Impact of COVID-19 Infection on the Outcome of Patients With Ischemic Stroke

Joan Martí-Fàbregas, MD, PhD; Daniel Guisado-Alonso, MD; Raquel Delgado-Mederos, MD, PhD; Alejandro Martínez-Domeño, MD; Luis Prats-Sánchez, MD, PhD; Marina Guasch-Jiménez, MD; Pere Cardona, MD; Ana Núñez-Guillén, MD; Manuel Requena, MD; Marta Rubiera, MD, PhD; Marta Olivé, MD; Alejandro Bustamante, MD; Meritxell Gomis, MD, PhD; Sergio Amaro, MD, PhD; Laura Llull, MD, PhD; Xavier Ustrell, MD; Gislaine Castilho de Oliveira, RN; Laia Seró, MD; Manuel Gomez-Choco, MD, PhD; Luis Mena, MD; Joaquín Serena, MD, PhD; Saima Bashir Viturro, MD; Francisco Purroy, MD, PhD; Mikel Vicente, MD; Ana Rodríguez-Campello, MD, PhD; Angel Ois, MD, PhD; Esther Catena, MD; Maria Carmen Garcia-Carreira, MD; Oriol Barrachina, MD; Ernest Palomeras, MD, PhD; Jerzky Krupinski, MD, PhD; Marta Almeria, MD; Josep Zaragoza, MD; Patricia Esteve, MD; Dolores Cocho, MD, PhD; Antia Moreira, MD; Cecile van Eendenburg, MD; Javier Emilio Codas, MD; Natalia Pérez de la Ossa, MD, PhD; Mercè Salvat, RN; Pol Camps-Renom, MD, PhD

Disclosures

Stroke. 2021;52(12):3908-3917. 

In This Article

Results

Patients

We studied a total of 701 patients, whose mean age was 72.3±13.3 years and 424 (60.5%) of them were men. A total of 91 (13%) patients were diagnosed with COVID-19 infection and 610 without (including 206 patients who were not tested, but had no clinical, radiological or epidemiological suspicion of COVID-19).

Only in 5 (5.5%) patients, the infection was diagnosed before the stroke and in the remainder, COVID-19 was detected after hospitalization. Among patients with confirmed COVID-19 infection, 42 (46.2%) presented respiratory insufficiency during hospitalization (pO2 <60 mm Hg) requiring oxygen therapy, 26 (28.6%) were admitted to the ICU and 20 (22.0%) required mechanical ventilation. Table 1 shows details of demographics, vascular risk factors, clinical data, blood test, and treatment aspects. Bivariate comparison between patients with confirmed COVID-19 infection and patients without are shown also in Table 1. Both groups were similar for most variables, except that the median baseline NIHSS score was 2 points higher in the COVID-19 group compared with the non-COVID-19 group at admission (median NIHSS [IQR], 8 [3–18] versus 6 [2–14]; P=0.049) and at the 72 hours follow-up (median NIHSS [IQR], 4 [1–14] versus 3 [1–8]; P=0.042). Also, patients with COVID-19 were less frequently admitted to the Stroke Unit (31.9% versus 55.7%; P<0.001) and by cons, they were more frequently admitted to the ICU (28.6% versus 3.3%; P<0.001). As expected, some analytical abnormalities known to be associated with the SARS-CoV-2 infection such as lymphopenia, elevation of D-dimer levels or a prolonged prothrombin time were more frequent in patients with COVID-19.

There were 239 patients diagnosed with a large-vessel occlusion (LVO) and 136 (56.9%) of them underwent MT. There were 39 (42.9%) patients with a LVO in the COVID-19 group and 200 (32.8%) in the non-COVID-19 group (P=0.059). Clinical characteristics of the patients diagnosed with LVO are detailed in Table I in the Data Supplement. Remarkably, baseline NIHSS score, proportion of patients who received fibrinolysis, proportion of patients treated with MT and rates of successful recanalization were similar between patients with and without COVID-19.

During the first week of recruitment, patients with COVID-19 represented the 41.7% of the totals of strokes while none COVID-19 patients were detected during the last week of the study. Figure I in the Data Supplement shows the weekly proportion of patients with COVID-19 during the recruitment.

Primary Outcome

We obtained the mRS score at 3 months from 679 patients and 22 patients were lost during the follow-up. The shift analysis showed a median mRS score at 3 months of 4 (IQR, 2–6) in the patients with COVID-19 and 3 (IQR, 1–4) in the non-COVID-19 patients (P<0.001; Figure 1). Ordinal logistic regression analysis of the primary end point showed a common odds ratio (indicating the odds of worsening of 1 point on the mRS) of 2.26 (95% CI, 1.49–3.43; P<0.001) in the presence of COVID-19. After adjusting by age and baseline NIHSS score the common odds ratio was 2.03 (95% CI, 1.31–3.13; P=0.001).

Figure 1.

Scores on the modified Rankin Scale at 3 mo according to the coronavirus disease 2019 (COVID-19) infection status.

The proportion of patients with a favourable functional outcome at 3 months of follow-up, was 30/89 (33.7%) in the COVID-19 group and 277/590 (47.0%) in the non-COVID-19 group, which represents a risk ratio for poor functional outcome of 1.25 (95% CI, 1.06–1.48; P=0.019). However, in the multivariable logistic regression analysis, COVID-19 infection was not independently associated with the probability of poor functional outcome after adjusting by age, baseline NIHSS score, admission to the ICU and prior history of diabetes. Details of the bivariate and the multivariable logistic regression analyses are shown in Table 2 and Table 3. Obesity was not associated with functional outcome when comparing patients with and without COVID-19 infection (13.4% versus 16.1%, P=0.312). After excluding patients without a confirmed PCR test (n=206), the results of the multivariable logistic regression analysis did not change.

We observed that patients with LVO and COVID-19 were less likely to achieve a favourable functional outcome (33.3%) compared to patients without COVID-19 (50.5%), thought this difference was not statistically significant (P=0.079). In a multivariable logistic regression sensitivity analysis including only patients with LVO, COVID-19 was not independently associated with poor outcome after adjusting for age, baseline NIHSS, admission to ICU and reperfusion therapies (intravenous thrombolysis and MT; odds ratio, 1.68 [95% CI, 0.63–4.49]; P=0.297).

Secondary Outcome

Mortality rate at 90 days was 39.3% among patients with COVID-19 and 16.1% in the non-COVID-19 patients, which represents a risk ratio of 2.44 (95% CI, 1.78–3.35; P<0.001). Figure 2 shows the Kaplan-Meier survival curve for both groups. In the multivariable Cox regression analysis, COVID-19 infection was independently associated with the probability of death within 3 months from the index stroke with a hazard ratio (HR) of 3.14 (95% CI, 2.10–4.71; P<0.001) after adjusting by age, baseline NIHSS score and admission to the Stroke Unit. Details of the bivariate and the multivariable logistic regression analyses are shown in Table II in the Data Supplement and Table 4. Neither obesity (HR, 0.65 [95% CI, 0.36–1.15]; P=0.135) nor diabetes (HR, 1.07 [95% CI, 0.75–1.54], P=0.710) was associated with higher mortality in patients with COVID-19 infection compared with patients without COVID-19 infection. After excluding patients without a confirmed PCR test (n=206), the SARS-CoV-2 infection persisted independently associated with mortality with a HR of 2.77 (95% CI, 1.80–4.25; P<0.001). Details of these bivariate and the multivariable Cox regression analyses are shown in Table III in the Data Supplement.

Figure 2.

Kaplan-Meier survival curve for mortality at 3 mo according to the coronavirus disease 2019 (COVID-19) infection status.

Of 131 patients who died during the follow-up, the cause of death was known for 93 (71.0%). Approximately, 1 out of 4 patients (22.1%) died from stroke complications and 20 (15.3%) died from COVID-19 complications. More details of the causes of death are summarized in Table IV in the Data Supplement.

Again, we focused in the subgroup of patients with LVO and we observed that patients with COVID-19 in this subgroup were more likely to die at 3 months (36.7%) compared to patients without COVID-19 (20.6%) with a HR of 2.96 (95% CI, 1.48–5.95; P=0.002) in the adjusted multivariable Cox regression analysis.

Markers of Infection Severity in Patients With COVID-19

In the multivariable Cox regression analysis, receiving anticoagulation therapy during hospitalization and baseline D-dimer levels were independently associated with mortality after adjusting by age, admission to the Stroke Unit and baseline NIHSS score. Details of the analysis on severity markers associated with the infection are detailed in Table V in the Data Supplement.

Stroke Outcomes and Admission Site in Patients With COVID-19

After excluding patients who required admission to the ICU, we observed a favourable outcome in 11 (40.7%) patients with COVID-19 who were admitted in a Stroke Unit versus 13 (35.1%) of patients who were admitted to a COVID unit (P=0.647). Similarly, we noted 10 (37.0%) patients with COVID-19 who died after being admitted to a Stroke Unit compared with 16 (43.2%) who were not (P=0.618).

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