Impact of Vaccination Status on Outcome of Patients With COVID‐19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy

Background Data on impact of COVID‐19 vaccination and outcomes of patients with COVID‐19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. Methods and Results This was a retrospective analysis of patients with COVID‐19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID‐19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID‐19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007–1.417]; P=0.041). Conclusions Our study demonstrated no impact of COVID‐19 vaccination on angiographic or clinical outcome of COVID‐19–positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID‐19 was confirmed.


T
he COVID-19 pandemic has affected millions of people worldwide, leading to unprecedented challenges for health care systems.Among the many challenges posed by the virus is the increased risk of complications, including acute ischemic stroke (AIS), with an incidence of 6% to 46% among hospitalized patients with COVID-19. 1,2In addition, recent studies of large series of patients with COVID-19 infection have reported a devastating clinical outcome of patients with AIS attributable to large-vessel occlusion treated with mechanical thrombectomy (MT), with mortality rates up to 31%. 3,4ince the end of 2020, several vaccines, such as Comirnaty (BNT162b2, Pfizer-BioNTech), Spikevax (mRNA-1273, Moderna), Vaxzevria (ChAdOx1 nCoV-19, AstraZeneca), and Jcovden (Ad26.COV-2.S, Johnson & Johnson/Janssen), have been approved for emergency use in response to the COVID-19 pandemic, with growing evidence of the safety and efficacy of vaccination against the SARS-CoV-2. 5[8][9][10] However, precise analyses of the preventive role of vaccination in patients with COVID-19 experiencing AIS because of large-vessel occlusion are still lacking.
Our study focuses on how vaccination status affects angiographic and clinical outcomes in patients with COVID-19 and AIS undergoing MT and provides insight into the potential benefits of vaccination in this vulnerable patient population.

METHODS
The data that support the findings of this study are available from the corresponding author on reasonable request.We conducted a retrospective study of patients with COVID- 19  Baseline characteristics, including respiratory status during hospitalization, technical features, complications, angiographic variables, and clinical outcomes were noted.The cause of the occlusion was based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.There were no limitations on procedural characteristics, including the use of different thrombectomy techniques and intra-arterial thrombolysis, which were left to the attending neuroradiologist's discretion.Endovascular treatment was performed with approved MT devices, using stent retrievers, large-bore aspiration catheters, or a combination of both.
Reperfusion was measured by the modified Thrombolysis in Cerebral Infarction (mTICI) scale score.The clinical efficacy outcome was the rate of functional independence as measured by the modified Rankin Scale (mRS) score and defined as 0 to 2 at discharge.All National Institutes of Health Stroke Scale (NIHSS) and mRS grades were assessed by a consultant neurologist.Postinterventional symptomatic intracranial hemorrhage (sICH) was graded according to the ECASS (European Cooperative Acute Stroke Study) criteria. 11

CLINICAL PERSPECTIVE
What Is New?According to the guidelines of the respective local ethics committees, ethical approval was given when necessary for this anonymous retrospective study, which was conducted in accordance to the Declaration of Helsinki.A patient's consent for treatment was obtained according to the individual institutional guidelines.Because of the retrospective nature of the study, additional informed consent was deemed unnecessary.

Statistical Analysis
Qualitative parameters are presented as numbers and percentages and compared with the χ 2 and the Fisher exact test, when appropriate.Ordinal and quantitative parameters are presented as median and interquartile range, unless otherwise indicated.Group comparisons of these parameters were performed with Mann-Whitney U test or the 2-sided Student t-test, when appropriate.
The primary outcome of interest was the mRS score at discharge, where a score between 0 and 2 was to be considered to be favorable.A multivariable analysis adjusted for confounders was conducted to test the association of the variables (age, sex, stroke onset, intravenous thrombolysis [IVT], vaccination status, occlusion site [M1, M2, M3, A1, A2, or basilar artery], patients with acute COVID-19, respiratory status of patients with acute COVID-19 [none versus ventilation and none versus intubation], TOAST cardioembolic, TOAST, small-vessel occlusion, tandem occlusion, baseline aspect, NIHSS score at admission, mRS score at pretreatment, final TICI [2a], final TICI [2b], final TICI [3], final TICI [1], groin to final recanalization, anesthesia [analgosedation], complications [subarachnoid hemorrhage and sICH], other complications, atrial fibrillation, arterial hypertension, diabetes, dyslipidemia, and smoker) with this outcome.For this, a smoothed ridge regression with a logit-link function was used.Ridge regression was used because of its ability to produce robust estimates, especially when dealing with smaller sample sizes. 12issing values were not imputed.Calculations were performed using SPSS software, version 25 (IBM SPSS Statistics for Windows, IBM Corp, Armonk, NY), and R, version 4.3 (R Foundation for Statistical Computing, Vienna, Austria).P<0.05 was considered statistically significant.

RESULTS
A total of 137 of 6163 screened patients (2.2%) from 20 tertiary stroke centers with COVID-19 infection and known vaccination status were treated with MT because of vessel occlusions between January 2020 and January 2023 (Figure).

Baseline Characteristics
Of the 137 patients, 48 were previously vaccinated (VAX) and 89 were not vaccinated (NoVAX).Patient baseline characteristics are reported in Table 1.
Acute respiratory failure requiring noninvasive ventilation or intubation was more frequent in the NoVAX group compared with the VAX group (Table 1).Atrial fibrillation was more frequent in the VAX group than in the NoVAX group, but without statistical significance.Stroke characteristics did not differ significantly between groups: median baseline NIHSS score and Alberta Stroke Program Early CT [Computed Tomography] Score were 17 and 9 in both groups, respectively.The rate of pretreatment functional independence (mRS score, ≤2) was 69.6% in the VAX group and 61.8% in the NoVAX group.Vessel occlusion was localized in the anterior circulation in most patients, most commonly in M1 (Table 1).Occlusions in M2 were significantly more frequent in the NoVAX group (Table 1).

Multivariable Analysis
We performed a multivariable analysis to identify predictors associated with an unfavorable outcome (mRS score, 3-6) at discharge using an induced smooth ridge regression (Table 3).In the analysis, factors potentially associated with an unfavorable outcome were: acute COVID-

DISCUSSION
In this multicenter, retrospective analysis, we observed no significant difference in angiographic and clinical outcomes between vaccinated and unvaccinated patients.The rates of successful and complete final reperfusion in both groups were high (mTICI ≥2b: 87% NoVAX and 85% VAX; mTICI 3: 44% NoVAX and 40% VAX) and comparable to other MT studies during and before the pandemic. 4,11,12In our study, we could not observe an effect of vaccination on recanalization; in particular, we found no evidence that vaccination reduced clot burden. 13The 6 patients who received the Ad26.COV-2.S vaccine (Johnson & Johnson/Janssen) and the ChAdOx1-S vaccine (AstraZeneca), both vaccines based on an adenoviral vector, did not exhibit the prothrombotic state of vaccine-induced immune thrombotic thrombocytopenia.Nevertheless, vaccine-induced immune thrombotic thrombocytopenia, characterized by thrombosis at atypical sites combined with thrombocytopenia, has been observed in individuals after vaccination with the 2 previously mentioned adenoviral vector-based agents and appears to be exceedingly rare following the vaccination of >400 million people worldwide. 14ur retrospective analysis revealed a higher rate of sICH in the VAX group compared with the NoVAX group (15% VAX versus 5% NoVAX; P=0.05).Consistent with this, a higher rate of IVT was observed in vaccinated patients.A systematic review analyzing thromboembolic and bleeding events after vaccination against SARS-CoV-2 demonstrated no increased risk of hemorrhage and death from thromboembolism and hemorrhage after vaccination against SARS-CoV-2 across all vaccine platforms. 15herefore, it is unlikely that the high rate of sICH in our study was related to the vaccination status, and it is more likely that other confounders (such as IVT) contributed.
Most important, our study demonstrated that vaccinated and unvaccinated patients with COVID-19 and AIS had similar devastating outcomes, although the reperfusion rates were high.The VAX group showed a slightly higher rate of functional independence (mRS score, ≤2) and a higher median NIHSS score at discharge compared with the NoVAX group, although without statistical significance.Consistent with a previous study of a large series of patients with COVID-19 treated with MT because of large-vessel occlusion, the mortality rate was high, up to 30%. 4 Compared with studies with non-COVID-19 populations, the mortality in our study is twice as high as in the meta-analysis from Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke (15%).To date, few studies have focused on the effect of vaccination status in patients with stroke with or without the additional diagnosis of COVID-19 infection. 16,17El Naamani et al reported rates of functional independence (mRS score, ≤2) of 30.6% in the NoVAX group and 45.4% in the VAX group (P=0.044) of 203 COVID-19positive patients with stroke.Mortality was 20.2% in unvaccinated individuals and 7.8% in vaccinated individuals (P=0.033).The authors discuss that the administration of the vaccine and the consequent modulation of the immune system by minimizing the prothrombotic and proinflammatory milieu of COVID-19 may reduce the severity of stroke and, therefore, may be the basis for the improved outcome of vaccinated patients. 16,17It remains unknown why our study could not find a significant difference in short-term clinical outcome between the 2 groups.It is likely that significant differences in baseline characteristics, such as the significantly higher rate of M2 occlusions in the NoVAX group, may affect the outcome.However, all factors considered, acute COVID-19 infection proved to be an independent factor for unfavorable outcome in multivariable analysis, as previously demonstrated in other studies. 18,19Therefore, the distinction between acute and subsided COVID-19 infection is critical in terms of its impact on clinical outcome.
The main limitations of our study are the retrospective and multicenter design, including attendant selection bias and bias attributable to different COVID-19 waves with correspondingly different severity of disease progression.The sample size limits the conclusions of these data.Although we used a robust multivariable model, it can only test for association and not directly for causality.Therefore, a careful prospective study using more elaborate modeling should be conducted in a future study.In addition, we did not correct for multiple testing, which could lead to inflation of the type 1 error rate.Furthermore, no formal sample size or power analysis was performed.
In addition, patients not receiving IVT had worse outcome, but it is likely that the results observed here represent confounding by indication that patients with IVT contraindications are more likely to have serious comorbidities and, therefore, worse outcomes.
Nevertheless, vaccination remains the safest strategy for avoiding hospitalizations, long-term health outcomes, and death.This general health care recommendation remains untouched by the present results.

CONCLUSIONS
In our study, we did not observe an impact of COVID-19 vaccination on the angiographic or clinical outcome of COVID-19-positive patients with AIS undergoing MT.Moreover, we found similarly devastating outcomes with high rates of mortality in vaccinated and unvaccinated patients with stroke.

Figure .
Figure.Flowchart of the study population.PCR indicates polymerase chain reaction.

Table 1 .
Baseline Characteristics of Unvaccinated and Vaccinated Patients With COVID-19 Infection Undergoing MT Data are given as number (percentage) or number/total (percentage) unless otherwise indicated.ACA indicates anterior cerebral artery; ASPECTS, Alberta Stroke Program Early CT [Computed Tomography] Score; BA, basilar artery; ICA, internal carotid artery; IQR, interquartile range; MCA, middle cerebral artery; mRS, modified Rankin Scale; MT, mechanical thrombectomy; NIHSS, National Institutes of Health Stroke Scale; PCA, posterior cerebral artery; and TOAST, Trial of Org 10172 in Acute Stroke Treatment.

Table 2 .
Angiographic and Clinical Outcomes of Unvaccinated and Vaccinated Patients With COVID-19 Infection Undergoing MT Data are given as number (percentage) or number/total (percentage) unless otherwise indicated.IQR indicates interquartile range; mRS, modified Rankin Scale; MT, mechanical thrombectomy; mTICI, modified Thrombolysis in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; SAH, subarachnoid hemorrhage; and sICH, symptomatic intracranial hemorrhage.

Table 3 .
Results of the Multivariable Analysis for an Unfavorable Outcome Score; BA, basilar artery; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; SAH, subarachnoid hemorrhage; sICH, symptomatic intracranial hemorrhage; TOAST, Trial of Org 10172 in Acute Stroke Treatment; TICI, Thrombolysis in Cerebral Infarction.*P<0.05.