Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Neutrophil-Lymphocyte ratio is associated with poor clinical outcome after mechanical thrombectomy in stroke in patients with COVID-19.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is emerging as an important biomarker of acute physiologic stress in a myriad of medical conditions, and is a confirmed poor prognostic indicator in COVID-19. OBJECTIVE: We sought to describe the role of NLR in predicting poor outcome in COVID-19 patients undergoing mechanical thrombectomy for acute ischemic stroke. METHODS: We analyzed NLR in COVID-19 patients with large vessel occlusion (LVO) strokes enrolled into an international 12-center retrospective study of laboratory-confirmed COVID-19, consecutively admitted between March 1, 2020 and May 1, 2020. Increased NLR was defined as ≥7.2. Logistic regression models were generated. RESULTS: Incidence of LVO stroke was 38/6698 (.57%). Mean age of patients was 62 years (range 27-87), and mortality rate was 30%. Age, sex, and ethnicity were not predictive of mortality. Elevated NLR and poor vessel recanalization (Thrombolysis in Cerebral Infarction (TICI) score of 1 or 2a) synergistically predicted poor outcome (likelihood ratio 11.65, p = .003). Patients with NLR > 7.2 were 6.8 times more likely to die (OR 6.8, CI95% 1.2-38.6, p = .03) and almost 8 times more likely to require prolonged invasive mechanical ventilation (OR 7.8, CI95% 1.2-52.4, p = .03). In a multivariate analysis, NLR > 7.2 predicted poor outcome even when controlling for the effect of low TICI score on poor outcome (NLR p = .043, TICI p = .070). CONCLUSIONS: We show elevated NLR in LVO patients with COVID-19 portends significantly worse outcomes and increased mortality regardless of recanalization status. Severe neuro-inflammatory stress response related to COVID-19 may negate the potential benefits of successful thrombectomy.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study

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Age and Acute Ischemic Stroke Outcome in North American Patients With COVID-19.

Background Acute ischemic stroke (AIS) in the context of COVID-19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS-CoV-2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID-19 who were diagnosed with AIS, the median age was 63 years (range, 27-94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, (P=0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P=0.047). After multivariable adjustment for possible confounders, a 1-year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90-0.99; P=0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02-1.10; P=0.007). Conclusions AIS in the context of COVID-19 affects young patients at much greater rates than pre-pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

The impact of Parkinson's disease on manifestations and outcomes of Covid-19 patients: A systematic review and meta-analysis.

Parkinson's disease (PD) patients who contracted Coronavirus disease 2019 (Covid-19) had a decline in motor functions; nevertheless, there is limited evidence on whether PD patients have a higher risk for contracting Covid-19 or have worse outcomes. This is the first systematic review and meta-analysis to review the impact of PD on the prognosis of Covid-19 patients. We performed a systematic search through seven electronic databases under the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analyses statement (PRISMA) guidelines. The R software version 4.0.2 was used to calculate pooled sample sizes and their associated confidence intervals (95%CI). Finally, we included 13 papers in this study. The pooled prevalence rate of Covid-19 was 2.12% (95%CI: 0.75-5.98). Fever, cough, fatigue and anorexia were the most common symptoms with a rate of 72.72% (95% CI: 57.3 - 92.29), 66.99% (95% CI: 49.08-91.42), 61.58% (95% CI: 46.69-81.21) and 52.55% (95% CI: 35.09-78.68), respectively. The pooled rates were 39.89% (95% CI: 27.09-58.73) for hospitalisation, 4.7% (95% CI: 1.56-14.16) for ICU admission and 25.1% (95%CI: 16.37-38.49) for mortality. On further comparison of hospitalisation and mortality rates among Covid-19 patients with and without PD, there were no significant differences. In conclusion, the prevalence and prognosis of Covid-19 patients seem comparable in patients with PD and those without it. The increased hospitalisation and mortality may be attributed to old age and co-morbidities.

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. METHODS: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. RESULTS: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. CONCLUSION: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads to mortality. Outcomes of patients with COVID-19-related ARDS compared to ARDS unrelated to COVID-19 is not well characterized. AREAS COVERED: We performed a systematic review of PubMed, Scopus, and MedRxiv 11/1/2019 to 3/1/2021, including studies comparing outcomes in COVID-19-related ARDS (COVID-19 group) and ARDS unrelated to COVID-19 (ARDS group). Outcomes investigated were duration of mechanical ventilation-free days, intensive care unit (ICU) length-of-stay (LOS), hospital LOS, and mortality. Random effects models were fit for each outcome measure. Effect sizes were reported as pooled median differences of medians (MDMs), mean differences (MDs), or odds ratios (ORs). EXPERT OPINION: Ten studies with 2,281 patients met inclusion criteria (COVID-19: 861 [37.7%], ARDS: 1420 [62.3%]). There were no significant differences between the COVID-19 and ARDS groups for median number of mechanical ventilator-free days (MDM: -7.0 [95% CI: -14.8; 0.7], p = 0.075), ICU LOS (MD: 3.1 [95% CI: -5.9; 12.1], p = 0.501), hospital LOS (MD: 2.5 [95% CI: -5.6; 10.7], p = 0.542), or all-cause mortality (OR: 1.25 [95% CI: 0.78; 1.99], p = 0.361). Compared to the general ARDS population, results did not suggest worse outcomes in COVID-19-related ARDS.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study.

BACKGROUND: While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE: To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS: A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS: Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION: LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.

Efficacy of convalescent plasma therapy for COVID-19: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID-19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID-19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full-text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta-analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = -0.49 days [95% CI = -3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID-19.

Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.

Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report.

Thromboembolism is a known phenomenon in patients with Coronavirus disease 2019 (COVID-19). Recent investigations have revealed that a significant proportion of those hospitalized with severe COVID-19 demonstrate clinical and laboratory markers compatible with hypercoagulability, which is differentiated from disseminated intravascular coagulation (DIC), termed COVID-associated coagulopathy. Additionally, there is increasing concern for development of acute ischemic stroke because of this hypercoagulable state. We present a patient with COVID-19 pneumonia who was managed with unfractionated heparin (UFH) infusion and developed a large ischemic infarct shortly after cessation of the infusion. In retrospect, the patient's coagulation parameters were consistent with overt DIC, although some of these parameters are easily masked by the effects of UFH. These findings emphasize the importance of anticoagulation as well as its careful discontinuation, as failure to do so may result in a significant thromboembolic event.

Etiologic Subtypes of Ischemic Stroke in SARS-CoV-2 Patients in a Cohort of New York City Hospitals.

Objective: To describe the ischemic stroke subtypes related to coronavirus disease 2019 (COVID-19) in a cohort of New York City hospitals and explore their etiopathogenesis. Background: Most neurological manifestations are non-focal, but few have reported the characteristics of ischemic strokes or investigated its pathophysiology. Methods: Data were collected prospectively April 1-April 15, 2020 from two centers in New York City to review possible ischemic stroke types seen in COVID-19-positive patients. Patient presentation, demographics, related vascular risk factors, associated laboratory markers, as well as imaging and outcomes were collected. Results: The age of patients ranged between 27 and 82 years. Approximately 81% of patients had known vascular risk factors, the commonest being hypertension (75%) followed by diabetes (50%) coronary disease or atrial fibrillation. Eight patients presented with large vessel occlusion (LVO) with median age 55 years (27-82) and all were male. Eight patients presented with non-LVO syndromes, with median age 65.5 years (59-82) and most were female (62.5%). Both groups were 50% African Americans and 37.5% South Asian. Both groups had similar D-dimer levels although other acute phase reactants/disease severity markers (Ferritin, CRP, procalcitonin) were higher in the LVO group. The LVO group also had a significantly higher mortality compared to the non-LVO group. The most common etiology was cryptogenic (6 patients) followed by small vessel occlusion (3 patients) and undetermined-unclassified (3 patients). For the remaining 4 patients, 2 were identified as cardioembolic and 2 with large artery atherosclerosis. Conclusion: COVID-19-related ischemic events can present as small vessel occlusions, branch emboli or large vessel occlusions. The most common etiology is cryptogenic. Patients with LVO syndromes tend to be younger, male and may have elevated acute inflammatory markers.