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COVID-19 Is an Independent Risk Factor for Acute Ischemic Stroke



Background and purpose: Coronavirus disease 2019 (COVID-19) is an active worldwide pandemic with diverse complications. Stroke as a presentation has not been strongly associated with COVID-19. The authors aimed to retrospectively review a link between COVID-19 and acute stroke. Materials and methods: We conducted a retrospective case-control study of 41 cases and 82 control subjects matched by age, sex, and risk factors. Cases were patients who underwent stroke alert imaging with confirmed acute stroke on imaging between March 16 and April 5, 2020, at 6 hospitals across New York City. Control subjects were those who underwent stroke alertimaging during the same timeframe without imaging evidence of acute infarction. Data pertaining to diagnosis of COVID-19 infection, patient demographics, and risk factors were collected. A univariate analysis was performed to assess the covariate effect of risk factors and COVID-19 status on stroke imaging with positive findings. Results: The mean age for cases and controls was 65.5 ± 15.3 years and 68.8 ± 13.2 years, respectively. Of patients with acute ischemic stroke, 46.3% had COVID-19 infection compared with 18.3% of controls (P = .001). After adjusting for age, sex, and risk factors, COVID-19 infection had a significant independent association with acute ischemic stroke compared with control subjects (OR, 3.9; 95% CI, 1.7-8.9; P = .001). Conclusions: We demonstrated that COVID-19 infection is significantly associated with imaging confirmation of acute ischemic stroke, and patients with COVID-19 should undergo more aggressive monitoring for stroke.
COVID-19 Is an Independent Risk Factor for Acute Ischemic
P. Belani, J. Schefflein, S. Kihira, B. Rigney, B.N. Delman, K. Mahmoudi, J. Mocco, S. Majidi, J. Yeckley,
A. Aggarwal, D. Lefton, and A.H. Doshi
BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is an active worldwide pandemic with diverse complications.
Stroke as a presentation has not been strongly associated with COVID-19. The authors aimed to retrospectively review a link
between COVID-19 and acute stroke.
MATERIALS AND METHODS: We conducted a retrospective case-control study of 41 cases and 82 control subjects matched by
age, sex, and risk factors. Cases were patients who underwent stroke alert imaging with conrmed acute stroke on imaging
between March 16 and April 5, 2020, at 6 hospitals across New York City. Control subjects were those who underwent stroke aler-
timaging during the same timeframe without imaging evidence of acute infarction. Data pertaining to diagnosis of COVID-19 infec-
tion, patient demographics, and risk factors were collected. A univariate analysis was performed to assess the covariate effect of
risk factors and COVID-19 status on stroke imaging with positive ndings.
RESULTS: The mean age for cases and controls was 65.5 615.3 years and 68.8 613.2 years, respectively. Of patients with acute is-
chemic stroke, 46.3% had COVID-19 infection compared with 18.3% of controls (P¼.001). After adjusting for age, sex, and risk fac-
tors, COVID-19 infection had a signicant independent association with acute ischemic stroke compared with control subjects (OR,
3.9; 95% CI, 1.78.9; P¼.001).
CONCLUSIONS: We demonstrated that COVID-19 infection is signicantly associated with imaging conrmation of acute ischemic
stroke, and patients with COVID-19 should undergo more aggressive monitoring for stroke.
ABBREVIATIONS: COVID-19 ¼coronavirus disease 2019; SARS-CoV-2 ¼Severe Acute Respiratory Syndrome coronavirus 2; RT-PCR ¼reverse transcriptase
polymerase chain reaction
In December 2019, a novel Severe Acute Respiratory Syndrome
coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China.
Coronavirus disease 2019 (COVID-19), the clinical manifestation
of SARS-CoV-2 infection, has since spread into a worldwide pan-
According to the World Health Organization, as of April
22, 2020, at least 2.5 million confirmed cases of COVID-19 have
been detected in 213 countries, with at least 169,000 patients
dying from their disease or complications thereof.
From the initial outbreak in China, transmission was identified
from respiratory droplets and fomites, with symptoms initially
reported as fever, dyspnea, cough, and severe hypoxia. With greater
clinical experience, a broader spectrum of symptoms has emerged,
such as gastrointestinal disease, headache, altered mental status,
anosmia, and confusion.
An acute hemorrhagic necrotizing ence-
phalopathy has also been noted secondary to COVID-19 infection.
Even before COVID-19, antecedent respiratory infections
have been known to increase the short-term risk of ischemic
Early reports from China indicate that neurologic
symptoms are seen in approximately 36% of patients hospitalized
with COVID-19.
Poor outcomes with COVID-19 infection
have an association with vascular risk factors such as hyperten-
sion, coronary artery disease, and diabetes mellitus.
It has been
proposed that the SARS-CoV-2 virus can cause a cytokine storm
through angiotensin-converting enzyme 2 receptor binding, lead-
ing to a hypercoagulable state and an increased incidence of vas-
cular thromboses in patients with COVID-19.
To our knowledge, no peer-reviewed study has been pub-
lished in the literature evaluating the incidence of acute ischemic
stroke associated with COVID-19 when controlling for traditional
Received April 23, 2020; accepted after revision May 17.
From the Departments of Diagnostic, Molecular and Interventional Radiology
(P.B., J.S., S.K., B.R., B.N.D., K.M., J.Y., A.A., D.L., A.H.D.), and Neurosurgery (J.M., S.M.),
Icahn School of Medicine at Mount Sinai, New York, New York.
Please address correspondence to Puneet Belani, MD, Department of Diagnostic,
Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai
and The Mount Sinai Hospital, One Gustave L. Levy Place, Box 1234, New York, NY
10029; e-mail:
Indicates open access to non-subscribers at
AJNR Am J Neuroradiol :2020 1
Published June 25, 2020 as 10.3174/ajnr.A6650
Copyright 2020 by American Society of Neuroradiology.
vascular risk factors. With the dramatic rise in patients with
COVID-19 in New York City in March 2020, the authors began to
observe a disproportionately greater incidence of stroke among
patients with COVID-19 compared with the non-COVID-19 pop-
ulation. The authors believe there may be an association between
COVID-19 infection and stroke risk. In this study, our objectives
were the following: 1) to determine whether infection with
COVID-19 is indeed associated with increased incidence of
stroke, and 2) to assess whether COVID-19 is an independent
risk factor for stroke when controlling for conventional vascular
risk factors.
Patient Selection
The project was conducted as a retrospective case-control study
with data gathered from 6 hospitals spread across the boroughs
of Manhattan, Queens, and Brooklyn in New York City. The 6
hospitals consisted of 1 large academic hospital and 5 smaller
community hospitals. Institutional review board approval was
obtained on an expedited basis. A total of 139 patients had stroke
alert for acute neurologic symptoms between March 16 and April
5, 2020. All patients with stroke alert had a noncontrast head CT
performed followed by vascular imaging (generally a CT angiog-
raphy) unless there was a medical contraindication or clinical
instability. Patients were included for the following reasons: 1)
They had activated stroke alert, 2) CT head and vascular imaging,
and 3) clinical data documenting COVID-19 status. Patients pre-
senting primarily with hemorrhage, tumor, and vasculitis were
excluded (n¼12). Patients with no clinical data were excluded
(n¼1). This step yielded a total of 126 patients. Patients with
acute ischemic stroke (small- or large-vessel occlusions) were
matched with patients without stroke by age, sex, and major vas-
cular risk factors on a 1:2 case-to-control ratio, which resulted in
41 cases and 82 control patients (3 patients were excluded from
the control group to maintain this ratio). Thus, the final cohort
number was 123 patients. The presence or absence of stroke was
confirmed on CT and/or MR imaging by a board-certified radiol-
ogist with fellowship training in neuroradiology. Patients were
deemed to have acute stroke on imaging if they had acute loss of
gray-white differentiation on CT or a diffusion-restricting focus
on MR imaging consistent with infarct. If the initial CT findings
were negative but there was a persistent clinical suspicion for
stroke, it was confirmed or refuted on brain MR imaging unless
there was a contraindication.
Control subjects were defined as inpatients and those in the
emergency department with negative neurologic findings on
imaging (CT or MR imaging) for acute stroke in the setting of a
clinical suspicion for acute stroke. Patients with initial negative
imaging findings were followed up clinically and also on repeat
imaging (if deemed clinically necessary) to verify the absence
of acute stroke. Vascular risk factors, which were obtained from
the medical record, included hypertension, coronary artery dis-
ease, diabetes mellitus type 2, atrial fibrillation, congestive heart
failure, dyslipidemia, current or former smoking status, evidence
of prior stroke, and body mass index corresponding to over-
weight (2529.9 kg/m
)orobesity($30 kg/m
). Data pertaining
to a concurrent diagnosis of COVID-19 infection and patient
demographics were also collected from the electronic medical re-
cord. COVID-19 infection was confirmed by in-house in vitro
reverse transcriptase polymerase chain reaction (RT-PCR) of na-
sopharyngeal swabs performed on the cobas 6800/8800 systems
(Roche Diagnostics) under emergency authorization from the US
Food and Drug Administration. Patients were considered nega-
tive for COVID-19 negative if the RT-PCR test findings were
Statistical Analysis
Patients whose imaging and clinical findings were consistent with
acute ischemic infarct were matched by age, sex, and the number
of major vascular risk factors against controls whose imaging and
clinical findings were inconsistent with acute ischemic infarct.
There were 2 controls for every case.
test was performed for categoric variables, and
attest was performed for continuous variables for evaluation of
the statistical difference between case and control groups. All tests
were 2-tailed, and a Pvalue of .05 was considered statistically sig-
nificant. All statistical analyses were conducted with the SPSS sta-
tistical package for Windows, Version 25 (IBM).
Clinical Characteristics of the Patient Population
Stroke alerts were most commonly activated for patients with
hemiplegia, hemisensory loss, dysarthria, facial droop, aphasia,
and acute altered mental status. Our patient population consisted
of 123 patients, of whom 41 patients who had an acute ischemic
stroke (anterior or posterior circulation) were matched for age,
sex, and vascular risk factors with 82 patients without stroke. The
mean age for cases and controls was 65.5 615.3 years and 68.8 6
13.2 years, respectively. Sex composition was identical between
groups, with 56.1% men in each.
Risk Factor Analysis
There was no statistically significant difference in age, sex, or
major vascular risk factors between case and control subject
groups (Table). COVID-19 infection was confirmed in 19 of 41
patients (46.3%) with acute ischemic stroke, compared with 15 of
82 patients (18.3%) in the control group. The COVID-19 infec-
tion rate was significantly higher in patients with acute ischemic
stroke compared with control subjects (P¼.001).
After we adjusted for age, sex, and major vascular risk factors,
COVID-19 infection was found to be independently and signifi-
cantly associated with patients with acute ischemic stroke com-
pared with control subjects with an OR of 3.9 (95% CI, 1.78.9;
We found that COVID-19 is an independent risk factor for imag-
ing-confirmed acute ischemic stroke during stroke alerts evalua-
tion, after controlling for traditional vascular risk factors. This
finding suggests that COVID-19 infection is associated with
increased morbidity and mortality that transcends the primary
cardiopulmonary sequelae from the infection. It has been
observed that a large number of patients affected with COVID-19
have underlying vascular disease. A meta-analysis of 6 published
2Belani 2020
studies from China including 1527 patients with COVID-19
reported common comorbid conditions, including diabetes
(9.7%), cardiovascular disease (16.4%), and hypertension
In particular, patients with severe COVID-19 had a 3-
fold higher incidence of cardiovascular disease than those with
mild-to-moderate disease.
Multiple studies have reported that recent respiratory infec-
tions are known to increase the short-term risk of ischemic
For example, Grau et al
reported that bacte-
rial and viral infections were risk factors for embolic and throm-
botic infarcts. They found that infection within the preceding
week was a risk factor for cerebral ischemia in age-adjusted mul-
tiple logistic regression analysis (OR, 2.9; 95% CI, 1.316.4). Of
221 patients with COVID-19 at a hospital in Wuhan,
11 (5%)
developed acute ischemic stroke. This patient group was signifi-
cantly older and more likely to have cardiovascular risk factors
and severe COVID-19 infection. They were more likely to have
an increased inflammatory response and a hypercoagulable state
manifested by elevated C-reactive protein and D-dimer levels.
Our study attempts to evaluate the impact of COVID-19 on
stroke irrespective of other vascular risk factors. Patients with
acute stroke and controls without stroke belonged to the same
medical system and clinical setting. Our study confirms that there
was a significantly greater incidence of acute ischemic stroke in
patients with COVID-19 infection compared with those without
the infection. After we adjusted for major vascular risk factors, a
diagnosis of COVID-19 was associated with significantly more
cases than in control subjects.
Several theories link infectious/inflammatory syndromes with
an increased risk of stroke, probably due to the different mecha-
nisms involving prothrombotic state, changes in lipid metabolism
and platelet aggregation, alterations in endothelial function, and
plaque instability and rupture.
The current favored mecha-
nism involves SARS-CoA-2 binding to the angiotensin-convert-
ing enzyme 2 receptor, potentially leading to a cytokine storm
and ultimately to a hypercoagulable state in patients with
Additionally, critically ill patients with SARS-
CoV-2 often show elevated D-dimer levels and platelet counts,
which may render patients prone to acute cerebrovascular
It has been shown in a mouse influenza
model that after the selective blocking of cytokines,
there was a reduction in infarction volume and
improved survival.
Limitations of our study are those that apply to all
retrospective case-control studies. We tried to limit
confounding variables like demographics and medical
risk factors for stroke to reduce bias. We reduced refer-
ral bias by incorporating stroke alert cases from multi-
ple hospitals across various communities in New York
City. Another limitation is our sample size of 123
patients; however, these are all patients with stroke
alerts presenting at 6 hospitals, which consisted of 1
large academic hospital and 5 smaller community hos-
pitals, during a short time span of 2.5 weeks.
Additionally, it is possible that some patients with clin-
ical and radiologic signs of infection who tested posi-
tive for COVID-19 on RT-PCR could be falsely
positive and with other viral or bacterial respiratory infections
The sensitivity and specificity of the RT-PCR test used for the
diagnosis of COVID-19 has not been definitively established
because the test is approved under emergency use authorization.
It is also possible that we may have under-represented the num-
ber of patients with COVID-19 (ie, clinically asymptomatic car-
riers who were not tested for COVID-19), but this could affect
both the stroke and nonstroke outcomes. Finally, another impor-
tant consideration is the possibility of unexpected selection bias
with higher thresholds for presentation to the hospital due to
social distancing/fear of a hospital setting during the pandemic.
This coupled with an overall increased prevalence of COVID-19
may confound the true effect of COVID-19 on stroke risk.
To our knowledge, this is the first study to link SARS-CoV-2 with
an increased risk of imaging-confirmed acute ischemic stroke
when accounting for confounding risk factors. Future endeavors
may assess whether this relationship holds true in a larger popu-
lation and with the pathophysiologic mechanisms (such as the
proinflammatory prothrombotic state and cytokine storm) inher-
ent in COVID-19 that drive this association. Attempts should
also be made to see whether the association holds true for large-
vessel and small-vessel strokes. Patients with COVID-19 should
be evaluated early for acute neurologic changes, and timely work-
up should be performed in patients suspected of having stroke to
reduce morbidity and mortality.
Disclosures: Bradley N. DelmanUNRELATED:Payment for Lectures Including
Service on Speakers Bureaus: Bayer HealthCare Pharmaceuticals, Comments:ad
hoc lectures, averaging 1 per year. Daniel LeftonUNRELATED: Expert
Testimony: Various.
1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China. Lancet
2020;395:497506 CrossRef Medline
2. World Health Organization. WHO Director-Generalsopening
remarks at the media briefing on COVID-19 20 May 2020. May 20,
Demographic characteristics of case and control subjects
Variables Cases (n=41) Controls (n=82) PValue
Age (mean) (yr) 65.6 615 68.8 613 .24
Male sex 56.1% (23) 56.1% (46) 1.00
COVID-19 (1) 46.3% (19) 18.3% (15) .001
Diabetes mellitus type 2 48.8% (20) 43.9% (36) .61
Hypertension 73.2% (30) 73.2% (60) 1.00
Coronary artery disease 29.3% (12) 34.1% (28) .59
Congestive heart failure 12.2% (5) 15.9% (13) .59
Dyslipidemia 43.9% (18) 46.3% (38) .80
Atrial brillation 29.3% (12) 18.3% (15) .18
Prior stroke 22% (9) 31.7% (26) .26
BMI ¼2529.9 kg/m
22% (9) 32.9% (27) .21
BMI .30 kg/m
39% (16) 23.2% (19) .09
Smoking status 34.1% (14) 28.0% (23) .31
Current 12.2% (5) 7.3% (6) .29
Former 22% (9) 20.7% (17) .53
Note:BMI indicates body mass index.
AJNR Am J Neuroradiol :2020 3
3. World Health Organization. Coronavirus disease 2019. 2020 April
2019. Accessed April 30, 2020
4. Mahajan A, Hirsch JA. Novel coronavirus: what neuroradiologists
as citizens of the world need to know. AJNR Am J Neuroradiol
2020;41:55254 CrossRef Medline
5. Jiang F, Deng L, Zhang L, et al. Review of the clinical characteristics
of coronavirus disease. J Gen Intern Med 2020;35:154549 CrossRef
6. World Health Organization. COVID-19: Operational guidance for
maintaining essential health services during an outbreak. March 25,
outbreak. Accessed March 25, 2020
7. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19associated acute
hemorrhagic necrotizing encephalopathy: CT and MRI features.
Radiology 2020 Mar 31. [Epub ahead of print] CrossRef Medline
8. Zurrú MC, Alonzo C, Brescacín L, et al. Recent respiratory infection
predicts atherothrombotic stroke: case-control study in a Buenos
Aires healthcare system. Stroke 2009;40:198690 CrossRef Medline
9. Cowan LT, Lutsey PL, Pankow JS, et al. Inpatient and outpatient
infection as a trigger of cardiovascular disease: the ARIC study. J
Am Heart Assoc 2018;7:e009683 CrossRef Medline
10. Grau AJ, Buggle F, Heindl S, et al. Recent infection as a risk factor
for cerebrovascular ischemia. Stroke 1995;26:37379 CrossRef
11. Grau AJ, Buggle F, Becher H, et al. Recent bacterial and viral infec-
tion is a risk factor for cerebrovascular ischemia: clinical and bio-
chemical studies. Neurology 1998;50:196203 CrossRef Medline
12. Bova IY, Bornstein NM, Korczyn AD. Acute infection as a risk fac-
tor for ischemic stroke. Stroke 1996;27:220406 CrossRef Medline
13. Clayton TC, Thompson M, Meade TW. Recent respiratory infection
and risk of cardiovascular disease: case-control study through a
general practice database. Eur Heart J 2008;29:96103 CrossRef
14. Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors
for ischemic stroke. Stroke 2003;34:251832 CrossRef
15. Becher H, Grau A, Steindorf K, et al. Previous infection and other
risk factors for acute cerebrovascular ischaemia: attributable risks
and the characterisation of high-risk groups. J Epidemiol Biostat
2000;5:27783 Medline
16. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of
Hospitalized Patients with Coronavirus Disease 2019 in Wuhan,
China. JAMA Neurol 2020 April 10. [Epub ahead of print] CrossRef
17. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mor-
tality of adult inpatients with COVID-19 in Wuhan, China: a ret-
rospective cohort study. Lancet 2020;395:105462 CrossRef
18. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cyto-
kine storm syndromes and immunosuppression. Lancet 2020;395:
10334CrossRef Medline
19. Connors JM, Levy JH. COVID-19 and its implications for throm-
bosis and anticoagulation. Blood 2020 Apr 27. [Epub ahead of print]
20. Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular
metabolic diseases on COVID-19 in China. Clin Res Cardiol 2020;
109:53138 CrossRef Medline
21. Avula A, Nalleballe K, Narula N, et al. COVID-19 presenting as
stroke. Brain Behav Immun 2020 Apr 28. [Epub ahead of print]
CrossRef Medline
22. Ameriso SF, Wong VL, Quismorio FP, et al. Immunohematologic
characteristics of infection-associated cerebral infarction. Stroke
1991;22:100409 CrossRef Medline
23. Mittleman MA, Mostofsky E. Physical, psychological and chemical
triggers of acute cardiovascular events: preventive strategies.
Circulation 2011;124:34654 CrossRef Medline
24. Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infec-
tion with COVID-19 and other coronaviruses. Brain Behav Immun
2020 Mar 30. [Epub ahead of print] CrossRef Medline
25. Muhammad S, Haasbach E, Kotchourko M, et al. Influenza virus
infection aggravates stroke outcome. Stroke 2011;42:78391
CrossRef Medline
4Belani 2020
... LVOs, defined as blockages of the proximal intracranial arteries in the anterior or posterior circulation, account for approximately 10 to 30% of acute ischemic strokes in the general population [17][18][19]. Patients with COVID-19 appear to be at heightened risk of having a LVO [17,[20][21][22]. In addition, patients with COVID-19 who have LVOs are younger than patients without COVID-19 with LVOs [28]. ...
... As mentioned above, LVOs are common in COVID-19 patients [13,17,20,21]. LVOs place large cerebral territories at ischemic risk and cause high rates of morbidity and mortality without further treatment. ...
Full-text available
Purpose of Review To describe a comprehensive review of the epidemiology, pathophysiology, and treatment of stroke in the era of COVID-19. Recent Findings COVID-19 is associated with myriad neurological disorders, including cerebrovascular disease. While ischemic stroke is the most common, COVID-19 is associated with an increased risk of intracranial hemorrhage, arterial dissection, posterior reversible encephalopathy syndrome, and cerebral venous sinus thrombosis. In this review, we discuss the epidemiology, pathophysiology, and treatment of stroke due to COVID-19. In addition, we describe how COVID-19 has changed the landscape of stroke systems of care and the effect this has had on patients with cerebrovascular disease. Summary While COVID-19 is associated with a heightened risk of stroke, the pandemic has led to advances in stroke systems of care that may reduce the long-term burden of stroke.
... Therefore, the actual incidence of stroke in patients with COVID-19 may be even higher [58]. In support of these theoretical considerations, another study confirmed a significantly higher incidence of acute ischemic stroke in patients with COVID-19 infection when compared to those without [59]. ...
Full-text available
Since the very beginning of the COVID-19 pandemic, numerous researchers have made an effort to determine the molecular composition of the SARS-CoV-2 virus, and the exact pathomechanism through which the virus exerts such a devastating effect on the host/infected organism. Recent scientific evidence highlights the affinity of the virus towards ACE2 receptors, which are widespread in multiple human systems, including the central nervous system (CNS) and cerebral vessels. Such an affinity may explain endothelial dysfunction and damage that is observed in COVID-positive patients in histopathological studies, with subsequent dysregulation of the cerebral circulation leading to transient or acute cerebrovascular accidents. In this paper, we aimed to evaluate the effects of COVID-related hypoxemia and direct viral invasion on the cerebral circulation, with special respect to the postulated pathomechanism, vulnerable groups of patients, clinical course and outcomes, as well as diagnostic imaging findings.
... Des mesures de l'efficacité de la manipulation expérimentale et des questions liées à la contamination au virus des participants ont été introduites à ce niveau. (Belani et al. [2020] ; Fifi et Mocco [2020]). Dès lors la question de la sensibilisation de la population étudiante aux risques associés au virus nous semble primordiale. ...
... [24][25][26][27][28][29][30] Similar to the present study, other analyses also support that COVID-19 is an independent predictor of LVO, less favorable functional outcome at followup, and increased mortality. [19,[30][31][32][33] The underlying pathophysiology that drives poorer outcomes for AIS in COVID-19 patients is subject to ongoing investigation. However, it is likely that COVID-19 influences patient conditioning for recovery post-stroke. ...
Background: Previous studies suggest that the mechanisms and outcomes in COVID-19-associated stroke differ from those with non-COVID-19 strokes, but there is limited comparative evidence focusing on these populations. Therefore, we aimed to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. Methods: A cross-sectional, international multicenter retrospective study of consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable adjusted analysis was conducted. Results: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p<0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (mTICI 3), COVID-19 was associated with lower odds of complete revascularization [OR=0.33; 95% CI=0.23-0.48; p<0.001], which persisted on multivariable modelling with adjustment for other predictors [aOR=0.30; 95% CI=0.12-0.77; p=0.012]. Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p<0.001). Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and suffered higher morbidity/mortality rates.
... Although a causal relationship between coronaviruses and stroke has not yet been established, supporting evidence exists in several publications. First, there is an independent association between COVID-19 and acute ischemic stroke after controlling for other vascular risk factors (9). Further, in a study of 17,799 hospitalized patients with SARS-CoV-2 infection, our team reported a pooled stroke risk of 0.9% while ischemic stroke occurred in 79% of patients, hemorrhagic stroke in 17%, and 4% had cerebral venous thrombosis (10). ...
... 19,[31][32][33][34][35][36][37][38][39][40][41] Existing theories of causation fail to account for the fact that stroke in COVID-19 is radiologically identical to stroke unassociated with COVID-19 being associated with a high incidence of large vessel occlusion (LVO) Stroke suggesting an embolic cause. 32,33,[42][43][44][45][46][47] In this article, we describe how disruption of the lung tricompartment in the presence of inflammatory cytokines, hypoxia, endotheliopathy, and hypercoagulability leads to in situ thrombosis within the draining pulmonary venules, from which emboli may dislodge into the systemic circulation, causing stroke. 9 Immunothrombotic disruption of the alveolar-capillary barrier results in not only dislodgement of immune-rich emboli but also discharge of RNA which is extremely thrombogenic (RNAaemia) and other viral proteins into the circulation, which could exacerbate immunothrombosis in the cerebral vasculature in a manner similar to that occurring in the lungs. ...
The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.
... Since early in the coronavirus disease 2019 (COVID-19) pandemic, there have been anecdotal reports from around the globe of reduced presentations and hospitalizations for stroke and other acute medical conditions, including myocardial infarction. These reduced presentations occurred despite an increased risk for both acute thrombotic events [1][2][3][4] and intracranial hemorrhages [5][6][7] in patients with COVID-19. The SARS-CoV-2 virus can infect the vascular endothelial cells, which abundantly express ACE-2 (angiotensin-converting enzyme-2) [8][9][10], the entry receptor of the virus. ...
Decreases in acute stroke presentations have been reported during the coronavirus disease 2019 (COVID-19) pandemic surges. A recent study by Bojti et al. (GeroScience. 2021;43:2231–2248) sought to understand the relationship of public health mandates in Hungary as they were implemented with acute ischemic stroke admissions and interventions during two separate COVID-19 waves. We sought to perform a similar analysis of changes in ischemic stroke care at two distinct medical institutions in the USA. Two separate institutions and systems of ischemic stroke care were evaluated through a regional comprehensive stroke center telestroke service and a Veterans Affairs (VA) inpatient stroke and neurorehabilitation service. Telestroke consultations in a single system in Chicago, IL, were significantly decreased during the first COVID-19 wave during severely restricted public health mandates (z-score < − 2), and were less depressed during a subsequent wave with less severe restrictions (z-score approaching − 1), which resembles findings in Hungary as reported by Bojti et al. In contrast, inpatient admissions during the first and second COVID-19 waves to a VA stroke and neurorehabilitation service in Oklahoma City remained unchanged. The Chicago and Hungary patterns of stroke presentations suggest that public perceptions, as informed by regional health mandates, might influence healthcare-seeking behavior. However, the VA experience suggests that specific patient populations may react differently to given public health mandates. These observations highlight that changes in stroke presentation during the COVID-19 pandemic may vary regionally and by patient population as well as by the severity of public health mandates implemented. Further study of COVID-19-related public health policies on acute stroke populations is needed to capture the long-term impact of such policies. Learning from the real-time impact of pandemic surges and public health policy on presentation of acute medical conditions, such as ischemic stroke, may prove valuable for designing effective policies in the future.
... Extracorporeal membrane oxygenation (ECMO) is required in conditions such as hypercoagulability, thrombosis, and coagulopathy. When comparing COVID-19-related stroke cases to older patients with vascular risk factors, data analysis from several reports shows that younger patients with low prevalence of standard stroke risk factors and elevated markers of inflammation (ferritin) and coagulation outnumber COVID-19-related stroke cases [16,23,32,36,[43][44][45][46][47]. As a result, endotheliitis caused by direct viral invasion and inflammation caused by cytokine storm may be the COVID-19-peculiar mechanisms underlying such anomalies [48,49]. ...
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Stroke is a fatal morbidity that needs emergency medical admission and immediate medical attention. COVID-19 ischemic brain damage is closely associated with common neurological symptoms, which are extremely difficult to treat medically, and risk factors. We performed literature research about COVID-19 and ischemia in PubMed, MEDLINE, and Scopus for this current narrative review. We discovered parallel manifestations of SARS-CoV-19 infection and brain ischemia risk factors. In published papers, we discovered a similar but complex pathophysiology of SARS-CoV-2 infection and stroke pathology. A patient with other systemic co-morbidities, such as diabetes , hypertension, or any respiratory disease, has a fatal combination in intensive care management when infected with SARS-CoV-19. Furthermore, due to their shared risk factors, COVID-19 and stroke are a lethal combination for medical management to treat. In this review, we discuss shared pathophysiology, adjuvant risk factors, challenges, and advancements in stroke-associated COVID-19 therapeutics.
Long-term neurological and mental complications of COVID-19, the so-called post-COVID syndrome or long COVID, affect the quality of life. The most persistent manifestations of long COVID include fatigue, anosmia/hyposmia, insomnia, depression/anxiety, and memory/attention deficits. The physiological basis of neurological and psychiatric disorders is still poorly understood. This review summarizes the current knowledge of neurological sequelae in post-COVID patients and discusses brain demyelination as a possible mechanism of these complications with a focus on neuroimaging findings. Numerous reviews, experimental and theoretical studies consider brain demyelination as one of the mechanisms of the central neural system impairment. Several factors might cause demyelination, such as inflammation, direct effect of the virus on oligodendrocytes, and cerebrovascular disorders, inducing myelin damage. There is a contradiction between the solid fundamental basis underlying demyelination as the mechanism of the neurological injuries and relatively little published clinical evidence related to demyelination in COVID-19 patients. The reason for this probably lies in the fact that most clinical studies used conventional MRI techniques, which can detect only large, clearly visible demyelinating lesions. A very limited number of studies use specific methods for myelin quantification detected changes in the white matter tracts 3 and 10 months after the acute phase of COVID-19. Future research applying quantitative MRI assessment of myelin in combination with neurological and psychological studies will help in understanding the mechanisms of post-COVID complications associated with demyelination.
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Importance The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.
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Background Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection. The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.MethodsA meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed. Embase and PubMed were searched for relevant studies.ResultsA total of six studies with 1527 patients were included in this analysis. The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively. The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts. At least 8.0% patients with COVID-19 suffered the acute cardiac injury. The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.Conclusion Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19. On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.
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In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.
Objective Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 present with constitutional and respiratory symptoms, some patients present with atypical symptoms including gastrointestinal, cardiovascular, or neurological symptoms. Here we present a series of four COVID-19 patients with acute stroke as a presenting symptom. Methods We searched the hospital databases for patients presenting with acute strokes and suspected COVID-19 features. All patients that had imaging confirmed strokes and PCR confirmed COVID-19 were included in the study. Patients admitted to the hospital with PCR confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained. Results We identified four patients presenting with imaging confirmed acute strokes and PCR confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course. Conclusions Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed for a comprehensive understanding of the neurological pathology of COVID-19 and its effects on the nervous system.
The SARS-CoV-2 coronavirus (COVID-19) induced infection can be associated with a coagulopathy, findings consistent with infection induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury which can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19 associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.
Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.
Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.