Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients

Adnan I. Qureshi, MD; William I. Baskett, BS; Wei Huang, MA; Daniel Shyu, BS; Danny Myers, PhD; Murugesan Raju, PhD; Iryna Lobanova, MD; M. Fareed K. Suri, MD; S. Hasan Naqvi, MD; Brandi R. French, MD; Farhan Siddiq, MD; Camilo R. Gomez, MD; Chi-Ren Shyu, PhD

Disclosures

Stroke. 2021;52(3):905-912. 

In This Article

Discussion

Salient Findings

We identified several findings from the study of 103 acute ischemic stroke patients among 8163 patients with COVID-19. Patients with COVID-19 (compared with those without COVID-19) who developed acute ischemic stroke were older, more likely to be Black, and had a higher frequency of hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure. Patients with COVID-19 who developed acute ischemic stroke compared with those without acute ischemic stroke had higher cardiovascular events during hospitalization including cerebral edema, intracerebral hemorrhage, and myocardial infarction. Patients with COVID-19 and acute ischemic stroke compared with those without acute ischemic stroke were more likely to have multisystem involvement with acute kidney injury, hepatic failure, and respiratory failure. The in-hospital mortality and discharge to destination other than home were significantly higher in patients with COVID-19 and acute ischemic stroke compared with those without stroke. Patients with acute ischemic stroke had 2-fold higher risk of discharge to destination other than home or death compared with those without acute ischemic stroke among all patients with COVID-19 after adjustment for potential confounders. However, when acute ischemic stroke patients with COVID-19 were compared with those without COVID-19, there were minimal differences in baseline and clinical characteristics. There was a higher proportion of Black people among patients who had acute ischemic stroke and COVID-19 and compared with those with acute ischemic stroke without COVID-19. There was a higher rate of discharge to destination other than home or death in ischemic stroke patients with COVID-19 compared with those without COVID-19. Occurrence of COVID-19 was associated with a 1.2× higher risk of discharge to destination other than home or death among ischemic stroke patients after adjustment for potential confounders.

COVID-19 and Risk of Acute Ischemic Stroke

We found a low occurrence (1.3%) of acute ischemic stroke among COVID-19 patients. A similar prevalence (1%) of ischemic stroke was seen among patients without COVID-19 in our analysis. The initial estimates had suggested a higher proportion (≈5%) of patients with acute ischemic stroke among those hospitalized with COVID-19.[8] Other studies have suggested that the proportion of patients with acute ischemic stroke may range between 1% and 3% among those hospitalized with COVID-19 receiving standard thromboprophylaxis.[9–11] One study[16] reported that 0.9% of 3556 hospitalized patients with COVID-19 had acute ischemic stroke. Another recent study[1] reported that 1.6% of 1916 patients with emergency department visit or hospitalization related to COVID-19 experienced an acute ischemic stroke. Our findings suggest that most of the COVID-19 patients who develop acute ischemic stroke have preexisting cardiovascular risk factors for large vessel atherosclerosis, small vessel disease, and cardioembolism similar to acute ischemic stroke patients without COVID-19. Our findings may be somewhat different from the earlier observations from smaller case series that suggested that patients with COVID-19 who developed acute ischemic stroke were younger and without preexisting cardiovascular risk factors.[16,22,23] Other studies have reported findings similar to our findings[7,13,15] suggesting that even if COVID-19 was a predisposing factor, the risk was mainly seen in those who were already at risk for acute ischemic stroke due to other cardiovascular risk factors. Merkler et al[1] also reported that patients with COVID-19 had higher rates of hypertension, diabetes, coronary artery disease, chronic kidney disease, or atrial fibrillation compared with those with influenza.

COVID-19 and Outcome of Acute Ischemic Stroke

The higher risk of discharge to destination other than home or death among COVID-19 patients who also develop acute ischemic stroke may be multifactorial. Patients with COVID-19 and acute ischemic stroke have a much higher occurrence of multisystem involvement including acute kidney injury, hepatic failure, and respiratory failure. Our findings of higher in-hospital mortality and discharge to destination other than home in COVID-19 patients with ischemic stroke compared with those without stroke have been identified in other studies.[7,12,16,23] The rate of discharge to destination other than home was higher in acute ischemic stroke patients with COVID-19 compared with those without COVID-19, supporting the contribution of COVID-19 in determining the outcome in acute ischemic stroke patients. Patients with COVID-19 have multisystem involvement as mentioned previously[7,8,23] and elevation in serum markers of inflammation and fibrin activation,[7,13,16] all of which are shown to increase the rate of death or disability in patients with acute ischemic stroke. There is some evidence that the severity of neurological deficits may be greater[13,23] and response to mechanical thrombectomy more limited[24] in acute ischemic stroke patients with COVID-19. There was no difference between the rates of utilization of thrombolysis and mechanical thrombectomy among ischemic stroke patients with COVID-19 compared with those without COVID-19 in our analysis.

Implications for Practice

COVID-19 was diagnosed in most acute ischemic stroke patients at the same encounter as ischemic stroke. Therefore, acute ischemic stroke patients may present without a diagnosis of COVID-19 and not always occur in those with advanced stages of COVID-19.[2] COVID-19 is unlikely to be confirmed or excluded using laboratory assessment during the time frame for initial evaluation and decision-making in acute stroke patients. Therefore, an acute ischemic stroke patient with suspected COVID-19 has to be evaluated under the assumption that the patient has COVID-19. The high rate of discharge to destination other than home or death in acute ischemic stroke with COVID-19 may be related to multiple organ dysfunction/failure and is unlikely to be influenced from acute treatment of ischemic stroke. An assessment of the magnitude of multiple organ dysfunction maybe helpful in delineating the overall care paradigm in acute ischemic stroke patients considering the effect of COVID-19–related factors independent of stroke. Relatively low rates of intravenous thrombolysis and mechanical thrombectomy were seen in acute ischemic stroke patients with or without COVID-19. New challenges and delays in existing triage protocols for facilitating rapid transfers from emergency department to angiographic suite and between facilities may be partly responsible because of new protocols to ensure early detection of COVID-19 and reduction in transmission.[25,26]

Limitations

Certain aspects of the analysis may have direct implications for interpretation. Our analyses used Cerner deidentified COVID-19 dataset derived from large number of health care facilities. However, the dataset provides minimal details on the severity of neurological deficits and diagnostic study results (neuroimaging and laboratory tests), and, therefore, the exact reasons for differences in outcomes between patients with COVID-19 who developed acute ischemic stroke and those who did not could not be determined. 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 to identify acute ischemic stroke from the principle discharge diagnosis.[27] 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.[20,28] Discharge to home has a high negative predictive value (ability to exclude) for patients with a modified Rankin Scale score of 2 to 6 at 3 months. The positive predictive value of discharge to nursing home or skilled nursing facility is high (ability to include) for patients with a modified Rankin Scale score of 2 to 6 at 3 months.[21] Therefore, discharge destination may allow differentiation of patients with different functional outcomes with reasonable level of accuracy. The acute ischemic stroke patients without COVID-19 in the dataset were those who were screened for COVID-19 due to either history of exposure or respiratory symptoms. These patients may have clinical presentation suggestive of respiratory tract infections, which could mean that they may have other respiratory tract infections or even a small minority have undetected COVID-19 depending upon the screening tests undertaken.[29–31] Therefore, these patients may not be completely reflective of acute ischemic stroke patients in the general population. The high proportion of patients with a history of cigarette smoking and pneumonia among acute ischemic stroke patients without COVID-19 is presumably explained by this bias. Furthermore, the proportion of patients who have COVID-19 among all patients who were admitted with ischemic stroke during the same time period cannot be deduced. Since our analysis only includes patients who were hospitalized, those with transient ischemic attack and minor ischemic stroke maybe underrepresented. This underrepresentation is particularly prominent during the COVID-19 pandemic because patients with mild diseases are avoiding hospitalization in an effort to reduce exposure.[32] We estimated the proportion of patients with acute ischemic stroke (using same ICD-10-CM diagnosis codes or International Classification of Diseases, Ninth Revision, Clinical Modification equivalent) in the CERNER Health Facts database with similar design to provide data for qualitative comparisons. Patients with acute ischemic stroke constituted 0.72% of all hospitalized patients between January 1, 2000, and July 1, 2018 (A.I. Qureshi, W. Huang, I. Lobanova, unpublished data, 2020).

Conclusions

Acute ischemic stroke was infrequent in patients with COVID-19 and usually in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with the occurrence of acute ischemic stroke in patients with COVID-19. Among all acute ischemic stroke patients, COVID-19 was associated with increased risk of discharge to destination other than home or death for reasons that need to be determined.

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