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\begin{document}

\title{A Fatal Association of COVID-19 and Acute Type A Aortic Dissection}



\author[1]{Rana Irilouzadian}%
\author[1]{Hossein Salehi Omran}%
\author[1]{Toktam Alirezaei}%
\affil[1]{Shahid Beheshti University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 13, 2024}


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\selectlanguage{english}
\begin{abstract}
We represent a case with simultaneous COVID-19 and acute type A aortic
dissection. Type A aortic dissection, an aortic catastrophic event,
seems to have higher mortality on coexistence with COVID-19.%
\end{abstract}%



\sloppy


\textbf{A Fatal Association of COVID-19 and Acute Type A Aortic
Dissection}

\textbf{Rana Irilouzadian \textsuperscript{1}, Hossein Salehi
Omran\textsuperscript{1}, Toktam Alirezaei \textsuperscript{2*}}

Faculty of medicine, Shahid Beheshti University of Medical Sciences,
Tehran, Iran, emails: ranairilouzadian@gmail.com\emph{ORCID:
0000-0001-8849-329X,}hosseinsalehiomran@gmail.com

Cardiology Department of Shohadaye-Tajrish Hospital, Shahid Beheshti
University of Medical Sciences, Tehran, Iran, emails:
Alirezaei.toktam@sbmu.ac.ir\emph{ORCID: 0000-0002-4473-7093}

\textbf{*Author of correspondence:} Toktam Alirezaei, email:
Alirezaei.Toktam@sbmu.ac.ir

Address: Shohadaye-Tajrish Hospital, Tajrish sq., Tehran, Iran

Tel: +982125719

\textbf{Key Clinical Message}

We represent a case with simultaneous COVID-19 and acute type A aortic
dissection. Type A aortic dissection, an aortic catastrophic event,
seems to have higher mortality on coexistence with COVID-19.

\textbf{Keywords:} aortic dissection, COVID-19, coronavirus,
cardiovascular disorders

As the patient was deceased, a written informed consent was obtained
from the patient's next of kin to publish this report in accordance with
the journal's patient consent policy and all of the authors declare that
confidentiality of the patient was respected.



\textbf{Introduction}

Corona virus disease 2019 (COVID-19) is a respiratory disease caused by
novel corona virus, severe acute respiratory syndrome coronavirus 2
(SARS-COV-2), which was first reported in Wuhan city of China on
December 31, 2019 to world health organization \textsuperscript{1}.
Since then, more than 250 million people around the world have been
infected and unfortunately more than five millions of them have lost
their lives to date (November 2021) \textsuperscript{2}. Covid-19 can
present in a wide range of clinical manifestations, more commonly as
respiratory symptoms such as shortness of breath and cough. Furthermore,
it can manifest as cardiovascular symptoms such as palpitations and
chest pain \textsuperscript{3} and cardiovascular complications such as
aortic dissection \textsuperscript{4}. Aortic dissection is described as
a tear in the intima layer of aortic wall which allows blood to flow and
accumulate between aortic layers and can propagate along the length of
aorta. It can manifest as various symptoms such as chest pain, weakness,
fatigue and unequal extremity pulses and blood
pressures\textsuperscript{5}. Despite all advances in medicine in the
field of diagnostics and treatments, aortic dissection has still a high
rate of mortality which makes it extremely considerable
\textsuperscript{6}. In this report, we aim to present our patient with
aortic dissection and recent COVID-19 and report her final destiny.

\textbf{Case history/examination}

A 46 years old woman was admitted to our emergency room on September
21st 2021, with acute onset chest pain which was retrosternal and
radiating to the left arm and between two shoulders with a feeling of
heaviness in the chest. The pain had a continuous nature from two hours
before admission. In addition, she mentioned nausea, vomiting and cold
sweat. The patient was nonsmoker and had a past medical history of stage
1 hypertension based on ACC/AHA 2021 hypertension guidelines for about
three years and hyperlipidemia. She was under a single-drug treatment
with a daily dosage of 25 mg of losartan tablet for hypertension and was
under control. She was also affected by COVID-19 three weeks ago and
underwent outpatient treatment with remdesevir for five days during
which the patient didn't experience fluctuations in blood pressure.

On physical examination, a systolic blood pressure difference of 40 mmHg
between arms (140/80 mmHg in right arm versus 100/80 mmHg in left arm)
was detected by sphygmomanometer in the assessment of vital signs. Her
heart rate was 82 beats per minute. Respiratory rate was 16 per minute
and arterial O2 saturation was 96\%. Pulmonary and heart auscultation
were unremarkable. A discrepant pulse between left and right radial
artery was felt which the left radial pulse was weaker. Routine
neurological examination was normal, and the power in all limbs was 5/5,
with a Glasgow coma scale of 15/15. Pupils were 3 mm bilaterally equal
and reactive to light, the abdomen was soft and lax with no tenderness.

\textbf{Differential diagnosis, investigations and treatment}

Initial ECG showed normal sinus rhythm, normal axis with ST elevation in
aVR and V1 leads and ST depression in I, aVL, V4-6 leads (Figure 1).
According to patient's presentation with chest pain, unequal radial
pulses, a difference in blood pressures of arms and her ECG, aortic
dissection was the most likely diagnosis and aortic computed tomography
(CT) angiography was requested for the patient.

In laboratory tests, D-dimer was 4820 ng/ml (reference up to 600), serum
ferritin 417.4 ng/ml (reference 10-291), lactate dehydrogenase 666 U/lit
(reference 230-480), troponin 0.2 ng/ml (normal population \textless{}
0.05), CPK 58 U/lit (24-170), CK-MB 20 U/lit (reference 1-24),
C-reactive protein 16 mg/lit (reference up to 5.9), ESR 26 mm/h
(reference up to 20 in below 50 years old patients). Other para-clinical
tests were normal.

Following aortic CT angiography, aortic dissection type A according to
Stanford classification and type 1 according to DeBakey classification
was diagnosed for the patient.

The intimal flap started at aortic valve extending to ascending aorta,
aortic arch, descending thoracic aorta, abdominal aorta to right common
iliac artery and then terminating in right external iliac artery.
Dissection flap extension to right carotid artery, right common carotid
artery and left subclavian artery were noted (Figure 2). Right coronary
artery was supplied by true lumen and left main artery was supplied by
false lumen. The chest CT scan showed patchy ground glass opacity in
anterior segment of superior and middle lobes of right lung consistent
with COVID-19 infection.

Due to the diagnosis of aortic dissection, the patient was candidate for
emergency surgery and due to inadequate facilities, she was prepared to
be transferred to another hospital, but as soon as she entered the
ambulance, she became bradycardic, leading to asystole. Cardiopulmonary
resuscitation was performed and she was returned to the first hospital.
The patient underwent intubation and atropine injection, after which the
patient was successfully recovered after a few minutes and she regained
consciousness. After an hour, she was transferred to another hospital
for emergency surgery.

\textbf{Outcome and follow-up}

The patient was unfortunately expired before entering the operating
room.

\textbf{Discussion}

In this report, we described a 46 year old woman with past medical
history of stage 1 hypertension which was under control, hyperlipidemia
and recent COVID-19 whom represented with acute chest pain and cold
sweat. The patient reported no traumatic events and no history of
connective tissue disorders. Her clinical examination showed unequal
radial pulses and a blood pressure difference between arms. During
patient's hospitalization, her blood pressure was within the normal
range. The laboratory tests showed elevated D-dimer, troponin, ESR and
CRP. The diagnosis and management of aortic dissection in early stages
is of importance since it has numeric manifestations and can mimic other
life threatening events such as myocardial infarction and pulmonary
embolism \textsuperscript{7}. Silvestri et al., reviewed seventeen cases
of aortic pathology in patients with clinically suspected or PCR
confirmed COVID-19 and also reported hypertension as the most frequent
comorbidity; they suggested a potential link between COVID-19 and aortic
dissection \textsuperscript{8}.

There are some potential mechanisms for arterial pathology in COVID-19
patients. SARS-CoV-2 has spike proteins on its surface that binds a
receptor which is expressed in the endothelium called angiotensin
converting enzyme 2 (ACE-2). This means that SARS-CoV-2 can injure
vascular endothelium in the body \textsuperscript{9}. SARS-CoV-2
downregulates ACE-2 which leads to over activation of classical
renin-angiotensin system (RAS) and vasoconstriction\textsuperscript{10}.
ACE Inhibitor (ACEI) and angiotensin receptor blocking (ARB) drugs,
which are used commonly for hypertension as in our patient, upregulate
ACE-2 expression that can potentially increase the vascular entry of and
injury by SARS-CoV-2. On the other hand, upregulation of ACE-2 can have
vasodilatory and anti-inflammatory effects as a result of conversion of
angiotensin II to angiotensin 1-7\textsuperscript{11}. However, in a
study of 1128 hospitalized patients with COVID-19, those who took
ACEI/ARB drugs had a lower all-cause mortality than those who didn't
take \textsuperscript{12}.

Another possible cause of arterial dissection in COVID-19 patients can
be cytokine storm and inflammatory responses which leads to endothelial
dysfunction \textsuperscript{13}. Inflammation may cause rupture of
atherosclerotic plaque which can lead to dissection\textsuperscript{14}.
Studies have shown that the number of patients with aortic dissection
were increased during the influenza season\textsuperscript{15, 16}.
Akgul et al., presented an aortic dissection in a COVID-19 patient which
during the aortomy, they noticed significant aorta wall thickening as
seen in inflammatory aortic pathologies\textsuperscript{17}. Their
finding is consistent with the potential association of inflammation
caused by SARS-CoV-2 with aortic dissection.

As it has been suggested before, SARS-CoV-2 is a virus that causes
multi-organ diseases and can manifests as life-threatening
events\textsuperscript{10}. Therefore, it is important to evaluate the
association between COVID-19 and aortic dissection and the
pathophysiology of it. Further studies are needed to establish this
association.

\textbf{Conflict of interest}

The authors have no conflict of interests to declare.

\textbf{Acknowledgement}

The authors of the present study sincerely thank all of the medical
staff in Shohadaye-Tajrish hospital, Tehran, Iran, who cooperated with
us for completion of this study. All of the data in this report was
extracted from the patient's hospital medical records.

\textbf{Ethical statement}

As the patient was deceased, a written informed consent was obtained
from the patient's next of kin. All of the authors declare that
confidentiality of the patient was respected.

\textbf{Funding}

There is no funding to the present study.

\textbf{Author's contribution}

Rana Irilouzadian: conceptualization, writing original draft, review and
editing

Hossein Salehi Omran: data collection, writing original draft

Toktam Alirezaei: data curation, supervision, review and editing

\textbf{References}

1. Ciotti M, Ciccozzi M, Terrinoni A, Jiang WC, Wang CB, Bernardini S.
The COVID-19 pandemic. \emph{Crit Rev Clin Lab Sci} . Sep
2020;57(6):365-388. doi:10.1080/10408363.2020.1783198

2. WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020.
Available online:~https://covid19.who.int/~(last cited:~{[}November
12,2021{]})

3. Baj J, Karaku\selectlanguage{polish}ł\selectlanguage{english}a-Juchnowicz H, Teresi\selectlanguage{polish}ń\selectlanguage{english}ski G, et al. COVID-19: Specific
and Non-Specific Clinical Manifestations and Symptoms: The Current State
of Knowledge. \emph{J Clin Med} . Jun 5 2020;9(6)doi:10.3390/jcm9061753

4. Fukuhara S, Tang H, Kim KM, et al. Type A Aortic Dissection During
COVID-19 Pandemic: Report From Tertiary Aortic Centers in the United
States and China. \emph{Semin Thorac Cardiovasc Surg} . Summer
2021;33(2):303-312. doi:10.1053/j.semtcvs.2020.10.034

5. Patel PD, Arora RR. Pathophysiology, diagnosis, and management of
aortic dissection. \emph{Ther Adv Cardiovasc Dis} . Dec
2008;2(6):439-68. doi:10.1177/1753944708090830

6. Karthikesalingam A, Holt PJ, Hinchliffe RJ, Thompson MM, Loftus IM.
The diagnosis and management of aortic dissection. \emph{Vasc
Endovascular Surg} . Apr 2010;44(3):165-9. doi:10.1177/1538574410362118

7. Volvovitch D, Ram E, Cohen H, Kogan A, Sternik L, Raanani E. Acute
pulmonary embolism following acute type A aortic dissection in a patient
with COVID-19. \emph{Journal of Cardiac Surgery} . 2021;36(4):1566-1568.
doi:https://doi.org/10.1111/jocs.15389

8. Silvestri V, Recchia GE. Aortic Pathology During COVID - 19
Pandemics. Clinical Reports in Literature and Open Questions on the two
Co-Occurring Conditions. \emph{Annals of Vascular Surgery} .
2021;75:109-119. doi:10.1016/j.avsg.2021.02.037

9. Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich
S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses
in the Age of Coronavirus Disease 2019: A Review. \emph{JAMA Neurology}
. 2020;77(8):1018-1027. doi:10.1001/jamaneurol.2020.2065

10. Divani AA, Andalib S, Di Napoli M, et al. Coronavirus Disease 2019
and Stroke: Clinical Manifestations and Pathophysiological
Insights.\emph{J Stroke Cerebrovasc Dis} . 2020;29(8):104941-104941.
doi:10.1016/j.jstrokecerebrovasdis.2020.104941

11. Guo J, Huang Z, Lin L, Lv J. Coronavirus Disease 2019 (COVID-19) and
Cardiovascular Disease: A Viewpoint on the Potential Influence of
Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers
on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2
Infection. \emph{Journal of the American Heart Association} .
2020;9(7):e016219-e016219. doi:10.1161/JAHA.120.016219

12. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of
Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor
Blockers With Mortality Among Patients With Hypertension Hospitalized
With COVID-19. \emph{Circ Res} . 2020;126(12):1671-1681.
doi:10.1161/CIRCRESAHA.120.317134

13. Markus HS, Brainin M. COVID-19 and stroke---A global World Stroke
Organization perspective. \emph{International Journal of Stroke} .
2020;15(4):361-364. doi:10.1177/1747493020923472

14. Oz K, Iyigun T, Karaman Z, et al. Prognostic Value of Neutrophil to
Lymphocyte Ratio and Risk Factors for Mortality in Patients with
Stanford Type A Aortic Dissection. \emph{Heart Surg Forum} . Jun 30
2017;20(3):E119-e123. doi:10.1532/hsf.1736

15. Mehta RH, Manfredini R, Bossone E, et al. The winter peak in the
occurrence of acute aortic dissection is independent of
climate.\emph{Chronobiol Int} . 2005;22(4):723-9.
doi:10.1080/07420520500179605

16. Ashur C, Norton E, Farhat L, et al. Higher admission rates and
in-hospital mortality for acute type A aortic dissection during
Influenza season: a single center experience. \emph{Sci Rep} . Mar 13
2020;10(1):4723. doi:10.1038/s41598-020-61717-5

17. Akgul A, Turkyilmaz S, Turkyilmaz G, Toz H. Acute Aortic Dissection
Surgery in a Patient With COVID-19. \emph{Ann Thorac Surg} . Jan
2021;111(1):e1-e3. doi:10.1016/j.athoracsur.2020.06.005

\textbf{Images, graphs and videos}

Figure 1. Initial ECG of patient: normal sinus rhythm, normal axis, ST
elevation in aVR and V1 leads and ST depression in I, aVL, V4-6 leads\selectlanguage{english}
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Figure 2. Aortic CT angiography: type A according to Stanford
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