key: cord-1020488-rwqxtspj
authors: John, Seby; Hussain, Syed Irteza; Piechowski-Jozwiak, Bartlomiej; Dibu, Jamil; Kesav, Praveen; Bayrlee, Ahmad; Elkambergy, Hussam; John, Terrence Lee St; Roser, Florian; Mifsud, Victoria Ann
title: Clinical characteristics and admission patterns of stroke patients during the COVID 19 pandemic: A single center retrospective, observational study from the Abu Dhabi, United Arab Emirates
date: 2020-09-11
journal: Clin Neurol Neurosurg
DOI: 10.1016/j.clineuro.2020.106227
sha: 155991741fd38e43e3e3a39edf38a11fad313a7d
doc_id: 1020488
cord_uid: rwqxtspj

Objective: To compare ischemic and hemorrhagic stroke patients with COVID-19 to non-COVID-19 controls, and to describe changes in stroke admission patterns during the pandemic. Methods:This is a single center, retrospective, observational study. All consecutive patients admitted with primary diagnosis of ischemic/ hemorrhagic stroke between March1st -May10th 2020 were included and compared with the same time period in 2019. Results: There was a 41.9% increase in stroke admissions in 2020 (148 vs 210,P = .001). When comparing all ischemic strokes, higher rate of large vessel occlusion (LVO) (18.3% vs 33.8%,P = .008) and significant delay in initiation of mechanical thrombectomy after hospital arrival (67.75 vs 104.30 minutes,P = .001) was observed in 2020. When comparing all hemorrhagic strokes, there were no differences between the two years. Among 591 COVID-19 admissions, 31 (5.24%) patients with stroke including 19 with ischemic (3.21%) and 12 with hemorrhagic stroke (2.03%) were identified. Patients with COVID-19 and ischemic stroke were significantly younger (58.74 vs 48.11 years,P = .002), predominantly male (68.18% vs 94.74%,P = .016), had lesser vascular risk factors, had more severe clinical presentation (NIHSS 7.01 vs 17.05,P < .001), and higher rate of LVO (23.6% vs. 63.1%,P = .006). There was no difference in the rate of endovascular thrombectomy, but time to groin puncture was significantly longer in COVID-19 patients (83.41 vs 129.50 minutes,P = .003). For hemorrhagic stroke, COVID-19 patients did not differ from non-COVID-19 patients. Conclusions: Stroke continues to occur during this pandemic and stroke pathways have been affected by the pandemic. Stroke occurs in approximately 5% of patients with COVID-19. COVID-19 associated ischemic stroke occurs in predominantly male patients who are younger, with fewer vascular risk factors, can be more severe, and have higher rates of LVO. Despite an increase in LVO during the pandemic, treatment with mechanical thrombectomy has not increased. COVID-19 associated hemorrhagic stroke does not differ from non-COVID-19 hemorrhagic stroke patients.

Coronavirus Disease 2019 (COVID- 19) is an ongoing pandemic caused by infection with the severe acute respiratory syndrome corona virus-2 (SARS CoV-2) 1,2 . While the infection primarily causes respiratory symptoms, there are now multiple reports of COVID-19 affecting the central nervous system (CNS) ranging from meningitis/encephalitis to stroke [3] [4] [5] . In a single center study of 214 hospitalized patients with COVID -19 from Wuhan, China where the infection first occurred, up to 36.4% of patients had neurological manifestation including acute cerebrovascular disease with severe and non-severe infection in 5.7% and 0.8% of these patients J o u r n a l P r e -p r o o f respectively 3 . While the reasons for ischemic stroke in COVID-19 are unclear, hypotheses of an inflammatory cytokine storm triggered hypercoagulable state or endothelial damage have been postulated 6, 7 . However, as it stands, the mechanisms, phenotype and optimal management of ischemic stroke associated with COVID-19 still remain uncertain. The association of COVID-19 on hemorrhagic cerebrovascular disease is also unclear.

The World Health Organization declared COVID-19 as a s a pandemic on 11 th March 2020. As of June 1 st, at the time of manuscript writing, a total of 6,164,784 patients have been diagnosed globally, with 371,995 deaths 8 . The first case of COVID-19 in the United Arab Emirates (UAE) was diagnosed on January 29 th 2020. As of June 1st, there are a total of 34,557 diagnosed patients, with 264 deaths in the UAE 8 . Multiple published and anecdotal reports suggest that during the pandemic, there has been a drastic fall in the number of stroke patients being evaluated in the emergency room or being admitted to the hospital across continents 9, 10 .

There is an urgent need to understand stroke patterns during this pandemic since stroke remains an emergency, and untreated stroke will likely result in poorer clinical outcomes with concurrent significant resource burden on patients, hospitals, health care systems and populations.

Furthermore, we need to identify associations, predictors of severity, morbidly and mortality in patients with stroke and COVID-19 to better guide future management of these patients.

This is a retrospective, observational study of the effect of the COVID-19 pandemic on all admitted patients with primary diagnosis of acute ischemic or hemorrhagic stroke, all acute stroke alerts from the emergency room or for admitted inpatients, and all neurological consults Institutional Review Board approval was obtained prior to pursuing this study.

For baseline data, mean and standard deviations were calculated for continuous variables, while categorical variables were expressed as counts and percentages. P-values associated with group comparisons on continuous variables, categorical variables, and count variables were calculated using independent-sampled t-tests, Fisher's Exact test, and χ2 test respectively. All statistical analyses were performed using Microsoft R Open 3.5.1 software. The significance threshold was set at a 2-sided P value less than .05. Characteristics of all hemorrhagic stroke patients from 2019 compared to 2020 are detailed in Table 2 . Compared to 2019, there was a significant increase in patients with ICH in 2020 (24 vs 12, P=.045). SAH and other intracranial bleeds remained unchanged. There were no differences in the age or gender. Mean age in both years was approximately 49 (55.8% of patients overall were < 50 years of age). Cardiovascular risk factors were balanced. ICH score, Hunt-Hess score, modified Fischer Grade, and etiology of bleeds were similar. Surgical treatment including placement of an external ventricular drain, endovascular embolization and microsurgical clipping/resection or hematoma evacuation occurred at similar rates. There was no difference in in-hospital mortality or discharge/30-day MRS. Eight patients (19%) remained admitted in 2020 at last review of hospital charts. Discharge disposition was significantly different between the two years, but this was driven mainly by more patients in 2019 being repatriated to their home country which was limited in 2020 by air travel restriction.

Our hospital admitted its first COVID-19 patient on 11 th February 2020. Subsequently, the hospital admitted 2, 59, 392 and 239 COVID-19 patients in the months of February, March, April and May respectively. In the 10-week study period, 591 patients with COVID-19 were admitted to the hospital. Of these, 31 (5.24%) patients with stroke including 19 with ischemic (3.21%) and 12 with hemorrhagic stroke (2.03%) were identified. Characteristics of all stroke patients with COVID-19 are detailed in Table 3 . Patients were overwhelmingly male (90. Grade, and etiology of bleeds were similar. Surgical treatment occurred at similar rates. There was no difference in in-hospital mortality. Among the discharged patients, there was no difference in the discharge mars or discharge disposition.

This is the largest retrospective study from the Middle East that highlights the impact of the COVID-19 pandemic on patients hospitalized at our center with both ischemic stroke and hemorrhagic stroke. CCAD has played a unique role during this pandemic in that not only did it serve as a COVID-19 center, but it continued to serve as the center of excellence for stroke care within the emirate of Abu Dhabi and therefore has continued to receive a large proportion of stroke patients. During the study period there was an increase in stroke alerts and admissions for both ischemic and hemorrhagic stroke when compared to 2019. This could be explained by other centers no longer taking care of such patients during the current pandemic and by a possible alteration in referral patterns. There was also a dramatic increase in presentation of ischemic strokes by EMS which may be due to a variety of factors including severity of disease, a shift in EMS referral patterns but also the effects of curfew hours and prohibition of self-travel. These and direct ambulance transfers (29% less) 10 . According to the most recent European Stroke Organization press release there was an 80% drop in stroke service provision in 426 stroke services surveyed, as well as a decrease in hospital attendance of stroke patients 15 .While the increase in stroke patient volumes cannot be generalized to imply an increase in incidence of stroke during the pandemic, it does highlight the importance of having capacity and access for stroke patients in healthcare systems, as the data from this review suggests that strokes continued to occur in this part of the world during the pandemic.

With regards to our institutional stroke pathway workflow, there was no significant increase in door to needle times for intravenous thrombolysis for ischemic stroke during the pandemic.

However, a significant delay in door to groin times for mechanical thrombectomy was observed. which could manifest as more ischemic strokes related to endothelial injury and hypercoagulable state. In addition, our cohort of COVID-19 ischemic strokes suffered more severe strokes with higher NIHSS and had significantly higher rate of LVOs. This has been observed by other series J o u r n a l P r e -p r o o f across the globe which suggests an association between a COVID-19 mediated hypercoagulable state and thromboembolism [25] [26] [27] [28] . In addition to a sepsis induced coagulopathy that can be seen with COVID 19 there is evidence that the SARS-CoV-2 virus binds to the Angiotensin converting enzyme 2 (ACE2) receptor present on brain and endothelial smooth cells that consequently can increase inflammation, clotting and vasoconstriction that could potentially lead to ischemic stroke 29 . One recent case series has also highlighted three COVID 19 cases of multiple cerebral and limb infarctions and elevated antiphospholipid antibodies which have an association with both arterial and venous thrombotic events 30 . Our current review did not include any data on these biomarkers. Further studies looking at inflammatory hypercoagulable markers along with the ACE2 pathway will need to be done to establish the pathophysiology of COVID-19 in ischemic stroke.

A striking and simultaneously concerning finding in our study is that though the LVO rate in our COVID-19 ischemic stroke cohort was substantially higher, the rate of endovascular thrombectomy did not increase. This could be explained by overall severity of systemic illness and advanced stages of ischemia at the time of presentation that may have prevented patients from being eligible for treatment with endovascular thrombectomy.

Our data has limited longitudinal follow up as we are still in the midst of the crisis. However preliminarily data suggests that COVID-19 patients with ischemic stroke tend to have poorer outcomes which can be as a consequence of the severity of the stroke but also the presence of severe multisystemic disease related to the infection itself. 

Our study is limited by the fact that it is a retrospective observational study with a small sample at a single center leading to inherent selection bias. Both ischemic and hemorrhagic stroke patients admitted during the two time periods were well balanced as far as baseline demographics and risk factors are concerned, allowing for a valid comparison of patients.

However, stroke patients with or without COVID-19 could have been admitted to other centers J o u r n a l P r e -p r o o f during the study period. As we are still in the midst of the pandemic, longitudinal outcome data is limited.

Our initial experience has highlighted some important trends. Firstly, stroke continues to occur during this pandemic and health systems need to have capacity to deal with stroke. Secondly COVID-19 associated ischemic stroke occurs in predominantly male patients who are younger, with fewer vascular risk factors, and can be more severe, with higher rates of LVO. Thirdly despite an increase in LVO during the pandemic treatment with mechanical thrombectomy has not increased which will likely translate to worse outcomes. Fourthly COVID-19 associated hemorrhagic stroke does not differ from non COVID-19 hemorrhagic stroke patients. Finally stroke pathway times have and will be impacted by the pandemic and it is vital that stroke centers continue to analyze their own data to reduce time to treatments while also balancing safety and personal protection of the caregivers involved. To assess the full impact of the pandemic on stroke care a post pandemic multicenter retrospective review will aid in drawing more meaningful conclusions.

All authors have reviewed the manuscript thoroughly and consent to its submission to Clinical Neurology and Neurosurgery. There are no conflicts of interests for any of the authors. We also confirm that this manuscript is submitted solely to Clinical Neurology and Neurosurgery and is not under consideration with any other journal. J o u r n a l P r e -p r o o f COPD-Chronic obstructive pulmonary disease, ILD-Interstitial lung disease, CT-Computed tomography .593

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