DOI: 10.1111/jocs.

14596

REVIEW ARTICLE

At the heart of COVID‐19

Inayat Hussain Khan BSc (Hons)1 | Syeda Anum Zahra1 | Sevim Zaim2 |
3
Amer Harky MBChB, MRCS, MSc

1
Department of Medicine, St George's Hospital
Medical School, London, UK
2
Department of Medicine, University of
Liverpool School of Medicine, Liverpool, UK
3
Department of Cardiothoracic Surgery,
Liverpool Heart and Chest Hospital,
Liverpool, UK
Correspondence
Amer Harky, MBChB, MRCS, MSc, Department
of Cardiothoracic Surgery, Liverpool Heart and
Chest Hospital, Liverpool L14 3PE, UK.
Email: aaharky@gmail.com
Abstract
Coronavirus disease (COVID‐19) first presented in Wuhan, Hubei province, China in
December 2019. Since then, it has rapidly spread across the world, and is now
formally considered a pandemic. The disease does not discriminate but increasing
age and the presence of comorbidities are associated with severe form of the dis-
ease and poor outcomes. Although the prevalence of COVID‐19 in patients with
cardiovascular disease is under‐reported, there is evidence that pre‐existing cardiac
disease can render individuals vulnerable. It is thought that COVID‐19 may have
both a direct and indirect effect on the cardiovascular system; however, the primary
mechanism of underlying cardiovascular involvement is still uncertain. Of particular
interest is the role of angiotensin‐converting enzyme 2, which is well known for its
cardiovascular effects and is also considered to be important in the pathogenesis of
COVID‐19. With a range of different drug candidates being suggested, effective
anti‐virals and vaccines are an area of on‐going research. While our knowledge of
COVID‐19 continues to rapidly expand, this review highlights recent advances in our
understanding of the interaction between COVID‐19 and the cardiovascular system.

KEYWORDS

cardiovascular, COVID‐19, heart

1 | INTRODUCTION In addition to increasing age, the severity of the disease is as-

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) which
causes coronavirus disease (COVID‐19) first emerged in the Chinese city
of Wuhan in December 2019 and has since traveled rapidly across the
globe with the World Health Organization (WHO) declaring a pandemic
1‐3
in March 2020. COVID‐19 is extremely contagious with each patient
infecting approximately three others (basic reproduction number,
R0 of ~3) and if not adequately dealt with, can lead to infection rates of
4
60%‐80% in a population. It is estimated that approximately 4% of cases
result in death, 14% present as severe cases and 5% require admission to
the intensive care unit (ICU).5 The fatality ratio shows a strong age
gradient for risk of death. In the United States, the fatality was reported
to be the highest in individuals aged ≥85 (10% to 27%) followed by
persons aged 65 to 84 years (3% to 11%) and <1% across younger ages.6
sociated with the presence of comorbidities. Most notably, in those
with severe COVID‐19, an increased presence of cardiovascular co-
morbidities has been reported.7 The National Health Commission of
China reported that 35% of patients diagnosed with COVID‐19 had
hypertension and 17% had coronary heart disease (CHD).8
Therefore, patients with cardiovascular disease (CVD) can present
with severe disease potentially leading to myocarditis, vasculitis, or
cardiac arrhythmias.9 Considering its worldwide spread and con-
sequences, researchers and health care professionals must be prepared
to tackle this disease and consider its impact on healthcare systems.
While our knowledge of COVID‐19 is evolving with a substantial
amount still unknown; this review discusses COVID‐19 and its
interaction with CVD and mechanism of cardiovascular involvement.
Interventions, management, and future directions will also be discussed.

Inayat Hussain Khan, Syeda Anum Zahra, and Sevim Zaim contributed equally to this work.

J Card Surg. 2020;1–8. wileyonlinelibrary.com/journal/jocs © 2020 Wiley Periodicals, Inc. | 1

2 |
2 | L IT E RA T UR E SE AR CH
A comprehensive literature search was done on PubMed, SCOPUS,
Embase, Cochrane database, Google scholar, and Ovid to identify the
articles that discussed the novel corona virus, COVID and its im-
plications on cardiovascular system. Key words used were “COVID,”
“SARS‐CoV‐2,” “SARS‐CoV,” “2019‐nCoV,” “COVID‐19,” “Novel
Corona virus.” The search terms were used as key words and in
combination as MeSH terms to maximize the output from literature
findings. A staged literature search was done, whereby a separate
literature search was performed for each section within this article
and all the relevant studies were identified and summarized sepa-
rately. If a paper is reporting on many aspects of the COVID, then the
results have been shared between different parts of this review.
The relevant articles are cited and referenced within each section
separately. No limits were placed on publication time or language of
the article.
All the relevant articles were identified and screened by three
authors; the results are summarized in narrative manner in each
relevant section within the text of this review. A summary table of
each section is provided where appropriate.
3 | V IR O LO GY
Belonging to the Coronavirinae subfamily, coronaviruses (CoV) are
known for their crown‐like appearance. Coronavirinae subfamily is
further classified by phylogenetic clustering into four groups: α, β, γ,
and δ CoV. The COVID‐19 pathogen belongs to the β‐CoV group.1,10
CoV has four major structural proteins: the nucleocapsid (N) protein,
envelope (E) protein, the membrane (M) protein, and the spike (S)
protein which allows attachment and fusion with the host receptor.10
SARS‐CoV‐2 can bind to the angiotensin‐converting enzyme 2
(ACE2) and enter the host cell.11 Severe pneumonia and acute lung
failure associated with SARS‐CoV‐2 is postulated to be due to sup-
12
pression of ACE2 expression. Kuba et al reported that ACE2 is a
crucial SARS‐CoV receptor in vivo, and the spike protein reduces
12
ACE2 expression. Moreover, the study found that acute lung fail-
ure induced by the injection of SARS‐CoV spike protein in mice could
be attenuated by blocking the renin‐angiotensin‐aldosterone system
12
(RAAS) pathway.
The animal reservoir of COVID‐19 is currently unknown, but the
viral genome was found to be approximately 88% similar to Bat
coronavirus and distant to the previously known SARS and Middle
1
East respiratory syndrome viruses. Therefore, it is thought to have
originated in bats with an intermediate amplification host before
being transmitted to animal handlers in the Chinese animal mar-
kets.13 The primary mode of transmission of the virus is through
13
person‐to‐person contact via respiratory droplets. The incubation
period of the virus is noted to be 2 to 14 days.13 Currently, there are
no anti‐virals or vaccines available against the virus, making it of
significant global concern due to the rapid spread and easy
transmission.
KHAN ET AL.
4 | EPIDERMOLOGY
WHO was informed of a cluster of 44 cases of pneumonia of un-
known etiology on 31st December 2019 in Wuhan.14,15 Since then,
COVID‐19 has caused wide‐scale socioeconomic disruption. As of
14th April 2020, there have been more than 2 million positive cases
of COVID‐19 with more than 120 000 deaths reported worldwide.16
Europe is now the epicenter of the disease with Italy being the most
terribly hit country with 19 470 deaths reported so far.16 In the UK,
there are currently over 93 000 cases with over 12 000 deaths.16
Figure 1A,B are graphical representations of spread and affected
regions. The reported number of confirmed cases and deaths are
rapidly increasing. Figure 2A,B show the most affected regions in
Europe and across the world.
The prevalence of COVID‐19 in patients with CVD is difficult to
estimate due to varying degrees of national surveillance and data col-
lection around the world. A Chinese meta‐analysis of 1527 patients with
COVID‐19 revealed a prevalence of 9.7% of diabetes mellitus (DM),
16.4% of cardiac, and cerebrovascular disease and 17% of hyperten-
sion.17 The presence of these comorbidities in patients has a significant
17
impact on their prognosis with increased risk of severe disease.
A report from the Chinese center for disease control and pre-
vention presented the clinical outcomes in 44 672 confirmed cases.18
The case fatality rate was higher in patients with hypertension, DM
and CVD (6%, 7.3%, and 10.5%, respectively) compared with the
overall 2.3% in the entire cohort.18
5 | MECH ANISM O F CA R DIOV ASCULAR
INVOLVEMENT
Although it is accepted that COVID‐19 has a significant impact on
cardiovascular health, the exact mechanism of this involvement is
still under debate. One theory is indirect cardiac involvement, con-
sidering immunological ageing is seen in older patients who are also
more susceptible to CVD.19 Additionally, comorbidities, such as hy-
perlipidaemia and DM also affect immune function.19 Dysregulated
immune function may increase susceptibility to COVID‐19 as well as
its severity. On the other hand, reports from China have shown
cardiac arrests, elevated cardiac biomarkers, abnormal electro-
cardiogram (ECG), and echocardiography findings even in patients
without pre‐existing CVD.20,21 This suggests there may be a direct
impact of COVID‐19 on cardiovascular health.
The effect of ACE inhibitors (ACE‐i) and angiotensin receptor
blockers (ARBs) used in various cardiovascular conditions, such as
hypertension, CHD, and congestive heart failure on COVID‐19 sus-
ceptibility and prognosis is currently controversial. Despite some
evidence supporting benefits in preventing lung injury, other evi-
dence suggests an increased risk of ACE2 plasma membrane ex-
pression.20 Currently, it is not possible to conclude whether ACE‐i
and ARBs are harmful in patients with COVID‐19; however, this can
be a possible explanation as to why patients with CVD are more
susceptible to COVID‐19 and tend to have a worse prognosis.20
KHAN ET AL. | 3

F I G U R E 1 A, The prevalence of COVID‐19 worldwide. WHO prevalence data as of 12th April 2020 represented graphically.16 Illustration
created using mapchart.net. B, Countries with highest cases. Displaying the countries in which the highest numbers of cases were confirmed.
WHO prevalence data as of 12th April 2020 represented graphically.16 COVID‐19, coronavirus disease; WHO, World Health Organization

Cardiovascular complications like acute coronary syndrome 6 | M YO C AR D IA L IN JU RY A ND TH E

(ACS) were also seen postinfection during the SARS‐CoV outbreak DE TERMENTAL E FFECTS
in 2002‐2003.9 There is evidence that with an acute infection,
risk of developing ACS in patients with pre‐existing CVD increases Myocardial injury is defined as troponin concentration >99th‐
and this can be due to the surge in circulating cytokine levels percentile upper reference limit and can occur due to myocardial
leading to atherosclerotic plaque instability as well as increased ischemia and other processes including myocarditis.26
22
myocardial demand. The mechanisms discussed can also In patients with COVID‐19, there is a higher prevalence of
cause ventricular dysfunction resulting in haemodynamic CVD and myocardial injury, particularly in patients admitted to
abnormalities and arrhythmias.23,32 Moreover, there have ICU. Amongst the initial 41 patients diagnosed with COVID‐19 in
been cases of COVID‐19 patients in China who developed Wuhan, five had myocardial injury evidenced by elevated levels of
reduced ejection fraction and had heart enlargement cardiac troponin‐I (Tn‐I) (>28 pg/mL). Four of these patients were
24,25
postinfection. admitted to ICU.2 This is strengthened by a case series including
4 |
138 patients with COVID‐19 which reported 22.2% of those
admitted to ICU had acute cardiac injury compared with only 2%
of non‐ICU patients (P < .001).21 Laboratory findings showed
median Tn‐I levels to be higher in those admitted to ICU than
non‐ICU patients (11.0 vs 5.1 pg/mL; P = .004). Similarly, median
F I G U R E 3 SARS‐Cov‐2 binding to ACE receptor. Original illustration created using BioRender. ACE, angiotensin‐converting enzyme;
SARS‐Cov‐2, severe acute respiratory syndrome coronavirus‐2
KHAN ET AL.
F I G U R E 2 A, COVID‐19 deaths in Europe.
Displaying the number of deaths reported in
Europe. WHO mortality data as of 12th April
2020 represented graphically.16 B, COVID‐19
deaths worldwide. Displaying the highest
number of deaths around the world. WHO
mortality data as of 12th April 2020
represented graphically.16 COVID‐19,
coronavirus disease; WHO, World Health
Organization
creatine kinase‐MB levels were also significantly higher in patients
with ICU compared with non‐ICU patients (I8 vs 13 U/L);
P < .001.21 This suggests that myocardial injury is a potential
complication of COVID‐19 highlighting the importance of under-
standing underlying mechanisms.
KHAN ET AL.
One explanation is the role of ACE2, which is highly expressed in
the lungs and the heart.27 ACE2 has been shown to act as a receptor for
SARS‐CoV‐2 (Figure 3). In a previous study, pulmonary infection with a
human strain of SARS‐CoV in mice resulted in ACE2 dependent myo-
cardial infarction.27 Furthermore, the investigators detected SARS‐COV
RNA in 7 out of 20 autopsy heart samples from patients infected with
SARS. Subsequent staining also demonstrated macrophage infiltration
with associated myocardial damage.27 Therefore, ACE2 may account for
the myocardial injury evident in COVID‐19 patients. Since RAAS in-
hibitors can alter the level of ACE‐2, the role of these drugs in
COVID‐19 is an avenue which requires further investigation.
There are other suggested mechanisms for myocardial injury.
The rise in Tn‐I does not occur in isolation but alongside the rise of
other inflammatory markers, such as ferritin, c‐reactive protein,
interleukin‐6 [IL‐6], interferon‐γ, tumor necrosis factor‐α, and lactate
dehydrogenase possibly representing a cytokine storm syndrome
(caused by dysregulation of T‐helper cells) or secondary haemopha-
gocytic lymphohistiocytosis.28 Understanding this is paramount,
as data from a multicentre study of patients with COVID‐19 in
Wuhan reported elevated ferritin and IL‐6 to be predictors of
mortality.29
Additionally, the respiratory manifestations of COVID‐19, such
as acute respiratory distress syndrome (ARDS) can result in oxidative
stress, hypoxia‐induced intracellular calcium release, and potentially
inflammation‐induced myocardial apoptosis.30,31 This highlights how
myocardial injury in the context of SARS‐CoV‐2 is potentially
multifactorial; therefore, representing a novel challenge for health-
care professionals in managing patients with COVID‐19.
7 | C AR D IA C A RR H YT H M IA S
Cardiac arrhythmias are known to occur in patients with
COVID‐19.23,32 Ventricular arrhythmias, as well as acute myo-
carditis, may present as the first clinical manifestation.32 The elec-
trolyte imbalance caused by COVID‐19 interacting with the RAAS
system can lead to hypokalemia increasing the risk of developing
arrhythmias.32 In a study mentioned above, the overall incidence of
arrhythmias was 16.7% in patients with COVID‐19.21 The incidence
was higher in patients requiring ICU admission (44.4%) compared
21
with those not requiring ICU admission (8.9%). Unfortunately, the
types of arrhythmias in these patients were not published yet. Guo
et al reported that in 187 patients with COVID‐19, 27.8% had
elevated troponin levels and in this group, malignant ventricular
arrhythmias were more frequent than those with normal troponin
33
levels (11.5% vs 5.2%). Therefore, the high incidence of ar-
rhythmias in patients with COVID‐19 could be due to electrolyte
and haemodynamic disturbances in the presence of high in-
flammatory stress.
Patients with inherited or acquired arrhythmias should be
monitored while undergoing supportive treatment as certain drugs
can promote arrhythmogenic activity.23 For example, drugs, such as
chloroquine and hydroxychloroquine, which are being investigated
| 5
for COVID‐19 treatment can cause prolongation of the QT interval
leading to the development of malignant arrhythmias.23 In addition, if
both chloroquine or hydroxychloroquine are administered with drugs
that inhibit the CYP3A4 enzyme, this could also significantly increase
the risk of QT interval prolongation.23 Therefore, continuous ECG
monitoring is necessary for these patients.
8 | V EN O U S T H R O M B O EM B O L I S M
It is known that inflammatory states increase the risk of venous
thromboembolism (VTE). It is likely that COVID‐19 patients with
respiratory failure, comorbidities and mobility issues will be at an
increased risk of VTE. A single center study consisting of 138
patients evaluated VTE risk using the Padua prediction score
(Table 1).34,35 Of these patients, 15 were critically unwell and were
all considered to be at higher risk for VTE compared with only 6.5%
of those not critically unwell.35
In terms of laboratory findings, a study found D‐dimer to be
higher in those admitted to ICU compared with non‐ICU patients
(414 vs 166 mg/L; P < .001).21 In a study including 179 patients
with COVID‐19, D‐dimer level ≥0.5 mg/L was present in 76.2% of
non‐survivors compared with only 47% of survivors. The uni-
variate analysis highlighted this as a risk factor associated with
death (odds ratio: 3.474 [1.152‐10.481]); P = .027).36 In critically
unwell patients, VTE is of significant concern. In a recent study
with 81 patients with COVID‐19, Cui et al showed that 20 de-
veloped lower extremity VTE, of which eight patients died. Older
age, lower lymphocyte levels and higher D‐dimer were associated
risk factors. Therefore, the risk of VTE must be assessed especially
in older patients with comorbidities and preventive therapies
should be given based on local guidelines.
T A B L E 1 Padua risk assessment model34
Padua risk assessment model
Features Score
Active cancer 3
Previous VTE 3
Reduced mobility 3
Known thrombophilic condition 3
Recent trauma and/or surgery (≤1 mo) 2
Age (≥70 y) 1
Heart and/or respiratory failure 1
Acute MI or ischemic stroke 1
Acute infection and/or rheumatologic disorder 1
Obesity (BMI ≥30 kg/m ) 2
1
Current hormonal therapy 1
Note: Total score of 4 and above = high risk, total score < 4 = low risk.
Abbreviations: BMI, body mass index; VTE, venous thromboembolism.
6 | KHAN ET AL.

9 | H AE MO D YN A M I C S H O CK

A recent paper illustrated the variety of cardiovascular presentations

in patients with COVID‐19, including the case of a 38‐year old man
with cardiogenic shock and ARDS. The initial presentation reflected a
COVID‐19 picture and cardiac involvement only became evident
after veno‐arterial extracorporeal membrane oxygenation (ECMO)
was started.37 In a case series including 191 patients with COVID‐19,
development of heart failure was significantly higher in non‐survivors
compared with survivors (52% vs 21%; P < .0001).38 There are many
potential causes for this, including ACS, arrhythmias, stress‐induced
cardiomyopathy and fulminant myocarditis.
There are multiple potential mechanisms of cardiac involvement
in COVID‐19 (Figure 4). Therefore, it is essential to have a low
threshold for considering cardiac involvement, as cardiac and re-
spiratory symptoms may overlap and even be masked.

10 | I NT E R VE N TI O N S AN D M A N A G E M EN T

Currently, there are no approved treatments that are shown to be

safe and effective for COVID‐19, therefore management is mainly
supportive. The aim is to recognize the disease early, relieve symp-
toms, and support organ function.39
Hospitalization may be required in severe cases, and clinical
frailty scale can be used to assess if admission to critical care is
necessary.39,40 A common complication of COVID‐19 is ARDS, so
oxygen therapy is required in approximately 14% of cases. If patients
are not responding to oxygen therapy, treatment can be escalated to
continuous positive airway pressure or bilevel positive airway pres-
sure, intubation, mechanical ventilation, or ECMO.39
Due to the increasing global burden of the disease, several off‐
label treatments are being used either as part of randomised control
trials or on a compassionate basis. WHO launched the “Solidarity”
trial on 22nd March 2020 intending to discover potential treatment
options to slow disease progression and reduce mortality rates. A
combination of drugs (Table 2) are under investigation.41 Remdesivir
initially developed for the treatment of Ebola, has shown in vitro
activity against SARS‐Cov‐2. Lopinavir and ritonavir are also anti-
virals commonly used to treat HIV which have shown potential for
COVID‐19 treatment. Anti‐malarials, such as chloroquine and hy-
droxychloroquine are also under investigation for their potential
prophylactic and therapeutic effects against COVID‐19.20
Losartan, which is an angiotensin‐II receptor antagonist is being
20
investigated for its potential therapeutic value in COVID‐19. As
mentioned before, there are concerns over the safety of RAAS in-
hibitors in COVID‐due to studies reporting conflicting results.43
Therefore, the Council on Hypertension of the European Society of
Cardiology has released a statement warning against commencing or
discontinuing ACE‐i and ARBs in the context of COVID‐19.44
Moreover, convalescent plasma transfusions from recovered
patients with COVID‐19 have shown promising results without ad-
42
verse effects. Intravenous Immunoglobulin therapy is currently
F I G U R E 4 Summary of effects of COVID‐19 on the
cardiovascular system. Original illustration created using BioRender.
CVD, cardiovascular disease; COVID‐19, coronavirus disease; RAAS,
renin‐angiotensin‐aldosterone system
being trialed in addition to multi‐antibody cocktails for both pro-
phylactic and treatment purposes.39 A summary of these current
treatments and those under investigation can be seen in Table 2.
11 | F U T U R E D I R E C T I O N S
There is a pressing need for public health education; this is particularly
important in those with pre‐existing CVD. A recent study from Hong
Kong compared ST‐elevation myocardial infarction (STEMI) pre-
sentation before and during the COVID‐19 pandemic. It is reported
that time from symptom onset to the first presentation was greater in
patients with STEMI during the COVID‐19 pandemic compared with 2
years before (318 vs 82 minutes, respectively). Similarly, door to
needle time was also increased (129 vs 84.5 minutes).45 Overall, this
suggests that patients with ACS are now more likely to present later
and reasons for this are multifactorial. Patients may perceive hospitals
to be areas at high risk of COVID‐19 transmission and, therefore,
delay presenting. Other reasons may include COVID‐19 screening,
availability of staff due to redeployment and time taken for staff to
wear personal protective equipment. Adjustments of established
protocols and local guidelines are necessary to help deal with
suspected ACS. In addition, clear communication is vital, so patients
are reassured that hospitals are still prepared to deal with
cardiac emergencies.
KHAN ET AL. | 7

T A B L E 2 A summary of current Interventions and treatments AU TH OR CO NTRIB UTION S

being used currently and those under investigation20,39,41,42 Inayat Hussain Khan: Planned the work, conducted literature search
Treatment Stage and writing the manuscript, reporting the work and responsible for
Supportive treatment the overall work content. Syeda Anum Zahra: Planned the work,
Noninvasive ventilation Used in ARDS conducted literature search and writing the manuscript, reporting
Invasive ventilation Used in ARDS if noninvasive the work and responsible for the overall work content. Sevim Zaim:
ventilation fails Planned the work, conducted literature search and writing the
ECMO Can be used depending on manuscript, reporting the work and responsible for the overall work
availability
content. Amer Harky: Planned the work, supervised the literature
Fluid resuscitation Used to preserve organ function
search, reviewed, and edited the written manuscript, supervised the
Antiviral treatment reported work and responsible for the overall work content.
Remdesevir In “Solidarity” clinical trial
Lopinavir In “Solidarity” clinical trial
ORCI D
Ritonavir In “Solidarity” clinical trial
Inayat Hussain Khan http://orcid.org/0000-0001-9209-1664
Chloroquine In “Solidarity” clinical trial
Syeda Anum Zahra http://orcid.org/0000-0003-0253-7330
Hydroxychloroquine In “Solidarity” clinical trial
Sevim Zaim http://orcid.org/0000-0002-1861-0531
RAAS inhibitors
Amer Harky http://orcid.org/0000-0001-5507-5841
Losartan Being investigated—not yet in
clinical trials

Immunomodulatory treatment
Convalescent plasma In clinical trials
Intravenous immunoglobulin Being trialed in small number of
cases
Antibody treatment In development
Abbreviations: ARDS, acute respiratory distress syndrome; ECMO,
extracorporeal membrane oxygenation; RAAS, renin‐angiotensin‐
aldosterone system.
There are also potential long‐term effects of COVID‐19 on the
cardiovascular system. A study including 25 recovered patients with
SARS 12 years postinfection found differences in lipid and glucose
metabolism compared with those not infected.46 It is too early to say
what is in store for COVID‐19 patients, but there is a need for follow
up as the clinical sequelae of these metabolic disorders are well
documented.
12 | C O NCL US I O N
COVID‐19 has presented as the most significant global health
emergency to date. Patients with pre‐existing CVD are vulnerable,
and studies indicate that COVID‐19 can have severe consequences
for this particular group of patients. Therefore, it may be appropriate
to risk‐stratify and triage patients with underlying CVD on
admission. Several potential areas require further research,
including pathogenesis and therapeutics; this is, essential as in-
creasing evidence will help to substantiate current management
pathways. Until then, there is hope that COVID‐19 can be conquered
and emerging evidence will unfold to elucidate what is at the heart of
COVID‐19.
CO NFLICT OF I NTERE STS
The author declares that there are no conflict of interests.
R E F E R E N CE S
1. Ren L, Wang Y, Wu Z, et al. Identification of a novel coronavirus
causing severe pneumonia in human. Chin Med J. 2020:1.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:
497‐506.
3. World Health Organization. WHO Director‐General's opening remarks
at the media briefing on COVID‐19—11 March 2020. https://www.who.
int/dg/speeches/detail/who‐director‐general‐s‐opening‐remarks‐at‐the‐
media‐briefing‐on‐covid‐19‐‐‐11‐march‐2020. Accessed 12 April 2020.
4. Flahault A. Has China faced only a herald wave of SARS‐CoV‐2? The
Lancet. 2020;395(10228):947.
5. Grech V. Unknown unknowns—COVID‐19 and potential global mor-
tality. Early Hum Dev. 2020;144:105026.
6. Bialek S, Boundy E, Bowen V, et al. Severe outcomes among patients with
coronavirus disease 2019 (COVID‐19)—United States, February
12–March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(12):343‐346.
7. Guan W, Liang W, Zhao Y, et al. Comorbidity and its impact on 1590
patients with Covid‐19 in China: a nationwide analysis. Eur Respir J.
2020:2000547.
8. Zheng Y, Ma Y, Zhang J, et al. COVID‐19 and the cardiovascular
system. Nat Rev Cardiol. 2020.
9. Madjid M, Safavi‐Naeini P, Solomon S, et al. Potential effects of
coronaviruses on the cardiovascular system. JAMA Cardiol.
2020.
10. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure,
replication, and pathogenesis. J Med Virol. 2020;92(4):418‐423.
11. Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel
coronavirus from Wuhan: an analysis based on decade‐long Structural
studies of SARS coronavirus. J Virol. 2020;94:7.
12. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting
enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nature
Med. 2005;11(8):875‐879.
13. Kolifarhood G, Aghaali M, Saadati H, et al. Epidemiological and clinical
aspects of COVID‐19; a narrative review. Journals.sbmu.ac.ir. 2020.
[Internet]. http://journals.sbmu.ac.ir/AAEM/index.php/AAEM/article/
view/620. Accessed 11 April 2020.
14. Guan W, Ni H, Hu Y, et al. Clinical characteristics of coronavirus
disease 2019 in China. N Engl J Med. 2020.
15. World Health Organisation. Pneumonia of unknown cause—China.
https://www.who.int/csr/don/05‐january‐2020‐pneumonia‐of‐unkown‐
cause‐china/en/. Accessed 11 April 2020.
8 |
16. World Health Organisation. Coronavirus disease 2019 (COVID‐19)
situation report—83 [Internet]. 2020. https://www.who.int/publications‐
detail/infection‐prevention‐and‐control‐during‐health‐care‐when‐novel‐
coronavirus‐(ncov)‐infection‐is‐suspected‐20200125. Accessed 12
April 2020.
17. Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular
metabolic diseases on COVID‐19 in China. Clin Res Cardiol. 2020.
18. Wu Z, McGoogan J. Characteristics of and important lessons from the
coronavirus disease 2019 (COVID‐19) outbreak in China. JAMA.
2020;323(13):1239.
19. Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considera-
tions for patients, health care workers, and health systems during the
coronavirus disease 2019 (COVID‐19) pandemic. JACC. 2020.
20. Clerkin KJ, Fried JA, Raikhelkar J, et al. Coronavirus disease 2019
(COVID‐19) and cardiovascular disease. Circulation. 2020.
21. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized
patients with 2019 novel coronavirus–infected pneumonia in Wuhan,
China. JAMA. 2020;323(11):1061‐1069.
22. Bonow RO, Fonarow GC, O'Gara PT, et al. Association of coronavirus
disease 2019 (COVID‐19) with myocardial injury and mortality. JAMA
Cardiol. 2020.
23. Wu C, Postema P, Arbelo E, et al. SARS‐CoV‐2, COVID‐19 and in-
herited arrhythmia syndromes. Heart Rhythm. 2020.
24. Hu H, Ma F, Wei X, et al. Coronavirus fulminant myocarditis saved
with glucocorticoid and human immunoglobulin. Eur Heart J. 2020.
25. Zeng JH, Liu Y‐X, Yuan J, et al. First case of COVID‐19 infection with
fulminant myocarditis complication: case report and insights. Infec-
tion. 2020.
26. Chapman A, Adamson P, Mills N. Assessment and classification of
patients with myocardial injury and infarction in clinical practice.
Heart. 2016;103(1):10‐18.
27. Oudit G, Kassiri Z, Jiang C, et al. SARS‐coronavirus modulation of
myocardial ACE2 expression and inflammation in patients with SARS.
Eur J Clin Invest. 2009;39(7):618‐625.
28. Seguin A, Galicier L, Boutboul D, et al. Pulmonary involvement in
patients with hemophagocytic lymphohistiocytosis. Chest. 2016;
149(5):1294‐1301.
29. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to
COVID‐19 based on an analysis of data of 150 patients from Wuhan,
China. Intensive Care Med. 2020.
30. Rivara M, Bajwa E, Januzzi J, et al. Prognostic significance of elevated
cardiac troponin‐T levels in acute respiratory distress syndrome pa-
tients. PLoS One. 2012;7(7):e40515.
31. Court O, Kumar A, Parrillo J, et al. Clinical review: myocardial de-
pression in sepsis and septic shock. Crit Care. 2002;6(6):500.
32. Kochi A, Tagliari A, Forleo G, et al. Cardiac and arrhythmic compli-
cations in Covid‐19 patients. J Cardiovasc Electrophysiol. 2020.
33. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal
outcomes of patients with coronavirus disease 2019 (COVID‐19).
JAMA Cardiol. 2020.
KHAN ET AL.
34. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for
the identification of hospitalized medical patients at risk for venous
thromboembolism: the padua prediction score. J Thromb Haemost.
2010;8(11):2450‐2457.
35. Xu J, Wang L, Zhao L, et al. Risk assessment of venous thromboem-
bolism and bleeding in COVID‐19 patients. Pulmonology. 2020.
36. Du R, Liang L, Yang C, et al. Predictors of mortality for patients with
COVID‐19 pneumonia caused by SARS‐CoV‐2: a prospective cohort
study. Eur Respir J. 2020:2000524
37. Fried J, Ramasubbu K, Bhatt R, et al. The variety of cardiovascular
presentations of COVID‐19. Circulation. 2020.
38. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for
mortality of adult inpatients with COVID‐19 in Wuhan, China: a
retrospective cohort study. The Lancet. 2020;395(10229):
1054‐1062.
39. Beeching NFT, Fowler R. Coronavirus disease 2019 (COVID‐19): BMJ
best practice; 2020. https://bestpractice.bmj.com/topics/en‐gb/
3000168. Accessed 11 April 2020.
40. Zaim S, Chong JH, Sankaranarayanan V, et al. COVID‐19 and Multi‐
Organ Response, Current Problems in Cardiology, 2020, https://doi.org/
10.1016/j.cpcardiol.2020.100618
41. World Health Organisation. “Solidarity” clinical trial for COVID‐19
treatments 2020. https://www.who.int/emergencies/diseases/novel‐
coronavirus‐2019/global‐research‐on‐novel‐coronavirus‐2019‐ncov/
solidarity‐clinical‐trial‐for‐covid‐19‐treatments. Accessed 11 April 2020.
42. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma
therapy in severe COVID‐19 patients. Proc Natl Acad Sci. 2020:
202004168
43. Khashkhusha TR, Chan JSK, Harky A. ACE inhibitors and COVID‐19: we
don't know yet. J Card Surg. 2020. https://doi.org/10.1111/jocs.14582
44. European Society of Cardiology. Position statement of the ESC
council on hypertension on ACE‐inhibitors and angiotensin receptor
blockers [Internet]. Escardio.org. 2020. https://www.escardio.org/
Councils/Council‐on‐Hypertension‐(CHT)/News/position‐statement‐of‐
the‐esc‐council‐on‐hypertension‐on‐ace‐inhibitors‐and‐ang. Accessed
12 April 2020.
45. Tam C, Cheung K, Lam S, et al. Impact of coronavirus disease 2019
(COVID‐19) outbreak on ST‐segment–elevation myocardial in-
farction care in Hong Kong, China. Circ Cardiovasc Qual Out-
comes. 2020.
46. Wu Q, Zhou L, Sun X, et al. Altered lipid metabolism in recovered
SARS patients twelve years after infection. Sci Rep. 2017;7:1.
How to cite this article: Khan IH, Zahra SA, Zaim S, Harky A.
At the heart of COVID‐19. J Card Surg. 2020;1–8.
https://doi.org/10.1111/jocs.14596