Research International Journal of Stroke 2021, Vol. 16(5) 573–584 Global impact of COVID-19 on ! 2021 World Stroke Organization stroke care Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1747493021991652 journals.sagepub.com/home/wso SVIN COVID-19 global registry Abstract Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thromb- ectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, 19.7 to 18.7), 11.5% (95%CI, 12.6 to 10.6), and 12.7% (95%CI, 13.6 to 11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High- volume COVID-19 centers (20.5%) had greater declines in mechanical thrombectomy volumes than mid- (10.1%) and low-volume (8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospital- izations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes. Keywords COVID-19, stroke care, acute ischemic stroke, mechanical thrombectomy, intracranial hemorrhage, epidemiology Received: 16 December 2020; accepted: 8 January 2021 immunological, and coagulation disorders, COVID-19 Introduction has been reported in association with a broad array of In December 2019, a novel highly pathogenic virus, neurological disorders including encephalitis, Guillain- severe acute respiratory syndrome coronavirus 2 Barre syndrome, seizures, ischemic, and hemorrhagic (SARS-CoV-2), caused an infectious disease involving strokes.1 Some groups reported an increase in crypto- multiple organ systems termed coronavirus disease genic strokes involving young patients with 2019 (COVID-19). COVID-19 holds a unique balance SARS-CoV-2 infection, possibly in association with between high transmissibility and low-to-moderate endothelial inflammation and thrombotic diathesis.2–7 morbidity and mortality that has led to a nearly uni- Others reported a decline in the rates of stroke hospi- versal spread with devastating consequences world- talizations and the proportion of patients receiving wide. On 11 March 2020, the World Health Organization declared a global pandemic as COVID- Corresponding author: 19 hospitalizations and emergency medical system acti- Thanh N. Nguyen, Boston Medical Center, Boston University School of vations increased. As a potential consequence of its Medicine, Boston, MA 02118, USA. neurotropism as well as the inflammatory, Email: thanh.nguyen@bmc.org International Journal of Stroke, 16(5) 574 International Journal of Stroke 16(5) reperfusion therapies (intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT)) for acute Methods ischemic stroke (AIS). Notably, many of these studies Data are available upon request to the corresponding originated from global epicenters for the pandemic sup- author. porting the notion that the indirect or collateral damage of COVID-19 on systems of care has had a greater impact on stroke patients than the viral infec- Study design tion itself.3,5,8–12 However, most of these reports were This was a cross-sectional, observational, retrospective limited to regional or country-specific analyses, and study evaluating monthly and weekly volumes of con- thus, the extent to which the COVID-19 outbreak has secutive patients hospitalized with a diagnosis of impacted global stroke systems of care has not been COVID-19, stroke, MT, and ICH. The diagnoses previously assessed. Importantly, given the profound were identified by their related ICD-10 codes (primary, benefit of MT in AIS, the global public health impact secondary, or tertiary discharge codes) and/or classifi- of such declines, if confirmed, adds to the devastation cations in stroke databases at participating centers. caused by COVID-19. Setting and participants Aims and hypotheses Data were collected from collaborators of the Society of We conducted an international, observational study Vascular and Interventional Neurology, the Middle East on the impact of the COVID-19 pandemic on North Africa Stroke and Interventional Neurotherapies stroke care at the height of the COVID-19 pandemic. Organization, the Japan Society of Vascular and Our primary aim was to evaluate the effect of Interventional Neurology, and academic partners from COVID-19 on stroke care as measured by the 6 continents, 40 countries, and 187 CSCs. To reduce changes in volumes for overall stroke hospitaliza- bias, only centers providing the full dataset required tions, ischemic stroke/transient ischemic attacks for any given analysis were included in that specific ana- (TIA) admissions, ICH admissions, and MT proced- lysis. Centers were screened for potential confounders ures across the pre-pandemic and pandemic periods that could explain unexpected changes in volumes. One in a multinational pool of comprehensive stroke cen- center in Vietnam was excluded from the MT secondary ters (CSC). The study compared the three initial analysis due to an abrupt increase in volume attributed months of the pandemic (1 March 2020–31 May to the purchase of automated imaging software. One 2020) with (1) the immediately preceding months center in Brazil was excluded from the stroke admission (December 2019–February 2020 for overall volume analysis because it became the designated center for and November 2019–February 2020 for monthly stroke patients, resulting in tripling of their volumes. volume) as the primary analysis and (2) the equiva- lent three months in the previous year (1 March Study variables and outcomes measures 2019–30 May 2019) as the secondary analysis. The reason for this analytic hierarchy was an a priori The overall and mean monthly volumes for stroke hos- expectation that the volumes for both stroke admis- pitalizations, admissions for ischemic stroke/TIA, and sions and MT procedures would increase over time admissions for ICH and MT procedures were compared due to the growing evidence supporting the broader across the pandemic and pre-pandemic periods for the utilization of MT.13–15 While the primary analysis overall population and across the low, mid, and high provided a realistic picture of stroke care utilization volume strata based on mean monthly volume tertiles prior to COVID-19, the secondary analysis allowed for COVID-19 hospitalizations (10.6 vs. >10.6–103.6 for the assessment for potential seasonal variations.16 vs. >103.6 COVID-19 admissions/month), stroke We hypothesized that in the face of the pandemic’s admissions (46.2 vs. >46.2–78.4 vs. >78.4 stroke strain on healthcare infrastructure, (1) a reduction in all admissions/month), and MT interventions (4.8 vs. four aforementioned measurements of stroke care >4.8 to 11.4 vs. >11.4 procedures/month). would take place over the pandemic, (2) centers with higher COVID-19 inpatient volumes would report greater decreases in stroke admissions and MT proced- Statistical analysis ure volumes, (3) the degree of decline in stroke admis- We first compared overall hospital volumes for stroke sions and MT procedure volumes would be less admissions (overall stroke, ischemic, and ICH) and MT profound in high-volume compared to low-volume procedures between the pre-pandemic and the pan- stroke centers, and (4) a geographic variation would demic period. For this analysis, the percentage change exist in the intensity of decline in stroke care. in the number of admissions or procedures between the International Journal of Stroke, 16(5) Nogueira et al. 575 two time periods was calculated. The three-month pre- considered that the investigators did not have access pandemic period was restricted to three months before to protected health information, and thus no IRB over- the pandemic (1 December 2019–29 February 2020) to sight was required since the study did not meet the fed- keep it consistent with the three months during the eral description of human subject research. This study COVID-19 pandemic group (1 March 2020–31 May is reported in accordance with the Strengthening the 2020). The 95% confidence intervals for percentage Reporting of Observational studies in Epidemiology change were calculated using the Wilson procedure (STROBE) statement. without continuity correction. The analyses were repeated within each tier (low, mid, and high) of centers classified based on COVID-19 hospitalizations, stroke Results admissions, and MT procedures. The relative percent- A total of 16,141, 26,699, and 21,576 stroke hospital- age change in overall volume between low, mid, and izations (overall n ¼ 64,416) and 3397, 5191, and 4533 high-volume centers was tested using the z-test of pro- MT procedures (overall n ¼ 13,121) were included portion. We also looked at relative change in overall across the three-month prior year, three-month imme- volume by continent. diately pre-pandemic, and three-month pandemic peri- In the second analysis, we compared monthly hos- ods, respectively. pital volumes (admissions or procedures/hospital/ month) for our outcome of interests between the pre-pandemic and the pandemic period. For the pre- Overall stroke hospitalization volumes pandemic period, for each hospital, the monthly hos- In the primary analysis of overall volume, stroke hos- pital volume was calculated from November 2019 to pitalization volumes were 26,699 admissions in the February 2020 and compared to the monthly hospital three months immediately before compared to 21,576 volume during the pandemic period (1 March 2020–31 admissions during the pandemic, representing a 19.2% May 2020). The data were analyzed in a mixed design (95%CI, 19.7 to 18.7, N ¼ 121 sites) drop, Table 1. using a repeated-measures analysis of variance (PROC The stroke hospitalization decline had a geographic MIXED analysis in SAS) to account for the paired data variation: Asia, 20.5% (95%CI, 21.2 to 19.8); structure and potential covariates. The auto-regressive, North America, 20.6% (95%CI, 21.4 to 19.7); compound symmetrical, and unstructured variance- Europe, 11.2% (95%CI, 12.3 to 10.1); covariance matrix structures were analyzed for the South America, 15.9% (95%CI, 17.9 to 14.0); best model determined by Akaike’s Information Oceania, 11.6% (95%CI, 14.4 to 9.3); Africa, Criterion. The unstructured matrix was the best fit 48.1% (95%CI, 55.8 to 40.5), Table S1. In an and used for most analyses. The monthly hospital analysis of monthly volume, after adjustment for peak volume analysis was adjusted for peak COVID-19 COVID-19 volume by country and continent, the volume for each country and the continent. Estimated number of hospitalizations for stroke/month/hospital marginal means were calculated using the LSMEANS (adjusted mean (SE)) declined from 76.4 (12.3) pre- statement in PROC MIXED. Similar to the overall pandemic to 64.2 (12.0) during the pandemic volume analysis, monthly volume analysis was repeated (p < 0.0001), Table 1. within low, mid, and high tier of centers based on their COVID-19 hospitalizations, stroke admissions, and MT procedures as well as by the continent. Mechanical thrombectomy procedural volumes Finally, for our secondary objective, we compared MT volume data was represented by 176 centers in the the relative change in overall volume and change in primary analysis with 5191 procedures in the three monthly hospital volume during the COVID-19 pan- months immediately preceding compared to 4533 pro- demic and corresponding three months from 2019 (1 cedures during the first three months of the pandemic, March 2019–31 May 2019). All data were analyzed representing a 12.7% (95%CI, 13.6 to 11.8) decline, using SAS version 9.4 (SAS Institute), and the signifi- Table 2. The volume reduction varied: Asia, 9.8% cance level was set at a p-value of <0.05. (95%CI, 11.3 to 8.4); North America, 14.5% (95%CI, 16.2 to 12.9); Europe, 14.4% (95%CI, 16.4 to 12.6); South America, 12.4% (95%CI, Funding and ethics 19.0 to 7.9), Oceania, 9.4% (95%CI, 13.4 to This was an investigator-initiated project with no fund- 6.5); Africa, 21.2% (95%CI, 37.8 to 10.7), ing. The first and last authors wrote the first draft of the Table S2. The adjusted mean (SE) number of MT pro- manuscript with subsequent input of all co-authors. cedures/month/center decreased from 10.9 (1.3) pre- The institutional review boards from the coordinating pandemic to 9.8 (1.3) during the pandemic sites (Emory University and Boston University) (p < 0.0001), Table 2. There were 120 centers that International Journal of Stroke, 16(5) 576 International Journal of Stroke 16(5) Table 1. Stroke admissions overall and monthly volumes immediately before and during the COVID-19 pandemic Overall volume Monthly volumea Change Immediately before During COVID-19 N n1 n2 % (95%CI) N Adjusted mean (SE) p Overall 119 26,699 21,576 –19.2 (19.7 – 18.7) 121 76.4 (12.3) 64.2 (12.0) <0.0001 Hospital COVID-19 volumeb Low 38 7612 6654 12.6 (13.4 – 11.9) 38 62.4 (31.4) 53.9 (30.7) 0.002 Mid 31 7495 6008 19.8 (20.8 – 19.0) 34 84.8 (10.5) 71.0 (8.7) 0.002 High 30 7163 5534 22.7 (23.7 – 21.8) 33 90.1 (9.8) 72.9 (9.3) <0.0001 Hospital stroke volumec Low 40 3536 3003 –15.1 (–16.3 – –13.9) 40 28.7 (2.6) 24.5 (2.5) <0.0001 Mid 37 6804 5609 –17.6 (–18.5 – –16.7) 40 62.7 (2.7) 53.1 (3.3) <0.0001 High 37 14,994 12,400 –17.3 (–17.9 – –16.7) 41 134.1 (21.6) 111.6 (20.8) <0.0001 N: number of hospitals; n1: number of admissions immediately before COVID-19 pandemic; n2: number of admissions during COVID-19 pandemic; CI: confidence interval; SE: standard error. Note: The n1 is based on 3 months before (December 2019–February 2020) COVID-19 pandemic. a The monthly volume analysis is adjusted for peak COVID-19 volume for each country and the continent. b p: low vs. mid  0.0001; low vs. high  0.0001; mid vs. high  0.0001. c p: low vs. mid ¼ 0.001; low vs. high ¼ 0.002; mid vs. high ¼ 0.588. Table 2. Mechanical thrombectomy overall and monthly volumes immediately before and during the COVID-19 pandemic Overall volume Monthly volumea Change Immediately before During COVID-19 N n1 n2 % (95%CI) N Adjusted mean (SE) p Overall 176 5191 4533 12.7 (13.6 – 11.8) 173 10.9 (1.3) 9.8 (1.3) <0.0001 Hospital COVID-19 volumeb Low 44 952 869 8.7 (10.7 – 7.1) 44 11.2 (3.6) 10.5 (3.5) 0.044 Mid 45 1370 1232 10.1 (11.8 – 8.6) 45 11.7 (1.2) 10.8 (1.2) 0.004 High 45 1602 1273 20.5 (22.6 – 18.6) 46 7.8 (2.2) 5.7 (2.2) <0.0001 Hospital MT volumec Low 59 459 412 –10.2 (–13.4 – –7.8) 60 2.6 (0.36) 2.3 (0.36) 0.082 Mid 55 1294 1092 –15.6 (–17.7 – –13.7) 55 8.1 (0.46) 7.0 (0.50) 0.0002 High 58 3432 3029 11.7 (12.9 – 10.7) 58 18.8 (1.8) 16.8 (1.7) 0.0002 N: number of hospitals; n1: number of procedures immediately before COVID-19 pandemic; n2: number of procedures during COVID-19 pandemic; CI: confidence interval; SE: standard error; MT: mechanical thrombectomy. The n1 is based on three months before (December 2019–February 2020) COVID-19 pandemic. a The monthly volume analysis is adjusted for peak COVID-19 volume for each country and the continent. b p: low vs. mid ¼ 0.259; low vs. high  0.0001; mid vs. high  0.0001. c p: low vs. mid ¼ 0.004; low vs. high ¼ 0.345; mid vs. high ¼ 0.0003. International Journal of Stroke, 16(5) Nogueira et al. 577 reported concomitant monthly data on stroke admis- Figure 1. Weekly volume of stroke admissions (ischemic sion and MT volume. The adjusted mean (SE) monthly and hemorrhagic) and COVID-19 hospitalizations volumes. proportion of MT relative to stroke admissions remained stable across the pre-pandemic and pandemic Ischemic Stroke, ICH vs COVID-19 admissions 1800 9000 periods (17.8 (2.2)% vs. 18.5 (2.2)%, respectively; p ¼ Weekly number of Ischemic Stroke, ICH volume 1600 8000 0.150). This proportional stability in MT performance Weekly number of COVID-19 admissions 1400 7000 was consistent across all COVID-19 and MT hospital- 1200 6000 ization volumes strata, Table S3. 1000 5000 800 4000 600 3000 Ischemic stroke/TIA and intracranial hemorrhage 400 2000 volumes 200 * 1000 0 0 The ischemic stroke/TIA admission volumes declined April week3 April week 1 April week 2 April week 4 Jan week 1 Jan week 2 Jan week 3 Jan week 4 Feb week 1 Feb week 2 Feb week 3 Feb week 4 March week 1 March week 2 March week 3 March week 5 Dec week 1 Dec week 2 Dec week 3 Dec week 4 Dec week 5 May week 1 May week 2 May week 3 May week 4 March week 4 from 19,882 to 16,884 patients across the three months preceding versus the pandemic months, corresponding Ischemic Stroke only ICH COVID Hospitalizaons to a 15.1% (95%CI, 15.6 to 14.6, N ¼ 113 sites) reduction with an adjusted mean (SE) number of ische- *Peak of 1235 COVID hospitalizations in the second week of February, predom- inantly from one hospital in Wuhan, China. mic stroke or TIA/month/center decreasing from 64.3 (6.8) to 55.6 (6.5) across the two epochs (p < 0.0001). Complete results are presented in Table S4. The ICH admission volumes, submitted by 100 sites, decreased from 4002 to 3540 patients across the three Figure 2. Weekly volume of mechanical thrombectomy and months immediately before versus the pandemic COVID-19 hospitalizations. months, representing an 11.5% (95%CI, 12.6 to 10.6) decline with the adjusted mean (SE) number Mechanical Thrombectomy vs COVID-19 Hospitalizaons 400 9000 of hospitalizations for ICH/month/center dropping Weekly number of COVID-19 Hospitalizaons 350 8000 Weekly number of MT volume from 13.4 (2.6) to 11.6 (2.6) across the two periods 300 7000 (p < 0.0001), Table S5. 250 6000 5000 200 4000 150 Changes in stroke care metrics during the 100 3000 2000 * pandemic as a function of COVID-19 50 1000 0 0 hospitalization volumes April week3 April week 1 April week 2 April week 4 Jan week 1 Jan week 2 Jan week 3 Jan week 4 Feb week 1 Feb week 2 Feb week 3 Feb week 4 Dec week 1 Dec week 2 Dec week 3 Dec week 4 Dec week 5 March week 1 March week 2 March week 3 March week 4 March week 5 May week 1 May week 2 May week 3 May week 4 Figures 1 and 2 provide the weekly volume of stroke admissions (ischemic and hemorrhagic), MT, and Mechanical Thrombectomy COVID Hospitalizaons COVID-19 hospitalizations. COVID-19 hospital *Peak of 1235 COVID hospitalizations in the second week of February, predom- weekly volume data was available for 131 centers. inantly from one hospital in Wuhan, China. There was an early peak of 1235 COVID-19 hospital- izations in February which predominantly originated from one hospital in Wuhan, China. Significant reduc- tions in the mean monthly volumes were seen for all stroke care metrics across all tertiles of low, mid, and (12.6%; 95%CI, 13.4 to 11.9; p < 0.0001) high COVID-19 hospitalization volumes. COVID-19 centers, Table 1. The exception was ICH volumes in high-volume COVID-19 centers which did not show a statistically Changes in stroke care metrics during the significant difference (Tables 1, S4, and S5). High- pandemic as a function of stroke center MT and volume COVID-19 centers (20.5%; 95%CI, 22.6 to 18.6) had greater declines in MT volumes than admission volumes mid- (10.1%; 95%CI, 11.8 to 8.6; p < 0.0001) Significant declines in the mean monthly volumes were and low-volume (8.7%; 95%CI, 10.7 to 7.1; observed for all stroke/MT metrics across low-, mid-, p < 0.0001) COVID-19 centers, Table 2. Likewise, and high-volume stroke/MT centers except MT vol- high-volume COVID-19 centers (22.7%; 95%CI, umes in low-volume MT centers showed a trend in 23.7 to 21.8) had greater reductions in stroke hos- decline (Tables 1, 2, S4, and S5). Mid-volume stroke pitalization volumes than mid- (19.8%; 95%CI, centers (17.6%; 95% CI, 18.5 to 16.7) demon- 20.8 to 19.0; p < 0.0001) and low-volume strated greater decreases in stroke admission volumes International Journal of Stroke, 16(5) 578 International Journal of Stroke 16(5) than low-volume (15.1%; 95%CI, 16.3 to 13.9; the pandemic. While at first glance this might suggest p < 0.0001) centers, Table 1. that the intra-hospital workflow was maintained, it is possible that this was not the case since one would actually expect an increase in the MT ratio relative to Secondary objective stroke admissions as many studies have now demon- Table S6 depicts the volumes for overall stroke, ische- strated that there was a preferential decline in patients mic stroke/TIA, ICH hospitalizations, and MT proced- presenting with milder strokes during the pan- ures during the first three months of the pandemic demic.4,11,18–20 The decreases in the amount of stroke versus the corresponding period in the prior year. care were noted across centers with high, mid, and low Compared to the prior year, there were significant COVID-19 hospitalization burden and also across declines in the monthly volumes for stroke and ischemic high, mid, and low volume stroke and MT centers. stroke/TIA admissions but not for ICH and MT. As hypothesized, centers with higher COVID-19 inpa- tient volumes suffered more declines. Contrary to our Associations between the diagnoses of COVID-19 expectations, the declines in stroke hospitalizations and MT volumes were more profound in mid-(and high-) and stroke volume than low-volume stroke centers. This might be There were 124 centers that reported patients with con- related to the fact that larger centers were more likely to comitant stroke (all subtypes) and SARS-CoV-2 infec- become the preferred destination for COVID-19 refer- tion. To reduce bias, 13 centers with no COVID-19 rals leading to capacity issues. Finally, we confirmed a patients were excluded, leaving 111 eligible centers. A broad geographic variation in the patterns of stroke diagnosis of any stroke was present in 791 of 54,366 care decline. (1.45%; 95% CI 1.35–1.55) COVID-19 hospitaliza- Our results align with recent reports emphasizing the tions. There was geographic variation with incidences collateral effects of the COVID-19 pandemic on stroke ranging from 0.43% (95%CI 0.08–2.38) in Oceania to systems of care from China,10,18 Spain,3,19 Italy,21,22 11.9% in South America (95%CI 10.05–14.03), Table France,9,23 Germany,12 Brazil,20 Canada,24 and S7. Conversely, 784 of the 20,250 (3.9%, 95% CI 3.61– United States,5,11,25,26 showing declines in the volumes 4.14) overall stroke admissions were diagnosed with for MT, IVT, and stroke hospitalizations over the pan- COVID-19 with proportions varying from 0.14% demic (Table S9–11). Some of these studies also (95%CI 0.03–0.78) in Oceania to 8.93% in South reported delays in hospital arrival times18,21,25 and America (95%CI 7.54–10.55), Table S8. treatment workflow.9,21 Our analysis adds to the grow- ing literature regarding the collateral damage of COVID-19 on stroke care with the advantage of pro- Discussion viding a broader global perspective. While the overall We noted a significant global decline in all measured data clearly points to a significant reduction in the stroke care metrics in the current study including the quantity of stroke care provided during the pandemic, numbers of mechanical thrombectomy procedures it also depicts variations within and across the different (12.7%), overall stroke admissions (19.2%), ische- regions reflecting the diversity in the epidemiology for mic stroke/TIA admissions (15.1%), and intracranial COVID-19 as well as in the socio-cultural behaviors, hemorrhage hospitalization volumes (11.5%) during healthcare logistics, and infrastructure encountered the COVID-19 pandemic as compared to the immedi- across the globe. Indeed, our study demonstrated ately preceding three months, confirming our primary important geographic variations in the proportional hypothesis. Volume reductions were also seen in rela- declines for both stroke hospitalization and MT vol- tion to the equivalent period in the prior year for stroke umes. Notably, our analysis may have underestimated admissions and ischemic/TIA admissions. The intensity the impact of geographic disparities in healthcare of the decline was more pronounced when comparing resources and related socio-economic factors as we the pandemic period with the immediate three months only included thrombectomy capable centers which prior than with the same months in 2019 (MT: 12.7% are known to have better infrastructure than the more vs. 6.0%; stroke admissions: 19.2% vs. 12%). This fol- commonly found primary stroke centers. Moreover, lowed our a priori expectations in face of the expan- there was a higher geographic variation in the propor- sions in MT indications along with its progressive but tional decline for stroke hospitalization (Asia, 20.5%; gradual global implementation in developed and North America, 20.6%; Europe, 11.2%; South developing countries.17 Interestingly, despite the abso- America, 15.9%, Oceania, 11.6%; Africa, lute decrease in MT volumes, the proportion of MT 48.1%) than mechanical thrombectomy (Asia, relative to stroke admissions remained stable during 9.8%; North America, 14.5%; Europe, 14.4%; International Journal of Stroke, 16(5) Nogueira et al. 579 South America, 12.4%, Oceania, 9.4%; Africa, contained centers with high and low COVID-19 hospi- 21.2%) volumes. As seen in relation to the stability talization admissions, high and low stroke admission, in the MT ratio relative to stroke admissions, this might and MT volumes, permitting the generation of multiple have been related to the favored decline in milder hypotheses and endpoints. strokes over the course of the pandemic.4,11,18–20 The limitations of this study were that the diagnosis Given the growing evidence supporting the association of stroke/TIA/ICH, thrombectomy volume in some between COVID-19 and thromboembolic events, it centers was obtained using hospital ICD administrative would be expected that the stroke incidence would codes, and verification for accurate diagnosis was not rise at the precipice of the pandemic. Several factors universally undertaken. The centers contributing to may explain this paradoxical global decrease in these data have systems in place to track stroke admis- stroke, MT, and ICH volumes observed in this study. sions; thus, the relative changes in volume from this As this decline in stroke volume was seen in centers analysis are likely accurate. Details on patient-level with low or non-existent COVID-19 hospitalizations, data including demographics, stroke subtypes, and clin- hospital access due to the COVID-19 hospitalization ical outcomes were not collected as these were not the burden was unlikely a major factor.12 As elective sur- focus of the study. As with any other study, our data geries were canceled with the pandemic, a decrease in may underestimate true rates of concomitant SARS- perioperative stroke may have played a role. It is also CoV2 infection with a stroke diagnosis depending on conceivable that the environmental situation of a lock- the frequency of testing at each site and across the down, with improved patient behaviors or medication study period. The definition of the pandemic period compliance, may be protective in decreasing vascular was arbitrary since the outbreak started and peaked events.27 A reduction in exposure to other common at different times at different locations. After adjust- viruses that may play a role in triggering vascular ment for peak COVID-19 volume for each country events may have also reduced stroke risk. However, it and continent, the monthly volume declines were is unlikely that true incidence of stroke declined and retained for all stroke metrics (stroke hospitalization, more likely the behavioral and infrastructural changes MT, ICH). As the penetration of MT remains limited related to the pandemic led to a reduction of admission in many countries,17 some geographic regions were not of AIS patients, especially during the initial phases of represented (i.e. central Africa). We did not collect data public lockdown. Fear of contracting SARS-CoV-2 on the timing or intensity of social distancing policies may have led many patients with milder stroke presen- including lockdown implementation across the different tations to avoid seeking medical attention.4,11,18–20 localities which likely played an important role in the Physical distancing measures may have prevented reported stroke care decline. Finally, the sampling patients from the timely witnessing of a stroke. varied with the availability of complete data in each Our subgroup of 111 centers including 54,366 subset of the analysis. COVID-19 hospitalizations is the largest sample report- ing the concomitant diagnoses of stroke and SARS- Summary CoV-2 infection to date. Our 1.45% stroke rate in COVID-19 hospitalizations is similar to the pooled There was a significant global decline in mechanical incidence of 1.1–1.2% (range, 0.9–2.7%) of hospita- thrombectomy and stroke admissions over the three lized COVID-19 patients.28,29 Some variations in the months studied during the pandemic. These decreases proportions are expected given the different definitions were seen regardless of COVID-19 admission burden, (all strokes vs. ischemic only) and populations involved individual pre-pandemic stroke, and MT volumes. (all hospitalized vs. severely infected only) across stu- Thus, it is critical to expeditiously raise public awareness dies. We also provide a new perspective on this rela- to prevent the additional healthcare consequences asso- tionship by reporting an incidence of 3.9% (784/20,250) ciated with the lack of stroke treatment. These findings for SARS-CoV-2 infection across all stroke admissions can inform regional stroke networks preparedness29 in among centers with documented COVID-19 the face of a future pandemic or anticipated surge of hospitalization. COVID-19 cases in order to ensure that the access and quality of stroke care remains preserved despite the crises imposed by the continuous spread of the virus. Study strengths and limitations The strength of our study was the large volume of Acknowledgements patients (n ¼ 64,416) and a high number of centers Patrick Nicholson, MD, Jasmine Johann, MSN, FNP-BC, (n ¼ 187) contributing data from a diverse population Judith Clark, RN, Matt Metzinger, MBA, CPHQ, across six continents and 40 countries. Our study Jefferson, Kamini Patel, RN, MBA, Janis Ginnane, RN. International Journal of Stroke, 16(5) 580 International Journal of Stroke 16(5) Disclosures Santiago Ortega-Gutierrez41, Mudassir Farooqui41, Ameer Dr Nguyen: Medtronic. E. Hassan42, Allan Taylor43, Bertrand Lapergue44, Arturo Dr Nogueira: Stryker; Cerenovus/Neuravi; Ceretrieve. Consoli45, Bruce CV Campbell46, Malveeka Sharma47, Dr Walker: Medtronic, Cerenovus. Melanie Walker48, Noel Van Horn49, Jens Fiehler49, Huy Thang Nguyen50, Quoc T.Nguyen50, Daisuke Watanabe51, Hao Zhang52, Huynh V. Le53, Viet Q. Nguyen53, Ruchir Declaration of conflicting interests Shah54, Thomas Devlin54, Priyank Khandelwal55, Italo The author(s) declared no potential conflicts of interest with Linfante56, Wazim Izzath57, Pablo M.Lavados58, Veronica respect to the research, authorship, and/or publication of this V. Olavarrı́a58, Gisele Sampaio Silva59, Anna Verena de article. Carvalho Sousa60, Jawad Kirmani61, Martin Bendszus62, Tatsuo Amano63, Ryoo Yamamoto64, Ryosuke Doijiri65, Funding Naoki Tokuda66, Takehiro Yamada67, Tadashi Terasaki68, The author(s) received no financial support for the research, Yukako Yazawa69, Jane G. Morris70, Emma Griffin71, John authorship, and/or publication of this article. Thornton71, Pascale Lavoie72, Charles Matouk73, Michael D. Hill74, Andrew M. Demchuk74, Monika Killer-Oberpfalzer75, ORCID iDs Fadi Nahab76, Dorothea Altschul77, Anna Ramos-Pachón78, Natalia Pérez de la Ossa78, Raghid Kikano79, William Y Mansour https://orcid.org/0000-0001-8814-6431 Boisseau80, Gregory Walker81, Steve M. Cordina82, Ajit Zhongming Qiu https://orcid.org/0000-0002-1622-9526 Puri83, Anna Luisa Kuhn83, Dheeraj Gandhi84, Pankajavalli James E Siegler https://orcid.org/0000-0003-0287-3967 Ramakrishnan85, Roberta Novakovic-White86, Alex Chebl87, Laura Mechtouff https://orcid.org/0000-0001-9165-5763 Odysseas Kargiotis88, Alexandra Czap89, Alicia Zha89, Omer Eker https://orcid.org/0000-0002-5696-5368 Hesham E. Masoud90, Carlos Lopez90, David Ozretic91, Raoul Pop https://orcid.org/0000-0003-4417-1496 Fawaz Al-Mufti92, Wenjie Zie93, Zhenhui Duan94, Juan F Arenillas https://orcid.org/0000-0001-7464-6101 Zhengzhou Yuan95, Wenguo Huang96, Yonggang Hao97, Mahmoud Mohammaden https://orcid.org/0000-0002- Jun Luo98, Vladimir Kalousek99, Romain Bourcier100, 7393-9989 Romain Guile100, Steven Hetts101, Hosam M. Al-Jehani102, Simon Nagel https://orcid.org/0000-0003-2471-6647 Adel AlHazzani103, Elyar Sadeghi-Hokmabadi104, Mudassir Farooqui https://orcid.org/0000-0003-3697-5697 Mohamed Teleb , Jeremy Payne , Jin Soo Lee106, Ji 105 105 Ameer E Hassan https://orcid.org/0000-0002-7148-7616 Man Hong106, Sung-Il Sohn107, Yang-ha Hwang108, Dong Allan Taylor https://orcid.org/0000-0002-2692-2068 Hoon Shin,109, Hong Gee Roh110, Randy Edgell111, Rakesh Bertrand Lapergue https://orcid.org/0000-0002-8993-2175 Khatri112, Ainsley Smith113, Amer Malik114, David Bruce CV Campbell https://orcid.org/0000-0003-3632- Liebeskind115, Nabeel Herial116, Pascal Jabbour116, Pedro 9433 Magalhaes117, Atilla Ozcan Ozdemir118, Ozlem Aykac118, Noel Van Horn https://orcid.org/0000-0001-5764-1982 Takeshi Uwatoko119, Tomohisa Dembo120, Hisao Ryoo Yamamoto https://orcid.org/0000-0001-8585-9831 Shimizu , Yuri Sugiura , Fumio Miyashita123, Hiroki 121 122 Takehiro Yamada https://orcid.org/0000-0001-5196-1934 Fukuda124, Kosuke Miyake125, Junsuke Shimbo126, Yusuke Yukako Yazawa https://orcid.org/0000-0003-3891-0221 Sugimura127, Andre Beer-Furlan128, Krishna Joshi128, Jane Morris https://orcid.org/0000-0001-5256-8165 Luciana Catanese129, Daniel Giansante Abud130, Octavio Michael D Hill https://orcid.org/0000-0002-6269-1543 Pontes Neto131, Masoud Mehrpour132, Amal Al Hashmi133, Thanh Nguyen https://orcid.org/0000-0002-2810-1685 Mahar Saqqur134, Abdulrahman Mostafa135, Johanna T. Fifi136, Syed Hussain137, Seby John137, Rishi Gupta138, Authors Rotem Sivan-Hoffmann139, Anna Reznik139, Achmad Raul G. Nogueira1,*, Mohamad Abdalkader2, Muhammed Fidaus Sani140, Serdar Geyik141, Eşref Akıl141, Anchalee M. Qureshi3, Michael R. Frankel4, Ossama Yassin Churojana142, Abdoreza Ghoreishi143, Mohammad Mansour5,**, Hiroshi Yamagami6,#, Zhongming Qiu7, Saadatnia144, Ehsan Sharifipour145, Alice Ma146, Ken Mehdi Farhoudi8, James E. Siegler9, Shadi Yaghi10, Eytan Faulder146, Teddy Wu147, Lester Leung148, Adel Malek149, Raz11, Nobuyuki Sakai12,#, Nobuyuki Ohara13,#, Michel Barbara Voetsch150, Ajay Wakhloo151, Rodrigo Rivera152, Piotin14, Laura Mechtouff15, Omer Eker16, Vanessa Danny Moises Barrientos Iman153, Aleksandra Pikula154, Chalumeau17, Timothy J. Kleinig18, Raoul Pop19, Jianmin Vasileios-Arsenios Lioutas155, Gotz Thomalla156, Lee Liu20, Hugh S.Winters21, Xianjin Shang22, Alejandro Birnbaum157, Paolo Machi158, Gianmarco Bernava158, Rodriguez Vasquez23, Jordi Blasco24, Juan F.Arenillas25, Mollie McDermott159, Dawn Kleindorfer159, Ken Wong160, Mario Martinez-Galdamez26, Alex Brehm27, Marios- Mary S.Patterson161, Jose Antonio Fiorot,Jr162, Vikram Nikos Psychogios27, Pedro Lylyk28, Diogo C.Haussen29, Huded163, William Mack164, Matthew Tenser164, Clifford Alhamza R.Al-Bayati29, Mahmoud H. Mohammaden29, Eskey165, Sumeet Multani166, Michael Kelly167, Vallabh Luı́sa Fonseca30, M Luı́s Silva31, Francisco Montalverne32, Janardhan168, Oriana Cornett169, Varsha Singh169, Yuichi Leonardo Renieri33, Salvatore Mangiafico33, Urs Fischer34, Murayama170, Maxim Mokin171, Pengfei Yang172, Xiaoxi Jan Gralla35,Donald Frei36, Chandril Chugh37, Brijesh Zhang172, Congguo Yin173, Hongxing Han174, Ya Peng175, P.Mehta38, Simon Nagel39, Markus Mohlenbruch40, Wenhuo Chen176, Roberto Crosa177, Michel Eli Frudit178, International Journal of Stroke, 16(5) Nogueira et al. 581 Jeyaraj D.Pandian179, Anirudh Kulkarni179, Yoshiki 15 Neurologie, Hospices Civils de Lyon, France Yagita180, Yohei Takenobu181, Yuji Matsumaru182, Satoshi 16 Neuroradiologie, Hospices Civils de Lyon, France Yamada183, Ryuhei Kono184, Takuya Kanamaru185, 17 Hôpital Bicetre, Paris, France Hidekazu Yamazaki86, Manabu Sakaguchi187, Kenichi 18 Royal Adelaide Hospital, Australia Todo188, Nobuaki Yamamoto189, Kazutaka Sonoda190, 19 Hôpitaux Universitaires de Strasbourg, France Tomoko Yoshida191, Hiroyuki Hashimoto192, Ichiro 20 Changhai Hospital, Shanghai, China Nakahara193, Elena Cora, MD194, David Volders194, Celina 21 Royal Prince Alfred Hospital, Sydney, Australia Ducroux195, Ashkan Shoamanesh196, Johanna Ospel197, 22 Yijishan Hospital of Wannan Medical College, China Artem Kaliaev198, Saima Ahmed199, Umair Rashid199, 23 Neurology, Hospital Clinic de Barcelona, Spain Leticia C. Rebello200, Vitor Mendes Pereira201, Robert 24 Interventional Neuroradiology, Hospital Clinic de Fahed202, Michael Chen203, Sunil A Sheth204, Lina Barcelona, Spain Palaiodimou205, Georgios Tsivgoulis205, Ronil Chandra206, 25 Neurology, Hospital Clı́nico Universitario, Valladolid, Feliks Koyfman207, Thomas Leung208, Houman Khosravani Spain 209 , Sushrut Dharmadhikari210, Giovanni Frisullo,211, Paolo 26 Interventional Neuroradiology, Hospital Clı́nico Calabresi,211, Alexander Tsiskaridze,212, Nino Lobjanidze,212, Universitario, Valladolid, Spain Mikayel Grigoryan,213, Anna Czlonkowska,214, Diana 27 University Hospital Basel, Switzerland Aguiar de Sousa,215, Jelle Demeestere216, Conrad Liang217, 28 Clı́nica Sagrada Familia, Buenos Aires, Argentina Navdeep Sangha218, Helmi L. Lutsep219, Óscar Ayo- 29 Neurology, Grady Memorial Hospital, Emory University, Martı́n220, Antonio Cruz-Culebras221, Anh D.Tran222, Atlanta, Georgia, USA Chang Y.Young,223, Charlotte Cordonnier224, Francois 30 Stroke, Centro Hospitalar Universitário de São João, Caparros224, Maria Alonso De Lecinana225, Blanca Portugal Fuentes225, Dileep Yavagal226, Tudor Jovin227, Laurent 31 Neuroradiology, Centro Hospitalar Universitário de São Spelle228, Jacques Moret228, Pooja Khatri229, Osama João, Portugal Zaidat230, Jean Raymond231, Sheila Martins232, Thanh 32 Hospital Geral de Fortaleza, Brazil Nguyen233*. On behalf of the SVIN COVID-19 Global 33 Careggi University Hospital, Florence, Italy 34 Registry, the Middle East North Africa Stroke and Neurology, University Hospital Bern, Switzerland 35 Interventional Neurotherapies Organization (MENA- Interventional Neuroradiology, University Hospital Bern, SINO)** and Japanese Vascular and Interventional Switzerland 36 Neurology Society (JVIN)# Swedish Medical Center, USA 37 *Drs. Nogueira and Nguyen contributed equally to this MAX Superspecialty Hospital, India 38 article. Memorial Neuroscience Institute, Florida 39 1 Neurology, University Hospital Heidelberg, Germany Neurology, Grady Memorial Hospital, Emory University, 40 Neuroradiology, University Hospital Heidelberg, Germany Atlanta, Georgia, USA 41 2 Neurology, University of Iowa, USA Radiology, Boston Medical Center, Boston University 42 Neurosciences, Valley Baptist Medical Center, Harlingen, School of Medicine, Boston, USA 3 Texas, USA Radiology, Radiation Oncology, Boston Medical Center, 43 Neurosurgery, University of Cape Town, South Africa Boston University School of Medicine, Boston, USA 44 4 Neurology, Hôpital Foch, France Neurology, Grady Memorial Hospital, Emory University, 45 Interventional Neuroradiology, Hôpital Foch, France Atlanta, Georgia, USA 46 5 Royal Melbourne Hospital, Melbourne, Australia Neurology Department, Stroke and Neurointervention 47 Neurology, University of Washington, Seattle, USA Division, Alexandria University Hospital, Alexandria 48 Neurosurgery, University of Washington, Seattle, USA University, Egypt 49 6 Interventional Neuroradiology, Universitätsklinikum Stroke Neurology, National Hospital Organization, Osaka Hamburg-Eppendorf, Germany National Hospital, Japan 50 7 People’s 115 Hospital, Vietnam Neurology, Xinqiao Hospital of the Army Medical 51 IMS Tokyo-Katsushika General Hospital, Japan University, Chongqing, China 52 8 Affiliated Hangzhou First People’s Hospital, China Tabriz University, Iran 53 9 Hue Central Hospital, Vietnam Neurology, Cooper Neurological Institute, Cooper 54 Erlanger Medical Center, USA University Hospital, Camden, New Jersey, USA 55 10 Rutgers University, USA Neurology, Radiology, New York University School of 56 Miami Cardiac and Vascular Institute, USA Medicine, New York, USA 57 11 Nottingham University Hospitals, United Kingdom Radiology, Neurology, New York University School of 58 Clı́nica Alemana, Universidad del Desarrollo, Chile Medicine, New York, USA 59 12 Universidade Federal de Sao Paulo Hospital Israelita Neurosurgery, Kobe City Medical Center General Hospital, Albert Einstein, Brazil Kobe, Japan 60 13 Hospital Israelita Albert Einstein, Brazil Neurology, Kobe City Medical Center General Hospital, 61 Hackensack Meridian Health, New Jersey, USA Kobe, Japan 62 14 Neuroradiology, University Hospital Heidelberg, Germany Fondation Ophtalmologique Adolphe de Rothschild, 63 Kyorin University, Japan 64 Yokohama Brain and Spine France Center, Japan International Journal of Stroke, 16(5) 582 International Journal of Stroke 16(5) 65 121 Iwate Prefectural Central Hospital, Japan Nara City Hospital, Japan 66 122 Japanese Red Cross Kyoto Daiichi Hospital, Japan Toyonaka Municipal Hospital, Japan 67 123 Kyoto Second Red Cross Hospital, Japan Kagoshima City Hospital, Japan 68 124 Japanese Red Cross Kumamoto Hospital, Japan Japanese Red Cross Matsue Hospital, Japan 69 125 Kohnan Hospital, Japan Shiroyama Hospital, Japan 70 126 Neurology, Maine Medical Center, USA Niigata City General Hospital, Japan 71 127 Beaumont Hospital, Dublin, Ireland Sugimura Hospital, Kumamoto, Japan 72 128 Hopital Enfant Jesus, Quebec City, Canada Rush University Medical Center, USA 73 129 Yale New Haven Hospital, USA Neurology, McMaster University, Canada 74 130 Neurology, University of Calgary, Canada Interventional Neuroradiology, Ribeirão Preto Medical 75 University Hospital Salzburg, Austria School, Brazil 76 131 Emory University School of Medicine, USA Neurosciences, Ribeirão Preto Medical School, Brazil 77 132 Valley Hospital, New Jersey, USA Shahid Beheshti University, Iran 78 133 University Hospital Germans Trias i Pujol, Barcelona, Khoula Hospital, Ministry of Health, Oman 134 Spain Hamad Medical Corporation, Qatar 79 135 Lau Medical Center, Beirut, Lebanon Alexandria University Hospital, Egypt Hamad Medical 80 CHU Montreal, Canada Corporation, Qatar 81 136 University of Ottawa, Canada Mount Sinai Health System, New York, USA 82 137 University of South Alabama, USA Cleveland Clinic Abu Dhabi, UAE 83 138 University of Massachusetts Medical Center, USA WellStar Health, Marietta, Georgia, USA 84 139 University of Maryland, USA Rambam Health Care, Israel 85 140 Riverside Regional Medical Center, Virginia, USA General Hospital Dr. Soetomo, Indonesia 86 141 UT Southwestern, Dallas, Texas, USA Istanbul Aydın University, Turkey 87 142 Henry Ford Health System, Detroit, USA Siriraj Hospital, Thailand 88 143 Metropolitan Hospital, Piraeus, Greece Zanjan University, Iran 89 144 UTHealth McGovern Medical School, Houston, USA Isfahan University, Iran 90 145 SUNY Upstate Medical University Hospital, USA Qom University, Iran 91 146 University Hospital Centre Zagreb, Croatia Royal North Shore Hospital, Australia 92 147 Westchester Medical Center, USA Christchurch Hospital, Christchurch , New Zealand 93 148 Xinqiao Hospital of the Army Medical University, China Neurology, Tufts Medical Center, USA 94 149 Wuhan No.1 Hospital, China Neurosurgery, Tufts Medical Center, USA 95 150 Affiliated Hospital of Southwest Medical University, China Neurology, Beth Israel Lahey Health, USA 96 151 Maoming Traditional Chinese Medicine Hospital, China Interventional Neuroradiology, Beth Israel Lahey Health, 97 Shaw Shaw Hospital, China USA 98 152 Mianyang 404 Hospital, China Neuroradiology, Instituto de Neurocirugia Dr. Asengo, 99 University Clinical Hospital Center Sestre Milosrdnice, Chile 153 Croatia National Institute of Neurological Sciences of Lima, Peru 100 154 CHU Nantes, France University of Toronto, Canada 101 155 University of California San Francisco, USA Neurology, Beth Israel Lahey Health, USA 102 156 King Fahad Hospital of the University, Saudi Arabia Neurology, Universitätsklinikum Hamburg-Eppendorf, 103 King Saud University, Saudi Arabia Germany 104 157 Tabriz University, Iran University of Texas San Antonio, USA 105 158 Banner Desert Medical Center, USA University Hospitals of Geneva, Switzerland 106 159 Ajou University Hospital, Korea University of Michigan, USA 107 160 Kyemyung University, Korea Royal London Hospital, United Kingdom 108 161 Kyungpook National University Hospital, Korea Bon Secours Mercy Health, USA 109 162 Gachon University Gil Hospital, Korea Hospital-Estadual Central, Brazil 110 163 Konkuk University Hospital, Korea NH Mazumdar Shaw Medical Center, India 111 164 St. Louis University, USA University of Southern California, USA 112 165 Texas Tech University, USA Dartmouth Hitchcock Medical Center, Lebanon, New 113 Cooper University Hospital, USA Hampshire, USA 114 166 University of Miami, USA Neurology, Bayhealth Medical Center, Delaware, USA 115 167 UCLA, Los Angeles, USA Neurosurgery, University of Saskatchewan, Canada 116 168 Thomas Jefferson University Hospital, USA Medical City Plano Texas, USA 117 169 Hospital Sao Jose, Brazil St. Joseph’s University Medical Center, USA 118 170 Eskisehir Osmangazi University, Turkey Jikei University School of Medicine, Japan 119 171 Saga-ken Medical Centre Koseikan, Japan University of South Florida, USA 120 172 Saitama Medical Center, Japan Changhai Hospital, Shanghai, China International Journal of Stroke, 16(5) Nogueira et al. 583 173 230 Affiliated Hangzhou First People’s Hospital, China Bon Secours Mercy Health, Toledo, Ohio, USA 174 231 Linyi City People Hospital, China CHU Montreal, Canada 175 232 First People’s Hospital, China Hospital de Clı́nicas de Porto Alegre, Brazil 176 233 Zhangzhou Municipal Hospital, China Radiology, Neurology, Boston Medical Center, USA 177 Centro Endovascular Neurológico Médica, Uruguay 178 Universidade Federal de Sao Paulo, Brazil 179 Christian Medical College, India Supplemental material 180 Supplemental material for this article is available online. 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