Frank Annie1, Mark C Bates2, Aravinda Nanjundappa2, Deepak L Bhatt3, Mohamad Alkhouli4. 1. Charleston Area Medical Center Institute (CAMC) for Academic Medicine and CAMC Health, Education and Research Institute, Charleston, West Virginia. 2. Charleston Area Medical Center Institute (CAMC) for Academic Medicine and CAMC Health, Education and Research Institute, Charleston, West Virginia; West Virginia University, Charleston Division, Charleston, West Virginia. 3. Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts. 4. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: Alkhouli.Mohamad@mayo.edu.
The COVID-19 epidemic has led to an unpreceded disruption in health care systems worldwide. Concerns have been recently raised about young patients with COVID-19 presenting with large ischemic strokes. Data on stroke in COVID-19patients remain limited to a few case reports. In this focused analysis, we investigated the incidence and outcomes of acute ischemic stroke in young adults using a multinational database.We queried the TriNetx Research Network to select patients <50 years of age with laboratory confirmed COVID-19infection between January 20, 2020 to April 24, 2020. Patients were identified as COVID-19 positive if they had a billable code for COVID-19 and had an associated positive laboratory confirmation of the infection (eTable-1). TriNetX is a global federated health research network providing access to statistics on electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from patients in predominately large healthcare organizations. The TriNetx database (COVID-19 Research Network) is a network of 37 global healthcare organizations (36% based in the United States [US] and 64% outside of the US). The diagnosis of acute ischemic stroke was established via validated international classification of diseases 10th revision diagnosis codes. Descriptive statistics were presented as frequencies with percentages for categorical variables and as mean ± standard deviation for continuous measures. Baseline characteristics were compared using a Pearson chi-squared test for categorical variables and an independent-samples t test for continuous variables. All-cause mortality was displayed in the 2 cohorts using the Kaplan Meier method, and statistical significance of the differences between the 2 groups were assessed with the Log-Rank Test.A total of 9,358 COVID-19 positive patients age ≤50 years of age were identified in the database, of whom 33.2% were hospitalized for severe symptoms. The incidence of acute ischemic stroke was 64/9,358 (0.7%). Compared with patients who did not experience a stroke, those with acute ischemic strokes were older (39.3 ± 9.0 vs 36.7 ± 8.5 years, p < 0.001), but had similar proportions of females (60.9% vs 60.4%, p = 0.93). They, however, had higher prevalence of key co-morbidities: hypertension (61.0% vs 11.7%); diabetes (32.8% vs 6.5%); heart failure (15.6% vs 1.5%), nicotine dependence (34.4% vs 5.9%); obesity (46.9% vs 17.4%); chronic obstructive lung disease (15.6% vs 1.0%); prior history of stroke (28.1% vs 0.5); and renal insufficiency (15.6% vs 2.0%), p < 0.001 for all. Median follow up was 16.5 days in the stroke cohort and 36.5 days in the no stroke cohort. All-cause mortality occurred in 10/64 patients (15.6%) in the stroke cohort vs. 58/9,294 patients (0.6%) in the no stroke cohort. In the Kaplan Meier survival analysis, patients with stroke had significantly lower odds of survival compared with those without stroke (p-log rank <0.001) (Figure 1
).
Figure 1
Kaplan meier survival analysis of young adults with COVID-19 with or without stroke.
Kaplan meier survival analysis of young adults with COVID-19 with or without stroke.To our knowledge, this is the first study to report the incidence and outcomes of acute ischemic stroke in young adults with COVID-19infection. We found a low overall incidence but a grim prognosis of acute ischemic stroke among unselected young adults with COVID-19. The findings of this analysis need to be interpreted in the context of its limitations. Due to the nature of this observational database, it is not possible to distinguish whether patients presented with strokes then tested positive for COVID-19 or vice versa. Also, given the lack of a control arm without COVID-19, these findings cannot confirm an association between COVID-19 and increased risk of ischemic stroke especially with the higher prevalence of comorbidities in the stroke cohort.
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