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Cerebrovascular disease is associated with COVID-19

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Review
Cerebrovascular disease is associated
with an increased disease severity in
patients with Coronavirus Disease 2019
(COVID-19): A pooled analysis of
published literature
International Journal of Stroke
0(0) 1–5
! 2020 World Stroke Organization
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/1747493020921664
journals.sagepub.com/home/wso
Gaurav Aggarwal1 , Giuseppe Lippi2,* and
Brandon Michael Henry3,*
Abstract
Introduction: There is an urgent need to identify patients at high risk during the ongoing coronavirus disease (COVID19) pandemic. Whether a history of stroke is associated with increased severity of disease or mortality is unknown.
Method: We pooled studies from published literature to assess the association of a history of stroke with outcomes in
patients with COVID-19.
Results: A pooled analysis of 4 studies showed a 2.5-fold increase in odds of severe COVID-19. While a trend was
observed, there was no statistically significant association of stroke with mortality in patients with COVID-19 infection.
Discussion: Our findings are limited by a small number of studies and sample size.
Conclusion: There is a 2.5-fold increase in odds of severe COVID-19 illness with a history of cerebrovascular disease.
Keywords
Cerebrovascular disease, COVID-19, Coronavirus
Received: 29 March 2020; accepted: 5 April 2020
Introduction
Coronavirus Disease 2019 (COVID-19) infection is an
ongoing pandemic, characterized by high morbidity
and mortality. There is an urgent need to identify clinical and biological predictors of severity and mortality
associated with COVID-19 infection for judicious use
of limited resources. Data are scant about the risk factors and therapies for COVID-19, and most of the predictions are currently based on prior experience with
severe acute respiratory syndrome (SARS) and
Middle East respiratory syndrome (MERS). A history
of cerebrovascular disease in patients with SARS and
MERS was shown to be associated with worse outcomes and increased healthcare resource utilization.1,2
Moreover, cerebrovascular disease was found to be
associated with increased 90-day mortality in community acquired pneumonia.3 Whether cerebrovascular
disease predicts outcomes in patients with COVID-19
is unknown. Few studies have been published with
varying results, further limited by the small sample
size number of patients with cerebrovascular disease.
As such, in this article, we aim to carry out a pooled
analysis of current studies.
Methods
We conducted PUBMED, EMBASE, and Cochrane
Central Register of Controlled Trials searches, using
1
Department of Medicine, Jersey City Medical Center, Jersey City, USA
Section of Clinical Biochemistry, Department of Neuroscience,
Biomedicine and Movement, University of Verona, Verona, Italy
3
Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children’s
Hospital Medical Center, Cincinnati, USA
2
*These authors share senior authorship in this work.
Corresponding author:
Brandon Michael Henry, Cardiac Intensive Care Unit, The Heart Institute,
Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue,
Cincinnati, OH 45229, USA.
Email: Brandon.henry@cchmc.org
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1 (1.2%)
54%
52 (26–78)
a
Age data presented as median (IQR) or mean (SD). MV: mechanical ventilation; ICU: intensive care unit; NR: not reported.
82 (58.6%)
2 (3.4%)
43%
64 (25–87)
58 (41.4%)
140
Zhang et al.10
Respiratory distress/
insufficiency
0 (0%)
30%
51.9 (12.9)
20 (38.5%)
7 (22%)
34%
64.6 (11.2)
32 (61.5%)
52
Yang et al.9
Death
1 (1%)
48%
51 (37–62)
102 (73.9%)
6 (16.7%)
39%
66 (57–78)
36 (26.1%)
138
Wang et al.8
Clinical variables,
MV, death
5 (6%)
35%
50 (44–81)
82 (54.6%)
7 (10%)
28%
67 (15–81)
68 (45.3%)
150
Ruan et al.7
Death
51.8%
53 (41.25–62)
166 (36.7%)
8 (2.8%)
45.8%
61 (51–69)
286 (63.3%)
452
Qin et al.6
Respiratory distress/
insufficiency
42%
45 (34–57)
926 (84.3%)
4 (2.3%)
42%
52 (40–65)
173 (15.7%)
1099
Guan et al.5
Admission to ICU,
MV, Death
Age (yrs)a
n (%)
Age (yrs)a
n (%)
Outcomes
Sample
size
An initial search included as many as 1683 publications. After removing duplicated or overlapping publications and excluding reviews and editorials, a total
number of 21 documents could be initially identified
(Supplementary Table 1). Fifteen studies were excluded
because they did not provide the rate of cerebrovascular disease. One additional study was identified from
the reference list of included articles. A total of seven
articles were hence selected. The article by Mo et al. was
excluded as a majority of patients in both groups had
severe disease on admission.4 Thus, the final pooled
analysis included six studies.5–10 Four studies compared
cerebrovascular disease in severe vs. non-severe cases,
with a sample of 1829 confirmed COVID-19 patients
(553, 30.2% being severe cases). A total number of 49
patients (2.6%) were classified as having a history of
cerebrovascular disease or stroke.5,6,8,10 Two studies
with 202 patients (100, 49.5% being non-survivors)
Table 1. Characteristics of included studies
Results
Study
Severe patients/non-survivors
Women (%)
Cerebrovascular
disease n (%)
Non-severe patients/survivors
Women (%)
Cerebrovascular
disease n (%)
the terms ‘‘Coronavirus’’ OR ‘‘COVID-19’’ AND
‘‘stroke’’, OR ‘‘cerebrovascular disease’’ and their various combinations, until 31 March 2020. We then
searched major journals reporting articles about
COVID-19 infection for additional studies. We also
hand-searched the bibliography of original studies and
review articles to find other potentially eligible studies.
Studies that fulfilled the following criteria were
included: (1) studies reporting history of cerebrovascular
disease in patients with COVID-19 and (2) reporting outcomes of interest. Studies were independently assessed for
eligibility and bias risk by two authors (GA and BMH).
Data were then extracted by the same authors.
Disagreements were resolved by consensus.
A clinically validated definition of ‘‘severe disease’’
(i.e. patients requiring mechanical ventilation, vital life
support, intensive care unit admission, death) was
required. As the number of studies was limited, no
evaluation of bias or publication bias was performed.
A pooled analysis was performed to estimate the odds
ratio (OR) and 95% confidence interval (CI) of cerebrovascular disease in COVID-19 patients with or without severe disease and in non-survivors versus
survivors. The statistical analysis was carried out
using MetaXL, software Version 5.3 (EpiGear
International Pty Ltd, Sunrise Beach, Australia), with
inverse variance model. A leave-one-out sensitivity analysis was performed to probe sources of heterogeneity.
Moreover, to evaluate the impact of mean age among
severe patients on the association of cerebrovascular
disease with severity of COVID-19, a random effects
meta-regression using log OR was employed. The
study was performed in compliance with the
Declaration of Helsinki and local legislation.
3 (1.8%)
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11 (1.2%)
2
Aggarwal et al.
3
Figure 1. Results of meta-analysis showing association of cerebrovascular disease with severity of disease and mortality in
patients with COVID-1.
Figure 2. Meta-regression plot for impact of age on association of cerebrovascular disease on disease severity in COVID-19.
compared the rate of cerebrovascular disease in
COVID-19 patients who did not survive vs. survived,
with 19 (9.4%) classified as non-survivors.7,9 Essential
characteristics of the included studies are listed in
Table 1.
The results of pooled analysis are presented in
Figure 1. In the four studies on severity, only one
study by Wang et al. individually had a significant
OR for cerebrovascular disease and COVID-19 severity.8 However, in pooled analysis, cerebrovascular
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4
disease was found to be associated with a statistically
significant increased risk of a severe form of COVID-19
(OR: 2.55 (95% CI: 1.18 to 5.51), I2 ¼ 29%, Cochran’s
Q, p ¼ 0.24). Although heterogeneity was low, a leaveone-out sensitivity analysis was still performed. Only
excluding the study by Wang et al. significantly altered
the results of the analysis and appeared to be the source
of heterogeneity (OR: 1.88 (95% CI: 0.828 to 4.29),
I2 ¼ 0%, Cochran’s Q, p ¼ 0.90).8 In the limited
pooled analysis of mortality studies, a non-significant
trend was found when evaluating association of cerebrovascular disease and enhanced risk of mortality in
COVID-19 patients (OR: 2.33 (95% CI: 0.77 to 7.04),
I2 ¼ 30%, Cochran’s Q, p ¼ 0.23). In the meta-regression analysis, a non-significant trend was observed
between mean age of patients with severe COVID-19
and log odds of cerebrovascular disease and COVID-19
severity (correlation coefficient 0.1582, 95% CI:
0.0575 to 0.3740, p ¼ 0.15) (Figure 2). Limited studies
prevented a meta-regression for mortality.
Discussion
In our pooled analysis of published studies to date,
cerebrovascular disease was found to be associated
with a 2.5-fold increased odds of severe disease in
patients with COVID-19 infection. There was also a
non-significant trend with cerebrovascular disease and
odds of mortality in COVID-19 patients.
Studies in patients with SARS have previously found
higher risk of critical illness and multiorgan dysfunction in patients with cerebrovascular disease.11
Cerebrovascular disease is associated with high morbidity, mortality, and financial burden in the United
States.12 In the current COVID-19 pandemic situation,
healthcare resources are a limitation, so that predicting
which patients are at higher risk could be helpful in
optimizing allocation of human and technical
resources.13
The main limitation of this pooled analysis is the
limited number of studies with small sample size.
However, at this stage with the ongoing pandemic,
our findings may provide early insights into building
models for risk stratification and help in judicious use
of limited healthcare resources. Due to the small
number of studies, we did not use any exclusion criteria
and we also did not perform analysis for risk of bias.
Sensitivity analysis was performed which showed the
results for disease severity were mainly driven by the
study by Wang et al. Age may be a confounding variable in our analysis. We did perform a meta-regression
to assess the impact of mean age of severe patients on
association of cerebrovascular disease with severity of
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COVID-19, which suggested the association is more
pronounced in older individuals. However, there were
not enough studies to perform a meta-regression on the
mortality endpoint. Hence, studies with larger sample
size and number of events are needed to confirm our
findings. Nonetheless, we encourage physicians to
advise patients with a history of cerebrovascular disorders to take enhanced precautions during the
ongoing pandemic.
Conclusion
In our pooled analysis, cerebrovascular disease was
found to be associated with a 2.5-fold increased disease severity in patients with COVID-19. However,
larger studies are needed to confirm these findings.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Gaurav Aggarwal
https://orcid.org/0000-0002-8180-9287
Supplemental material
Supplemental material for this article is available online.
References
1. Chen CY, Lee CH, Liu CY, Wang JH, Wang LM and
Perng RP. Clinical features and outcomes of severe acute
respiratory syndrome and predictive factors for acute
respiratory distress syndrome. J Chin Med Assoc 2005;
68: 4–10.
2. Lee SY, Khang YH and Lim HK. Impact of the 2015
Middle East respiratory syndrome outbreak on emergency care utilization and mortality in South Korea.
Yonsei Med J 2019; 60: 796–803.
3. Mandal P, Chalmers JD, Choudhury G, Akram AR and
Hill AT. Vascular complications are associated with poor
outcome in community-acquired pneumonia. QJM 2011;
104: 489–495.
4. Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of
refractory COVID-19 pneumonia in Wuhan, China. Clin
Infect Dis 2020. Epub ahead of print. 16 March 2020.
DOI: 10.1093/cid/ciaa270.
5. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of
coronavirus disease 2019 in China. N Engl J Med 2020.
Aggarwal et al.
6.
7.
8.
9.
Epub ahead of print 28 February 2020. DOI: 10.1056/
NEJMoa2002032.
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune
response in patients with COVID-19 in Wuhan, China.
Clin Infect Dis 2020. Epub ahead of print. 12 March 2020.
DOI: 10.1093/cid/ciaa248.
Ruan Q, Yang K, Wang W, Jiang L and Song J. Clinical
predictors of mortality due to COVID-19 based on an
analysis of data of 150 patients from Wuhan, China.
Intensive Care Med 2020. Epub ahead of print. 3 March
2020. DOI: 10.1007/s00134-020-05991-x.
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138
hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China. JAMA 2020.
Epub ahead of print. 7 February 2020. DOI: 10.1001/
jama.2020.1585.
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes
of critically ill patients with SARS-CoV-2 pneumonia in
Wuhan, China: a single-centered, retrospective,
5
10.
11.
12.
13.
observational study. Lancet Respir Med 2020. Epub
ahead of print. 24 February 2020. DOI: 10.1016/S22132600(20)30079-5.
Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics
of 140 patients infected with SARS-CoV-2 in Wuhan,
China. Allergy 2020. Epub ahead of print. 19 February
2020. DOI: 10.1111/all.14238.
Hu SS, Yang YJ, Zhu ML, et al. Effects of underlying
cerebrocardiovascular diseases on the incidence of critical
conditions and multiple organs dysfunction syndrome in
severe acute respiratory syndrome cases. Zhonghua Yi
Xue Za Zhi 2004; 84: 1257–1259.
Virani SS, Alonso A, Benjamin EJ, et al. Heart disease
and stroke statistics—2020 update: a report from the
American Heart Association. Circulation 2020; 141:
e139–e596.
Emanuel EJ, Persad G, Upshur R, et al. Fair allocation
of scarce medical resources in the time of Covid-19.
N Engl J Med 2020.
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