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Utilization and Outcomes of Acute Revascularization Treatments in Ischemic Stroke Patients with SARS-CoV-2 Infection

      Highlights

      • SARS-CoV-2 infected patients have less use of acute revascularization treatments.
      • SARS-CoV-2 infected patients have higher odds of death or non-routine discharge.
      • No modifying effect of acute revascularization treatments on outcomes.

      Abstract

      Objectives

      Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy).

      Materials and Methods

      We analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and determined the odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders.

      Results

      Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5–0.8, p = 0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8–5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9–2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p = 0.9) or death or non-routine discharge (p = 0.2).

      Conclusions

      Patients with acute ischemic stroke with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.

      Key Words

      Introduction

      Our understanding of outcomes in acute ischemic stroke patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following acute revascularization treatments (as intravenous thrombolysis and/or thrombectomy) is based on small case series.
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      Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel.
      cautioned regarding the potential for high rate of death or disability and post thrombolytic intracerebral hemorrhage (ICH)s in acute ischemic stroke patients with SARS-CoV-2 infection due to elevated concentrations of inflammation and hypercoagulability markers such as leukocytosis, and C reactive protein and D dimers and multisystem dysfunction.
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      Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel.
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      and recommended further studies to address these concerns.
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      • Borhani-Haghighi A.
      • Ciccone A.
      • Gomez C.R.
      • Gurkas E.
      • Hsu C.Y.
      • Jani V.
      • et al.
      Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel.
      We performed this analysis to understand utilization and associated outcomes of acute revascularization treatments in acute ischemic stroke patients with SARS-CoV-2 infection.

      Methods

      We analyzed the data from the Cerner de-identified COVID-19 dataset.

      C. Corporation. Cerner provides access to de-identified patient data for COVID-19 research and vaccine development. https://www.cerner.com/newsroom/cerner-provides-access-to-de-identified-patient-data-for-covid-19-research-and-vaccine-development. Published 2020. Accessed.

      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Raju M.
      • Lobanova I.
      • Suri M.F.K.
      • Naqvi S.H.
      • Shyu C.R.
      Facilitating the study of relationships between COVID-19 and cardiovascular health outcomes using cerner Real-World COVID-19 deidentified dataset.
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      • Baskett W.I.
      • Huang W.
      • Lobanova I.
      • Naqvi S.H.
      • Shyu CR.
      Re-infection with SARS-CoV-2 in patients undergoing serial laboratory testing.
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Myers D.
      • Lobanova I.
      • Ishfaq M.F.
      • Naqvi S.H.
      • French B.R.
      • Chandrasekaran P.N.
      • Siddiq F.
      • et al.
      Intracerebral hemorrhage and coronavirus disease 2019 in a cohort of 282,718 hospitalized patients.
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Lobanova I.
      • Ishfaq M.F.
      • Naqvi S.H.
      • French B.R.
      • Siddiq F.
      • et al.
      Subarachnoid hemorrhage and COVID-19: An analysis of 282,718 patients.
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Lobanova I.
      • Naqvi S.H.
      • Thompson V.S.
      • Shyu CR.
      Effect of race and ethnicity on in-hospital mortality in patients with COVID-19.
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Raju M.
      • Lobanova I.
      • Suri M.F.K.
      • Naqvi S.H.
      • French B.R.
      • et al.
      Acute ischemic stroke and COVID-19: An analysis of 27 676 patients.
      which included data from 62 contributing Cerner Real-World Data health systems from United States between December 1, 2019 and January 1, 2021. The dataset is available through Cerner Corporation after submission and approval of research protocol and analysis plan. The dataset includes data for patients who qualified for inclusion based on the following criteria:
      • (1)
        Patient has a minimum of one emergency department or inpatient encounter with a discharge diagnosis code that could be associated with exposure to or clinical suspicion of SARS-CoV-2 infection; OR
      • (2)
        Patient has a minimum of one emergency department or inpatient encounter with a positive laboratory test for a SARS-CoV-2 infection.
      Our analysis included patients with prior medical history from the past 5 years to ensure completeness of the records of potential comorbidities which constituted approximately 76% of the total cohort. Patients in whom no previous medical encounter occurred during the past 5 years were excluded. Encounters with missing data for certain non-essential variables such as gender were included.
      In general, the Cerner de-identified COVID-19 dataset comprise more than 100 clinical and nonclinical variables associated with hospital stays, including primary and secondary diagnoses, primary and secondary procedures, patients' admission and discharge status, and patient demographic information. Cerner Corporation has established Health Insurance Portability and Accountability Act-compliant operating policies to establish de-identification for Cerner Real-World Data.
      We used the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) primary diagnosis codes I63, I65 and I66 to identify the patients admitted with acute ischemic stroke. We also used ICD-10 procedure codes to estimate the proportion of patients who underwent mechanical thrombectomy (03CG3ZZ, 03CG3Z7, 03CH3Z7, 03CJ0ZZ, 03CJ3ZZ, 03CK3Z7, 03CK3ZZ, 03CL3Z7, 03CL3ZZ, 03CL0ZZ, 03CP3ZZ, 03CY3ZZ, 00C73ZZ) and/or intravenous thrombolysis administration (3E03317 and 3E06317). The ICD-10-CM codes were also used to identify the patients with other medical co-morbidities and in-hospital events: hypertension (I10, O10.0, O10.9, I16 and I67.4), diabetes mellitus (E08, E09, E10, E11 and E13), atrial fibrillation (I48), hyperlipidemia (E78), malignancy (Z85), nicotine dependence (F17), subarachnoid hemorrhage (I60), ICH (I61 and I62.9), pulmonary embolism (I26), acute myocardial infarction (I21), transient cerebral ischemic attack (G45), congestive heart failure (I09.81, I11.0 and I50) and peripheral vascular disease (I71, I79.0, I73.9, Z95.8 and Z95.9), pneumonia (J12-J18), respiratory failure (J96), urinary tract infection (N30.0, N30.9, N34.1, N34.2 and N39.0), acute kidney injury (AKI) (N17), septic shock (A41 and R65.21), hepatic failure (K72), cardiac arrest (I46), systemic inflammatory response syndrome(SIRS) (R65.1), and deep venous thrombosis (I82).
      The primary outcome was in-hospital death. The secondary outcome was a composite of death or non-routine discharge (discharge to destinations other than home, such as short-term hospitals or other facilities including intermediate care and skilled nursing homes).

      Statistical analysis

      We performed a logistic regression analysis including all ischemic stroke patients to identify the odds of receiving acute revascularization treatments in the presence of SARS-CoV-2 infection after adjusting for age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous subarachnoid hemorrhage, previous ICH, previous acute myocardial infarction, previous transient cerebral ischemic attack, congestive heart failure, peripheral vascular disease, deep venous thrombosis, or previous pulmonary embolism.
      We performed four logistic regression analyses to determine the independent effect of SARS-CoV-2 infection on 1/. death and 2/. death or non-routine discharge. Analysis 1 and 2 included patients who underwent acute revascularization treatments and analysis 3 and 4 included all acute ischemic stroke patients. Potential confounders included age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous subarachnoid hemorrhage, previous ICH, previous acute myocardial infarction, previous transient cerebral ischemic attack, congestive heart failure, peripheral vascular disease, deep venous thrombosis, previous pulmonary embolism. We entered use of acute revascularization treatments as an interaction term in analysis 3 and 4. Any p-values less than 0.05 are considered significant. All the analyses were done using R (version 3.6.1).

      Results

      Overall cohort of ischemic stroke patients

      The proportions of men, African American, and Hispanic, and patients with diabetes mellitus, previous subarachnoid hemorrhage, congestive heart failure and deep venous thrombosis were significantly higher among those with SARS-CoV-2 infection (see Table 1). The in-hospital mortality (21.4% versus 7.0%, p < 0.0001) and non-routine discharges (76.1% versus 60.4%, p < 0.0001) were higher among acute ischemic stroke patients with SARS-CoV-2 infection than in those without SARS-CoV-2 infection (see Table 1).
      Table 1Characteristics and outcomes for ischemic stroke patients according to SARS-CoV-2 infection status.
      ItemsPatients with new ischemic strokeIschemic stroke patients who received acute revascularization treatments
      SARS-CoV-2 infection-presentSARS-CoV-2 infection -absentp-valueSARS-CoV-2 infection-presentSARS-CoV-2 infection -absentp-value
      Total212222217961588
      Age (in years)69.8 ± 13.570.5 ± 13.70.8693
      < 3538(1.8%)401(1.8%)0.96262(2.1%)38(2.4%)0.8466
      35–49124(5.8%)1218(5.5%)0.486110(10.4%)131(8.2%)0.4566
      50–65553(26.1%)5588(25.2%)0.357325(26%)441(27.8%)0.7131
      > 651407(66.3%)15010(67.6%)0.238359(61.5%)978(61.6%)0.9799
      Gender*
      Men1167(55%)11183(50.3%)0.000463(65.6%)799(50.3%)0.0036
      Women947(44.6%)10953(49.3%)0.000433(34.4%)783(49.3%)0.0045
      Race/ethnicity
      White, Non-Hispanic924(43.5%)13488(60.7%)< 0.000147(49.0%)1000(63.0%)0.0060
      African American462(21.8%)3537(15.9%)< 0.000110(10.4%)187(11.8%)0.6874
      Asian or Pacific Islander34(1.6%)454(2%)0.16591(1.0%)29(1.8%)0.5725
      Hispanic510(24%)3280(14.8%)< 0.000126(27.1%)266(16.8%)0.0094
      Other192(9%)1458(6.6%)< 0.000112(12.5%)106(6.7%)0.0299
      Pre-existing medical conditions
      Hypertension1884(88.8%)19837(89.3%)0.474678(81.3%)1405(88.5%)0.0340
      Diabetes mellitus1315(62%)11085(49.9%)< 0.000149(51%)676(42.6%)0.1035
      Atrial fibrillation735(34.6%)7380(33.2%)0.185234(35.4%)497(31.3%)0.3989
      Hyperlipidemia1680(79.2%)17270(77.7%)0.127672(75%)1211(76.3%)0.7785
      Malignancy351(16.5%)4355(19.6%)0.000612(12.5%)257(16.2%)0.3387
      Nicotine dependence443(20.9%)5896(26.5%)< 0.000121(21.9%)437(27.5%)0.2275
      Previous ischemic stroke837(39.4%)8954(40.3%)0.44123(24%)640(40.3%)0.0015
      Previous subarachnoid hemorrhage47(2.2%)296(1.3%)0.0011(1%)10(0.6%)0.6266
      Previous intracerebral hemorrhage43(2%)419(1.9%)0.65062(2.1%)23(1.4%)0.6174
      Previous pulmonary embolism54(2.5%)485(2.2%)0.27933(3.1%)24(1.5%)0.2216
      Previous acute myocardial infarction183(8.6%)1893(8.5%)0.87054(4.2%)106(6.7%)0.3341
      Previous transient cerebral ischemic attack143(6.7%)1981(8.9%)0.00076(6.3%)114(7.2%)0.7312
      Congestive heart failure818(38.5%)7666(34.5%)0.000234(35.4%)445(28%)0.1189
      Peripheral vascular disease709(33.4%)7532(33.9%)0.648518(18.8%)461(29%)0.0302
      New in-hospital events
      Pneumonia1398(65.9%)5871(26.4%)< 0.000148(50%)298(18.8%)< 0.0001
      Respiratory failure1236(58.2%)6417(28.9%)< 0.000153(55.2%)432(27.2%)< 0.0001
      Urinary tract infection848(40%)7493(33.7%)< 0.000129(30.2%)431(27.1%)0.5125
      Acute kidney injury1215(57.3%)8793(39.6%)< 0.000146(47.9%)467(29.4%)0.0001
      Septic shock872(41.1%)4867(21.9%)< 0.000127(28.1%)228(14.4%)0.0003
      Hepatic failure96(4.5%)573(2.6%)< 0.00010(0%)21(1.3%)0.2569
      Subarachnoid hemorrhage56(2.6%)486(2.2%)0.17816(6.3%)73(4.6%)0.4570
      Intracerebral hemorrhage89(4.2%)943(4.2%)0.912410(10.4%)157(9.9%)0.8660
      Acute myocardial infarction279(13.1%)2202(9.9%)< 0.00015(5.2%)98(6.2%)0.7022
      Transient ischemic attack107(5%)1530(6.9%)< 0.00012(2.1%)93(5.9%)0.1197
      Cardiac arrest166(7.8%)842(3.8%)< 0.00017(7.3%)51(3.2%)0.0333
      Pulmonary embolism126(5.9%)993(4.5%)0.0024(4.2%)58(3.7%)0.7950
      Systemic inflammatory response syndrome76(3.6%)682(3.1%)0.19472(2.1%)36(2.3%)0.9063
      Deep venous thrombosis218(10.3%)1957(8.8%)0.02382(2.1%)115(7.2%)0.0536
      Treatments provided
      Received thrombolysis or thrombectomy96(4.5%)1588(7.1%)< 0.0001---
      Received only thrombolysis55(2.6%)751(3.4%)0.0525---
      Received only thrombectomy35(1.6%)729(3.8%)< 0.0001---
      Intubation/mechanical ventilation344(16.2%)1514(6.8%)< 0.000123(24%)173(10.9%)0.0001
      Outcome
      Non-routine discharge1615(76.1%)13412(60.4%)< 0.000176(79.2%)895(56.4%)< 0.0001
      Expired in hospital455(21.4%)1556(7%)< 0.000121(21.9%)104(6.5%)< 0.0001
      Abbreviation used: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2
      Information regarding gender was not available in a small number of records

      Utilization of acute revascularization treatment

      The proportions of patients who received acute revascularization treatments among acute ischemic stroke patients with SARS-CoV-2 infection were lower than those without SARS-CoV-2 infection (4.5% versus 7.1%, p < 0.0001). Among ischemic stroke patients, 55(2.6%) and 751 (3.4%) received intravenous thrombolysis only, 35 (1.6%) and 729 (3.8%) received mechanical thrombectomy only, and 6 (0.3%) and 108 (0.5%) received both, in patients with and without SARS-CoV-2 infection, respectively. Patients with SARS-CoV-2 infection were significantly less likely to receive acute revascularization treatments among patients with ischemic stroke (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.5-0.8, p = 0.0001). Other factors associated with receiving receive acute revascularization treatments were African American race (OR 0.6, 95% CI 0.6-0.8, p < 0.0001), diabetes mellitus (OR 0.7, 95% CI 0.7–0.8, p < 0.0001), malignancy (OR 0.8, 95% CI 0.7–1.0, p = 0.01), previous subarachnoid hemorrhage (OR 0.5, 95% CI 0.3–0.9, p = 0.02), congestive heart failure (OR 0.8, 95% CI 0.7–0.9, p = 0.002), and peripheral vascular disease (OR 0.8, 95% CI 0.7–0.9, p = 0.001).

      Characteristics and outcomes of patients receiving acute revascularization treatment

      Patients with SARS-CoV-2 infection who received acute revascularization treatments were more likely to have pneumonia, respiratory failure, AKI, septic shock, cardiac arrest, and require intubation/mechanical ventilation. The proportion of patients who died during hospitalization (21.9% versus 6.5%, p < 0.0001) and those with non-routine discharge (79.2% versus 56.4%, p < 0.0001) were significantly higher among patients with SARS-CoV-2 infection compared with those without SARS-CoV-2 infection (See Table 1). The proportion of patients who experienced subarachnoid hemorrhage (1% versus 0.6%) or ICH (2.1% versus 1.4%) were similar between patients with and without SARS-CoV-2 infection.
      Among all ischemic stroke patients who received acute revascularization treatments, SARS-CoV-2 infection was associated with increased odds of death (OR 4.1, 95% CI 2.3-7.2) (see Table 2) and death or non-routine discharge (OR 3.0, 95% CI 1.8–5.1) (see Table 2) after adjusting for potential confounders.
      Table 2Summary of the results of the multivariate models.
      VariablesOdds Ratio (95% Confidence Intervals)
      Patients who underwent acute revascularization treatmentsAll ischemic stroke patients
      Predictors of deathPredictors of death or non-routine dischargePredictors of deathPredictors of death or non-routine discharge
      Age < 35 years1.0(1.0–1.0)1.0(1.0–1.0)1.0(1.0–1.0)1.0(1.0–1.0)
      Age 35-49 years2.9(0.6–14.7)1.3(0.6–2.7)1.3(0.8–2.1)1.3(1.0–1.6)
      Age 50-65 years1.4(0.3–6.7)1.4(0.7–2.8)1.3(0.9–2.0)1.6(1.3–2.0)
      Age > 65 years2.2(0.5–10.5)2.0(1.0–4.0)1.6(1.0–2.3)2.4(1.9–2.9)
      Men1.0(0.7–1.5)0.8(0.6–1.0)1.2(1.1–1.4)0.9(0.9–1.0)
      White1.0(1.0–1.0)1.0(1.0–1.0)1.0(1.0–1.0)1.0(1.0–1.0)
      African American0.9(0.5–1.6)1.1(0.8–1.5)1.1(1.0–1.3)0.9(0.8–1.0)
      Asian or Pacific Islander0.8(0.2–3.7)1.3(0.6–3.0)1.2(0.9–1.7)0.8(0.7–1.0)
      Hispanic1.2(0.7–2.0)1.3(0.9–1.7)1.1(1.0–1.3)0.9(0.8–0.9)
      Other race/ethnicity1.0(0.5–2.1)0.8(0.5–1.1)1.2(1.0–1.4)0.8(0.7–0.9)
      Hypertension0.8(0.5–1.4)1.5(1.1–2.1)0.7(0.6–0.8)1.2(1.1–1.3)
      Diabetes mellitus1.0(0.7–1.6)1.1(0.9–1.4)1.2(1.1–1.4)1.4(1.3–1.4)
      Atrial fibrillation1.4(0.9-2.1)1.6(1.3-2.0)1.7(1.5-1.8)1.5(1.4–1.6)
      Hyperlipidemia0.4(0.3–0.6)0.8(0.6–1.0)0.6(0.6–0.7)0.8(0.8–0.9)
      Malignancy1.5(0.9–2.4)1.5(1.1–2.0)1.1(0.9–1.2)1.1(1.0–1.2)
      Nicotine dependence0.5(0.3–0.9)1.2(0.9–1.5)0.9(0.8–1.0)1.1(1.0–1.1)
      Previous ischemic stroke0.7(0.5–1.1)0.6(0.5–0.8)0.7(0.7–0.8)0.7(0.7–0.8)
      Previous subarachnoid hemorrhage0(0–9999)0.8(0.2–2.9)1.1(0.8-1.6)1.4(1.1–1.8)
      Previous intracerebral hemorrhage1.0(0.1–8.1)1.3(0.5–3.2)1.4(1.0–1.9)1.4(1.1–1.8)
      Previous acute myocardial infarction1.3(0.6–2.7)0.9(0.6–1.3)1.0(0.9–1.2)1.0(0.9–1.1)
      Previous transient cerebral ischemic attack0.6(0.2–1.6)0.6(0.4–0.9)0.8(0.6–0.9)0.9(0.8–1.0)
      Congestive heart failure2.0(1.3–3.0)1.9(1.5–2.4)1.6(1.5–1.8)1.5(1.4–1.6)
      Peripheral vascular disease1.4(0.9–2.1)0.9(0.7–1.1)1.2(1.1-1.3)1.0(1.0–1.1)
      Deep venous thrombosis1.8(1.0–3.4)1.9(1.2–3.1)1.3(1.2–1.5)1.6(1.5–1.8)
      Previous pulmonary embolism0.7(0.2–2.7)2.0 (0.7–5.3)1.0(0.7–1.3)1.0(0.8–1.2)
      SARS-CoV-2 infection4.1(2.3–7.2)3.0 (1.8–5.1)3.4(3.0–3.9)2.1(1.9–2.3)
      Received acute revascularization treatments--1.0(0.8–1.2)0.9(0.8–1.0)
      Interaction between acute revascularization treatments and SARS-CoV-2 infection--1.0(0.6–1.8)1.4(0.9–2.4)
      Abbreviation used: SARS-CoV-2: severe acute respiratory syndrome coronavirus-2

      Outcomes of acute ischemic stroke patients and interaction between SARS-CoV-2 infection and acute revascularization treatment

      SARS-CoV-2 infection was associated with increased odds of death (OR 3.4, 95% CI 3.0–3.9) (see Table 2) and death or non-routine discharge (OR 2.1, 95% CI 1.9–2.3) (see Table 2) after adjusting for potential confounders. Utilization of acute revascularization treatments was not associated with significantly higher odds of death (OR 1.0, 95% CI 0.8–1.2) (see Table 2) and death or non-routine discharge (OR 0.9, 95% CI 0.8–1.0) (see Table 2). The interaction term between SARS-CoV-2 infection and acute revascularization treatments was not significant for either death (p = 0.9) or death or non-routine discharge (p = 0.2) in the multivariate model.

      Discussion

      Utilization of acute revascularization treatments

      Patients who have acute ischemic stroke with SARS-CoV-2 infection are significantly less likely to receive acute revascularization treatments even though SARS-CoV-2 infection is not considered a contraindication for such treatments.
      • Qureshi A.I.
      • Abd-Allah F.
      • Al-Senani F.
      • Aytac E.
      • Borhani-Haghighi A.
      • Ciccone A.
      • Gomez C.R.
      • Gurkas E.
      • Hsu C.Y.
      • Jani V.
      • et al.
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      ,
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      Current guidelines recommend prompt revascularization treatments during the current pandemic because of the high mortality rate and severe neurological disability in untreated patients.
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      • Ben Maacha M.
      • Blanc R.
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      • Casseri T.
      • et al.
      Acute stroke management during the COVID-19 pandemic: does confinement impact eligibility for endovascular therapy?.
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      • Fischer U.
      • Khatri P.
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      • et al.
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      • Leadership A.
      Temporary emergency guidance to US stroke centers during the coronavirus disease 2019 (COVID-19) pandemic: on behalf of the American heart association/American stroke association stroke council leadership.
      Several studies have reported a reduction in rates of utilization of acute revascularization treatments, and increase in time to treatment among acute ischemic stroke patients during the SARS-CoV-2 infection pandemic.
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      • et al.
      Intravenous thrombolysis for acute ischaemic stroke during COVID-19 pandemic in Wuhan, China: a multicentre, retrospective cohort study.
      • Siegler J.E.
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      • Desai S.M.
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      • et al.
      Influence of the COVID-19 pandemic on treatment times for acute ischemic stroke: the society of vascular and interventional neurology multicenter collaboration.
      • Zhao J.
      • Li H.
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      • Fisher M.
      • Shen Y.
      • Liu R.
      Impact of the COVID-19 epidemic on stroke care and ootential solutions.
      • Qureshi A.I.
      • Agunbiade S.
      • Huang W.
      • Akhtar I.N.
      • Abraham M.G.
      • Akhtar N.
      • Al-Mufti F.
      • Aytac E.
      • Balgetir F.
      • Grigoryan M.
      • et al.
      Changes in neuroendovascular procedural volume during the COVID-19 pandemic: an international multicenter study.
      A relative reduction in number of mechanical thrombectomy procedures performed during the pandemic has been reported ranging from 21% in France, 25.3% in China, and 33% in in New York city compared with the procedures performed before the SARS-CoV-2 infection pandemic.
      • Hajdu S.D.
      • Pittet V.
      • Puccinelli F.
      • Ben Hassen W.
      • Ben Maacha M.
      • Blanc R.
      • Bracco S.
      • Broocks G.
      • Bartolini B.
      • Casseri T.
      • et al.
      Acute stroke management during the COVID-19 pandemic: does confinement impact eligibility for endovascular therapy?.
      ,
      • Zhao J.
      • Li H.
      • Kung D.
      • Fisher M.
      • Shen Y.
      • Liu R.
      Impact of the COVID-19 epidemic on stroke care and ootential solutions.
      ,
      • Kerleroux B.
      • Fabacher T.
      • Bricout N.
      • Moise M.
      • Testud B.
      • Vingadassalom S.
      • Ifergan H.
      • Janot K.
      • Consoli A.
      • Ben Hassen W.
      • et al.
      Mechanical thrombectomy for acute ischemic stroke amid the COVID-19 outbreak: decreased activity, and increased care delays.
      An international study from 11 institutions from the United States and 7 international institutions found 8% reduction in mechanical thrombectomy procedures between 2019 and 2020, which was more prominent in regions with high prevalence of SARS-CoV-2 infection.
      • Qureshi A.I.
      • Agunbiade S.
      • Huang W.
      • Akhtar I.N.
      • Abraham M.G.
      • Akhtar N.
      • Al-Mufti F.
      • Aytac E.
      • Balgetir F.
      • Grigoryan M.
      • et al.
      Changes in neuroendovascular procedural volume during the COVID-19 pandemic: an international multicenter study.
      Another study from 187 comprehensive stroke centers.
      • Nogueira R.G.
      • Abdalkader M.
      • Qureshi M.M.
      • Frankel M.R.
      • Mansour O.Y.
      • Yamagami H.
      • Qiu Z.
      • Farhoudi M.
      • Siegler J.E.
      • Yaghi S.
      • et al.
      Global impact of COVID-19 on stroke care.
      reported a 12.7% decrease in mechanical thrombectomy procedures during SARS-CoV-2 infection pandemic with greater reduction in hospitals with higher SARS-CoV-2 infected patient admissions. Our findings suggest that the disproportionately lower utilization of acute revascularization treatments in SARS-CoV-2 infected patients may be contributing the overall decline observed in previous studies.
      The restricted use of acute revascularization treatments in SARS-CoV-2 infected patients may be due to increased delays from stroke onset to treatment consideration.
      • Hajdu S.D.
      • Pittet V.
      • Puccinelli F.
      • Ben Hassen W.
      • Ben Maacha M.
      • Blanc R.
      • Bracco S.
      • Broocks G.
      • Bartolini B.
      • Casseri T.
      • et al.
      Acute stroke management during the COVID-19 pandemic: does confinement impact eligibility for endovascular therapy?.
      ,
      • Zhao J.
      • Li H.
      • Kung D.
      • Fisher M.
      • Shen Y.
      • Liu R.
      Impact of the COVID-19 epidemic on stroke care and ootential solutions.
      ,
      • Kerleroux B.
      • Fabacher T.
      • Bricout N.
      • Moise M.
      • Testud B.
      • Vingadassalom S.
      • Ifergan H.
      • Janot K.
      • Consoli A.
      • Ben Hassen W.
      • et al.
      Mechanical thrombectomy for acute ischemic stroke amid the COVID-19 outbreak: decreased activity, and increased care delays.
      attributed to screening and preventive strategies to reduce transmission
      • Alhazzani W.
      • Moller M.H.
      • Arabi Y.M.
      • Loeb M.
      • Gong M.N.
      • Fan E.
      • Oczkowski S.
      • Levy M.M.
      • Derde L.
      • Dzierba A.
      • et al.
      Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
      in initial evaluation, and performance of neuroimaging, and mechanical thrombectomy. There may be reluctance in using acute revascularization treatments due to presence of elevated concentration of inflammation and hypercoagulability markers
      • Qureshi A.I.
      • Abd-Allah F.
      • Al-Senani F.
      • Aytac E.
      • Borhani-Haghighi A.
      • Ciccone A.
      • Gomez C.R.
      • Gurkas E.
      • Hsu C.Y.
      • Jani V.
      • et al.
      Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel.
      ,
      • Tiainen M.
      • Meretoja A.
      • Strbian D.
      • Suvanto J.
      • Curtze S.
      • Lindsberg P.J.
      • Soinne L.
      • Tatlisumak T.
      Helsinki stroke thrombolysis registry G. body temperature, blood infection parameters, and outcome of thrombolysis-treated ischemic stroke patients.
      ,
      • Hsu P.J.
      • Chen C.H.
      • Yeh S.J.
      • Tsai L.K.
      • Tang S.C.
      • Jeng JS.
      High plasma D-dimer indicates unfavorable outcome of acute ischemic stroke patients receiving intravenous thrombolysis.
      and reports of high mortality in patients with SARS-CoV-2 infection who were treated with acute revascularization treatments.
      • Sangalli D.
      • Polonia V.
      • Colombo D.
      • Mantero V.
      • Filizzolo M.
      • Scaccabarozzi C.
      • Salmaggi A.
      A single-centre experience of intravenous thrombolysis for stroke in COVID-19 patients.
      • Cappellari M.
      • Zini A.
      • Sangalli D.
      • Cavallini A.
      • Reggiani M.
      • Sepe F.N.
      • Rifino N.
      • Giussani G.
      • Guidetti D.
      • Zedde M.
      • et al.
      Thrombolysis and bridging therapy in patients with acute ischaemic stroke and COVID-19.
      • Escalard S.
      • Maier B.
      • Redjem H.
      • Delvoye F.
      • Hebert S.
      • Smajda S.
      • Ciccio G.
      • Desilles J.P.
      • Mazighi M.
      • Blanc R.
      • et al.
      Treatment of acute ischemic stroke due to large vessel occlusion with COVID-19: Experience from paris.
      Patients with SARS-CoV-2 infection may be excluded due to hepatic dysfunction
      • Guan W.J.
      • Ni Z.Y.
      • Hu Y.
      • Liang W.H.
      • Ou C.Q.
      • He J.X.
      • Liu L.
      • Shan H.
      • Lei C.L.
      • Hui D.S.C.
      • et al.
      Clinical characteristics of coronavirus disease 2019 in China.
      and coagulopathy (elevated prothrombin time,  international normalized ratio, activated partial thromboplastin time, or reduced platelet count). The relatively high rate of renal insufficiency with subsequent AKI in patients with SARS-CoV-2 infection
      • Cheng Y.
      • Luo R.
      • Wang K.
      • Zhang M.
      • Wang Z.
      • Dong L.
      • Li J.
      • Yao Y.
      • Ge S.
      • Xu G.
      Kidney disease is associated with in-hospital death of patients with COVID-19.
      may delay or preclude administration of contrast for computed tomography angiography and/or perfusion to identify appropriate candidates.

      Outcomes of patients receiving acute revascularization treatments

      Among patients who received acute revascularization treatments, patients with SARS-CoV-2 infection had significantly higher adjusted odds for in hospital death (OR 4.1) and also for death and non-routine discharge (OR 3.0). However, the higher rates for in hospital death and also for non-routine discharge were also seen in SARS-CoV-2 infected patients in overall cohort of acute ischemic stroke patients suggesting no unique effect of acute revascularization treatments. These adverse outcomes are related to higher rates of pneumonia, respiratory failure, AKI, septic shock, cardiac arrest, and requirement for intubation/mechanical ventilation in SARS-CoV-2 infected ischemic stroke patients. We did not see any modifying effect (interaction term p > 0.05) of acute revascularization treatments in the relationship between SARS-CoV-2 infection and in hospital death or composite endpoint of death and non-routine discharge. The proportions of patients with post-treatment ICH or subarachnoid hemorrhage were similar in patients with and without SARS-CoV-2 infection receiving acute revascularization treatments.

      Implications for practice

      Our results do not support withholding acute revascularization treatments in SARS-CoV-2 infected patients as we did not identify any higher risk of post treatment ICH or subarachnoid hemorrhage. However, the outcome of patients with SARS-CoV-2 infection and ischemic stroke is probably determined by the severity of multi-organ dysfunction and may obscure some or all of the benefit of acute revascularization treatments. An international panel
      • Qureshi A.I.
      • Abd-Allah F.
      • Al-Senani F.
      • Aytac E.
      • Borhani-Haghighi A.
      • Ciccone A.
      • Gomez C.R.
      • Gurkas E.
      • Hsu C.Y.
      • Jani V.
      • et al.
      Management of acute ischemic stroke in patients with COVID-19 infection: report of an international panel.
      recommended assessment of the magnitude of organ dysfunction using Sequential Organ Failure Assessment score
      • Moreno R.
      • Vincent J.L.
      • Matos R.
      • Mendonca A.
      • Cantraine F.
      • Thijs L.
      • Takala J.
      • Sprung C.
      • Antonelli M.
      • Bruining H.
      • et al.
      The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. working group on sepsis related problems of the ESICM.
      to delineate the overall care paradigm in acute stroke patients in accord with the expected prognosis. Other factors such as older age, cardiovascular diseases, secondary infections, acute respiratory distress syndrome, acute renal injury and laboratory findings of lymphopenia and elevated hepatic enzymes, and inflammatory markers associated with increased mortality may have to considered at time of decision making.
      • Zhou F.
      • Yu T.
      • Du R.
      • Fan G.
      • Liu Y.
      • Liu Z.
      • Xiang J.
      • Wang Y.
      • Song B.
      • Gu X.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
      • Wu C.
      • Chen X.
      • Cai Y.
      • Xia J.
      • Zhou X.
      • Xu S.
      • Huang H.
      • Zhang L.
      • Zhou X.
      • Du C.
      • et al.
      Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China.
      • Shi S.
      • Qin M.
      • Shen B.
      • Cai Y.
      • Liu T.
      • Yang F.
      • Gong W.
      • Liu X.
      • Liang J.
      • Zhao Q.
      • et al.
      Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.

      Limitations

      We used Cerner de-identified COVID-19 dataset
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Raju M.
      • Lobanova I.
      • Suri M.F.K.
      • Naqvi S.H.
      • Shyu C.R.
      Facilitating the study of relationships between COVID-19 and cardiovascular health outcomes using cerner Real-World COVID-19 deidentified dataset.
      ,
      • Qureshi A.I.
      • Baskett W.I.
      • Huang W.
      • Shyu D.
      • Myers D.
      • Raju M.
      • Lobanova I.
      • Suri M.F.K.
      • Naqvi S.H.
      • French B.R.
      • et al.
      Acute ischemic stroke and COVID-19: An analysis of 27 676 patients.
      which provides minimal details on the time interval between symptom onset to arrival, severity of neurological deficits, and diagnostic study results (neuroimaging and laboratory tests), or the exact reasons for exclusion from acute revascularization treatments. There is probably a selection bias towards inclusion of patients with greater severity of symptoms by limiting the analysis to emergency department and hospitalized patients. The dataset also depends on the accuracy of diagnosis and procedures codes. ICD-10 diagnosis codes have a high positive predictive value to identify acute ischemic stroke from the principle discharge diagnosis.
      • Alhajji M.
      • Kawsara A.
      • Alkhouli M.
      Validation of acute ischemic stroke codes using the international classification of diseases tenth revision.
      The ICD-10 codes can identify 98% of all patients receiving intravenous thrombolysis and 87% of all patients receiving mechanical thrombectomy.
      • Zachrison K.S.
      • Li S.
      • Reeves M.J.
      • Adeoye O.
      • Camargo C.A.
      • Schwamm L.H.
      • Hsia RY.
      Strategy for reliable identification of ischaemic stroke, thrombolytics and thrombectomy in large administrative databases.
      The discharge functional outcome cannot be measured with the available data, and the closest index was using the destination of discharge as done in previous studies using Nationwide Inpatient Sample data.
      • Hassan A.E.
      • Chaudhry S.A.
      • Grigoryan M.
      • Tekle W.G.
      • Qureshi AI.
      National trends in utilization and outcomes of endovascular treatment of acute ischemic stroke patients in the mechanical thrombectomy era.
      ,
      • Qureshi A.I.
      • Chaudhry S.A.
      • Sapkota B.L.
      • Rodriguez G.J.
      • Suri MF.
      Discharge destination as a surrogate for modified rankin Scale defined outcomes at 3- and 12-months poststroke among stroke survivors.

      Conclusions

      Patients with acute ischemic stroke patients with SARS-CoV-2 infection were significantly less likely to receive acute revascularization treatments and had higher rates of death or non-routine discharge regardless of use of acute revascularization treatments.

      Declaration of Competing Interest

      AIQ has received consultation fees from AstraZeneca.

      Grant support

      WIB is supported by theNational Institutes of Health (5T32LM012410). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding source.

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