Retrospective Analysis in Efficacy and Safety of Modified Stroke Protocol During the COVID-19 Epidemic: Real-World Experience from a Single Healthcare System

Retrospective Analysis in Efficacy and Safety of Modified Stroke Protocol During the COVID-19 Epidemic: Real-World Experience from a Single Healthcare System | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Retrospective Analysis in Efficacy and Safety of Modified Stroke Protocol During the COVID-19 Epidemic: Real-World Experience from a Single Healthcare System Wei-Sheng Wang, Hong-Jie Jhou, Shey-Lin Wu, Chi-Hsiang Tung, Mu-Chien Sun, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5849308/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Introduction The COVID-19 pandemic has posed significant challenges to healthcare systems and public health. We wonder whether modified stroke protocol (MSP) could provide timely treatment with comparable efficacy in acute stroke care. Methods Participants were victims of acute ischemic stroke who underwent endovascular therapy between January 2021 and July 2021. Modified stroke protocol (MSP) claims to conduct nasopharyngeal swab nucleic acid amplification test (NAAT) immediately while encountering a stroke patient suspected of having COVID-19. The efficacy outcome included good functional outcome (mRS score, 0 to 2 at 90 days). Safety outcomes were symptomatic intracranial hemorrhage within 36 hours and overall mortality at 3 months. Results Of the 61 patients with acute ischemic stroke who received endovascular therapy enrolled in our analysis, 17 patients were in the MSP group. Overall, there were comparable rates of good functional outcome between the MSP group (23.5%) and the usual care group (23.8%) (OR, 1.54; 95% CI, 0.25 to 9.39). Mortality at 90 days was equivalent: 29.4% in the MSP group and 26.2% in the usual care group (OR, 0.64; 95% CI, 0.10 to 4.17). The risk of symptomatic intracranial hemorrhage within 36 hours was 17.6% in the MSP group and 6.8% in the usual care group (OR, 0.16; 95% CI, 0.01 to 4.37). Conclusions Acute ischemic stroke patients in the MSP group had similar functional outcome with those in the usual care group, without significant increase in the rate of mortality at 3 months and symptomatic intracranial hemorrhage within 36 hours. acute ischemic stroke endovascular thrombectomy intravenous thrombolysis COVID-19 pandemic modified stroke protocol Figures Figure 1 Figure 2 Figure 3 Figure 4 1. INTRODUCTION The COVID-19 pandemic has posed significant challenges to healthcare systems and public health worldwide.[1; 2] In the realm of stroke care, the pandemic has engendered decreased numbers of thrombolysis and thrombectomy, lower reperfusion rates, longer onset-to-puncture times, and higher in-hospital mortality rates.[3; 4; 5; 6] Additionally, healthcare providers must consider infectious risks to multidisciplinary clinical teammates.[7; 8] Therefore, implementing a comprehensive protected protocol on code stroke is essential for striking a balance between timely management and efficient resource utilization while mitigating the risks of COVID-19 transmission. In response to the ongoing COVID-19 epidemic in Taiwan, the Central Epidemic Command Center declared a nationwide level 3 epidemic alert on May 19, 2021. Our institute, Changhua Christian Healthcare System (CCHS), has since implemented a modified stroke protocol (MSP) based on the recommendation of the Taiwan Stroke Society.[ 9 ] The purpose of this protocol is to maintain the high quality of acute stroke care while ensuring the safety of our members. When encountering a stroke patient suspected of having COVID-19, we immediately conduct nasopharyngeal swab nucleic acid amplification test (NAAT). With personal protective equipment (PPE) in place, neurologists carry out reperfusion evaluation in a timely manner. After the COVID-19 negativity is disclosed, the patient receives reperfusion therapy as usual based on the time-window. However, if the patient tests positive for COVID-19, they will only be eligible for rtPA treatment. Our retrospective study aimed to provide insights into the effects of the COVID-19 pandemic on stroke care and the effectiveness of the modified protocol in mitigating the risks of COVID-19 transmission. We found no statistically significant differences between the modified stroke protocol (MSP) group and the usual care group in onset-to-perfusion time, door-to-puncture time, and reperfusion rate during the nationwide level 3 epidemic alert from May 19, 2021, to July 27, 2021. Demographic data, including age, gender, pre-stroke mRS, mean NIHSS, intravenous thrombolysis rate, ischemic-core volume, and mismatch volume, were all comparable between the two groups. Notably, the contribution of our medical laboratory professionals to operating nucleic acid amplification test (NAAT) day and night without a break was instrumental in implementing this protocol. This single tertiary stroke center study in implementing a modified stroke protocol (MSP) during level 3 alert highlights the importance of being prepared for possible upcoming epidemic diseases and developing strategies to ensure high-quality acute stroke care while ensuring the safety of healthcare providers. 2. METHODS Study Centers and Trial Design The study was conducted in Changhua, Taiwan, at Changhua Christian Healthcare System (CCHS) with a tertiary referral institution and a comprehensive stroke center. This was an observational, retrospective, unicenter study between January 2021 and July 2021, with a planned minimum follow-up of 3 months. This study was approved by the CCH Institutional Review Board (No. 210819). Upon visited by a stroke patient suspected of having COVID-19 during the nationwide level 3 epidemic, nasopharyngeal swab nucleic acid amplification test (NAAT) is conducted immediately. After reperfusion evaluation by duty neurologists with personal protective equipment (PPE) in time, the patient would receive reperfusion therapy as usual based on the time-window if the COVID-19 negativity is disclosed; otherwise, the patient would only be eligible for rtPA treatment. The following reperfusion therapy is based on the Guidelines for the Early Management of Patients With Acute Ischemic Stroke From the American Stroke Association[ 10 ] and Taiwan National Health Insurance. Our perfusion techniques include computed tomography perfusion imaging and RAPID automated software.[ 11 ] Without absolute contraindications, rtPA is recommended for patients whose last normal time is within 4.5 hours. Extend protocol is also adopted for patients without large vessel occlusion whose last normal time is between 4.5 and 9 hours, or who suffer from wake-up stroke with estimated onset time within 9 hours.[ 12 ] Endovascular treatment with mechanical thrombectomy is preserved for those who have large vessel occlusion in internal carotid artery, middle cerebral artery (M1, M2), anterior cerebral artery, basilar artery, or vertebral artery; the time-window is 8 hours for anterior circulation and 24 hours for posterior circulation. Yet, for victims of anterior circulation over original time-window whose core area and mismatch ratio are eligible for DEFUSE[ 13 ] or DAWN[ 14 ] criteria, mechanical thrombectomy is also recommended. Study Population Patients with acute ischemic stroke (AIS) who underwent endovascular treatment with or without intravenous thrombolysis at CCHS were enrolled in the study between January 1, 2021 and July 31, 2021. This period coincided with the Taiwan Central Epidemic Command Center Taiwan government coordinated nationwide preventive strategies to intercept the spread of COVID-19. The Level 3 epidemic alert was from May 19, 2021 to July 27, 2021. Due to the unprecedented pandemic of COVID-19, our institute conducted a modified stroke protocol (MSP) on May 21, 2021 based on recommendation of the Taiwan Stroke Society to balance the benefit of efficacious hyperacute stroke management and the risk of infectious exposure of stroke team members (Fig. 1 ).[ 9 ] The patients were divided into two groups: MSP group or usual care group. Variable Extraction The following patients’ characteristics were identified: age, sex, hypertension, diabetes, hyperlipidemia, previous stroke, atrial fibrillation, smoking, alcohol, National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS) scores before stroke. Imaging indicators at the initial imaging included volume of irreversibly injured ischemic-core tissue, volume of ischemic penumbra tissue, and mismatch volume. The number of patients receiving intravenous thrombolysis was recorded. We also derived the time from stroke onset to the first time of reperfusion. Outcomes measurement The efficacy outcome included good functional outcome (mRS score, 0 to 2 at 90 days), excellent functional outcome (mRS, 0 to 1 at 90 days), and favorable functional outcome (mRS score, 0 to 3 at 90 days). Successful reperfusion was defined as a score of 2b or 3 on the modified Thrombolysis in Cerebral Infarction scale (ranges from 0 [no reperfusion] to 3 [full reperfusion in the distribution of the occluded artery]).[ 15 ] The safety outcomes were symptomatic intracranial hemorrhage within 36 hours and overall mortality at 3 months. Statistical Analysis The χ2 test and Fisher's exact test were applied to assess the categorical variables. Fisher's exact test was used when the data number was small. The independent t-test was used to assess the continuous variables. Missing values of each subject were not defaulted to negative, and the denominators were only reported cases. To examine the association between the period of nationwide level 3 epidemic alert and outcomes, univariate and multivariate logistic regression analyses were used. Results are expressed as odds ratios (ORs) with 95% confidence intervals (CIs). For time-to-event outcomes, the overall mortality at 3 months was calculated under the Kaplan–Meier method with the log-rank test. Significance set at P < .05. All analyses were performed using R (version 4.1.3; R Foundation for Statistical Computing, Vienna, Austria). 3. RESULTS Patient characteristics A total of 317 stroke patients (260 patients with ischemic stroke and 57 patients with hemorrhagic stroke) were admitted to our hospital. Only 61 patients with acute ischemic stroke following endovascular therapy with or without intravenous thrombolysis were included in our analysis (Fig. 2 ). There were 17 patients in the MSP group and the others were in the usual care group. Two patients were lost to follow-up. The demographic data of the patients at baseline were similar in the two groups, except for a lower percentage of patients with hypertension or atrial fibrillation in the MSP group (Table 1 ). In general, the mean age of the patients was 72.7 ± 11.5 years, and 47.5% were women. 41 patients were transferred from the regional hospital. None of the patients got COVID-19 pneumonia and no neuroradiologist was infected with COVID-19 after endovascular therapy. All patients received endovascular therapy and 15 (24.6%) used intravenous thrombolysis. The mean NIHSS score (17.3 ± 6.6 vs. 18.6 ± 6.5; p = 0.646) and the mean time from stroke onset to first reperfusion (386.4 ± 140.8 vs. 366.0 ± 184.3; p = 0.217) were not significant between the two groups. In terms of the imaging assessment, the mean volume of irreversibly injured ischemic-core tissue (37.3 ± 66.3 vs. 35.6 ± 44.0; p = 0.742), ischemic penumbra tissue (137.3 ± 117.4 vs. 136.6 ± 86.0; p = 0.804), and mismatch volume (100.0 ± 73.6 vs. 102.1 ± 73.1; p = 0.804) were similar in both groups. Table 1 Characteristics of the study patients Characteristics MSP (n = 17) Usual care (n = 44) P value Age (years) 70.29 ± 12.05 73.64 ± 11.28 0.389 Gender, n 0.963 Male 9(52.9%) 23(52.3%) Female 8(47.1%) 21(47.7%) Underlying disease Hypertension 9(64.3%) 42(95.5%) 0.007 # Diabetes 6(35.3%) 18(40.9%) 0.687 Hyperlipidemia 8(47.1%) 25(56.8%) 0.493 Previous stroke 4(23.5%) 7(15.9%) 0.481 # Atrial fibrillation 6(35.3%) 28(63.6%) 0.046 Smoking 3(17.6%) 11(25.0%) 0.738 # Alcohol 1(5.9%) 4(9.1%) 1.000 # Pre-stroke MRS 1.000 # 0 16(94.1%) 41(93.2%) 1 0 1(2.3%) 2 1(5.9%) 2(4.5%) Mean NIHSS score † 17.29 ± 6.59 18.59 ± 6.53 0.646 Treatment with intravenous thrombolysis 4(23.5%) 11(25.0%) 1.000 # Time from stroke onset to the first time of reperfusion (min) 386.44 ± 140.78 365.98 ± 184.25 0.217 Door to puncture time (min) 124.64 ± 52.77 132.53 ± 41.38 0.285 Imaging result Mean volume of irreversibly injured ischemic-core tissue at initial imaging ¶ (ml) 37.29 ± 66.32 35.63 ± 43.99 0.742 Mean volume of ischemic penumbra tissue at initial imaging ‖ (ml) 137.29 ± 117.42 136.56 ± 85.97 0.804 Mismatch volume at initial imaging (ml) 100.00 ± 73.60 102.05 ± 73.14 0.898 Reperfusion on digital subtraction angiography, modified TICI 2b or 3 — no./total no. (%) § 17(100.0%) 37(84.1%) 0.175 # #: Testing by Fisher exact test. † Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 (normal) to 42 (death), with higher scores indicating greater deficit. ¶ The volume of irreversibly injured ischemic-core tissue was calculated with the use of a threshold for relative cerebral blood flow of less than 30% of that in normal brain tissue. ‖ To define the critically hypoperfused tissue, ischemic penumbra tissue was calculated as the volume of tissue in which there had been delayed arrival of an injected tracer agent exceeding 6 seconds. § The modified Thrombolysis in Cerebral Infarction (TICI) scale ranges from 0 (no reperfusion) to 3 (full reperfusion in the distribution of the occluded artery). Efficacy outcomes In our analysis, 4 of 17 patients (23.5%) in the MSP group had a good functional outcome, compared to 10 of 44 patients (23.8%) in the usual care group (adjusted odds ratio, 1.54; 95% confidence interval [CI], 0.25 to 9.39) (Table 2 ). Figure 3 shows the distribution of the modified Rankin scale scores at 90 days in the two groups. A total of 3 patients (17.6%) in the MSP group and 4 patients (9.5%) in the usual care group had an excellent functional outcome (adjusted odds ratio, 2.13; 95% CI, 0.20 to 22.23). Of the favorable outcome, there was no significant difference between the two groups (35.3% vs 45.2%; adjusted odds ratio, 1.20; 95% CI, 0.22 to 6.63). 100% of the patients in the MSP group and 84.1% of the patients in the usual care group had successful postprocedural reperfusion. Table 2 Efficacy and Safety Outcomes Outcomes COVID period (n = 17) Non-COVID period (n = 44) Unadjusted value Adjusted value # Score of 0 to 1 on the modified Rankin scale at 3 months 3(17.6%) 4(9.5%) 2.04(0.40 − 10.26) 2.13(0.20 − 22.23) Score of 0 to 2 on the modified Rankin scale at 3 months 4(23.5%) 10(23.8%) 0.98(0.26 − 3.71) 1.54(0.25 − 9.39) Score of 0 to 3 on the modified Rankin scale at 3 months 6(35.3%) 19(45.2%) 0.66(0.21 − 2.12) 1.20(0.22 − 6.63) Mortality at 3 months 5(29.4%) 11(26.2%) 1.17(0.34 − 4.10) 0.64(0.10 − 4.17) Symptomatic intracranial hemorrhage within 36 hours after intervention 3(17.6%) 3(6.8%) 2.25(0.40 − 12.80) 0.16(0.01 − 4.37) #: All result of adjusted value were adjusted by age, sex, HTN, DM, Hyperlipidemia, Previous stroke, Atrial fibrillation, Smoking. Safety outcomes Mortality at 90 days was 29.4% in the MSP group and 26.2% in the usual care group (adjusted odds ratio, 0.64; 95% CI, 0.10 to 4.17); the corresponding time-to-event curves are shown in Fig. 4 (log-rank test p value = 0.65). The risk of symptomatic intracranial hemorrhage within 36 hours after the initiation of reperfusion therapy was 17.6% in the MSP group and 6.8% in the usual care group (adjusted odds ratio, 0.16; 95% CI, 0.01 to 4.37) (Table 2 ). After reperfusion therapy, there remained 5 patients (8.2%) receiving craniectomy; 3 of them were dead. 4. DISCUSSION Our study didn’t find significant differences in onset-to-perfusion time, door-to-puncture time, and reperfusion rate between the modified stroke protocol (MSP) and usual care groups during the nationwide level 3 epidemic alert from May 19, 2021, to July 27, 2021. The two groups were comparable in terms of demographics, including age, gender, pre-stroke mRS, mean NIHSS, intravenous thrombolysis rate, ischemic-core volume, and mismatch volume. Our medical laboratory professionals played an essential role in implementing the MSP by operating nucleic acid amplification test (NAAT) day and night without a break. However, healthcare organizations must prioritize preventing burnout among these professionals.[ 16 ] Compared with quality improvement data from the NYU Langone Health comprehensive stroke center during the COVID-19 pandemic, our successful recanalization rates (TICI ≥ 2b) were non-inferior, indicating the maturity of our neuroradiologists' techniques.[ 17 ] We attribute the longer door-to-puncture time in our study to the time spent explaining the procedure to the family and obtaining informed consent based on different customs. Regarding efficacy outcomes, there were no significant difference between the MSP group and usual care group in excellent functional outcome (modified Rankin Scale (mRS), 0 to 1 at 90 days), good functional outcome (mRS, 0 to 2 at 90 days), or favorable functional outcome (mRS, 0 to 3 at 90 days). Although patients in the MSP group tended to achieve excellent functional outcomes, and those in the usual care group leaned towards favorable functional outcomes, higher variability caused by the small study population may have contributed to this finding. In terms of safety concerns, the 90-day mortality rate was almost identical between the two groups. However, the risk of symptomatic intracranial hemorrhage within 36 hours was higher in the MSP group, albeit statistically insignificant. The corresponding time-to-event curves showed that the two curves were inseparable before 40 days, but gradually became lopsided since then. Therefore, the survival rate's definitive split at 120 days or even six months remains unknown. The MR CLEAN registry from the Netherlands and the SITS-TBY registry from the Czech Republic report a relative frequency of achieving a good functional outcome (mRS, 0 to 2 at 90 days) of around 36–44%. However, our frequency of achieving a good functional outcome was only around one-quarter.[ 18 ] Careful interpretation of the demographics in Table 1 revealed that even though the average age was similar with that in the MR CLEAN and SITS-TBY registries, our age distribution seemed to be more biphasic; it ranged from 43 to 93 with a median of 77, which indeed reflected aged populations. Moreover, our intravenous thrombolysis rate was one-third of that in the MR CLEAN and SITS-TBY registries. This finding indicates that most of the victims arrived at our institution beyond the time-window of 4.5 hours or had multiple comorbidities that contraindicated intravenous thrombolysis.[ 19 ] Notably, 67.2% (41 out of 61) of the patients came from referrals because the Changhua Christian Healthcare System (CCHS) is an integrated comprehensive stroke center in central Taiwan, responsible for Changhua, Nantou, and Yunlin counties, with an interdistance range of 30 to 40 minutes. As the first institution to hospitalize the first imported case of COVID-19 in Taiwan, the CCHS is experienced in formulating clinical practice implications to develop a more comprehensive healthcare system to fight epidemics.[ 20 ] Our study provides a real-world experience in a single tertiary center that ensures acute stroke care during pandemics. However, there remain several limitations to our study. First, retrospective databases may have several variabilities and potential confounding factors, despite our efforts to ensure similar demographics between the two groups. Second, our population was small-scale and limited to one healthcare system. Hence, the generalizability of the MSP protocol to other healthcare systems or pandemics remains undetermined. Third, our study focused only on acute reperfusion therapy during the COVID-19 pandemic. Other aspects, such as intensive care after reperfusion therapy, the interaction between antiviral agents and stroke preventive medication, and post-stroke rehabilitation, require further exploration and discussion. 5. CONCLUSION In conclusion, our study provides evidence that the MSP protocol can achieve comparable benefits and control COVID-19 infection risks simultaneously. Our results may serve as a reference for future emerging infectious diseases. Nevertheless, there is still a long way to go in improving stroke care and management to reduce disability and social burden. After all, COVID-19 will eventually pass, but stroke will remain a significant public health concern. Declarations Ethics approval and consent to participate This study was approved by the CCH Institutional Review Board approval (No. 210819). Written informed consent was not required, because this work is a retrospective observational study. Clinical Trial Not applicable. Consent for publication The authors confirm that they have obtained all necessary consent for publication of any personal information, images, or data included in this manuscript. The manuscript has not been submitted elsewhere, and all authors approve the final version for publication. Availability of data and material The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This research received no external funding. Authors' contributions YCC conceptualized the study. HJJ collected and then analyzed the data. WSW composed the manuscript. MCS, SLW and CHT critically reviewed and edited the manuscript. All authors contributed to the article, approved the final version to be published and agreed to be accountable for all aspects of the work. YCC and MCS are guarantors of the work. Acknowledgements Not applicable. References M.É. Czeisler, K. Marynak, K.E. Clarke, Z. Salah, I. Shakya, J.M. Thierry, N. Ali, H. McMillan, J.F. Wiley, and M.D. Weaver, Delay or avoidance of medical care because of COVID-19–related concerns—United States, June 2020. 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Lin, A locally transmitted case of SARS-CoV-2 infection in Taiwan. New England Journal of Medicine 382 (2020) 1070-1072. Additional Declarations No competing interests reported. Supplementary Files SupplementalmaterialsBMC.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 22 Jan, 2025 Editor assigned by journal 22 Jan, 2025 Submission checks completed at journal 22 Jan, 2025 First submitted to journal 17 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5849308","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":405785734,"identity":"ec4ae08a-25b1-477f-8107-35a45c8afea4","order_by":0,"name":"Wei-Sheng Wang","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei-Sheng","middleName":"","lastName":"Wang","suffix":""},{"id":405785735,"identity":"3c6e368e-be25-4d33-8a4a-1c90ba112c6e","order_by":1,"name":"Hong-Jie Jhou","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hong-Jie","middleName":"","lastName":"Jhou","suffix":""},{"id":405785736,"identity":"7c207f3a-16a2-4a7a-9966-d4dffed94330","order_by":2,"name":"Shey-Lin Wu","email":"","orcid":"","institution":"Chang Bing Show Chwan Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shey-Lin","middleName":"","lastName":"Wu","suffix":""},{"id":405785738,"identity":"a8667f7c-549d-446f-9674-b83733bdffb0","order_by":3,"name":"Chi-Hsiang Tung","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chi-Hsiang","middleName":"","lastName":"Tung","suffix":""},{"id":405785740,"identity":"64ae951c-8030-46f3-9849-7a2aaca99424","order_by":4,"name":"Mu-Chien Sun","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mu-Chien","middleName":"","lastName":"Sun","suffix":""},{"id":405785741,"identity":"72168031-76cb-4286-8118-8a359213ce8c","order_by":5,"name":"Yen-Chung Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBACNvbG5gcJBjYMDBLEauHjOXzM4ENFGlwLYZ1yEmkJkjPOHCZBCxvPGQNj3rbz8vyzGxgfV/xiqDM4QEgLe4/BY96224Yz7hxgNjzbxyBBWAvEltsJBhIJbJKNPQwSZgS1SOQYSPO2nSNJC9j7ByBaGn4QowUSyMmGM24kNhs2NkhI7iekRb4dHJV28vwzkg8+bPhjwy/ZQEALEmBsYGBsIzoNwMEfknWMglEwCkbBCAAAhgM/rOUQRfkAAAAASUVORK5CYII=","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yen-Chung","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-01-17 12:53:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5849308/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5849308/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74680392,"identity":"b3262b02-6550-4fe6-8228-f4e04c17ae2d","added_by":"auto","created_at":"2025-01-24 15:43:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27647,"visible":true,"origin":"","legend":"\u003cp\u003eModified stroke protocol (MSP) based on recommendation of the Taiwan Stroke Society to balance the benefit of efficacious hyperacute stroke management and the risk of infectious exposure of stroke team members.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/cc9fed721e9b977360d95f7b.png"},{"id":74680394,"identity":"251f1476-5133-4250-942f-1c7286a13120","added_by":"auto","created_at":"2025-01-24 15:43:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":228452,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram of the selection process for participant enrollment.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/3cd1101528b686288ad4caa2.png"},{"id":74680398,"identity":"f4c39327-c7a8-433c-8b61-8b37838c0551","added_by":"auto","created_at":"2025-01-24 15:43:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":186280,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of the modified Rankin scale scores at 90 days.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/5b69c18c233955742de7b91d.png"},{"id":74680840,"identity":"767eed47-c6ce-497d-af6f-6c62e5de4b1a","added_by":"auto","created_at":"2025-01-24 15:51:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":554118,"visible":true,"origin":"","legend":"\u003cp\u003eCorresponding time-to-event curves about survival probability (log-rank test p value = 0.65).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/3611a064f7a4ae2814d5331e.png"},{"id":74681726,"identity":"1563d807-b729-419a-8253-dfe997f6b310","added_by":"auto","created_at":"2025-01-24 15:59:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1589427,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/3f0e2bf6-599c-41aa-ba2b-c3445ac8d4f8.pdf"},{"id":74680395,"identity":"1a4e5462-f7e6-401c-8454-b4de8d60537b","added_by":"auto","created_at":"2025-01-24 15:43:29","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":94279,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalmaterialsBMC.docx","url":"https://assets-eu.researchsquare.com/files/rs-5849308/v1/b0c5f2eaba550d0b684d8a08.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Retrospective Analysis in Efficacy and Safety of Modified Stroke Protocol During the COVID-19 Epidemic: Real-World Experience from a Single Healthcare System","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eThe COVID-19 pandemic has posed significant challenges to healthcare systems and public health worldwide.[1; 2] In the realm of stroke care, the pandemic has engendered decreased numbers of thrombolysis and thrombectomy, lower reperfusion rates, longer onset-to-puncture times, and higher in-hospital mortality rates.[3; 4; 5; 6] Additionally, healthcare providers must consider infectious risks to multidisciplinary clinical teammates.[7; 8] Therefore, implementing a comprehensive protected protocol on code stroke is essential for striking a balance between timely management and efficient resource utilization while mitigating the risks of COVID-19 transmission.\u003c/p\u003e \u003cp\u003eIn response to the ongoing COVID-19 epidemic in Taiwan, the Central Epidemic Command Center declared a nationwide level 3 epidemic alert on May 19, 2021. Our institute, Changhua Christian Healthcare System (CCHS), has since implemented a modified stroke protocol (MSP) based on the recommendation of the Taiwan Stroke Society.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] The purpose of this protocol is to maintain the high quality of acute stroke care while ensuring the safety of our members.\u003c/p\u003e \u003cp\u003eWhen encountering a stroke patient suspected of having COVID-19, we immediately conduct nasopharyngeal swab nucleic acid amplification test (NAAT). With personal protective equipment (PPE) in place, neurologists carry out reperfusion evaluation in a timely manner. After the COVID-19 negativity is disclosed, the patient receives reperfusion therapy as usual based on the time-window. However, if the patient tests positive for COVID-19, they will only be eligible for rtPA treatment.\u003c/p\u003e \u003cp\u003eOur retrospective study aimed to provide insights into the effects of the COVID-19 pandemic on stroke care and the effectiveness of the modified protocol in mitigating the risks of COVID-19 transmission. We found no statistically significant differences between the modified stroke protocol (MSP) group and the usual care group in onset-to-perfusion time, door-to-puncture time, and reperfusion rate during the nationwide level 3 epidemic alert from May 19, 2021, to July 27, 2021. Demographic data, including age, gender, pre-stroke mRS, mean NIHSS, intravenous thrombolysis rate, ischemic-core volume, and mismatch volume, were all comparable between the two groups. Notably, the contribution of our medical laboratory professionals to operating nucleic acid amplification test (NAAT) day and night without a break was instrumental in implementing this protocol. This single tertiary stroke center study in implementing a modified stroke protocol (MSP) during level 3 alert highlights the importance of being prepared for possible upcoming epidemic diseases and developing strategies to ensure high-quality acute stroke care while ensuring the safety of healthcare providers.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cp\u003e \u003cb\u003eStudy Centers and Trial Design\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe study was conducted in Changhua, Taiwan, at Changhua Christian Healthcare System (CCHS) with a tertiary referral institution and a comprehensive stroke center. This was an observational, retrospective, unicenter study between January 2021 and July 2021, with a planned minimum follow-up of 3 months. This study was approved by the CCH Institutional Review Board (No. 210819).\u003c/p\u003e \u003cp\u003eUpon visited by a stroke patient suspected of having COVID-19 during the nationwide level 3 epidemic, nasopharyngeal swab nucleic acid amplification test (NAAT) is conducted immediately. After reperfusion evaluation by duty neurologists with personal protective equipment (PPE) in time, the patient would receive reperfusion therapy as usual based on the time-window if the COVID-19 negativity is disclosed; otherwise, the patient would only be eligible for rtPA treatment. The following reperfusion therapy is based on the Guidelines for the Early Management of Patients With Acute Ischemic Stroke From the American Stroke Association[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and Taiwan National Health Insurance. Our perfusion techniques include computed tomography perfusion imaging and RAPID automated software.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Without absolute contraindications, rtPA is recommended for patients whose last normal time is within 4.5 hours. Extend protocol is also adopted for patients without large vessel occlusion whose last normal time is between 4.5 and 9 hours, or who suffer from wake-up stroke with estimated onset time within 9 hours.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Endovascular treatment with mechanical thrombectomy is preserved for those who have large vessel occlusion in internal carotid artery, middle cerebral artery (M1, M2), anterior cerebral artery, basilar artery, or vertebral artery; the time-window is 8 hours for anterior circulation and 24 hours for posterior circulation. Yet, for victims of anterior circulation over original time-window whose core area and mismatch ratio are eligible for DEFUSE[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] or DAWN[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] criteria, mechanical thrombectomy is also recommended.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy Population\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePatients with acute ischemic stroke (AIS) who underwent endovascular treatment with or without intravenous thrombolysis at CCHS were enrolled in the study between January 1, 2021 and July 31, 2021. This period coincided with the Taiwan Central Epidemic Command Center Taiwan government coordinated nationwide preventive strategies to intercept the spread of COVID-19. The Level 3 epidemic alert was from May 19, 2021 to July 27, 2021. Due to the unprecedented pandemic of COVID-19, our institute conducted a modified stroke protocol (MSP) on May 21, 2021 based on recommendation of the Taiwan Stroke Society to balance the benefit of efficacious hyperacute stroke management and the risk of infectious exposure of stroke team members (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] The patients were divided into two groups: MSP group or usual care group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eVariable Extraction\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe following patients\u0026rsquo; characteristics were identified: age, sex, hypertension, diabetes, hyperlipidemia, previous stroke, atrial fibrillation, smoking, alcohol, National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS) scores before stroke. Imaging indicators at the initial imaging included volume of irreversibly injured ischemic-core tissue, volume of ischemic penumbra tissue, and mismatch volume. The number of patients receiving intravenous thrombolysis was recorded. We also derived the time from stroke onset to the first time of reperfusion.\u003c/p\u003e \u003cp\u003e \u003cb\u003eOutcomes measurement\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe efficacy outcome included good functional outcome (mRS score, 0 to 2 at 90 days), excellent functional outcome (mRS, 0 to 1 at 90 days), and favorable functional outcome (mRS score, 0 to 3 at 90 days). Successful reperfusion was defined as a score of 2b or 3 on the modified Thrombolysis in Cerebral Infarction scale (ranges from 0 [no reperfusion] to 3 [full reperfusion in the distribution of the occluded artery]).[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] The safety outcomes were symptomatic intracranial hemorrhage within 36 hours and overall mortality at 3 months.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical Analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe χ2 test and Fisher's exact test were applied to assess the categorical variables. Fisher's exact test was used when the data number was small. The independent t-test was used to assess the continuous variables. Missing values of each subject were not defaulted to negative, and the denominators were only reported cases. To examine the association between the period of nationwide level 3 epidemic alert and outcomes, univariate and multivariate logistic regression analyses were used. Results are expressed as odds ratios (ORs) with 95% confidence intervals (CIs). For time-to-event outcomes, the overall mortality at 3 months was calculated under the Kaplan\u0026ndash;Meier method with the log-rank test. Significance set at P\u0026thinsp;\u0026lt;\u0026thinsp;.05. All analyses were performed using R (version 4.1.3; R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003e \u003cb\u003ePatient characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 317 stroke patients (260 patients with ischemic stroke and 57 patients with hemorrhagic stroke) were admitted to our hospital. Only 61 patients with acute ischemic stroke following endovascular therapy with or without intravenous thrombolysis were included in our analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were 17 patients in the MSP group and the others were in the usual care group. Two patients were lost to follow-up.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe demographic data of the patients at baseline were similar in the two groups, except for a lower percentage of patients with hypertension or atrial fibrillation in the MSP group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In general, the mean age of the patients was 72.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5 years, and 47.5% were women. 41 patients were transferred from the regional hospital. None of the patients got COVID-19 pneumonia and no neuroradiologist was infected with COVID-19 after endovascular therapy. All patients received endovascular therapy and 15 (24.6%) used intravenous thrombolysis. The mean NIHSS score (17.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6 vs. 18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5; p\u0026thinsp;=\u0026thinsp;0.646) and the mean time from stroke onset to first reperfusion (386.4\u0026thinsp;\u0026plusmn;\u0026thinsp;140.8 vs. 366.0\u0026thinsp;\u0026plusmn;\u0026thinsp;184.3; p\u0026thinsp;=\u0026thinsp;0.217) were not significant between the two groups. In terms of the imaging assessment, the mean volume of irreversibly injured ischemic-core tissue (37.3\u0026thinsp;\u0026plusmn;\u0026thinsp;66.3 vs. 35.6\u0026thinsp;\u0026plusmn;\u0026thinsp;44.0; p\u0026thinsp;=\u0026thinsp;0.742), ischemic penumbra tissue (137.3\u0026thinsp;\u0026plusmn;\u0026thinsp;117.4 vs. 136.6\u0026thinsp;\u0026plusmn;\u0026thinsp;86.0; p\u0026thinsp;=\u0026thinsp;0.804), and mismatch volume (100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;73.6 vs. 102.1\u0026thinsp;\u0026plusmn;\u0026thinsp;73.1; p\u0026thinsp;=\u0026thinsp;0.804) were similar in both groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the study patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMSP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUsual care\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.29\u0026thinsp;\u0026plusmn;\u0026thinsp;12.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.64\u0026thinsp;\u0026plusmn;\u0026thinsp;11.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.963\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(52.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(47.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(95.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(40.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(56.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.493\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.481\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.738\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-stroke MRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(94.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(93.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean NIHSS score\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.29\u0026thinsp;\u0026plusmn;\u0026thinsp;6.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.646\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment with intravenous thrombolysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from stroke onset to the first time of reperfusion (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e386.44\u0026thinsp;\u0026plusmn;\u0026thinsp;140.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e365.98\u0026thinsp;\u0026plusmn;\u0026thinsp;184.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoor to puncture time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.64\u0026thinsp;\u0026plusmn;\u0026thinsp;52.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132.53\u0026thinsp;\u0026plusmn;\u0026thinsp;41.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImaging result\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean volume of irreversibly injured ischemic-core tissue at initial imaging\u003csup\u003e\u0026para;\u003c/sup\u003e (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.29\u0026thinsp;\u0026plusmn;\u0026thinsp;66.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.63\u0026thinsp;\u0026plusmn;\u0026thinsp;43.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean volume of ischemic penumbra tissue at initial imaging\u003csup\u003e‖\u003c/sup\u003e (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137.29\u0026thinsp;\u0026plusmn;\u0026thinsp;117.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136.56\u0026thinsp;\u0026plusmn;\u0026thinsp;85.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.804\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMismatch volume at initial imaging (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;73.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102.05\u0026thinsp;\u0026plusmn;\u0026thinsp;73.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReperfusion on digital subtraction angiography, modified TICI 2b or 3 \u0026mdash; no./total no. (%)\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(84.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.175\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e#: Testing by Fisher exact test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026dagger; Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 (normal) to 42 (death), with higher scores indicating greater deficit.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026para; The volume of irreversibly injured ischemic-core tissue was calculated with the use of a threshold for relative cerebral blood flow of less than 30% of that in normal brain tissue.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e‖ To define the critically hypoperfused tissue, ischemic penumbra tissue was calculated as the volume of tissue in which there had been delayed arrival of an injected tracer agent exceeding 6 seconds.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026sect; The modified Thrombolysis in Cerebral Infarction (TICI) scale ranges from 0 (no reperfusion) to 3 (full reperfusion in the distribution of the occluded artery).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eEfficacy outcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn our analysis, 4 of 17 patients (23.5%) in the MSP group had a good functional outcome, compared to 10 of 44 patients (23.8%) in the usual care group (adjusted odds ratio, 1.54; 95% confidence interval [CI], 0.25 to 9.39) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the distribution of the modified Rankin scale scores at 90 days in the two groups. A total of 3 patients (17.6%) in the MSP group and 4 patients (9.5%) in the usual care group had an excellent functional outcome (adjusted odds ratio, 2.13; 95% CI, 0.20 to 22.23). Of the favorable outcome, there was no significant difference between the two groups (35.3% vs 45.2%; adjusted odds ratio, 1.20; 95% CI, 0.22 to 6.63). 100% of the patients in the MSP group and 84.1% of the patients in the usual care group had successful postprocedural reperfusion.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEfficacy and Safety Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOVID period\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-COVID period\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnadjusted value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted value\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScore of 0 to 1 on the modified Rankin scale at 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4(9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e2.04(0.40\u0026thinsp;\u0026minus;\u0026thinsp;10.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c5\"\u003e \u003cp\u003e2.13(0.20\u0026thinsp;\u0026minus;\u0026thinsp;22.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScore of 0 to 2 on the modified Rankin scale at 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4(23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10(23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e0.98(0.26\u0026thinsp;\u0026minus;\u0026thinsp;3.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c5\"\u003e \u003cp\u003e1.54(0.25\u0026thinsp;\u0026minus;\u0026thinsp;9.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScore of 0 to 3 on the modified Rankin scale at 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6(35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e0.66(0.21\u0026thinsp;\u0026minus;\u0026thinsp;2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c5\"\u003e \u003cp\u003e1.20(0.22\u0026thinsp;\u0026minus;\u0026thinsp;6.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality at 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11(26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e1.17(0.34\u0026thinsp;\u0026minus;\u0026thinsp;4.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c5\"\u003e \u003cp\u003e0.64(0.10\u0026thinsp;\u0026minus;\u0026thinsp;4.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic intracranial hemorrhage within 36 hours after intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3(6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e2.25(0.40\u0026thinsp;\u0026minus;\u0026thinsp;12.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c5\"\u003e \u003cp\u003e0.16(0.01\u0026thinsp;\u0026minus;\u0026thinsp;4.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e#: All result of adjusted value were adjusted by age, sex, HTN, DM, Hyperlipidemia, Previous stroke, Atrial fibrillation, Smoking.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSafety outcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003eMortality at 90 days was 29.4% in the MSP group and 26.2% in the usual care group (adjusted odds ratio, 0.64; 95% CI, 0.10 to 4.17); the corresponding time-to-event curves are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e (log-rank test p value\u0026thinsp;=\u0026thinsp;0.65). The risk of symptomatic intracranial hemorrhage within 36 hours after the initiation of reperfusion therapy was 17.6% in the MSP group and 6.8% in the usual care group (adjusted odds ratio, 0.16; 95% CI, 0.01 to 4.37) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After reperfusion therapy, there remained 5 patients (8.2%) receiving craniectomy; 3 of them were dead.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eOur study didn\u0026rsquo;t find significant differences in onset-to-perfusion time, door-to-puncture time, and reperfusion rate between the modified stroke protocol (MSP) and usual care groups during the nationwide level 3 epidemic alert from May 19, 2021, to July 27, 2021. The two groups were comparable in terms of demographics, including age, gender, pre-stroke mRS, mean NIHSS, intravenous thrombolysis rate, ischemic-core volume, and mismatch volume. Our medical laboratory professionals played an essential role in implementing the MSP by operating nucleic acid amplification test (NAAT) day and night without a break. However, healthcare organizations must prioritize preventing burnout among these professionals.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eCompared with quality improvement data from the NYU Langone Health comprehensive stroke center during the COVID-19 pandemic, our successful recanalization rates (TICI\u0026thinsp;\u0026ge;\u0026thinsp;2b) were non-inferior, indicating the maturity of our neuroradiologists' techniques.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] We attribute the longer door-to-puncture time in our study to the time spent explaining the procedure to the family and obtaining informed consent based on different customs.\u003c/p\u003e \u003cp\u003eRegarding efficacy outcomes, there were no significant difference between the MSP group and usual care group in excellent functional outcome (modified Rankin Scale (mRS), 0 to 1 at 90 days), good functional outcome (mRS, 0 to 2 at 90 days), or favorable functional outcome (mRS, 0 to 3 at 90 days). Although patients in the MSP group tended to achieve excellent functional outcomes, and those in the usual care group leaned towards favorable functional outcomes, higher variability caused by the small study population may have contributed to this finding. In terms of safety concerns, the 90-day mortality rate was almost identical between the two groups. However, the risk of symptomatic intracranial hemorrhage within 36 hours was higher in the MSP group, albeit statistically insignificant. The corresponding time-to-event curves showed that the two curves were inseparable before 40 days, but gradually became lopsided since then. Therefore, the survival rate's definitive split at 120 days or even six months remains unknown.\u003c/p\u003e \u003cp\u003eThe MR CLEAN registry from the Netherlands and the SITS-TBY registry from the Czech Republic report a relative frequency of achieving a good functional outcome (mRS, 0 to 2 at 90 days) of around 36\u0026ndash;44%. However, our frequency of achieving a good functional outcome was only around one-quarter.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Careful interpretation of the demographics in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e revealed that even though the average age was similar with that in the MR CLEAN and SITS-TBY registries, our age distribution seemed to be more biphasic; it ranged from 43 to 93 with a median of 77, which indeed reflected aged populations. Moreover, our intravenous thrombolysis rate was one-third of that in the MR CLEAN and SITS-TBY registries. This finding indicates that most of the victims arrived at our institution beyond the time-window of 4.5 hours or had multiple comorbidities that contraindicated intravenous thrombolysis.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Notably, 67.2% (41 out of 61) of the patients came from referrals because the Changhua Christian Healthcare System (CCHS) is an integrated comprehensive stroke center in central Taiwan, responsible for Changhua, Nantou, and Yunlin counties, with an interdistance range of 30 to 40 minutes.\u003c/p\u003e \u003cp\u003eAs the first institution to hospitalize the first imported case of COVID-19 in Taiwan, the CCHS is experienced in formulating clinical practice implications to develop a more comprehensive healthcare system to fight epidemics.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Our study provides a real-world experience in a single tertiary center that ensures acute stroke care during pandemics. However, there remain several limitations to our study. First, retrospective databases may have several variabilities and potential confounding factors, despite our efforts to ensure similar demographics between the two groups. Second, our population was small-scale and limited to one healthcare system. Hence, the generalizability of the MSP protocol to other healthcare systems or pandemics remains undetermined. Third, our study focused only on acute reperfusion therapy during the COVID-19 pandemic. Other aspects, such as intensive care after reperfusion therapy, the interaction between antiviral agents and stroke preventive medication, and post-stroke rehabilitation, require further exploration and discussion.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eIn conclusion, our study provides evidence that the MSP protocol can achieve comparable benefits and control COVID-19 infection risks simultaneously. Our results may serve as a reference for future emerging infectious diseases. Nevertheless, there is still a long way to go in improving stroke care and management to reduce disability and social burden. After all, COVID-19 will eventually pass, but stroke will remain a significant public health concern.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the CCH Institutional Review Board approval (No. 210819). Written informed consent was not required, because this work is a retrospective observational study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that they have obtained all necessary consent for publication of any personal information, images, or data included in this manuscript. The manuscript has not been submitted elsewhere, and all authors approve the final version for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYCC conceptualized the study. HJJ collected and then analyzed the data. WSW composed the manuscript. MCS, SLW and CHT critically reviewed and edited the manuscript. All authors contributed to the article, approved the final version to be published and agreed to be accountable for all aspects of the work. YCC and MCS are guarantors of the work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eM.\u0026Eacute;. Czeisler, K. Marynak, K.E. Clarke, Z. Salah, I. Shakya, J.M. Thierry, N. Ali, H. McMillan, J.F. Wiley, and M.D. Weaver, Delay or avoidance of medical care because of COVID-19\u0026ndash;related concerns\u0026mdash;United States, June 2020. Morbidity and mortality weekly report 69 (2020) 1250.\u003c/li\u003e\n\u003cli\u003eS.J. Lange, M.D. Ritchey, A.B. Goodman, T. Dias, E. Twentyman, J. Fuld, L.A. Schieve, G. Imperatore, S.R. Benoit, and A. Kite‐Powell, Potential indirect effects of the COVID‐19 pandemic on use of emergency departments for acute life‐threatening conditions\u0026mdash;United States, January\u0026ndash;May 2020, Wiley Online Library, 2020, pp. 2612-2617.\u003c/li\u003e\n\u003cli\u003eJ. Zhao, H. Li, D. Kung, M. Fisher, Y. Shen, and R. Liu, Impact of the COVID-19 epidemic on stroke care and potential solutions. Stroke 51 (2020) 1996-2001.\u003c/li\u003e\n\u003cli\u003eS.D. Hajdu, V. Pittet, F. Puccinelli, W. Ben Hassen, M. Ben Maacha, R. Blanc, S. Bracco, G. Broocks, B. Bartolini, and T. Casseri, Acute stroke management during the COVID-19 pandemic: does confinement impact eligibility for endovascular therapy? Stroke 51 (2020) 2593-2596.\u003c/li\u003e\n\u003cli\u003eJ.N. Briard, C. Ducroux, G. Jacquin, W. Alesefir, W. Boisseau, N. Daneault, Y. Deschaintre, J. Eneling, L.C. Gioia, and D. Iancu, Early impact of the COVID-19 pandemic on acute stroke treatment delays. Canadian Journal of Neurological Sciences 48 (2021) 122-126.\u003c/li\u003e\n\u003cli\u003eA.H. Katsanos, L. Palaiodimou, R. Zand, S. Yaghi, H. Kamel, B.B. Navi, G. Turc, V. Benetou, V.K. Sharma, and D. Mavridis, Changes in stroke hospital care during the COVID-19 pandemic: a systematic review and meta-analysis. Stroke 52 (2021) 3651-3660.\u003c/li\u003e\n\u003cli\u003eH. Khosravani, P. Rajendram, L. Notario, M.G. Chapman, and B.K. Menon, Protected code stroke: hyperacute stroke management during the coronavirus disease 2019 (COVID-19) pandemic. Stroke 51 (2020) 1891-1895.\u003c/li\u003e\n\u003cli\u003eA.I. Qureshi, F. Abd-Allah, F. Al-Senani, E. Aytac, A. Borhani-Haghighi, A. Ciccone, C.R. Gomez, E. Gurkas, C.Y. Hsu, and V. Jani, Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel. International Journal of Stroke 15 (2020) 540-554.\u003c/li\u003e\n\u003cli\u003eC.-H. Liu, P.-S. Sung, C.-H. Chen, and C.-Y. Hsieh, 台灣腦中風學會針對急性中風流程因應 COVID-19 疫情調整之建議. 台灣中風醫誌 2 (2020) 1-4.\u003c/li\u003e\n\u003cli\u003eW.J. Powers, A.A. Rabinstein, T. Ackerson, O.M. Adeoye, N.C. Bambakidis, K. Becker, J. Biller, M. Brown, B.M. Demaerschalk, and B. Hoh, 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. stroke 49 (2018) e46-e99.\u003c/li\u003e\n\u003cli\u003eM. Straka, G.W. Albers, and R. Bammer, Real‐time diffusion‐perfusion mismatch analysis in acute stroke. Journal of Magnetic Resonance Imaging 32 (2010) 1024-1037.\u003c/li\u003e\n\u003cli\u003eH. Ma, B.C. Campbell, M.W. Parsons, L. Churilov, C.R. Levi, C. Hsu, T.J. Kleinig, T. Wijeratne, S. Curtze, and H.M. Dewey, Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. New England Journal of Medicine 380 (2019) 1795-1803.\u003c/li\u003e\n\u003cli\u003eG.W. Albers, M.P. Marks, S. Kemp, S. Christensen, J.P. Tsai, S. Ortega-Gutierrez, R.A. McTaggart, M.T. Torbey, M. Kim-Tenser, T. Leslie-Mazwi, A. Sarraj, S.E. Kasner, S.A. Ansari, S.D. Yeatts, S. Hamilton, M. Mlynash, J.J. Heit, G. Zaharchuk, S. Kim, J. Carrozzella, Y.Y. Palesch, A.M. Demchuk, R. Bammer, P.W. Lavori, J.P. Broderick, and M.G. Lansberg, Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med 378 (2018) 708-718.\u003c/li\u003e\n\u003cli\u003eR.G. Nogueira, A.P. Jadhav, D.C. Haussen, A. Bonafe, R.F. Budzik, P. Bhuva, D.R. Yavagal, M. Ribo, C. Cognard, and R.A. Hanel, Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. New England Journal of Medicine 378 (2018) 11-21.\u003c/li\u003e\n\u003cli\u003eO.O. Zaidat, A.J. Yoo, P. Khatri, T.A. Tomsick, R. Von Kummer, J.L. Saver, M.P. Marks, S. Prabhakaran, D.F. Kallmes, and B.-F.M. Fitzsimmons, Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 44 (2013) 2650-2663.\u003c/li\u003e\n\u003cli\u003eB. Nowrouzi‐Kia, J. Dong, B. Gohar, and M. Hoad, Factors associated with burnout among medical laboratory professionals in Ontario, Canada: An exploratory study during the second wave of the COVID‐19 pandemic. The International Journal of Health Planning and Management 37 (2022) 2183-2197.\u003c/li\u003e\n\u003cli\u003eS. Agarwal, E. Scher, N. Rossan-Raghunath, D. Marolia, M. Butnar, J. Torres, C. Zhang, S. Kim, M. Sanger, and K. Humbert, Acute stroke care in a New York City comprehensive stroke center during the COVID-19 pandemic. Journal of Stroke and Cerebrovascular Diseases 29 (2020) 105068.\u003c/li\u003e\n\u003cli\u003eP.M. Janssen, K. van Overhagen, J. Vinkl\u0026aacute;rek, B. Roozenbeek, H.B. van der Worp, C.B. Majoie, M. Bar, D. Čern\u0026iacute;k, R. Herzig, and L. Jur\u0026aacute;k, Between-Center Variation in Outcome After Endovascular Treatment of Acute Stroke: Analysis of Two Nationwide Registries. Circulation: Cardiovascular Quality and Outcomes 15 (2022) e008180.\u003c/li\u003e\n\u003cli\u003eW. Hacke, M. Kaste, E. Bluhmki, M. Brozman, A. D\u0026aacute;valos, D. Guidetti, V. Larrue, K.R. Lees, Z. Medeghri, and T. Machnig, Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. New England journal of medicine 359 (2008) 1317-1329.\u003c/li\u003e\n\u003cli\u003eY.-C. Liu, C.-H. Liao, C.-F. Chang, C.-C. Chou, and Y.-R. Lin, A locally transmitted case of SARS-CoV-2 infection in Taiwan. New England Journal of Medicine 382 (2020) 1070-1072.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"acute ischemic stroke, endovascular thrombectomy, intravenous thrombolysis, COVID-19 pandemic, modified stroke protocol","lastPublishedDoi":"10.21203/rs.3.rs-5849308/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5849308/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eThe COVID-19 pandemic has posed significant challenges to healthcare systems and public health. We wonder whether modified stroke protocol (MSP) could provide timely treatment with comparable efficacy in acute stroke care.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eParticipants were victims of acute ischemic stroke who underwent endovascular therapy between January 2021 and July 2021. Modified stroke protocol (MSP) claims to conduct nasopharyngeal swab nucleic acid amplification test (NAAT) immediately while encountering a stroke patient suspected of having COVID-19. The efficacy outcome included good functional outcome (mRS score, 0 to 2 at 90 days). Safety outcomes were symptomatic intracranial hemorrhage within 36 hours and overall mortality at 3 months.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 61 patients with acute ischemic stroke who received endovascular therapy enrolled in our analysis, 17 patients were in the MSP group. Overall, there were comparable rates of good functional outcome between the MSP group (23.5%) and the usual care group (23.8%) (OR, 1.54; 95% CI, 0.25 to 9.39). Mortality at 90 days was equivalent: 29.4% in the MSP group and 26.2% in the usual care group (OR, 0.64; 95% CI, 0.10 to 4.17). The risk of symptomatic intracranial hemorrhage within 36 hours was 17.6% in the MSP group and 6.8% in the usual care group (OR, 0.16; 95% CI, 0.01 to 4.37).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAcute ischemic stroke patients in the MSP group had similar functional outcome with those in the usual care group, without significant increase in the rate of mortality at 3 months and symptomatic intracranial hemorrhage within 36 hours.\u003c/p\u003e","manuscriptTitle":"Retrospective Analysis in Efficacy and Safety of Modified Stroke Protocol During the COVID-19 Epidemic: Real-World Experience from a Single Healthcare System","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 15:43:24","doi":"10.21203/rs.3.rs-5849308/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-22T18:45:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-22T12:11:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-22T12:09:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-01-17T12:49:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ab0d9664-089d-47a9-8e61-72d3abc00889","owner":[],"postedDate":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-01-30T13:53:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-24 15:43:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5849308","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5849308","identity":"rs-5849308","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}