key: cord-0915571-32wq80sm authors: Qureshi, Adnan I.; Baskett, William I.; Huang, Wei; Shyu, Daniel; Myers, Danny; Lobanova, Iryna; Ishfaq, Muhammad F.; Naqvi, S. Hasan; French, Brandi R.; Siddiq, Farhan; Gomez, Camilo R.; Shyu, Chi-Ren title: Subarachnoid Hemorrhage and Coronavirus Disease 2019: An Analysis of 282,718 Patients date: 2021-04-30 journal: World Neurosurg DOI: 10.1016/j.wneu.2021.04.089 sha: 35440142838f9519afe316fa55edcb96aa5d3426 doc_id: 915571 cord_uid: 32wq80sm Background Intracranial hemorrhage (including subarachnoid hemorrhage) has been reported in 0.3 to 1.2% of patients with coronavirus disease 2019 (COVID-19). However, no study has evaluated the risk of subarachnoid hemorrhage in COVID-19 patients. Methods We analyzed the data from 62 healthcare facilities using the Cerner de-identified COVID-19 dataset. Results A total of 86 (0.1%) and 376 (0.2%) subarachnoid hemorrhage patients among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of subarachnoid hemorrhage in COVID-19 patients (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.4-0.7, p<.0001) after adjusting for gender, age strata, race, hypertension and nicotine dependence/tobacco use. The proportions of patients who developed pneumonia (58.1% versus 21.3%, p<.0001), acute kidney injury (43% versus 27.7%, p=0.0005), septic shock (44.2% versus 20.7%, p<.0001) and respiratory failure (64.0% versus 39.1%, p<.0001) were significantly higher among subarachnoid hemorrhage patients with COVID-19 compared with those without COVID-19. The in-hospital mortality among subarachnoid hemorrhage patients with COVID-19 was significantly higher compared with those without COVID-19 (31.4% versus 12.2%, p<.0001). Conclusion The risk of subarachnoid hemorrhage was not increased in patients with COVID-19. The higher mortality in subarachnoid hemorrhage patients with COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of systemic co-morbidities. Intracranial hemorrhage (including subarachnoid hemorrhage) has been reported in 0.3 to 1.2% of patients with coronavirus disease 2019 (COVID-19) based on a review of nine cohort studies (n = 13,741 patients) 1 . Isolated aneurysmal and non-aneurysmal subarachnoid hemorrhages in patients with COVID-19 have been reported previously. [2] [3] [4] Although previous studies have evaluated the risk of ischemic stroke, 5, 6 no study has evaluated the risk of subarachnoid hemorrhage in COVID-19 patients. We performed this study to identify risk factors, co-morbidities, treatment strategies, and outcomes in patients with subarachnoid hemorrhage derived from a large cohort of COVID-19 patients. We analyzed the data from the Cerner de-identified COVID-19 dataset, a subset of Cerner Real-World Data extracted from the electronic medical records of health care facilities which have a data use agreement with Cerner Corporation. 7-9 The COVID-19 deidentified 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 diagnosis code that could be associated to COVID-19 exposure or infection; OR 2) Patient has a minimum of one emergency department or inpatient encounter with a positive laboratory test for a COVID-19. The methodological aspects of the dataset are available in another publication. 10 . We also used ICD-10-CM procedure codes and current procedural terminology codes to estimate the proportion of subarachnoid hemorrhage patients who underwent aneurysm treatment using surgical or endovascular treatment identified by ICD-10 procedure codes (03VG0CZ for surgical, 03LG3DZ for endovascular); or angioplasty (procedure codes 037G3DZ, 037G3ZZ). Intubation and mechanical ventilation were identified by ICD-10-CM codes 0BH17EZ and Z9911 or current procedural terminology codes 31500, 94656 and 94657 (for intubation) or 94002 to 94005 (for mechanical ventilation). The outcome was based on discharge destination and categorized as home or non-routine discharge. Discharge destination to home has been shown to predict none to mild disability while non-routine discharge predicts moderate to severe disability at 3 months post stroke. 12, 13 We performed this analysis to identify any significant differences in clinical characteristics between subarachnoid hemorrhage patients with and without COVID-19, as well as COVID-19 patients with and without subarachnoid hemorrhage. We performed logistic regression analysis including all patients in the dataset to identify the association between J o u r n a l P r e -p r o o f COVID-19 and subarachnoid hemorrhage. We adjusted for known risk factors for subarachnoid hemorrhage including age (age strata <35, 35-54, 55-70, and >70 years), gender, race/ethnicity, hypertension, nicotine dependence, and previous subarachnoid hemorrhage. All the analyses were done using R (version 3.6.1). Aneurysm treatment using endovascular treatment was performed in none of 85 COVID-19 patients and in 12 of 376 non-COVID-19 patients with subarachnoid hemorrhage. Aneurysm treatment using surgical treatment was performed in 2 of 376 non-COVID-19 patients with subarachnoid hemorrhage. The in-hospital mortality among subarachnoid hemorrhage patients with COVID-19 was significantly higher compared with those without COVID-19 (31.4% versus 12.2%, p<.0001). (see Table 1 ). In the multivariate model, there was a lower risk of subarachnoid hemorrhage in COVID-19 patients (OR 0.5, 95% CI 0.4-0.7, p<.0001) after adjusting for gender, age strata, race/ethnicity, hypertension and nicotine dependence/tobacco use. Other risk factors independently associated with subarachnoid hemorrhage were age 35-54 years (OR 1.8, 95% CI 1.2-2.5, p=.002), age 55-70 years (OR 2.6, 95% CI 1.8-3.7, p<.0001), age >70 years (OR 3.0, 95% CI 2.1-4.3, p<.0001), and hypertension (OR 1.7, 95% CI 1.3-2.1, p<.0001). During the COVID-19 admissions, pneumonia, pulmonary embolism, urinary tract infection, acute kidney injury, hepatic failure, cardiac arrest, acute myocardial infarction, septic shock, and respiratory failure were more frequent in COVID-19 patients with subarachnoid hemorrhage. The in-hospital mortality among COVID-19 patients with subarachnoid hemorrhage was significantly higher compared with COVID-19 patients without subarachnoid hemorrhage (31.4% versus 6.8%, p<.0001) (see Table 1 ). We found a low occurrence (0.1%) of subarachnoid hemorrhage among COVID-19 patients. A slightly higher prevalence (0.2%) of subarachnoid hemorrhage was seen among patients without COVID-19 in our analysis. It appeared that most subarachnoid hemorrhage were non-aneurysmal in nature. 14 The in-hospital mortality among subarachnoid hemorrhage patients with COVID-19 was significantly higher compared with those without COVID-19. A higher rate of cerebral ischemia in patients with COVID-19 and subarachnoid hemorrhage was expected based on SARS-CoV-2 causing a profoundly pro-inflammatory thrombotic state as discussed above. 6 The high rate of discharge to destination other than home or death in patients with subarachnoid hemorrhage with COVID-19 may be related to multiple organ dysfunction/failure and is unlikely to be influenced from treatment of neurological aspects of subarachnoid hemorrhage alone. An assessment of the magnitude of multiple organ dysfunction maybe helpful in delineating the overall care paradigm in subarachnoid hemorrhage patients. Several factors in patients with COVID-19 infection have been established, which can identify the patients at risk J o u r n a l P r e -p r o o f for in-hospital mortality, such as older age, high Sequential Organ Failure Assessment (SOFA) score, cardiovascular diseases, secondary infections, acute respiratory distress syndrome (ARDS), acute renal injury and laboratory findings of lymphopenia and elevated hepatic enzymes, C reactive protein, ferritin, creatinine phosphokinase, and fibrin D-dimers. [39] [40] [41] [42] Therefore, assessment of dysfunction in other organs using validated systems such as SOFA appears to be important to provide overall prognosis prior to determining the appropriate subarachnoid hemorrhage treatment. Our analyses used Cerner de-identified COVID-19 dataset derived from large number of healthcare facilities. However, the dataset provides minimal details on the severity of neurological deficits, and diagnostic study results, therefore, the exact reasons for differences in outcomes between subarachnoid hemorrhage patients with COVID-19 and those without COVID-19 could not be determined at a granular level. The dataset also depends on the accuracy of diagnosis and procedures listed in the data collection system. ICD-10 diagnosis codes have a high positive predictive value (96%) to identify subarachnoid hemorrhage from the principle discharge diagnosis. 43 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. 12, 44 Discharge to home has a very high negative predictive value (ability to exclude) for patients with a modified Rankin score of 2-6 at 3 months. 13 Therefore, discharge destination may allow differentiation of patients with different functional outcomes groups with reasonable level of accuracy. The subarachnoid hemorrhage patients without COVID-19 in the dataset were those who were screened for COVID-19 due to either J o u r n a l P r e -p r o o f Intracranial hemorrhage in coronavirus disease 2019 (COVID-19) patients Non-aneurysmal subarachnoid haemorrhage in COVID-19 Fatal aneurysmal subarachnoid hemorrhage in a young patient with COVID-19 infection Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel Cerner Corporation. 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The apparent decrease amid the COVID-19 pandemic Writing -Original Draft, Supervision, Project administration Methodology, Software, Formal analysis, Resources, Data Curation, Writing -Review & Editing Wei Huang: Formal analysis, Writing -Review & Editing Daniel Shyu: Methodology, Writing -Review & Editing Danny Myers: Investigation, Resources, Data Curation, Writing -Review & Editing Iryna Lobanova: Conceptualization, Writing -Review & Editing Conceptualization, Writing -Review & Editing S. Hasan Naqvi: Conceptualization, Writing -Review & Editing Brandi R. French: Conceptualization, Writing -Review & Editing Farhan Siddiq: Conceptualization, Writing -Review & Editing Camilo R. Gomez: Conceptualization, Writing -Review & Editing Chi-Ren Shyu: Conceptualization, Methodology, Supervision, Writing -Review & ARDS -acute respiratory distress syndrome CI -confidence interval COVID-19 -coronavirus disease 2019 ICD-10-CM -International Classification of Diseases, Tenth Revision, Clinical Modification IL -interleukin OR -odds ratio SARS-CoV-2 -severe acute respiratory syndrome coronavirus 2 SD -standard deviation SIRS -systemic inflammatory response syndrome SOFA -Sequential Organ Failure Assessment