12 '5¢ Aeeuey wo S10 punning my papeojsAog, Stroke BRIEF REPORT Acute Stroke in Times of the COVID-19 Pandemic A Multicenter Study Carolin Hoyer®, MD; Anne Ebert, PhD; Hagen B. Hutiner, MD; Volker Puetz, MD; Bernd Kaliminzer, MD; Kristian Barlinn, MD; Christian Haverkamp, MD; Andreas Harloff, MD; Jochen Brich, MD; Michael Platten, MD; Kristina Szabo, MD ‘BACKGROUND AND PURPOSE: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. ‘METHODS: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of ‘rips taken and hospital admission for stroke/transient ischemic attack. RESULTS: Only litle variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number ‘of admissions for transient ischemic atiack was observed (~85%, ~46%, ~42%h) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, -60%; thrombectomy, 61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 8 of 4 centers. ‘CONCLUSIONS: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period, Hence, raising public awareness is necessary to avoid serious healthcare and ‘economic consequences of undiagnosed and untreated strokes and transient ischemic attacks. Key Words: brain fschemia m pandemics m repertusion m stroke m thrombectomy 9) pandemic poses unprecedented challenges to healthcare systems worldwide. Infections and fatal- ties are continuously rising, necessitating restructuring of health services and the reallocation of resources in many places. Stroke is the second leading cause of death world- wide, and absolute numbers of incident strokes, survivors, T: ‘ongoing coronavirus disease 2019 (COVID- 1 stroke-related deaths, and disabilty-adjusted life-years are globally increasing. In high-income countries, tremen- dous efforts in improving prevention, acute treatment, and neurorehabilitation have led to a substantial decrease in the burden of stroke over the past 30 years.’ During the recent spread of COVID-19, neurologists worldwide have reported the impression of an apparent reduction of numbers of patients with acute stroke seeking medical CCarrspondance te Carln Hoyer MO, Department of Newology Unveraitmedn Mannheim, Theodor Kulzer -3, 68167 Mannheim, Germany El crc hoyer@umme “hie manuscript was sont to Mar Fisher, Sartor Contig Er orrvien by expert referees, edorial deco, and nal dposton, For Sources o Funding ad Disclose, se page 2227 © 2020 Ametean Heat Associton ne ‘Stoke's svalabo at wawahaourlsorg/oural/st 2224 July 2020 ‘Stroke, 2020;512224-2997, DOI: 10.1 161/STROKEAHA 120030095 CamScanner 3 Li3.5 4>9.ueal!12 '5¢ Aeeuey wo S10 punning my papeojsAog, Hoyer et al ‘Stroke and COVID-19 ‘emergency care.? Reasons for this phenomenon are not Understood although some suggest that patients’ fear of in-hospital infection causes avoidance behavior. The objective of this study was to assess and quantity the dynamics of admission for stroke and transient isch- ‘emic attack (TIA) and rates of reperfusion therapies dur- ing the COVID-19 pandemic and to estimate a potential impact of the partial lockdown in Germany. METHODS This retrospective cohort study was performed at 4 German comprehensive siroke centers (University Hospital Dresden, University Exlangen-Nuremberg, Medical Center University of Freiburg, University Medical Center Mannheim; A-D, not in alphabetic order), collectively treating about 6000 stroke and “TA patients per year Te study was approved by the respective local ethics committees. Written informed consent was waived «due to the retrospective characte ofthe investigation ‘Numbers of patients admitted with final diagnoses of isch- ‘emic stroke or TIA between January 1, 2019, Apil 14, 2019 (weeks 1-16), and between January 1, 2020, and April 12, 2020 (weeks 1-18), and information regarding reperfusion therapies (intravenous thrombolysis and mechanical throm- bectomy) were gathered from main discharge diagnosis docu- mentation according to the German diagnosis-related group system. Treatment was defined by Operation and Procedure Classification System codes for intravenous thrombolysis and thrombectomy, Week 12, beginning March 16, 2020, was defined as the ‘week when the COVID-19 pandemic began to impact public life in Germany. Extended measures for social distancing, for ‘example, through closure of schools/day care and partial lock down in all German federal states, were implemented beginning March 16, 2020, and were strongly advocated by the German ‘Chancellor in her television address on March 18, 2020. ‘Anonymized mobility data were obtained from Teralytcs, Zurich, Switzerland, and include the number of trips and Kilometers traveled in Dresden, Erlangen, Freiburg, and Mannheim. Mobility data are generated through the registra- tion of mobile phones with cell towers. Movements are reg- istered when an individual switches cell tower areas. They ae attributed to special aggregation areas. Mobility flows are ‘generated from the aggregation ofall movements in a certain time frame. Information regarding the local case numbers of COVID-19 infections was obtained from the Robert Koch Institute? ‘Anonymized data will be shared by request from any quali- fied investigator. Statistical Analysis Calendar weeks 1 to 11 and 12 to 1 were categorized into a vatiable epoch forthe years 2019 and 2020. The dependent variables were count of admitted strokes, TAs, intravenous thrombolysis, and thrombectomy. Poisson regression was used to test whether the rate of events (admissions for stroke/TIA, intravenous thrombolysis, thrombectomy) changed as a func~ tion of year (2019-2020), epach (weeks 1—11, early; weeks 12-15, late), and the interaction of year and epoch (reflecting Stroke, 2020(512224-2997, DOK: 10.1 161/STROKEAHA 120030395 the impact of the COVID-19 pandemic). This efectis expressed 1s an incidence rate ratio along with its 2-sided 95% Ci: incidence rate2020 Incidence rate ratio= incidence rate2019 incidence rate2020 = TUBE of events in late epoch2020 ‘number of events in early epoch2020 and where umber of events in late epoch2019 incidence rate2019 fas ‘number of events in early epoch 2019 For the covariance matrix, a robust estimator was chosen to account for possible overdispersion. Rank correlations (Spearman tho) were calculated to ana Iyze correlations between mobility and admission for isch- emic cerebrovascular events. PXO.05 indicates statistical significance. Statistical analysis was performed using IBM SPSS Statistics, version 25. RESULTS Only litle variation of admission rates was observed before and after week 11 in 2019 and between weeks 1 and 11 in 2019 and in 2020. Between early (weeks 1-11) and late (weeks 12-15) investigational peri- ods in 2019 and 2026, in all but center B, a signifi- cant decrease in the number of admissions for TIA was observed (center A: -85%; center C: ~43%; center D: ~46%). Moreover, in centers A and D, stroke admis- sion rates decreased significantly by 38% and 46%, as reflected by incidence rate ratios of 0.62 and 0.54, respectively (Table). A relevant effect of the year-by- epoch interaction on reperfusion therapies was found for center A with a significant drop in the thrombolysis rate by 60% and in the thrombectomy rate by 61%. For details, see the Table. Differences of cumulative admis sions for acute stroke and TIA in the 4 study centers between weeks 10 and 15 in 2020 and weeks 10 and 15 in 2019, as well as changes in mobility throughout the observation period in 2020, are shown in the Figure. From week 12 onward, a pronounced decrease in public mobilty was observed in all 4 cities, Positive corre- lations between the number of admissions due to stroke/ TIA and measures of mobility in the corresponding cities, were found for 3 of the 4 centers (center A-number of trips: r=0.54, P=0.045; kilometers traveled: 1,=0.54, P=0.047; center C—number of trips: r,=0.57, P=0.032; kilometers traveled: =0.54, 0.045; center D~kilome- ters traveled: r,=0.6 1, P=0.020). DISCUSSION This study identified an impact of the COVID-19 pan- demic on admissions for acute stroke and TIA and ly 2020 2095 CamScanner 3 Li3.5 4>9.ueal!12 '5¢ Aeeuey wo S10 punning my papeojsAog, Hoyer etal Stroke and COVID-19 ‘Table. IRRof Stroke Admissions and Reperfusion Therapies Between Early (Weeks 1-11) and Late (Weeks 12-18) Investigational Periods in 2019 and 2020 in Centers A to D IRR voto | 062 136 108 054 95% CL | 096-090 | 089-169 | 074-149 | 095-089 Pre | oor | sr” | 077 | ocos IRRTA 018 oat ose ona ssl | 004-081 047-175 | oa4-099 | 030-086 Prive | 000 | 07 | oor | oss IRRNT 040 090) 100 078 ssw or | 01-086 | 094-243 | o4e-21 | 026-219 Pun | oor | osse | 00s | 0620 IRR ME oso) 188 a | om seer | 7-087 087-404 | 048-200 | o3t-1.87 Pre | oo | o1c8 | oses | 0436 IRR Indestes indence rate rato: V7, Inavenoue tomboys: MTE. mechanical thrombectomy; and TIA, vansintschomic attack "AOS iniats state sgicance verifies observations recently made by neurologists in different countries? There are no reasons to assume that the incidence of stroke is decreasing, if anything, it may rise in the context of the pandemic, given the disease-associated predisposition for thromboembolic, events.‘ The 4 centers were affected differently: 3 of these hospitals are in federal states where the pandemic hit early and most severely (81.38, 89.76, 237.90 infec- tions/100.000 inhabitants during weeks 12-15, as reported by the Robert Koch Institute). In one center, ‘no significant impact of the COVID-19 pandemic was noted, which may be partly attributable to its location in a state with lower numbers of COVID-19 cases (66:39 infections/100000 inhabitants during weeks 12-18). It bears noting that in none of these centers were measures in place that changed the structure of pre- or early in-hospital stroke care during the pan- demic. Moreover, at no point since the beginning of the pandemic has there been a shortage of capacities for admission or patient care. While local characteristics may influence admission and reperfusion therapy rates, for example, through existing stroke networks or the size of a stroke center's catchment area, the decision to seek medical help in the first place, however, is independent of these factors. Alongside fear of infection, the confinement of patients to their home with family members as primary part ners of social interaction may result in communication sequences with delayed symptom disclosure and valida- tion of watch-and-wait strategies.® § in ween, Hoe Bo He Mette wiomarssmimc cmatrrsncn [ % Wess = a it 7 I = | @ @ 2 Figure. Difference (in percentage) of cumulative admissions for acute stroke (green) and transient ischemic attacks (TIA; blue) in 4 German comprehensive stroke centers between weeks 10 to 15 in 2020 and weeks 10 to 15 in 2019 (positive y axis) Difference (i percentage) of numberof tips (te) and klometors traveled (orange) inthe cowtesponding cities between weeks 210 11 and weeks 12 to 15 in 2020 (negative yaxis). WHO indicates Word Health Organization 2226 July 2020 ‘Stoke, 2020;512224-9997, DOI: 10.1 161/STROKEAHA 120080305 CamScanner 3 Li3.5 4>9.ueal!12 '5¢ Aeeuey wo S10 punning my papeojsAog, Hoyer et al ‘Stroke and COVID-19 itis noteworthy that reperfusion therapy rates, reflecting severe strokes, remained largely unaffected, Ths indicates that both patients and prehospital medical staff correctly recognize the need for urgent assessment and treatment despite the threat of coronavirus infection. However, with the decrease in the number of admissions most noticeable {for TIA, the fear of infection and adhering to advice from health organizations and poitcians likely outweighs the ‘concem over transient or mild neurological dysfunction Decreased public mobility may reflect the effective ness of stay-at-home orders as one constituent mea- sure of social distancing. As indicated by the positive correlation of lower admission rates for stroke/TIA with decreased public mobility during the pandemic, such measures may influence patients’ willingness to seek medical help for acute symptoms. On a related note, medical workers from all around the world have been ining campaigns urging people to stay home. Such ‘campaigns may contribute to decreasing admissions for acute stroke, if not balanced by raising and sustaining public awareness for stroke, in particular regarding the importance of timely diagnosis and treatment of acute neurological symptoms, for example, through social media or respective information on-site. Patients should be encouraged to seek medical care and be assured that, hospitals make every effort to prevent contact to poten- tially infectious patients. All ofthis is paramount to avoid serious healtheare and economic consequences result- ing from undiagnosed and untreated strokes. ARTICLE INFORMATION Received Apri 28, 2020; acopted May Affiliations Department of Neurology Medial Faculty Mannheim Heidelberg Unters Gr- many (© Hoyer AE, MP, KS). Deparnont of Newogy, Urvarty Hospital Stroke, 2020951:2224-2097, DOI: 10.1 161/STROKEAHA 120030395, angen, Gemany (HRM, 8K), Daparimet of Newlogy, Dresden Neuroas> cals Conor Ca Gustav Carus Unversity Hospital Tectrigche Unrest Oras er, Germany (UP, KE). Deparment of Neuiiogy and Cicical Newoscience (GH, 18) and nse of Diaz in Medicine (C-Haverkamg), Fact of Meine, Unersty of Freburg Germany ‘Acknowledgments ‘We thank Professor Nathias Gondan, Deparment of Paychology, University of Copenhagen, Denman fr satical ace Sources of Funding Dr Hoyer receives a gant or postdoctoral lecture quaifcaton whi the Oerpla Moat Program of Heideberg Unversity Disclosures Dr Hate reports research grants by Novartis Medvonle, UCB Pharma, and Portela Parmaceutcas Or Hue repos personal fes om Bayer AG, Booh- ‘ager gala, Daichi Sanyo, Medien, CLS Belvng, UCB Pharma and Pela Pharmaceteals Dr Kalminer reports speaker Fonraria from Dac Sankyo, Noa, Bayer AG, Bt Myers Squib, and Maton Dr Haves reports rants ftom the Geran Fedral Micky of Education and Research (GMBF) win the Medics! Informatics Fundeg Schema (MIRACUM, FRZ (012216064) MIRAGUN is fuded by the BMEE wihin the Medial fematics Funding Scheme (FZ 012216064). 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