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J Stroke > Volume 27(1); 2025 > Article
Marto, Strambo, Ntaios, Nguyen, Wrona, Escalard, Marcheselli, Mansour, Fuentes, Dorobek, Nowakowska-Kotas, Terecoasa, Coutinho, Carvalho-Dias, Calleja, Sargento-Freitas, Paiva-Nunes, Šrámek, Khandelwal, Meira, Abdalkader, Jabbour, Kovář, Ayo-Martin, Michel, Herzig, Członkowksa, Demeestere, Nogueira, Salerno, Wegener, Baumgartner, Cereda, Bianco, Beyeler, Arnold, Carrera, Machi, Altersberger, Bonati, Gensicke, Bolognese, Peters, Wetzel, Magriço, Nuno Ramos, Machado, Maia, Machado, Ferreira, Pinho-e-Melo, Paula, Correia, Castro, Azevedo, Albuquerque, Nuno-Alves, Ferreira-Pinto, Pereira, Rodrigues, Araújo, Rodrigues, Rocha, Pereira-Fonseca, Ribeiro, Varela, Malheiro, Cappellari, Zivelonghi, Sajeva, Zini, Mauro, Stefano, Migliaccio, Sessa, Gioia, Pezzini, Sangalli, Zedde, Pascarella, Ferrarese, Beretta, Diamanti, Schwarz, Frisullo, Seners, Sabben, Piotin, Maier, Charbonnier, Vuillier, Legris, Cuisenier, Vodret, Marnat, Liegey, Sibon, Flottmann, Broocks, Gloyer, Bohmann, Schaefer, Nolte, Audebert, Siebert, Sykora, Lang, Ferrari, Mayer-Suess, Knoflach, Gizewski, Stolp, Stolze, Nederkoorn, van-den-Wijngaard, de Meris, Lemmen, De Raedt, Vandervorst, Rutgers, Guilmot, Dusart, Bellante, Ostos, Gonzalez-Ortega, Martín-Jiménez, García-Madrona, Cruz-Culebras, Vera, Matute, Alonso-de-Leciñana, Rigual, Díez-Tejedor, Pérez-Sánchez, Montaner, Díaz-Otero, Perez-de-la-Ossa, Flores-Pina, Muñoz-Narbona, Chamorro, Rodríguez-Vázquez, Renú, Hernandez-Fernandez, Segura, Tejada-Meza, Sagarra-Mur, Serrano-Ponz, Hlaing, See, Simister, Werring, Kristoffersen, Nordanstig, Jood, Rentzos, Šimu˚ne, Krajíčková, Krajina, Mikulík, Cviková, Vinklárek, Školoudík, Roubec, Hurtikova, Hrubý, Ostry, Skoda, Pernicka, Kočí, Eichlová, Jíra, Panský, Mencl, Paloušková, Tomek, Janský, Olšerová, Havlíček, Malý, Trakal, Fiksa, Slovák, Karlińsk, Nowak, Sienkiewicz-Jarosz, Bochynska, Homa, Sawczynska, Slowik, Wlodarczyk, Wiącek, Tomaszewska-Lampart, Sieczkowski, Bartosik-Psujek, Bilik, Bandzarewicz, Zielińska-Turek, Obara, Urbanowski, Budrewicz, Guziński, Świtońska, Rutkowska, Sobieszak-Skura, Łabuz-Roszak, Dębiec, Staszewski, Stępień, Zwiernik, Wasilewski, Tiu, Radu, Negrila, Dorobat, Panea, Tiu, Petrescu, Özcan-Özdemir, Mahmoud, El-Samahy, Abdelkhalek, Al-Hashel, Ibrahim Ismail, Salmeen, Ghoreishi, Sabetay, Gross, Klein, El Naamani, Tjoumakaris, Abbas, Mohamed, Chebl, Min, Hovingh, Tsai, Khan, Nalleballe, Onteddu, Masoud, Michael, Kaur, Maali, Abraham, Bach, Ong, Babici, Khawaja, Hakemi, Rajamani, Cano-Nigenda, Arauz, Amaya, Llanos, Arango, Vences, Barrientos, Caetano, Targa, Scollo, Yalung, Nagendra, Gaikwad, Seo, and on Behalf of the Global COVID-19 Stroke Registry: Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment
Dear Sir:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of cerebrovascular and other thrombotic events [1]. Previous studies have shown that patients with acute ischemic stroke (AIS) and coronavirus disease 2019 (COVID-19) have a worse functional outcome than those without concomitant SARS-CoV-2 infection [2,3]. In patients receiving acute revascularization treatments, our large retrospective analysis of the Global COVID-19 Stroke Registry revealed higher rates of intracranial bleeding and worse clinical outcomes in patients with AIS and COVID-19 compared to contemporary AIS controls without COVID-19 [4]. Subsequent sub-analyses emphasized the impact of SARS-CoV-2 infection in this subgroup of patients showing differences in outcome between patients with asymptomatic COVID-19 and controls without COVID-19 [5].
Several factors can contribute to poorer outcomes in patients with AIS and COVID-19 undergoing acute revascularization treatments [2,3,6], including lower recanalization rates and higher rates of procedural complications after endovascular treatment (EVT) [7,8].
We aimed to assess recanalization outcomes and procedural complication rates in patients with AIS and COVID-19 undergoing EVT in an international cohort by comparing them with a contemporary control group of non-COVID-19 patients from the same centers.
We conducted a secondary analysis on the Global COVID-19 Stroke Registry [4]. Inclusion and exclusion criteria for the Global COVID-19 Stroke Registry were previously described [4]. For this study, only patients receiving EVT for intracranial occlusions were included (Supplementary Figure 1). All study procedures, study variables, and ethical standards were previously described [4].
The primary outcome of this study was recanalization after EVT assessed by the modified Thrombolysis in Cerebral Infarction (mTICI) score. Secondary procedural outcomes were: (1) successful recanalization after EVT (mTICI ≥2b); (2) first pass effect; (3) number of passes during EVT; and (4) procedure duration. Secondary safety outcomes were: (1) arterial perforation observed during EVT; (2) reocclusion during EVT; and (3) embolization into new non-ischemic territory during EVT. To assess the association of COVID-19 with the primary outcome and secondary procedural outcomes, we used multivariable regression models entering as independent variables the COVID-19 status together with prespecified baseline clinical and radiological variables identified from previous literature as variables known to be associated with the outcomes of interest. Depending on whether the outcome was ordinal, binary, or continuous, we used ordered logit regression, logistic regression, and quantile regression models, respectively. Data regarding EVT complications were available for all COVID-19 patients but only in a subset of controls. As such, to evaluate the association between COVID-19 and EVT complications, we performed a 1:3 propensity-score matching procedure between COVID-19 patients and the subset of controls with EVT complication data available. The association between COVID-19 and EVT complications was assessed using univariable binary logistic regression on the matched population. A detailed description on the statistical analysis methodology is available in Supplementary Methods.
Of the 15,128 patients included in the Global COVID-19 Stroke Registry, 8,292 fulfilled the inclusion criteria for the present analysis (Supplementary Figure 1). Of these, 497 (6.0%) patients were diagnosed with COVID-19. Comparisons between groups are shown in Table 1.
In the adjusted analysis, COVID-19 was associated with worse final mTICI score, lower successful recanalization, and a trend toward a lower first pass effect (Table 2).
EVT procedural complications were assessed in 493 (99.0%) patients with COVID-19 and in 2,275 (29.0%) controls. Control patients with and without data on procedural complications had similar baseline characteristics (Supplementary Table 1). Among patients with information on procedural complications after EVT, 491 with COVID-19 and 2,246 in the control group had complete data on the covariates selected for matching and were included in the analysis. After propensity-score matching of these patients, COVID-19 patients and their matched controls had a well-balanced distribution of baseline characteristics (Supplementary Figure 2). Patients with COVID-19 had higher rates of arterial perforation and reocclusion during EVT, and a trend toward higher rates of embolization into a new non-ischemic territory (Table 3).
In this secondary analysis on the Global COVID-19 Stroke Registry, we found that patients with COVID-19 had worse recanalization outcomes and higher rates of procedural complications such as arterial perforation and reocclusion in comparison with contemporaneous patients with AIS without COVID-19. To our knowledge, this was the first study to show such associations in a large sample of consecutive patients with and without COVID-19 that used adjustment for potential confounders. The presented results add to our previous finding, showing higher rates of intracranial bleeding and worse clinical outcomes in patients with AIS and COVID-19 compared to contemporary AIS controls without COVID-19 [9].
Several pathophysiological mechanisms associated with COVID-19 may explain these findings. Endothelial inflammation and dysfunction, induced platelet aggregation, coagulation cascade activation, and formation of antiphospholipid antibody complexes associated with COVID-19 likely lead to higher clot burden and clot adherence [9,10]. This complex interplay probably results in lower recanalization and increased rates of reocclusion. These same mechanisms, combined with SARS-CoV-2-induced hyperfibrinolysis and direct viral-mediated damage to the neurovascular unit [9,10] may contribute to lower integrity of vessel walls and to subsequent elevated rates of arterial perforation. Alternatively, emboli in patients with COVID-19 may be more difficult to recanalize and retrieve due to the activation of the coagulation cascade activation, requiring more aggressive and longer EVT procedures with increased perforation risk.
Our analysis has several strengths, including the large sample size from 30 countries across five continents, increasing the validity and generalizability of our results.
Limitations of our study include the retrospective design, non-blinded assessment, and absence of centralized imaging review, which may have influenced our results. The use of different thrombectomy equipment and techniques by stroke interventionists may have affected our results but were tentatively addressed by adjustment with a center cluster level variable. A significant number of centers did not report safety outcomes in control patients, which could have biased our results.
In conclusion, in this cohort study, patients with AIS and COVID-19 receiving EVT had lower rates of recanalization and a higher risk of arterial perforation and reocclusion, in comparison with contemporary AIS controls without COVID-19. These findings may contribute to the poorer outcome found in patients with AIS and COVID-19.

Supplementary materials

Supplementary materials related to this article can be found online at https://doi.org/10.5853/jos.2024.04077.
Supplementary Table 1.
Comparison between control patients included and excluded in procedural complications analysis
jos-2024-04077-Supplementary-Table-1.pdf
Supplementary Figure 1.
Inclusion flowchart.
jos-2024-04077-Supplementary-Fig-1,2.pdf
Supplementary Figure 2.
Standardized mean differences before (red points) and after (blue points) propensity-score matching (PSM) between the patients with COVID-19 and controls, for the variables used for matching. NIHSS, National Institutes of Health Stroke Scale; LVO, large vessel occlusion; ic-ICA, intracranial internal carotid artery; M1, middle cerebral artery (M1 segment); BA, basilar artery; IVT, intravenous thrombolysis.
jos-2024-04077-Supplementary-Fig-1,2.pdf

Notes

Funding statement
None
Conflicts of interest
Roman Herzig reports receiving research grants from the Ministry of Health of the Czech Republic (grant number DRO - UHHK 00179906) and Charles University, Czech Republic (grant number PROGRES Q40). Christian Nolte reports receiving research grants from the German Ministry of Research and Education, the German Center for Neurodegenerative Diseases, and the German Center for Cardiovascular Research. He has also received speaker and/or advisory fees from Abbott, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer Pharma. Stavropoula Tjoumakaris reports receiving advisory fees from Medtronic and MicroVention. Jiangyong Min reports receiving advisory fees from Medtronic and Abbott. Muhib-A Khan reports receiving research grants from the National Institute of Health, Spectrum Health-Michigan State University Research Alliance, and Genentech. Patrik Michel reports receiving research grants from the Swiss National Science Foundation and the Swiss Heart Foundation. All other authors report no conflicts of interest.
Author contribution
Conceptualization: JPM, DS, GN, PM. Study design: JPM, DS, GN, PM. Data collection: all authors. Statistical analysis: DS. Writing—original draft: JPM, DS; GN, PM. Writing—review & editing: all authors. Approval of final manuscript: all authors.

Table 1.
Baseline, stroke characteristics, imaging and treatment data
Variables Total (n=8,292) Controls (n=7,795) COVID-19 (n=497) P
Center volume* <0.01
 <100 671 (8.1) 585 (7.5) 86 (17.3)
 100-199 2,434 (29.4) 2,268 (29.1) 166 (33.4)
 200-299 3,343 (40.3) 3,194 (41.0) 149 (30.0)
 ≥300 1,844 (22.2) 1,748 (22.4) 96 (19.3)
Demographics
 Age (yr) 73 (63-81) 73 (63-81) 70 (60-79) <0.01
 Male sex 4,041 (48.8) 3,756 (48.2) 285 (57.3) <0.01
 Pre-stroke modified Rankin Scale 0.94
  0 5,831 (73.0) 5,474 (73.0) 357 (72.9)
  1 to 2 1,648 (20.6) 1,545 (20.6) 103 (21.0)
  3 to 5 513 (6.4) 483 (6.4) 30 (6.1)
Vascular risk factors
 Hypertension 5,763 (69.8) 5,434 (70.0) 329 (66.2) 0.08
 Diabetes mellitus 2,060 (24.8) 1,893 (24.4) 167 (33.6) <0.01
 Dyslipidemia 3,743 (45.4) 3,541 (45.7) 202 (40.6) 0.03
 Current smoking 1,734 (21.4) 1,646 (21.6) 88 (17.8) 0.05
 Atrial fibrillation 3,078 (37.3) 2,907 (37.5) 171 (34.5) 0.20
 Heart failure 1,183 (15.2) 1,109 (15.2) 74 (15.6) 0.85
 Coronary artery disease 1,330 (16.4) 1,247 (16.3) 83 (17.3) 0.64
 Active cancer 368 (5.0) 345 (5.0) 23 (5.1) 0.988
Treatment at stroke onset
 Oral anticoagulants 1,648 (19.9) 1,535 (19.8) 113 (22.7) 0.13
 Antiplatelets 2,101 (25.5) 1,980 (25.6) 121 (24.4) 0.62
 Statins 2,630 (33.7) 2,484 (33.9) 146 (30.9) 0.20
Stroke characteristics
 LTSW-to-door (min) 120 (66-263) 120 (66-264) 120 (61-260) 0.36
 Admission NIHSS 16 (10-20) 16 (10-20) 17 (12-21) <0.01
 Vascular territories 0.40
  Carotid 7,371 (90.0) 6,924 (88.9) 447 (90.1)
  Vertebrobasilar 729 (8.8) 693 (8.9) 36 (7.3)
  Multiple 186 (2.2) 173 (2.2) 13 (2.6)
 Admission systolic BP (mm Hg) 148 (130-165) 148 (130-165) 144 (130-160) <0.01
 Admission blood glucose (mmol/L) 6.9 (5.9-8.4) 6.9 (5.9-8.4) 7.2 (6.1-9.2) <0.01
Acute imaging
 ASPECTS (or pc-ASPECTS) 9 (8-10) 9 (8-10) 9 (7-10) <0.01
 Most proximal arterial occlusion 0.11
  Intracranial ICA 1,766 (21.3) 1,654 (21.2) 112 (22.5)
  MCA M1 4,156 (50.1) 3,906 (50.1) 250 (50.3)
  MCA M2-4 1,500 (18.1) 1,414 (18.1) 86 (17.3)
  ACA A1-2 48 (0.6) 46 (0.6) 2 (0.4)
  PCA P1-2 116 (1.4) 109 (1.4) 7 (1.4)
  BA 522 (6.3) 498 (6.4) 24 (4.8)
  V4 105 (1.3) 100 (1.3) 5 (1.0)
  Other 79 (0.9) 68 (0.9) 11 (2.2)
 Tandem lesion 1,255 (15.2) 1,166 (15.0) 89 (17.9) 0.09
Stroke etiology <0.01
 Large artery atherosclerosis 1,599 (19.3) 1,498 (19.2) 101 (20.3)
 Cardioembolism 3,921 (47.3) 3,715 (47.7) 206 (41.5)
 Small vessels disease 26 (0.3) 25 (0.3) 1 (0.2)
 Dissection 188 (2.3) 178 (2.3) 10 (2.0)
 Other determined cause 386 (4.7) 320 (4.1) 66 (13.3)
 Undetermined 2,172 (26.2) 2,059 (26.4) 113 (22.7)
Acute revascularization treatment
 IV thrombolysis 3,866 (46.6) 3,655 (46.9) 211 (42.5) 0.06
 LTSW-to-puncture (min) 273 (187-412) 272 (187-412) 285 (190.2-410.8) 0.63
 General anesthesia 2,941 (35.7) 2,718 (35.1) 223 (45.0) <0.01
Values are presented as median (interquartile range) or as n (%).
LTSW, last-time-seen-well; NIHSS, National Institutes of Health Stroke Scale; BP, blood pressure; ASPECTS, Alberta Stroke Program Early CT Score; pc-ASPECTS, posterior circulation ASPECTS; ICA, internal carotid artery; MCA, middle cerebral artery; ACA, anterior cerebral artery; PCA, posterior cerebral artery; BA, basilar artery; V4, vertebral artery, segment 4.
* Refers to the number of patients included by each center in the study.
Table 2.
Recanalization outcomes after endovascular treatment
Variables Total (n=8,292) Controls (n=7,795) COVID-19 (n=497) Crude OR (95% CI) Adjusted OR (95% CI)
Final mTICI 0.70 (0.58 to 0.86)* 0.72 (0.59 to 0.89)*
 0-1 658 (8.0) 597 (7.7) 61 (12.3)
 2a 442 (5.3) 404 (5.2) 38 (7.6)
 2b 2,111 (25.5) 1,988 (25.5) 123 (24.7)
 2c 877 (10.6) 815 (10.5) 62 (12.5)
 3 4,182 (50.6) 3,969 (51.1) 213 (42.9)
Successful recanalization (mTICI ≥2b) 7,170 (86.7) 6,772 (87.1) 398 (80.1) 0.59 (0.47 to 0.75) 0.59 (0.44 to 0.79)
First pass effect 2,498 (30.2) 2,376 (30.5) 122 (24.6) 0.74 (0.60 to 0.91) 0.79 (0.63 to 1.00)
Total number of device passes 1.21 (0.96 to 1.53) 1.13 (0.88 to 1.44)
 1 3,855 (46.5) 3,642 (46.7) 213 (42.9)
 2 1,972 (23.8) 1,860 (23.9) 112 (22.5)
 3 1,236 (14.9) 1,152 (14.8) 84 (16.9)
 >3 1,229 (14.8) 1,141 (14.6) 88 (17.7)
Procedure duration 40 (25-65) 40 (25-65) 40 (25-65) 0.00 (-3.74 to 3.74) -2.25 (-6.24 to 1.74)
Values are presented as median (interquartile range) or as n (%).
OR, odds ratio; CI, confidence interval; mTICI, modified Thrombolysis in Cerebral Infarction.
* Common adjusted odds ratio for higher mTICI;
Common adjusted odds ratio for higher number of passes;
Beta coefficient from quantile regression. Multivariable models displayed no multicollinearity (maximal variance inflation factor of 1.1).
Table 3.
Procedural complications during endovascular treatment
Variables Total (n=1,964) Controls (n=1,473) COVID-19 (n=491) Adjusted OR (95% CI) P
Arterial perforation observed during EVT 29 (1.5) 17 (1.2) 12 (2.4) 2.14 (1.12-4.10) 0.02
Embolization into a non-ischemic territory during EVT 76 (3.9) 48 (3.3) 28 (5.7) 1.79 (0.97-3.32) 0.06
Reocclusion of recanalized artery during EVT 89 (4.5) 46 (3.1) 43 (8.8) 2.98 (1.75-5.09) <0.01
Values are presented as numbers (proportions).
OR, odds ratio; CI, confidence interval; EVT, endovascular treatment.

References

1. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-690.
crossref pmid pmc
2. Ntaios G, Michel P, Georgiopoulos G, Guo Y, Li W, Xiong J, et al. Characteristics and outcomes in patients with COVID-19 and acute ischemic stroke: the global COVID-19 stroke registry. Stroke 2020;51:e254-e258.
pmid
3. Perry RJ, Smith CJ, Roffe C, Simister R, Narayanamoorthi S, Marigold R, et al. Characteristics and outcomes of COVID-19 associated stroke: a UK multicentre case-control study. J Neurol Neurosurg Psychiatry 2021;92:242-248.
crossref pmid
4. Marto JP, Strambo D, Ntaios G, Nguyen TN, Herzig R, Czlonkowska A, et al. Safety and outcome of revascularization treatment in patients with acute ischemic stroke and COVID-19: the global COVID-19 stroke registry. Neurology 2023;100:e739-e750.
pmid pmc
5. Strambo D, Marto JP, Ntaios G, Nguyen TN, Michel P; Global COVID-19 Stroke Registry. Effect of asymptomatic and symptomatic COVID-19 on acute ischemic stroke revascularization outcomes. Stroke 2024;55:78-88.
pmid
6. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 2020;324:782-793.
crossref pmid
7. Escalard S, Maïer B, Redjem H, Delvoye F, Hébert S, Smajda S, et al. Treatment of acute ischemic stroke due to large vessel occlusion with COVID-19: experience from Paris. Stroke 2020;51:2540-2543.
crossref pmid pmc
8. Cagnazzo F, Piotin M, Escalard S, Maier B, Ribo M, Requena M, et al. European multicenter study of ET-COVID-19. Stroke 2021;52:31-39.
pmid
9. Sashindranath M, Nandurkar HH. Endothelial dysfunction in the brain: setting the stage for stroke and other cerebrovascular complications of COVID-19. Stroke 2021;52:1895-1904.
crossref pmid pmc
10. Sagris D, Papanikolaou A, Kvernland A, Korompoki E, Frontera JA, Troxel AB, et al. COVID-19 and ischemic stroke. Eur J Neurol 2021;28:3826-3836.
crossref pmid pmc pdf

Appendices

Appendix 1.

Full author list
jos-2024-04077-Appendix-1.pdf


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