Ischemic Stroke Occurs Less Frequently in COVID-19 Patients

In This Article

Abstract and Introduction

Abstract

Background and Purpose: The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies. We investigated the association between COVID-19 and stroke.

Methods: We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020. A mixed-effects logistic regression analysis and a propensity score–weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke. Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke.

Results: Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke. Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16–0.40]). This association was consistent in all age groups. Our results were robust in sensitivity analyses, including propensity score–weighted regression models. In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54–31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81–1.25]).

Conclusions: Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19.

Introduction

There has been recent speculation that coronavirus disease 2019 (COVID-19) is associated with increased risk of fatal ischemic stroke in young adults.^[1–3] Multiple theories have been proposed for the pathophysiology of this association, with a procoagulable state in infected patients as the most commonly proposed mechanism.^[1] However, several researchers and clinicians are indicating a decreased occurrence of ischemic stroke across the world during the COVID-19 pandemic.^[4–6] The drop in perceived occurrence has been so dramatic that many societies and advocacy groups have issued statements^[6] urging patients to not delay stroke care in fear of being exposed to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus causing COVID-19.^[7] Indeed there has been evidence found for delays in stroke care due to the pandemic.^[8] However, no large multi-institutional observational studies support either observation.^[9] Despite extensive literature on similar concerns for influenza,^[10–12] the evidence for COVID-19 is comprised mainly of small, single-institution case series, without control for confounders and limited generalization. The prior report on stroke and COVID-19 in young adults is limited by selection bias, focusing only on the patients with most severe stroke seen by the neuro-interventional team.^[1] This selection reflects the different preferences and backgrounds of the treating physicians, as well as specific patient characteristics. In addition, although concurrent stroke and SARS-CoV-2 infection have been documented in international series before,^[13–15] the impact of COVID-19 on stroke outcomes has not been studied. There has been no prior report attempting to account for these limitations through different analytic approaches in a cross-section of patients with COVID-19 of all ages.

We used a comprehensive cross-section of hospital discharges from a large NY-based healthcare system to study the association of COVID-19 with the occurrence of ischemic stroke. The frequency of unfavorable outcomes in patients with ischemic stroke concurrent SARS-CoV-2 infection was also analyzed. Mixed-effects logistic regression and a propensity score matched logistic regression was used to control for confounding.

Table 1. Patient Characteristics
	Total	Ischemic stroke		No stroke		P value*
	N=24 808	N=566		N=24 242
		%	N	%	N
COVID-19	10.1%	3.9%	22	10.3%	2491	0.0000
Age, y
<50	31.0%	6.4%	36	31.5%	7647	0.0000
50–59	12.3%	10.8%	61	12.4%	3002	0.2786
60–69	16.4%	21.9%	124	16.2%	3936	0.0004
70–79	17.2%	23.3%	132	17.1%	4147	0.0001
>80	23.1%	37.6%	213	22.7%	5510	0.0000
Female	52.8%	53.5%	303	52.8%	12 789	0.7460
Race
White	71.1%	71.2%	403	71.1%	17 245	1.0000
Black	12.2%	17.0%	96	12.1%	2932	0.0006
Asian	1.8%	3.2%	18	1.8%	431	0.0206
Other	14.8%	8.7%	49	15.0%	3634	0.0000
Comorbidities
Hypercholesterolemia	36.6%	56.2%	318	36.1%	8750	0.0000
Hypertension	31.1%	51.4%	291	30.6%	7428	0.0000
Coronary artery disease	23.8%	28.1%	159	23.7%	5743	0.0173
Diabetes	24.5%	32.9%	186	24.3%	5900	0.0000
Smoking	11.2%	10.1%	57	11.3%	2733	0.4075
Chronic obstructive pulmonary disease	9.9%	10.4%	59	9.9%	2395	0.7206
Alcohol	5.5%	2.5%	14	5.6%	1361	0.0017
Congestive heart failure	7.1%	5.8%	33	7.1%	1733	0.2614
Peripheral vascular disease	2.7%	2.7%	15	2.7%	664	1.0000
Chronic renal failure	15.9%	17.0%	96	15.9%	3848	0.5212
Insurance
Medicare	43.8%	64.5%	365	43.4%	10 513	0.0000
Private	41.8%	26.5%	150	42.1%	10 213	0.0000
Self pay	2.5%	2.8%	16	2.5%	603	0.7073
Workman's comp	0.8%	0.0%	0	0.8%	193	0.0589
No fault	0.6%	0.0%	0	0.6%	137	0.1319
Other	4.8%	2.8%	16	4.9%	1186	0.0305
Facility
Hospital 1	12.9%	4.2%	24	13.1%	3166	0.0000
Hospital 2	22.1%	21.7%	123	22.1%	5361	0.8683
Hospital 3	30.2%	31.3%	177	30.2%	7326	0.6225
Hospital 4	7.2%	13.4%	76	7.1%	1713	0.0000
Hospital 5	13.6%	16.6%	94	13.6%	3287	0.0426
Hospital 6	14.0%	12.7%	72	14.0%	3389	0.4277

COVID-19 indicates coronavirus disease 2019.
*P values based on χ² tests.

Table 2. Models Examining the Association of Ischemic Stroke (and Myocardial Infarction) and COVID-19
	Stroke or TIA*	P value	Ischemic stroke*	P value
	OR (95% CI)	P value	OR (95% CI)	P value
Unadjusted analysis	0.35 (0.23–0.55)	<0.001	0.40 (0.24–0.64)	<0.001
	OR (95% CI)	P value	OR (95% CI)	P value
Mixed-effects regression†	0.25 (0.16–0.40)	<0.001	0.29 (0.18–0.48)	<0.001
Propensity score–matched regression‡	0.24 (0.15–0.38)	<0.001	0.28 (0.17–0.46)	<0.001
Inverse-weighted propensities‡	0.33 (0.28–0.39)	<0.001	0.37 (0.30–0.45)	<0.001
	TIA*		Myocardial infarction*
	OR (95% CI)		OR (95% CI)
Unadjusted analysis	0.20 (0.07–0.54)	<0.001	0.87 (0.68–1.12)	0.264
Mixed-effects regression†	0.14 (0.10–0.38)	<0.001	0.89 (0.69–1.16)	0.382
Propensity score–matched regression‡	0.12 (0.04–0.33)	<0.001	0.88 (0.68–1.15)	0.341
Inverse-weighted propensities‡	0.18 (0.13–0.27)	<0.001	0.84 (0.75–0.94)	0.025

COVID-19 indicates coronavirus disease 2019; OR, odds ratio; and TIA, transient ischemic attack.
*All regressions were based on logistic models.
†Hospital ID was used as a fixed-effects variable.
‡The propensity score was calculated using the following variables: age, sex, race, insurance, medical comorbidities, and all pairwise interactions.

Table 3. Models Examining the Association of COVID-19 With Unfavorable Outcomes in Patients With Acute Ischemic Stroke
	Mortality*	P value	Discharge to rehabilitation*	P value
	OR (95% CI)	P value	OR (95% CI)	P value
Unadjusted analysis	9.68 (3.55–26.4)	<0.001	2.19 (0.75–6.38)	0.143
Logistic regression†	10.50 (3.54–31.18)	<0.001	2.45 (0.81–1.25)	0.103

COVID-19 indicates coronavirus disease 2019; and OR, odds ratio.
*All regressions were based on step-wise logistic models.
†Hospital ID was used as a fixed-effects variable.