Background: While the most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia, there is a growing basis of published peer-reviewed cases reporting stroke in the setting of SARS-CoV-2 infection. The peer-reviewed literature suggests an increased risk of cerebrovascular accident (CVA) in the setting of COVID-19 infection. Methods: We searched 3 databases (PubMed, MEDLINE, and CINAHL) with search terms COVID-19, novel coronavirus, stroke, and cerebrovascular accident. Case series and case studies presenting patients positive for both COVID-19 and CVA published from January 1 through September 1, 2020, were included. Data collection and analysis was completed and risk of bias assessed. Results: The search identified 28 studies across 7 counties comprising 73 patients. Amongst patients hospitalized for COVID-19 infection and CVA, the average age was 60; the most common preexisting conditions were hypertension and diabetes mellitus, and those without preexisting conditions were significantly younger with an average age of 47. Amongst hospitalized patients with COVID-19 and CVA, there was a bimodal association with COVID-19 infection severity with majority of patients classified with mild or critical COVID-19 infection. Discussion: The data suggest SARS-CoV-2 is a risk factor for developing stroke, particularly in patients with hypertension and diabetes. Furthermore, the younger average age of stroke in patients with SARS-CoV-2, particularly those patients with zero identifiable preexisting conditions, creates high suspicion that SARS-CoV-2 is an independent risk factor for development of stroke; however, this cannot yet be proven without comparable control population. The data suggest the risk of developing CVA in the setting of COVID-19 infection is not dependent upon severity of illness. Continued studies must be done to understand the epidemiologic factors of COVID-19 infection and stroke and the pathophysiology of the COVID-associated hypercoagulable state.

As of October 2020, novel coronavirus, or COVID-19 infection by the SARS-CoV-2 virus, had an impact of over 35 million confirmed cases and 1 million deaths worldwide [1]. While SARS-CoV-2 most commonly affects the lungs causing bilateral pneumonia, respiratory failure, and acute respiratory distress syndrome, a wide variety of neurologic findings have been associated with the virus [2]. The most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia [3, 4]. Additionally, there is a growing basis of published peer-reviewed cases reporting stroke and SARS-CoV-2 infection. A systematic review found that patients with a past medical history of stroke were 3 times more likely to die of COVID-19 but concluded stroke is not a complication of COVID-19 [4]. Two separate studies found that the incidence of stroke in patients with confirmed COVID-19 was between 5 and 5.7% in small community hospitals in Wuhan, China [5, 6]. These patients were associated with severe illness, risk factors such as hypertension, diabetes, and history of coronary artery disease, or prior cerebrovascular disease [5].

The peer-reviewed literature suggests an increased risk of stroke or cerebrovascular accident (CVA) in the setting of COVID-19 infection [4, 5]. However, the nature of this association remains to be elucidated. Whether risk of stroke in the setting of COVID-19 infection is independent of age, severity of infection, and comorbidities is not well documented within the literature. Our goal was to conduct a systematic review to better understand the clinical picture and presentation of patients with stroke and confirmed COVID-19 infection and to assess comorbid risk factors associated with stroke and COVID-19 such age, sex, severity of COVID-19 infection, and past medical history.

Search Strategy and Selection Criteria

Our methods adhere to the guidelines established by PRISMA. We conducted a systematic review in the following databases: PubMed, MEDLINE, and CINAHL. Search terms included COVID-19, novel coronavirus, stroke, and cerebrovascular accident. There were no language restrictions used during literary search. The last search was performed from January 1, 2020, through September 1, 2020.

Inclusion Criteria

Articles that addressed the clinical case of COVID-19-positive patients, with confirmed diagnosis of stroke with imaging studies positive, were included. Only case reports or case series published in full text with peer reviews were included in data review. Published, peer-reviewed case reports or case series found under the aforementioned search terms were included.

Exclusion Criteria

No article earlier than 2020 was considered. Literature reviews, commentaries, and case reports on stroke rule outs were excluded.

Data Collection and Risk of Bias Assessment

Screening by title and abstract was conducted independently by 2 investigators (A.A. and I.D.). Full-text review was conducted independently by all authors. Data abstraction was conducted independently by 2 investigators (A.A. and A.P.) using a standardized form shared between all authors. A third investigator resolved any differences of opinion in data gathering (I.D.).

Outcomes of interest in the study included clinical picture on presentation to care, age, sex, past medical history, infection severity, and treatment modalities. Severity of COVID-19 infection was determined by standards outlined by the WHO [7]. Data collected included first author, type of article, country of publication, number of patients, age, sex, COVID-19 severity, included imaging, presenting symptom, and past medical history including prior CVA, coronary artery disease, hypertension, hyperlipidemia, obesity, diabetes, chronic kidney disease, and atrial fibrillation.

Risk for bias in data extraction was found to be minimal as the majority of data extracted were empirical in nature. Standardized published guidelines were used to assess COVID-19 severity based on published qualitative symptomatology [7].

Data Analysis

Means, percentages, and standardized deviations were calculated in Google Sheets. Statistical analysis comparing average ages amongst independent variables was analyzed using 1-tailed, independent t test analysis through VassarStats. Qualitative data were summarized through counts in Google Sheets.

Initial search yielded 71 studies. After removing 29 duplicates, 42 articles were reviewed by abstract and title. Publications identified to be reviews, commentaries, and case reports with stroke rule outs were excluded. After initial screen, 28 articles met inclusion criteria and subsequently underwent full-text review (Fig. 1).

Fig. 1.

PRISMA flow diagram.

Fig. 1.

PRISMA flow diagram.

Close modal

Of the 28 articles assessed, 16 were case reports and 11 case series (Table 1). Seven countries were represented in the published studies: USA (17), Spain (3), Italy (3), United Kingdom (1), Philippines (1), Turkey (1), and China (1) (Table 1). Across all articles, 73 patients were assessed, of which 42% were females (Table 2). The average age of the study population was 60 years (Table 2; Fig. 2).

Table 1.

Study characteristics [8‒35]

 Study characteristics [8‒35]
 Study characteristics [8‒35]
Table 2.

Patient characteristics

 Patient characteristics
 Patient characteristics
Fig. 2.

Average age of patients hospitalized for COVID-19 infection and CVA. CVA, cardiovascular accident; F, female; M, male; NPMH, no past medical history; PMH, past medical history.

Fig. 2.

Average age of patients hospitalized for COVID-19 infection and CVA. CVA, cardiovascular accident; F, female; M, male; NPMH, no past medical history; PMH, past medical history.

Close modal

No statistical difference was seen in average age between males and females who were hospitalized with COVID-19 and CVA (Fig. 2; p = 0.97). Of the patients hospitalized with COVID-19 infection and CVA, those with no past medical history were significantly younger than those with one or more underlying medical conditions, with an average age of 47 as compared to 64, respectively (Fig. 2; p < 0.01). Nevertheless, of the study population, only 23% had no past medical history (Fig. 3). Of note, the most common comorbid conditions were hypertension and diabetes mellitus, at 52 and 36%, respectively (Fig. 3).

Fig. 3.

Average age and presenting symptom of patients hospitalized for COVID-19 infection and CVA. CVA, cardiovascular accident; COV, COVID-19; F, female; M, male.

Fig. 3.

Average age and presenting symptom of patients hospitalized for COVID-19 infection and CVA. CVA, cardiovascular accident; COV, COVID-19; F, female; M, male.

Close modal

Amongst hospitalized patients with COVID-19 and stroke, 50% presented to care for COVID-19 infection and were subsequently found to have stroke while 50% presented to care for symptoms of stroke and were subsequently found to be positive for COVID-19 infection (Table 2; Fig. 3). There was no statistical difference in age between patients with presenting symptom of COVID-19 as compared to those with presenting symptom of CVA (Fig. 3; p = 0.88). Amongst hospitalized patients with COVID-19 and CVA, there was a bimodal distribution of COVID-19 infection severity, as defined by the WHO, with the majority of patients classified with either mild or critical illness; a minority of patients presented were ­asymptomatic or presented with moderate-severe illness (Fig. 5).

A COVID-19-induced hypercoagulable state has been well documented in the peer-reviewed literature; however, most cases suggest an increase in predominantly venous thromboembolic events such as deep vein thromboses and life-threatening pulmonary embolism [36, 37]. There is some emerging evidence of increased arterial dysfunction, with COVID-19-associated myocardial infarction/acute coronary syndrome and pulmonary intravascular coagulopathy [38, 39]. The current study further suggests a COVID-19-induced intravascular coagulopathy with increased risk for arteriolar thromboembolic events including CVA.

According to the American Heart Association, the average age of stroke is 65 [40]. While our systematic review cannot be compared to the national average as the patient populations differ in size, country of origin, and setting, it is notable that the average age of patients hospitalized for COVID-19 and CVA is younger than the national average for stroke. Furthermore, patients hospitalized for COVID-19 and CVA without prior comorbid conditions were significantly younger than the national average.

The prevalence of preexisting conditions noted by the study was relatively unsurprising, as they reflect the prevalence within the general population with the highest prevalence of hypertension and diabetes mellitus (Fig. 4). The data suggest the risk of developing CVA in the setting of COVID-19 infection is not dependent upon severity of illness (Fig. 5). This finding is contrary to the peer-reviewed literature, which has suggested risk of CVA in the setting of COVID-19 infection to be associated with critical illness [5].

Fig. 4.

Number of patients hospitalized for COVID-19 infection and CVA as stratified by past medical history and sex. CVA, cardiovascular accident; CAD, coronary artery disease; HTN, hypertension; HLD, hyperlipidemia; Obs, obesity; DM, diabetes mellitus; CKD, chronic kidney disease; AF, atrial fibrillation; NPMH, no past medical history.

Fig. 4.

Number of patients hospitalized for COVID-19 infection and CVA as stratified by past medical history and sex. CVA, cardiovascular accident; CAD, coronary artery disease; HTN, hypertension; HLD, hyperlipidemia; Obs, obesity; DM, diabetes mellitus; CKD, chronic kidney disease; AF, atrial fibrillation; NPMH, no past medical history.

Close modal
Fig. 5.

Number of patients hospitalized with COVID-19 and CVA as stratified by COVID-19 infection severity. CVA, cardiovascular accident.

Fig. 5.

Number of patients hospitalized with COVID-19 and CVA as stratified by COVID-19 infection severity. CVA, cardiovascular accident.

Close modal

The nature of our systematic review does not allow the study population to be adequately compared to a control population, and therefore an independent risk for developing stroke in the setting of COVID-19 infection could not be isolated. It remains to be seen whether the association between COVID-19 infection and stroke is causal in nature. Additional drawbacks to the study include a limited sample size with high variance. Continued studies must be done to understand the epidemiologic factors of COVID-19 infection and stroke and the pathophysiology of the COVID-associated hypercoagulable state.

The data suggest SARS-CoV-2 is a risk factor for developing stroke, particularly in patients with hypertension and diabetes. Furthermore, the younger average age of stroke in patients with SARS-CoV-2, particularly those patients with zero identifiable preexisting conditions, creates high suspicion that SARS-CoV-2 is an independent risk factor for development of stroke.

In the setting of the global coronavirus pandemic, patients younger than 65 years old, particularly those without risk factors for stroke, who present with CVA should be treated as a patient under investigation for SARS-CoV-2 with proper precautionary measures put in place. Furthermore, patients with known COVID-19 infection with acute change in mental status or sudden onset of focal neurological deficit should be highly concerning for SARS-CoV-2-associated CVA and should be immediately assessed for stroke. Additionally, patients with SARS-CoV-2, particularly those with hypertension, diabetes, hyperlipidemia, or prior CVA, should have neurological assessments regularly to ensure any possible stroke is diagnosed and managed.

The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

The authors ensure all ethical standards were upheld in the process of research and writing the manuscript. The research did not require ethical approval as the data used are completely HIPAA protected, publicly available, and previously published. No human subjects were used, contacted, or in any way comprised in the research.

The authors have no conflicts of interest to declare.

This research was supported in part by HCA Healthcare and/or an HCA Healthcare affiliated entity. The authors nor the research received neither grant, scholarship, nor funding from any funding agency in the public, commercial, or not-for-profit sectors.

Amira Athanasios is the Principle Investigator. Ivy Daley is the co-investigator. Anjali Patel is the co-investigator. Olu Oyesanmi is the co-investigator.

Publicly available datasets were used in this study. All data used can be found in the specific references. All data analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

1.
Johns Hopkins Coronavirus Resource Center. COVID-19 map. Available from: coronavirus.jhu.edu/map.html.
2.
Mao
L
,
Jin
H
,
Wang
M
.
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China
.
JAMA Neurol
.
2020
;
77
(
6
):
683
90
.
3.
Carod-Artal
FJ
.
Neurological complications of coronavirus and COVID-19. Complicaciones neurológicas por coronavirus y COVID-19
.
Rev Neurol
.
2020
;
70
(
9
):
311
22
.
4.
Trejo-Gabriel-Galán
JM
.
Ictus como complicación y como factor pronóstico de COVID-19
.
Neurología
.
2020 Jun
;
35
(
5
):
318
22
. English, Spanish. Epub 2020 May 6. PMID: 32493597; PMCID: PMC7200328. http://dx.doi.org/10.1016/j.nrl.2020.04.015.
5.
Li
Y
,
Li
M
,
Wang
M
,
Zhou
Y
,
Chang
J
,
Xian
Y
,
.
Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study
.
2020 March 3
. Available from: https://ssrn.com/abstract=3550025.
6.
Mao L, Jin H, Wang M. Neurologic manifestations.
7.
World Health Organization
.
Clinical management of COVID-19: interim guidance, 27 May 2020
.
Geneva
:
World Health Organization
;
2020
. WHO/2019-nCoV/clinical/2020.5.
8.
Acharya
S
,
Diamond
M
,
Anwar
S
,
Glaser
A
,
Tyagi
P
.
Unique case of central retinal artery occlusion secondary to COVID-19 disease
.
IDCases
.
2020
;
21
:
e00867
.
9.
Al Saiegh
F
,
Ghosh
R
,
Leibold
A
,
Avery
MB
,
Schmidt
RF
,
Theofanis
T
,
.
Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke
.
J Neurol Neurosurg Psychiatry
.
2020 Aug
;
91
(
8
):
846
8
. Epub 2020 Apr 30. PMID: 32354770. http://dx.doi.org/10.1136/jnnp-2020-323522.
10.
Avula
A
,
Nalleballe
K
,
Narula
N
,
Sapozhnikov
S
,
Dandu
V
,
Toom
S
,
.
COVID-19 presenting as stroke
.
Brain Behav Immun
.
2020
;
87
:
115
9
.
11.
Ballvé-Martín
A
,
Boned
S
,
Rubiera
M
.
Complicación trombótica de neumonía grave por COVID-19: ictus por embolismo paradójico atípico [Thrombotic complication of severe COVID-19 pneumonia: stroke due to atypical paradoxical embolism]
.
Rev Neurol
.
2020 Sep 1
;
71
(
5
):
186
90
. Spanish. PMID: 32729110.
12.
Barrios-López
JM
,
Rego-García
I
,
Muñoz Martínez
C
,
Romero-Fábrega
JC
,
Rivero Rodríguez
M
,
Ruiz Giménez
JA
,
.
Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal
.
Neurologia
.
2020
;
35
(
5
):
295
302
.
13.
Beyrouti
R
,
Adams
ME
,
Benjamin
L
,
Cohen
H
,
Farmer
SF
,
Goh
YY
,
.
Characteristics of ischaemic stroke associated with COVID-19
.
J Neurol Neurosurg Psychiatry
.
2020 Aug
;
91
(
8
):
889
91
. Epub 2020 Apr 30. PMID: 32354768; PMCID: PMC7231545. http://dx.doi.org/10.1136/jnnp-2020-323586.
14.
Co
COC
,
Yu
JRT
,
Laxamana
LC
,
David-Ona
DIA
.
Intravenous thrombolysis for stroke in a COVID-19 positive filipino patient, a case report
.
J Clin Neurosci
.
2020
;
77
:
234
6
.
15.
Deliwala
S
,
Abdulhamid
S
,
Abusalih
MF
,
Al-Qasmi
MM
,
Bachuwa
G
.
Encephalopathy as the sentinel sign of a cortical stroke in a patient infected with coronavirus disease-19 (COVID-19)
.
Cureus
.
2020 May 14
;
12
(
5
):
e8121
.
16.
Doo
FX
,
Kassim
G
,
Lefton
DR
,
Patterson
S
,
Pham
H
,
Belani
P
.
Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis
.
Clin Imaging
.
2020 Jul 16
;
69
:
94
101
.
17.
Dumitrascu
OM
,
Volod
O
,
Bose
S
,
Wang
Y
,
Biousse
V
,
Lyden
PD
.
Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban
.
J Stroke Cerebrovasc Dis
.
2020
;
29
(
8
):
104982
.
18.
Elshereye
A
,
Erdinc
B
.
Multiple lacunar cerebral infarcts as the initial presentation of COVID-19
.
Cureus
.
2020 Aug 10
;
12
(
8
):
e9638
. PMID: 32789103. http://dx.doi.org/10.7759/cureus.9638.
19.
Fara
MG
,
Stein
LK
,
Skliut
M
,
Morgello
S
,
Fifi
JT
,
Dhamoon
MS
.
Macrothrombosis and stroke in patients with mild covid-19 infection
.
J Thromb Haemost
.
2020
;
18
(
8
):
2031
3
. Published online ahead of print, 2020 May 28. http://dx.doi.org/10.1111/jth.14938.
20.
Gill
I
,
Chan
S
,
Fitzpatrick
D
.
COVID-19-associated pulmonary and cerebral thromboembolic disease
.
Radiol Case Rep
.
2020
;
15
(
8
):
1242
9
.
21.
Goldberg
MF
,
Goldberg
MF
,
Cerejo
R
,
Tayal
AH
.
Cerebrovascular disease in COVID-19
.
AJNR Am J Neuroradiol
.
2020 Jul
;
41
(
7
):
1170
2
. Epub 2020 May 14. PMID: 32409316PMC7357639. http://dx.doi.org/10.3174/ajnr.A6588.
22.
Klein
DE
,
Libman
R
,
Kirsch
C
,
Arora
R
.
Cerebral venous thrombosis: a typical presentation of COVID-19 in the young
.
J Stroke Cerebrovasc Dis
.
2020
;
29
(
8
):
104989
.
23.
Mahboob
S
,
Boppana
SH
,
Rose
NB
,
Beutler
BD
,
Tabaac
BJ
.
Large vessel stroke and COVID-19: case report and literature review
.
eNeurologicalSci
.
2020 Jun 16
;
20
:
100250
. Published. http://dx.doi.org/10.1016/j.ensci.2020.100250.
24.
Morassi
M
,
Bagatto
D
,
Cobelli
M
,
D’Agostini
S
,
Gigli
GL
,
Bnà
C
,
.
Stroke in patients with SARS-CoV-2 infection: case series
.
J Neurol
.
2020
;
267
(
8
):
2185
92
.
25.
Oxley
TJ
,
Mocco
J
,
Majidi
S
,
Kellner
CP
,
Shoirah
H
,
Singh
IP
,
.
Large-vessel stroke as a presenting feature of covid-19 in the young
.
N Engl J Med
.
2020
;
382
(
20
):
e60
.
26.
Papi
C
,
Spagni
G
,
Alexandre
A
,
Calabresi
P
,
Della Marca
G
,
Broccolini
A
.
Unprotected stroke management in an undiagnosed case of severe acute respiratory syndrome coronavirus 2 infection
.
J Stroke Cerebrovasc Dis
.
2020 Sep
;
29
(
9
):
104981
. Epub 2020 May 23. PMID: 32807416; PMCID: PMC7245230. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104981.
27.
Reddy
ST
,
Garg
T
,
Shah
C
,
Nascimento
FA
,
Imran
R
,
Kan
P
,
.
Cerebrovascular disease in patients with COVID-19: a review of the literature and case series
.
Case Rep Neurol
.
2020
;
12
(
2
):
199
209
. Published 2020 Jun 11. http://dx.doi.org/10.1159/000508958.
28.
Rudilosso
S
,
Esteller
D
,
Urra
X
,
Chamorro
Á
.
Thalamic perforating artery stroke on computed tomography perfusion in a patient with coronavirus disease 2019
.
J Stroke Cerebrovasc Dis
.
2020
;
29
(
8
):
104974
.
29.
Saggese
CE
,
Del Bianco
C
,
Di Ruzza
MR
,
Magarelli
M
,
Gandini
R
,
Plocco
M
.
COVID-19 and stroke: casual or causal role
.
Cerebrovasc Dis
.
2020
;
49
:
341
4
. Published online ahead of print, 2020 Jul 7.
30.
Sangalli
D
,
Polonia
V
,
Colombo
D
,
Mantero
V
,
Filizzolo
M
,
Scaccabarozzi
C
,
.
A single-centre experience of intravenous thrombolysis for stroke in COVID-19 patients
.
Neurol Sci
.
2020 Sep
;
41
(
9
):
2325
9
. Epub 2020 Jul 12. PMID: 32656711; PMCID: PMC7354364. http://dx.doi.org/10.1007/s10072-020-04591-3.
31.
TunÇ
A
,
ÜnlÜbaŞ
Y
,
Alemdar
M
,
AkyÜz
E
.
Coexistence of COVID-19 and acute ischemic stroke report of four cases
.
J Clin Neurosci
.
2020
;
77
:
227
9
.
32.
Valderrama
EV
,
Humbert
K
,
Lord
A
,
Frontera
J
,
Yaghi
S
.
Severe acute respiratory syndrome coronavirus 2 infection and ischemic stroke
.
Stroke
.
2020 Jul
;
51
(
7
):
e124
7
. Epub 2020 May 12. PMID: 32396456. http://dx.doi.org/10.1161/STROKEAHA.120.030153.
33.
Wang
A
,
Mandigo
GK
,
Yim
PD
,
Meyers
PM
,
Lavine
SD
.
Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics
.
J Neurointerv Surg
.
2020
;
12
(
7
):
648
53
.
34.
Zahid
MJ
,
Baig
A
,
Galvez-Jimenez
N
,
Martinez
N
.
Hemorrhagic stroke in setting of severe COVID-19 infection requiring extracorporeal membrane oxygenation (ECMO)
.
J Stroke Cerebrovasc Dis
.
2020 Sep
;
29
(
9
):
105016
. Epub 2020 Jun 6. PMID: 32807431; PMCID: PMC7275181.
35.
Zhai
P
,
Ding
Y
,
Li
Y
.
The impact of COVID-19 on ischemic stroke
.
Diagn Pathol
.
2020 Jun 29
;
15
(
1
):
78
. Published 2020 Jun 29. http://dx.doi.org/10.1186/s13000-020-00994-0.
36.
Bilaloglu
S
,
Aphinyanaphongs
Y
,
Jones
S
,
Iturrate
E
,
Hochman
J
,
Berger
JS
.
Thrombosis in hospitalized patients with COVID-19 in a New York city health system
.
JAMA
.
2020
;
324
(
8
):
799
.
37.
Wichmann
D
,
Sperhake
JP
,
Lütgehetmann
M
,
Steurer
S
,
Edler
C
,
Heinemann
A
,
.
Autopsy findings and venous thromboembolism in patients with COVID-19
.
Ann Intern Med
.
2020
:
M20
2003
. Published online ahead of print, 2020 May 6.
38.
Lodigiani
C
,
Iapichino
G
,
Carenzo
L
,
Cecconi
M
,
Ferrazzi
P
,
Sebastian
T
,
.
Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy
.
Thromb Res
.
2020
;
191
:
9
14
.
39.
Mcgonagle
D
,
O’Donnell
JS
,
Sharif
K
,
Emery
P
,
Bridgewood
C
.
Pulmonary intravascular coagulopathy in COVID-19 pneumonia: authors’ reply
.
Lancet Rheumatol
.
2020
;
2
(
8
):
e460
.
40.
Virani
SS
,
Alonso
A
,
Benjamin
EJ
,
Bittencourt
MS
,
Callaway
CW
,
Carson
AP
,
.
Heart disease and stroke statistics – 2020 update: a report from the American Heart Associationexternal icon
.
Circulation
.
2020
;
141
(
9
):
e139
596
.