Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications


Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. 

The study findings were published in the peer reviewed journal: Neurology (The medical journal of the American Academy of Neurology).

Background and objectives COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19.

Methods Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes.

Subgroup analyses were performed according to treatment groups (IVT-only and EVT). Results Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT).

Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16–2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20–2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23–1.99), 24-hour (OR 2.47; 95% CI 1.58–3.86) and 3-month mortality (OR 1.88; 95% CI 1.52–2.33). COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26–1.60).

Discussion Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients.

Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis.

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.4,15 Current guidelines recommend prompt revascularization treatments during the current pandemic because of the high mortality rate and severe neurological disability in untreated patients.16, 17, 18

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.19, 20, 21, 22 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.16,21,23

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.22

Another study from 187 comprehensive stroke centers.24 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.16,21,23 attributed to screening and preventive strategies to reduce transmission25 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 markers4,6,7 and reports of high mortality in patients with SARS-CoV-2 infection who were treated with acute revascularization treatments.1, 2, 3

Patients with SARS-CoV-2 infection may be excluded due to hepatic dysfunction5 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 infection26 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 panel4 recommended assessment of the magnitude of organ dysfunction using Sequential Organ Failure Assessment score27 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.28, 29, 30

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