matched cohort of IS-COVID patients to patients within the IS controls who had pneumonia (IS-PNA), created with inverse-probability-weighting (IPW). RESULTS: In the primary analysis, we included 166,586 IS controls and 2086 IS-COVID from 312 hospitals in 46 states. Compared to IS controls, IS-COVID were less likely to have hypertension, dyslipidemia, or be smokers, but more likely to be male, younger, have diabetes, obesity, acute renal failure, acute coronary syndrome, venous thromboembolism, intubation, and comorbid intracerebral or subarachnoid hemorrhage (all p<0.05). Black and Hispanic patients accounted for 21.7% and 7.4% of IS controls, respectively, but 33.7% and 18.5% of IS-COVID (p<0.001). IS-COVID, versus IS controls, were less likely to receive alteplase (1.8% vs 5.6%, p<0.001), mechanical thrombectomy (4.4% vs. 6.7%, p<0.001), to have favorable discharge (33.9% vs. 66.4%, p<0.001), but more likely to die (30.4% vs. 6.5%, p<0.001). In the matched cohort of patients with IS-COVID and IS-PNA, IS-COVID had a higher risk of death (IPW-weighted OR 1.56, 95% CI 1.33-1.82) and lower odds of favorable discharge (IPW-weighted OR 0.63, 95% CI 0.54-0.73). CONCLUSIONS: Ischemic stroke patients with COVID-19 are more likely to be male, younger, and Black or Hispanic, with significant increases in morbidity and mortality compared to both ischemic stroke controls from 2019 and to patients with ischemic stroke and pneumonia.
ABSTRACT
Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.