| Accepted: 23 May 2020

DOI: 10.1111/jth.14938

CASE REPORT

Macrothrombosis and stroke in patients with mild Covid-19
infection
Michael G. Fara1
| Laura K. Stein1 | Maryna Skliut1 | Susan Morgello1,2 |
Johanna T. Fifi3 | Mandip S. Dhamoon1
1
Department of Neurology, Icahn School of
Medicine at Mount Sinai, New York, NY, USA

Abstract

2

Coronavirus disease 2019 (COVID-19) is a pandemic disease currently affecting mil-

Departments of Neuroscience and
Pathology, Icahn School of Medicine at
Mount Sinai, New York, NY, USA
3
Departments of Neurology and
Neurosurgery, Icahn School of Medicine,
New York, NY, USA

Correspondence
Michael G. Fara, Icahn School of Medicine at
Mount Sinai, One Gustave L. Levy Place, Box
1052, New York, NY 10029, USA.
Email: [email-masked]

lions of people worldwide. Its neurological implications are poorly understood, and
further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID-19, but nothing is known about coagulopathy in patients
with milder disease. We describe cases of patients in New York City presenting with
stroke secondary to large vessel thrombosis without occlusion, incidentally found to
have COVID-19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe
COVID-19. Our cases suggest that even in the absence of severe disease, patients
with COVID-19 may be at increased risk of thrombus formation leading to stroke,
perhaps resulting from viral involvement of the endothelium. Further systematic
study is needed because this may have implications for primary and secondary stroke
prevention in patients with COVID-19.
KEYWORDS

stroke, thrombosis, coronavirus, infection, carotid artery thrombosis

1 | I NTRO D U C TI O N

coagulopathy, it would seem plausible to associate the two phenomena. Here, we describe three SARS-CoV-2-infected individuals

Coagulopathy in patients with severe acute respiratory syndrome

with large artery stroke as their presenting illness in the absence of

coronavirus 2 (SARS-CoV-2) infection has been reported,1 and there

advanced COVID-19 and describe the details of their workup for co-

is evidence that the extent of coagulopathy correlates with sever-

agulopathy. One of these patients has been summarized in a recent

2

ity of respiratory illness. The predominant clinical sequelae of this
3

report of COVID-related stroke in patients younger than age 50.6

coagulopathy have been venous thromboembolic events, as well

The three patients presented to the emergency department with

as end-organ failure secondary to a microangiopathy believed to

stroke-like symptoms and were found to have sub-occlusive severe

be similar to disseminated intravascular coagulation.4 Stroke is also

stenosis of the common carotid artery and stroke within that distri-

recognized, and in the largest series to date, was seen in 5.7% of

bution. All three presented within 2 weeks in New York City during

those with critical illness in comparison to 0.8% of those with milder

the SARS-CoV-2 outbreak in April 2020. None had severe respira-

coronavirus disease 2019 (COVID-19) disease.5 Because severity

tory symptoms, but all three tested positive for SARS-CoV-2 by re-

of COVID-19 illness correlates with both large artery ischemia and

verse transcriptase–polymerase chain reaction assay.

Manuscript handled by: David Lillicrap
Final decision: David Lillicrap and 23 May 2020

One patient is a previously healthy 33-year-old woman who
developed numbness of her left hand that quickly progressed

© 2020 International Society on Thrombosis and Haemostasis
J Thromb Haemost. 2020;18:2031–2033.	

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FARA et al.

to hemiplegia and hemisensory loss of the left face, arm, and leg.
Computed tomography (CT) angiography revealed nonocclusive
thrombus in the right common carotid artery, extending into the
internal carotid artery, as well as lung findings suggestive of viral
pneumonia (Figure 1A). Subsequent magnetic resonance imaging
showed acute stroke within the territory of the right middle cerebral
artery, with magnetic resonance angiography showing no evidence
of underlying arterial dissection. She complained of a recent cough,
but did not develop fever or require supplemental oxygenation. She
was treated initially with aspirin and clopidogrel, but later switched
to apixaban 5 mg twice daily in accordance with our institution's

Essentials
• Thrombosis in the setting of Coronavirus disease 2019
[COVID-19] is reported but poorly understood.
• We report cases of large-artery thrombosis in the setting of mild COVID-19 disease.
• This suggests a previously undescribed large artery coagulopathy in patients with COVID-19.
• This may be due to viral involvement with the
endothelium.

emerging guidelines about venous thromboembolism prevention in
the setting of SARS-CoV-2 infection. Repeat CT angiography 10 days
after presentation showed near-complete resolution of the throm-

The second patient is a 77-year-old woman with hypertension,

bosis and no sign of an underlying vascular abnormality (Figure 1B).

hyperlipidemia, and bilateral thromboses of the deep leg veins discovered 2 months prior, prescribed aspirin, clopidogrel, and warfa-

A

rin (although subtherapeutic on presentation), who developed the

B

sudden onset of aphasia and left hemiparesis, and found to have
nonocclusive thrombosis of the distal right common carotid artery
(Figure 1C). She was coughing on presentation and was found to be
infected with SARS-CoV-2, but she did not develop a fever or require
supplemental oxygenation. She was treated with enoxaparin 1 mg/
kg every 12 hours, and on conventional angiography 1 week later,
the thrombosis had completely resolved and the vessel appeared
normal (Figure 1D).
The third patient is a 55-year-old man with diabetes but no
other medical history who presented with isolated left hand weakD

C

ness that progressed to weakness of the left face, arm, and leg. CT
angiography showed thrombosis within the right common carotid
artery extending into the internal carotid artery, which appeared occlusive or near-occlusive, in addition to lung parenchymal changes
suggestive of viral pneumonia (Figure 1E). He was taken for emergent conventional angiography, where the thrombosis was found
to be nonocclusive. Eptifibatide was given intra-arterially, and the

E

F

degree of stenosis was noted to lessen (Figure 1F). No mechanical
endovascular treatment was given, and he was subsequently treated
with a heparin infusion. He had low-grade fever at presentation and
required supplemental oxygenation but did not develop significant
respiratory distress.
Standard serological tests, as well as coagulation markers
sent by our institution on all patients testing positive for SARSCoV-2, were sent on all three patients. Notably, only one (patient
2) had significantly elevated D-dimer levels, whereas all three had
elevated C-reactive protein levels. Two of the three patients are

F I G U R E 1 For the first patient, CT angiography images show
(A) thrombus within the common carotid artery extending into the
internal carotid artery, (B) with subsequent near-total resolution.
For the second patient, CT angiography images (C) show thrombus
within the distal right common carotid artery; (D) conventional
angiography 1 week later shows resolution of the thrombus and
no evidence of arterial dissection. For the third patient, digital
subtraction angiography shows (E) severe nonocclusive thrombus
within the distal common carotid artery, with (F) subsequent mild
improvement in thrombus burden after local infusion of eptifibatide

young and without any evident source of thromboembolism; echocardiography was unremarkable and without evidence of patent
foramen ovale. One patient had mildly elevated anti-cardiolipin
antibodies, but otherwise none had serological evidence of the
antiphospholipid syndrome or of hyperhomocysteinemia, conditions known to be associated with arterial thrombosis.7 The third
patient, although older and with vascular risk factors, also did not
have radiographic or echocardiographic signs of a proximal source
of thromboembolism.

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FARA et al.

Taken together, these cases raise the possibility that, in addition
to the previously characterized venous thrombosis and microangiopathy potentially associated with SARS-CoV-2 infection, there may
also be a tendency toward large-vessel arterial thrombosis, which
has been reported in patients with SARS from a previous strain of
the coronavirus.8 There is an emerging hypothesis that virally mediated disruption of the endothelium may be playing a key role in
thrombus formation in patients infected by SARS-CoV-2; recently,
viral particles have been identified in systemic endothelia along with
accumulations of inflammatory cells and apoptosis (endotheliitis).9,10
Notably, all three of our patients had only mild symptoms of infection, suggesting a possible difference in pattern of thrombophilia in
patients with mild as opposed to severe disease. Whether there is a
connection between SARS-CoV-2 and arterial thrombosis leading to
stroke, and, if so, what the pathogenetic mechanism of this is, will
require further study.
C O N FL I C T O F I N T E R E S T
None of the authors has any real or potential conflicts of interest to
disclose.
AU T H O R C O N T R I B U T I O N S
Michael G. Fara is responsible for study design, literature review,
drafting the initial manuscript, and critical revising for intellectual

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content. Laura K. Stein is responsible for study design, literature
review, and critical revising for intellectual content. Maryna Skliut
is responsible for patient selection and collection of clinical data.
Susan Morgello is responsible for study design, literature review, and
critical revising for intellectual content. Johanna T. Fifi is responsible for study design, patient selection, and collection of clinical data.
Mandip S. Dhamoon is responsible for critical revising for intellectual
content.
ORCID
Michael G. Fara

https://orcid.org/0000-0002-9615-7189

How to cite this article: 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;18:2031–2033. https://doi.org/10.1111/jth.14938