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Research—Human—Clinical Studies: Endovascular

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

Jabbour, Pascal MD*; Dmytriw, Adam A. MD, MPH, MSc; Sweid, Ahmad MD*; Piotin, Michel MD§; Bekelis, Kimon MD; Sourour, Nader MD; Raz, Eytan MD#; Linfante, Italo MD**; Dabus, Guilherme MD**; Kole, Max MD††; Martínez-Galdámez, Mario MD‡‡; Nimjee, Shahid M. MD§§; Lopes, Demetrius K. MD‖‖; Hassan, Ameer E. DO¶¶; Kan, Peter MD##,***; Ghorbani, Mohammad MD†††; Levitt, Michael R. MD‡‡‡; Escalard, Simon MD§; Missios, Symeon MD; Shapiro, Maksim MD#; Clarençon, Frédéric MD; Elhorany, Mahmoud MD; Vela-Duarte, Daniel MD**; Tahir, Rizwan A. MD††; Youssef, Patrick P. MD§§; Pandey, Aditya S. MD§§§; Starke, Robert M. MD‖‖‖; El Naamani, Kareem MD*; Abbas, Rawad MD*; Hammoud, Bassel MD¶¶¶; Mansour, Ossama Y. MD###; Galvan, Jorge MD‡‡; Billingsley, Joshua T. MD‖‖; Mortazavi, Abolghasem MD†††; Walker, Melanie MD****; Dibas, Mahmoud MD; Settecase, Fabio MD, MSc††††; Heran, Manraj K. S. MD††††; Kuhn, Anna L. MD, PhD‡‡‡‡; Puri, Ajit S. MD‡‡‡‡; Menon, Bijoy K. MD§§§§; Sivakumar, Sanjeev MD‖‖‖; Mowla, Ashkan MD¶¶¶¶; D'Amato, Salvatore MD; Zha, Alicia M. MD####; Cooke, Daniel MD*****; Goyal, Mayank MD§§§§; Wu, Hannah MD†††††,‡‡‡‡‡,§§§§§; Cohen, Jake MD†††††,‡‡‡‡‡,§§§§§; Turkel-Parrella, David MD†††††,‡‡‡‡‡,§§§§§; Xavier, Andrew MD‖‖‖‖‖,¶¶¶¶¶; Waqas, Muhammad MBBS#####; Tutino, Vincent M. PhD#####; Siddiqui, Adnan MD#####; Gupta, Gaurav MD******; Nanda, Anil MD******; Khandelwal, Priyank MD******; Tiu, Cristina MD††††††; Portela, Pere C. MD‡‡‡‡‡‡; Perez de la Ossa, Natalia MD§§§§§§; Urra, Xabier MD‖‖‖‖‖‖; de Lera, Mercedes MD¶¶¶¶¶¶; Arenillas, Juan F. MD, PhD¶¶¶¶¶¶; Ribo, Marc MD######,*******; Requena, Manuel MD######,*******; Piano, Mariangela MD†††††††; Pero, Guglielmo MD†††††††; De Sousa, Keith MD‡‡‡‡‡‡‡; Al-Mufti, Fawaz MD§§§§§§§; Hashim, Zafar MD‖‖‖‖‖‖‖; Nayak, Sanjeev MD‖‖‖‖‖‖‖; Renieri, Leonardo MD¶¶¶¶¶¶¶; Aziz-Sultan, Mohamed A. MD; Nguyen, Thanh N. MD#######; Feineigle, Patricia PhD********; Patel, Aman B. MD; Siegler, James E. MD********; Badih, Khodr BSc††††††††; Grossberg, Jonathan A. MD‡‡‡‡‡‡‡‡; Saad, Hassan MD‡‡‡‡‡‡‡‡; Gooch, M. Reid MD*; Herial, Nabeel A. MD, MPH*; Rosenwasser, Robert H. MD*; Tjoumakaris, Stavropoula MD*; Tiwari, Ambooj MD, MPH†††††,‡‡‡‡‡,§§§§§

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doi: 10.1227/neu.0000000000001902
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Abstract

One of the peculiar features of coronavirus disease (COVID-19) is the increased incidence of thrombotic events in multiple organ systems due to multiple factors including the presence of the angiotensin-converting enzyme (ACE)-2 receptor on the surface of the vascular endothelium and the hypercoagulable state because of immune dysregulation.1-26 Great efforts have been invested in understanding the disease better and elucidating its manifestation and pathophysiology.1-26 We have learned a lot about the effect of COVID-19 on the central nervous system, particularly acute ischemic stroke (AIS). There remain limited data on the safety and outcomes of acute revascularization of large vessel occlusion (LVO) in patients with COVID-19. In this international multicenter series, we describe the safety and efficacy of acute revascularization of LVO in the setting of patients with COVID-19 compared with non-COVID-19 patients with LVO. We also examine the characteristics of patients with COVID-19 and identify predictors of complete revascularization and unfavorable outcomes. To the best of our knowledge, this is the largest multicenter study of patients with COVID-19 with LVO receiving mechanical thrombectomy (MT).

METHODS

We conducted an international multicenter retrospective study of patients with COVID-19 with AIS and LVO between February 25 and December 30, 2020 across 48 thrombectomy comprehensive stroke centers, predominantly from North America and Europe. The institutional review board of participating institutions reviewed and approved the study, and patient consent was waived. The remaining methods section is attached as Supplemental Digital Content, https://links.lww.com/NEU/C851.

Data Sharing Statement

The relevant anonymized patient-level data are available on reasonable request from the authors.

Ethical Approval

All procedures performed in the studies involving human participants were per the institutional review board ethical standards and national research committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

The study protocol was reviewed and approved by the University institutional review board. Following our institutional guidelines, all protected health information was removed, and individual patient consent was not required in the analysis of case series.

RESULTS

The total cohort composite was 575 patients, with 194 patients having concomitant COVID-19 and LVO and 381 patients having only LVO as a control group from 48 centers (Figure). The data are presented in Table 1.

F1
FIGURE.:
A, Bar graph showing a comparative analysis between COVID-19 group and the control group for baseline characteristics. B, Bar graph showing a comparative analysis between COVID-19 group and the control group for outcomes. COVID-19, coronavirus disease; TICI, thrombolysis in cerebral infarction.
TABLE 1. - Baseline Characteristics and Technical and Procedural Outcomes in Patients With Acute Ischemic Stroke in the Setting of COVID-19
Variable Cohort—patients with COVID-19 Non-COVID-19 patients P-value
Mean (SD, range)
N (%), mean ± SD; 95% CI; Median (range)
(n = 194)
Mean
N (%), mean ± SD; 95% CI; median (range)
(n = 381)
Baseline characteristics
 Age (y) 62.5 + 15.3; 60.0-64.8 71.2 + 15.9; 69.5-72.8 <.001
 Age <50 y 30 (15.5) 41 (10.8) .015
 Sex (female) 84 (43.3) 305 (80.1) <.001
 Prestroke mRS .002
  0-2 153 (90.0) 367 (96.3)
  3-5 17 (10.0) 14 (3.7)
Comorbidities
 Hypertension 119 (61.3) 266 (69.8) .098
 Chronic heart disease 35 (18.0) 131 (34.4) <.001
 Chronic lung disease 44 (22.7) 75 (19.7) .402
 Chronic kidney disease 19 (9.8) 6 (6.9) .446
 Chronic liver disease 10 (5.2) 10 (2.6) .148
 Diabetes mellitus type II 59 (30.4) 86 (22.6) .050
 Atrial fibrillation 47 (21.6) 148 (38.8) <.001
 New onset atrial fibrillation 13 (6.7)
 Absence of cerebrovascular risk factors 49 (25.3) 54 (14.2) .001
COVID-19 characteristics
 Severity per WHO classification
  Moderate 139 (75.5)
  Severe 29 (15.8)
  Critical 16 (8.7)
 Stroke as initial presentation of COVID-19 62 (32)
 Duration between COVID-19 diagnosis and stroke onset (d) 9.1 + 11.6; 7.3-10.8
Stroke characteristics
 ASPECTS 8; 8.0-9.0 9; 9.0-10.0 <.001
 No. of involved LVO 1.5 + 0.8; 1.3-1.6 1.2 + 0.5; 1.2-1.3 .004
 No. of involved LVO .006
  One vessel 66 (67.3) 300 (79.2)
  More than 1 vessel 32 (32.7) 79 (20.8)
 Stroke location (anterior circulation) 89 (90.8) 341 (90) .597
 Stroke onset to hospital door (h) 4.5 + 5.1; 3.6-5.3 7.1 + 5.8; 6.3-7.8 <.001
 Door to arterial access (h) 1.6 + 1.9; 1.3-1.9 1.2 + 1.3; 1.0-1.3 .005
 NIHSS at admission 17.5; 15.0-19.0 14.0; 13.0-15.0 <.001
Stroke treatment
 Tissue plasminogen activator 62 (32) 130 (34.1) .907
 Airway control (intubation) 58 (29.9) 72 (18.9) <.001
 No. of thrombectomy passes 1.9 + 1.4; 1.7-2.1 1.9 + 1.2; 1.8-2.0 .859
 Stenting 13 (6.7) 53 (13.9) .086
  Intracranial 7 (3.6) 39 (10.2) .005
  Extracranial 6 (3.1) 14 (3.7) .813
 Procedure duration (min) 62.2 + 47.3; 55.4-68.9 51.9 + 31.9; 48.7-55.2 .002
 mTICI score
  2B-3 158 (81.4) 326 (85.6) .284
  3 74 (38.1) 252 (66.1) <.001
Outcomes
 Complications .002
  Asymptomatic 9 (4.6) 54 (14.2)
  Symptomatic 11 (5.7) 22 (5.8)
 sICH 8 (4.1) 20 (5.3) .683
 NIHSS 24 h after MT 10.0; 7.0-12.0 11.0; 9.0-13.0 .710
 Length of hospital stay (d) 17.8 + 19.3; 14.8-20.8 8.4 + 8.6; 7.5-9.2 <.001
 mRS at discharge (3-6) 150 (77.3) 132 (34.6) .004
 mRS at 90 d (0-3) 20 (10.3) 144 (37.8) <.001
 Mortality (in hospital) 75 (38.7) 70 (18.4) <.001
ASPECTS, Alberta Stroke Program Early Computed Tomography Score; COVID-19, coronavirus disease; LVO, large vessel occlusion; mRS, modified Ranklin Scale; MT, mechanical thrombectomy; mTICI, modified thrombolysis in cerebral infarction; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; sICH, symptomatic intracerebral hemorrhage; WHO, World Health Organization.
Bold values indicate statistically significant value P ≤ .05.

There was a significant difference in the mean age of the patients with relatively younger patients in the COVID-19 cohort compared with the non–COVID-19 cohort (62.5 + 15.3 years vs 71.2 + 15.9 years; P < .001). In addition, there was a significantly higher proportion of patients less than or equal to 50 years (30, 18.5% vs 41, 10.8%; P = .015). There was a lower proportion of female patients in the COVID-19 group (84, 43.3% vs 305, 80.1%; <0.001). The functional status at stroke onset was significantly different, with a lower proportion of functional independence in the COVID-19 group (modified Ranklin Scale [mRS] 0-2: 153, 90.0% vs 367, 96.3%; 0.002).

Comorbidities

Chronic heart disease (35, 18.0% vs 131, 34.4% vs; P < .001) and atrial fibrillation (47, 24.2% vs 148, 39.6%; P < .001) were lower while diabetes mellitus type II was significantly higher (59, 30.4% vs 86, 22.9%; P = .050) in the COVID-19 group. Hypertension, chronic lung disease, and chronic liver disease frequency were similar between both groups. Moreover, lack of traditional cerebrovascular risk factors was observed at a higher proportion in the COVID-19 group (49, 25.3% vs 54, 14.2%; P = .001).

COVID-19 Characteristics

The severity of COVID-19 on stroke onset was moderate in 75.5% of cases (139), severe in 15.8% (29), and critical in 8.7% (16). The mean duration between COVID-19 symptoms and stroke onset was 9.1 + 11.6 days, and 34.1% cases (62) of the COVID-19 group had a stroke as the initial manifestation of the COVID-19 disease.

Stroke Characteristics

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) at admission was lower in the COVID-19 group (8 vs 9; P ≤ .001) while the National Institutes of Health Stroke Scale (NIHSS) score at admission was higher in the COVID-19 group (17.5; vs 14; P ≤ .001) (Figure A).

The mean number of involved vessels (1.5 + 0.8; vs 1.2 + 0.5; P = .004) and involvement of more than 1 vessel (32, 32.6% vs 79, 20.8%; P = .006) were higher in the COVID-19 group. Regarding location of the occlusion (anterior vs posterior circulation), there was no significant difference between both groups (anterior circulation: 89, 91.8% vs 341, 89.9%; P = .597).

The duration between stroke onset to hospital admission (in hours) was lower in the COVID-19 group (4.5 + 5.1 hours; vs 7.1 + 5.8 hours; P ≤ .001) while door to arterial access was higher in the COVID-19 group (1.6 + 1.9 hours vs 1.2 + 1.3 hours; P = .005).

Stroke Treatment

For stroke treatment, tissue plasminogen activator (tPA) administration was similar between both groups (62, 34.3% vs 130, 34.8%; P = .907). A higher proportion of MT procedures were performed under general anesthesia in the COVID-19 group (58, 31.5% vs 72, 19.1%; P ≤ 0.001).

The number of thrombectomy attempts was similar between both groups (1.9 + 1.4 vs 1.9 + 1.2; P = .859). Extracranial stenting was similar, whereas intracranial stenting was higher in the control group (7, 3.6% vs 39, 10.2%; P = .005).

The procedure duration to complete the MT procedure was prolonged by 11 mins in the COVID-19 group (62.2 + 47.3 vs 51.9 + 31.9; P = .002). Favorable revascularization (modified thrombolysis in cerebral infarction [mTICI] 2b-3) was similar between both groups (158, 83.6% vs 326, 86.9%; P = .284). However, complete revascularization (mTICI 3) was observed at a lower proportion in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001).

Complications, Functional Outcomes, and Mortality

There was no significant difference in symptomatic intracerebral hemorrhage (sICH) (8, 4.1% vs 20, 5.3%; P = .683) nor was there a significant difference in NIHSS score at 24 hours post-thrombectomy (10 vs 11; P = .710) between both groups.

The length of hospital stay was longer in the COVID-19 group by 9.4 days (17.8 + 19.3 days vs 8.4 + 8.6 days; P ≤ .001). Poor functional outcome at discharge (150, 79.8% vs 132, 66.7%; P = .004) was observed more frequently in the COVID-19 group, and favorable functional outcome at 90 days (20, 18.9% vs 144, 47.4%; P < .001) was observed less frequently in the COVID-19 group.

Mortality rate was higher by more than 2-fold in the COVID-19 group (75, 40.3% vs 70, 18.5%; P < .001) (Figure B).

Predictors of Revascularization mTICI 3

Univariate and multivariate analyses are presented in Table 2. Factors associated with good revascularization outcomes were female sex (odds ratio [OR]: 3.0, 95% CI: 1.7-5.4; P < .001), COVID-19 positivity (OR: 0.2, 95% CI: 0.3-0.5; P < .001), chronic heart disease (OR: 2.3, 95% CI: 1.4-4.1; P = .003), ASPECTS (OR: 1.2, 95% CI: 1.0-1.3; P = .001), number of vessels involved (OR: 0.7, 95% CI: 0.5-0.9; P = .017), and NIHSS score at admission (OR: 0.9, 95% CI: 0.9-1.0; P = .05) before propensity score analysis. After matching, female sex (OR: 1.7, 95% CI: 1.0-2.8; P = .02), COVID-19 positivity (OR: 0.3, 95% CI: 0.2-0.6; P < .001), ASPECTS (OR: 1.2, 95% CI: 1.1-1.4; P = .005), and NIHSS at admission (OR: 1.0, 95% CI: 0.9-1.0; P = .03) remained statistically significant in addition to chronic kidney diseases (OR: 2.7, 95% CI: 1.1-6.5; P = .026). Moreover, multivariate analysis performed after matching showed that the independent predictors of good revascularization are female sex (OR: 2.2, 95% CI: 1.2-3.9; P = .007), COVID positivity (OR: 0.4, 95% CI: 0.2-0.8; P = .004), chronic kidney diseases (OR: 3.0, 95% CI: 1.1-8.0; P = .034), and ASPECTS (OR: 1.2, 95% CI: 1.0-1.4; P = .014) (Table 2).

TABLE 2. - Univariate and Multivariable Analyses for Variables Associated With Revascularization mTICI 3 Before and After Propensity Score Analysis
Variable Univariate Univariate after propensity score analysis Multivariate
OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value
Sex (female) 3.0 1.7-5.4 <.001 1.7 1.0-2.8 .02 2.2 1.2-3.9 .007
Decreasing age 1.0 0.9-1.0 .195
COVID-19 0.3 0.2-0.5 <.001 0.3 0.2-0.6 <.001 0.4 0.2-0.8 .004
Chronic heart disease 2.3 1.4-4.1 .003
Chronic kidney disease 1.5 0.6-3.6 .348 2.7 1.1-6.5 .026 3.0 1.1-8.0 .034
ASPECTS 1.2 1.0-1.3 .001 1.2 1.1-1.4 .005 1.2 1.0-1.4 .014
Atrial fibrillation 1.4 0.9-2.0 .054
No. of vessels involved 0.7 0.5-0.9 .017
LVO location (anterior circulation) 0.9 0.5-1.7 .749
Tissue plasminogen activator 1.0 0.7-1.4 .060
NIHSS at admission 0.9 0.9-1.0 .050 1.0 0.9-1.0 .03
Onset to door 1.0 0.9-1.0 .070
Onset to arterial access 1.0 0.9-1.0 .229
ASPECTS, Alberta Stroke Program Early Computed Tomography Score; COVID-19, coronavirus disease; LVO, large vessel occlusion; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.
Bold values indicate statistically significant value P ≤ .05.

Predictors of Unfavorable Outcomes (modified Ranklin Scale 3-6)

Univariate and multivariate analyses are presented in Table 3. Factors associated with unfavorable outcomes were COVID-19 positivity (OR: 1.9, 95% CI: 1.2-3.1; P = .004), ASPECTS (OR: 0.8, 95% CI: 0.7-0.9; P = .002), NIHSS score at admission (OR: 1.1, 95% CI: 1.1-1.1; P < .001), onset to arterial access time (OR: 0.9, 95% CI: 0.9-1.0; P = .031), and thrombolysis in cerebral infarction (TICI) 2b-3 revascularization (OR: 0.4, 95% CI: 0.2-0.8; P = .009) before propensity score analysis. After matching, COVID-19 positivity (OR: 2.5, 95% CI: 1.3-5.1; P = .008), ASPECTS (OR: 0.7, 95% CI: 0.6-0.9; P = .005), NIHSS at admission (OR: 1.1, 95% CI: 1.1-1.2; P < .001), onset to arterial access time (OR: 1.0, 95% CI: 1.0-1.0; P = .035), and TICI 2b-3 revascularization (OR: 0.6, 95% CI: 0.4-0.9; P = .015) remained statistically significant in addition to increasing age (OR: 1.0, 95% CI: 1.0-1.0; P = .038), baseline functional status (OR: 2.3, 95% CI: 1.1-4.9; P = .026), diabetes mellitus type 2 (OR: 2.5, 95% CI: 1.2-5.5; P = .019), and onset to door time (OR: 1.0, 95% CI: 1.0-1.0; P = .045). Moreover, multivariate analysis performed after matching showed that the independent predictors of unfavorable outcomes are COVID positivity (OR: 2.6, 95% CI: 1.1-5.8; P = .025), increasing age (OR: 1.0, 95% CI: 1.0-1.1; P = .016), NIHSS at admission (OR: 1.1, 95% CI: 1.0-1.1; P = .005), and TICI 2b-3 (OR: 0.6, 95% CI: 0.4-1.0; P = .042) (Table 3).

TABLE 3. - Univariate and Multivariate Analyses for Variables Associated With Unfavorable Outcomes (mRS 3-6) Before and After Propensity Score Analysis
Variable Univariate Univariate after propensity score analysis Multivariate after propensity score analysis
OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value
Sex (female) 0.9 0.6-1.5 .736
Increasing age 1.0 1.0-1.0 .012 1.0 1.0-1.0 .038 1.0 1.0-1.1 .016
COVID-19 1.9 1.2-3.1 .004 2.5 1.3-5.1 .008 2.6 1.1-5.8 .025
NIHSS at admission 1.1 1.1-1.1 <.001 1.1 1.1-1.2 <.001 1.1 1.0-1.1 .005
Baseline functional status 1.6 1.1-2.4 .011 2.3 1.1-4.9 .026
Chronic heart disease 0.8 0.5-1.5 .619
Chronic lung disease 0.9 0.5-1.6 .821
Chronic kidney disease 1.5 0.6-3.5 .348
Chronic liver disease 2.6 0.6-11.7 .205
Hypertension 1.4 0.8-2.2 .186
Diabetes mellitus type II 1.4 0.8-2.4 .180 2.5 1.2-5.5 .019
Atrial fibrillation 0.8 0.5-1.3 .359
ASPECTS 0.8 0.7-0.9 .002 0.7 0.6-0.9 .005
No. of vessels involved 1.1 0.7-1.7 .578
LVO location (anterior circulation) 1.2 0.5-2.8 .682
Tissue plasminogen activator 0.8 0.5-1.2 .267
Onset to door 1.0 0.9-1.0 .280 1.0 1.0-1.0 .045
Onset to arterial access 0.9 0.9-1.0 .031 1.0 1.0-1.0 .035
General ET intubation 0.8 0.5-1.4 .448
Stenting 0.9 0.5-1.9 .908
Procedure duration 1.0 0.9-1.0 .053
TICI 2B-3 0.4 0.2-0.8 .009 0.6 0.4-0.9 .015 0.6 0.4-1.0 .042
ASPECTS, Alberta Stroke Program Early Computed Tomography Score; COVID-19, coronavirus disease; ET, endotracheal; LVO, large vessel occlusion; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; TICI, thrombolysis in cerebral infarction.
Bold values indicate statistically significant value P < .05

DISCUSSION

Key Points

This multicenter, comparative, retrospective study demonstrates that patients with COVID-19 with concomitant LVO have a grim prognosis, with a mortality rate reaching 40%. Moreover, COVID-19 increases the likelihood by 2.5-fold for unfavorable outcomes; in addition, it decreases the likelihood to achieve complete revascularization by 60%. Our findings further corroborate past series reporting poor outcomes in patients developing AIS in the setting of COVID-19.27-34 Moreover, previous efforts have demonstrated that COVID-19 was an independent predictor for LVO, poor outcomes, and increased mortality.33,35-37 The degree of recovery after an AIS is dependent on a complex set of factors that can be categorized into patient's characteristics (baseline functional status and comorbidities), stroke characteristics (severity and time lag to treat), concomitant pathologies, and complications. Ischemic brain tissue is highly vulnerable and requires optimal conditions for a potential recovery. The milieu produced by COVID-19 is the complete opposite of an optimal condition. COVID-19 induces vasculopathy, hypercoagulable state, myocarditis, arrhythmias, thrombotic microangiopathy, coagulopathy and thrombocytopenia, tropism to endothelial cells through ACE-2 receptor, and inhibition of angiotensin (1-7) production.1-26 It has been proposed that downregulation of ACE-2 leading to both arteriopathy and thrombosis may play a central role in the development of stroke during COVID-19.38,39

Apart from establishing that COVID-19 is an independent predictor of poor functional outcomes and reduces the likelihood of achieving complete revascularization, it is imperative to define the characteristics of such subjects developing LVO in the setting of COVID-19. Such an effort will enhance our understanding of the disease and may aid in improving prognostication.

Beginning with the patients' characteristics, the mean age of the COVID-19 group was significantly lower than the control group by 8.7 years. Numerous publications spanning across heterogeneous geographic areas reported similar findings.30,33,35,40-45 Similarly, the difference remains significant, almost by 10 years, compared with the Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) trial (71.1 years) and the study by Al Kasab et al (72 years).46,47 Moreover, the proportion of patients 50 years and younger was 2-fold higher compared with the control group. The reported incidence of LVO in young patients in non–COVID-19 settings ranges between 3.3% and 5%, whereas in the COVID-19 setting, it ranges between 16% and 19% (current study).48 The latter figures are almost 4-fold higher than the general population. Similar to previously reported data,31,33 sex preponderance was observed in this study with more men (by 2.8-fold) in the COVID-19 group. For comorbidities, patients with COVID-19 were more likely to lack cerebrovascular risk factors. Such findings have been previously reported by a group from New York and other institutions.40,43

Interpretation and Generalizability

Interestingly, only 75% of the patients who developed LVO had moderate COVID-19 severity according to the World Health Organization classification.49 It is paramount to emphasize that immune dysregulation resulting in a cytokine storm is a factor that has a pathophysiological significance in the development of stroke in COVID-19 disease.50-52 In addition, the duration between stroke onset and COVID-19 symptoms was 9 days; this includes patients who had a stroke as the initial manifestation of COVID-19, which constituted 34.1%.53 The Global COVID-19 Stroke Registry reported a median latency period between symptom onset and stroke of 7 days (IQR: 2-15).33 Historical data have consistently demonstrated an increased incidence of ischemic stroke during pandemics, often occurring within several days of the infection.54,55 The severity of stroke was more pronounced in the COVID-19 group based on the ASPECTS, NIHSS score at presentation, and the number of involved vessels. Although the NIHSS score was not significantly different between both groups 24 hours post-thrombectomy, this is because patients who were COVID-negative and presented with strokes were significantly older and had several comorbidities. On the other hand, patients with COVID-induced strokes were significantly younger with less comorbidities. Thus, after thrombectomy, NIHSS was affected by the severity of the stroke in patients with COVID and by the comorbidities in patients who were COVID-negative. The get with the guidelines (GWTG)-Stroke analysis reported similar findings after reviewing 1143 patients diagnosed with COVID-19: a higher NIHSS score at presentation and more LVOs.35 In our study, stroke care during the pandemic was not compromised as demonstrated by the rate of tPA administration, which was similar between both groups, whereas another study reported a relative global decline in IV thrombolysis during the first wave of the COVID-19 pandemic.56 The interval from symptom onset to hospital presentation was shorter in the COVID-19 group. The only prolonged time metric in the COVID-19 group was time to arterial access, by 24 minutes, which can be attributed to the workflow during the pandemic. Similar conclusions regarding stroke care during the pandemic were reported by a group from Switzerland, Spain, and the GWTG-Stroke consortium. They did not find any significant difference in the rate of IV-tPA or MT procedures between patients with COVID-19 and non–COVID-19 patients. Contrary to our finding, the Switzerland and Spain groups did not experience a delay in admission to arterial access44,45 while the GWTG-Stroke consortium reported a delay in admission to arterial access by a difference of 24 minutes, similar to our cohort.35

The complexity of the MT procedure is influenced by several factors, including clot burden and consistency. Complexity can be assessed by direct methods, such as filling a questionnaire after each case or simply providing a score, or by indirect methods based on the duration of the procedure, number of vessels involved, number of passes, achieving either complete or favorable revascularization, or technical complications. The COVID-19 group had a higher number of involved vessels, a similar number of passes, longer procedure duration by 11 minutes, and a lower proportion of complete revascularization. Patients with COVID-19 had a lower likelihood of achieving mTICI 3 by 60%, whereas mTICI 2b/3 reperfusion was similar between the 2 groups. Such outcomes, particularly sICH and favorable revascularization outcomes, have been reported in previous COVID-19 series43-45 and are in line with historic MT data.57

Finally, the unfavorable functional outcomes at discharge and follow-up were observed at a significantly lower proportion in the COVID-19 group. Moreover, mortality was more frequent as of 40%, and COVID-19 was associated with 2.5-fold poor outcomes. The mortality rate, when compared with prior published data, is significantly higher in this study. Similarly, the GWTG-Stroke consortium and the Global COVID-19 Stroke Registry demonstrated that COVID-19 was an independent predictor of poor outcomes and death.33,35 Despite a more extended hospital stay in the COVID-19 group by ∼10 days, the rate of sICH and NIHSS score at 24 hours post-thrombectomy were not significantly different. Poor outcomes have been reported in other pathologies occurring in the setting of COVID-19.

Limitations

Our article has strength and limitations. The main limitation of this study is its' retrospective design and the absence of randomization. In addition, there were significant differences in baseline characteristics between both cohorts such as age, sex, comorbidities, and baseline functional status. The period of treatment was also different between both cohorts. Finally, our study lacked weighted data analysis to account for volume contribution by each center. The strength of the article is the relatively large sample size, the international experience, and the comparative analysis performed.

CONCLUSION

COVID-19 is an independent predictor of poor outcomes and incomplete revascularization in patients with stroke due to a LVO. Patients are younger, tend to have less cerebrovascular risk factors, and suffer from higher morbidity/mortality rates.

Funding

This study did not receive any funding or financial support. Dr Starke's research is supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, and the National Institute of Health (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the authors' responsibility and do not necessarily represent the official views of the NIH.

Disclosures

Dr Jabbour is a consultant for Medtronic, MicroVention Balt, and Cerus Endovascular. Dr Tjoumakaris is a consultant for Medtronic and MicroVentions. Dr Gooch is a consultant for Stryker. Dr Starke has consulting and teaching agreements with Penumbra, Abbott, Medtronic, InNeuroCo, and Cerenovus. Dr Nguyen reports research support from Medtronic and the Society of Vascular and Interventional Neurology. Dr Siegler reports consulting fees from Ceribell: speaker's bureau for AstraZeneca (both unrelated to the present work). Drs Dabus and Patel have a relationship with Microvention and previously had relationships with Medtronic and Penumbra. Dr Hassan receives consultant/speaker fees from Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, and Galaxy Therapeutics. Dr Walker has a financial relationship with Johnson & Johnson. Dr Settecase has financial relationships with Stryker and Microvention. Dr Goyal has financial relationships with Medtronic, Cerenovus, and NoNO Inc. Dr Siddiqui has financial relationships with Cerenovus, Medtronic, and Microvention. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

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Supplemental Digital Content

Supplemental Digital Content. Continuation of methods section.

Keywords:

COVID-19; SARS-CoV-2; Central nervous system; Cerebrovascular disease; Hypercoagulable

Supplemental Digital Content

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