Webinar Seri 4 IDI NTB.

Peran Organisasi Profesi dalam

Masa Pandemi Covid 19

Covid 19 and dr. Acil Aryadi, SpJP

Cardiovascular Disease
 Covid 19
❖ Coronavirus disease 2019 (COVID-19), caused by a strain of
coronavirus known as severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2)
❖ R Ecountrie
First reported: Wuhan, China, in late December 2019 - > 200 VIEWS

a Structure of SARS-CoV-2 b Genome of SARS-CoV-2

S protein Non-structural proteins Structural proteins

M protein ORF1a S M N
5′ 3′
ORF1b E
Primary
translation
11
pp1a nsp1 nsp2 PLpro nsp4 3CL 6 7 8 910 S protein

pp1ab nsp1 nsp2 PLpro nsp4 3CL 6 7 8 9 10 RdRp Hel 14 15 16

E protein S1: attachment S2: fusion

ssRNA genome RBD S1/S2

N protein 1 1,273
❖
Compared with Mutations Insertion (four amino acids)
c Life cycle of SARS-CoV-2 SARS-CoV: Furin cleavage site

 11
pp1a nsp1 nsp2 PLpro nsp4 3CL 6 7 8 910 S protein

pp1ab nsp1 nsp2 PLpro nsp4 3CL 6 7 8 9 10 RdRp Hel 14 15 16

E protein

Life Cycle SARS CoV2

S1: attachment S2: fusion

ssRNA genome RBD S1/S2

N protein 1 1,273

Compared with Mutations Insertion (four amino acids)

c Life cycle of SARS-CoV-2 SARS-CoV: Furin cleavage site

Activation TMPRSS2 Attachment Release

ACE2 ACE2 Plasma
S protein priming membrane
by TMPRSS2 and
membrane fusion Endocytosis and
membrane fusion

Assembly Budding

Viral RNA release Viral RNA release

RNA genome Golgi
5′ 3′
RNA replication
Translation and packaging
pp1a and
pp1ab
RdRP M E
Replicase S
Proteolysis ER
– + Transcription
and translation

Nucleus

Fig. 1 | Structure, genome and life cycle of SARS-CoV-2. a | Corona- in SARS- CoV-2 but not in SARS- CoV, which introduces a novel furin
SARS CoV 2 Transmission
Covid 19 Natural History
4
Covid 19 in Patients with CV Disease F. Mai et al. / Journal of Cardiology 76 (2020) 453–458

. 1. Chronic comorbidities amongChronic comorbidities

3335 deceased COVID-19among 3335
patients deceased
in Italy COVID-19
as of June patients
4th, 2020. in Italy as ofby
(A) Comorbidities June 4th, (B)
gender. 2020Proportion of patients with 0, 1, 2, o
st 3 comorbidities: 4.1%, 14.8%, 21.5%, and 59.7%, respectively. HTN, hypertension; DM2, diabetes mellitus type 2; IHD, ischemic heart disease; AF, atrial fibrillation; C
onic kidney disease; COPD, chronic obstructive pulmonary disease; HF, heart failure.
❖ An analysis of 44,672 con rmed COVID-19 cases from Wuhan, China indicated increased case-fatality rates in
the presence of cardiovascular diseases (10.5%) and hypertension (6.0%) (overall case-fatality rate: 2.3%)
quently reported comorbidity, followed by diabetes and
❖
failure, as well as the impact of COVID-19 emergency on the clini
hemic heart disease (Fig. 1A and B) [9,10]. Although mortality course, including the fast triage, of patients with pre-existi
as much higher in men, the mean number of pre-existing cardiovascular conditions have been also pointed out [16]. The
seases was similar between genders (median ! standard devia- fore, a reciprocal influence is evident between COVID-19 a
fi
 Covid 19 and Myocardial Injury
Clerkin et al
❖ Observed in 7–20% of patients
with COVID-19.
❖ Associated with a worse
prognosis (x5 mech. Fig

Ventilation; x11 mortality nav

exp
My
cyto

Myocardial injury can result

inte
❖ gen
dys
acu

from the associated cytokine the

storm or myocardial
dysfunction from the direct
effect of SARS CoV 2. (eg, chronic obstructive pulmonary disease or asthma enzyme inhibitors and
❖ exacerbation).26,27 Similarly, a report from the National is common in cardiova
Health Commission of China comments that a subset coronary artery disease
of patients presented with palpitations and chest pain, DM). There are conflictin
Downloaded from

not the typical fever and cough.22 Based on available increase30–32 or have min
but limited data, it appears that the incidence of ful- SARS-CoV-2 entry into
minant myocarditis and profound cardiogenic shock is ure 4); however, ACE2 a
low; however, the rate of recovery and mode of treat- acute lung injury. In a

 Covid 19 and ACS

❖ COVID-19 can trigger ACS
❖ The mechanisms: plaque
rupture, coronary spasm or
micro-thrombi owing to
systemic in ammation or
cytokine storm
❖ Despite the potential for
COVID-19 to induce ACS, the
number of reported cases of ACS
was actually lower than during
pre-COVID-19 periods.
fl

 Covid 19 and Heart Failure

❖ Observed, 24% in all patients and
49% in patients who died
❖ Exacerbation of pre-existing
conditions, or the uncovering of
subclinical cardiac dysfunction.
❖ Pulmonary oedema, which is
usually accompanied by ARDS, is
mainly regarded as non-cardiogenic
❖ Potential contribution of pulmonary
congestion by heart failure should
be taken into consideration in high
risk CVD patients.

 Covid 19 and Arrhytmia

❖ Reported in 17% of all patients,
44% of patients in the ICU
❖ Exact contribution of
COVID-19 to cardiac
arrhythmias remains uncertain
❖ Myocardial injury or other
systemic causes such as fever,
sepsis, hypoxia, electrolyte
abnormalities and medications
can induce arrhytmia

 Covid 19 and Thrombosis

❖ COVID-19 is associated with coagulation abnormalities,
which can result in thromboembolic events
❖ Elevated D dimer associated with mortality
❖ Autopsy study revealed that deep vein thrombosis was
present in 7 of 12 patients
❖ The mechanisms are unclear. One hypothesis is that the severe
in ammatory response and endothelial damage induced by
COVID-19 in combination with underlying comorbidities
might predispose patients to a hypercoagulable state.
fl

 Covid 19 and RAAS

of angiotensin II
affects ACE2 direc
shown that treatm
increase the expre
Angiotensin I Angiotensin II Angiotensin (1–7)
other preclinical s
clinical studies, lo
Protective Harmful captopril133 or the
increased plasma
ACE inhibitors ARBs levels of ACE2, re
ACE ACE2
activity. However,
Plasma Angiotensin II
membrane receptor type 1
of upregulated AC
Cytoplasm heart failure135, aor
onary artery disea
to be attributable
Downregulation of ACE2 Cardiovascular diseases or ARBs on ACE2
by SARS-CoV-2 infection and lung injury baseline expressio
periods. Second, w
Fig. 3 | ACE2 as a part of the RAAS. Angiotensin II, the main effector molecule in the is harmful or prot
renin–angiotensin–aldosterone system (RAAS), is upregulated in many pathological itors or ARBs can
conditions, for which inhibition of angiotensin II by RAAS inhibitors is a common
has been found to
therapeutic strategy.Angiotensin-converting enzyme (ACE) produces angiotensin II
from angiotensin I, whereas ACE2 inactivates angiotensin II by converting it to susceptibility to v
Potential Drug-Disease Interaction
❖ Effect of RAAS Inhibitors on Covid 1
❖ Cardiovascular effects of antiviral drugs

 Effect of RAASI on Covid 19

❖ The effect of RAAS inhibitors
of a
on ACE2 is controversial affe
sho
inc
❖ Whether potential upregulation Angiotensin I Angiotensin II Angiotensin (1–7)
oth
clin
cap
of ACE2 is harmful or Protective Harmful
inc
ACE inhibitors ARBs lev
protective is uncertai ACE ACE2
act
Plasma Angiotensin II
membrane receptor type 1
of u
hea
❖ ACC, AHA, Chinese Society of Cytoplasm
ona
to b
Cardiology, ESC and the Heart Downregulation of ACE2
by SARS-CoV-2 infection
Cardiovascular diseases
and lung injury
or A
bas
Failure Society of America have Fig. 3 | ACE2 as a part of the RAAS. Angiotensin II, the main effector molecule in the
per
is h
renin–angiotensin–aldosterone system (RAAS), is upregulated in many pathological
issued statements conditions, for which inhibition of angiotensin II by RAAS inhibitors is a common
itor
has
therapeutic strategy.Angiotensin-converting enzyme (ACE) produces angiotensin II
recommending continuation of from angiotensin I, whereas ACE2 inactivates angiotensin II by converting it to sus
in A
angiotensin (1–7). Therefore, ACE2 has a protective effect against cardiovascular
AC
RAAS antagonists disease and lung injury. In the setting of coronavirus disease 2019, downregulation
of ACE2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ful
might be involved in mediating cardiovascular damage. ARB, angiotensin II receptor the
blocker. inh

Effect of RAAS inhibitors on COVID-19 Ca

Given that ACE2 is a receptor for SARS-CoV-2, clini- At
n

 be validated in large, randomized studies150. and therapeutic administration of re

Although chloroquine and hydroxychloroquine have shown to improve pulmonary functio
a long history of clinical use for numerous conditions, viral load in a mouse model of ME
these agents are also known to induce arrhythmias41,142,151. omized, double-blind, placebo-contro
Azithromycin, which has been assessed in combination 237 patients with COVID-19 in Chin

Cardiovascular Effects of Antiviral Drugs

with hydroxychloroquine as a treatment for COVID-19,
is also known to prolong the QT interval152. In a cohort
study of 90 patients with COVID-19 who received
associated with a numerically (but not
icant) faster time to clinical improvem
placebo155. Preliminary results from a
domized, multicentre, placebo-contro
1,063 patients with COVID-19 indic
Table 2 | Adverse cardiovascular effects of potential drugs to treat COVID-19 received remdesivir had a 31% faste
Drug Mechanism of action Cardiovascular adverse than those who received placebo (med
effects ery 11 days versus 15 days)157. Of not
Inhibitors of endocytosis
preliminary findings, the FDA granted
remdesivir for COVID-19 in May 2020
Camostat mesylate Inhibition of TMPRSS2 Not common demand for treatment of hospitalize
Chloroquine and Blockade of virus entry by QT interval prolongation optimal dosing and duration of treat
hydroxychloroquine multiple mechanisms investigation. Under the emergency u
Umifenovir Inhibition of S protein–ACE2 Not common, but limited 10-day treatment regimen (200 mg on
interaction and membrane fusion clinical data 100 mg per day for 9 days) is suggested
Inhibitors of synthesis of non-structural proteins ing invasive mechanical ventilation and
membrane oxygenation, and a 5-day t
Lopinavir–ritonavir Inhibition of 3-chymotrypsin-like Atrioventricular block
protease and cytochrome P450 suggested for patients with milder sym
3A4-related drug–drug prominent cardiovascular adverse effe
interaction remdesivir have not been reported s
Inhibitors of viral RNA replication become apparent with more widespre
Favipiravir Inhibition of RdRP Not common, but limited
clinical data Lopinavir–ritonavir. Lopinavir–riton
drug combination used for the prev
Remdesivir Inhibition of RdRP Not common, but limited
clinical data
ment of HIV infection and works by i
activity159. Lopinavir is available onl
Ribavirin Inhibition of RdRP Not common with ritonavir, which functions to slo
Others of lopinavir by inhibiting cytochrome
Azithromycin Macrolide antibiotic; used in QT interval prolongation In a randomized, controlled, open-la
combination with chloroquine 199 patients with COVID-19, no ben
or hydroxychloroquine with lopinavir–ritonavir treatmen
Tocilizumab IL-6 inhibition Hypertension standard care159. Gastrointestinal ad
ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; RdRP, more frequently reported in the lo
RNA-dependent RNA polymerase; S protein, spike protein. treatment group than in the standard
Covid
R E V I E W S 19 and CVD - Bidirectional Interaction

Cardiovascular diseases COVID-19

Underlying comorbidities
Hypertension Susceptibility
Coronary heart disease
Diabetes mellitus Viral
infection
Severity
Cardiovascular complications

Acute cardiac injury No

↑ Troponin level association?

Myocarditis Direct infection?

Acute Heart failure

coronary
syndrome

Pneumonia

Arrhythmia
QT prolongation Acute respiratory
VF or VT distress syndrome
AF
Thromboembolism

Common cardiovascular drugs Potential COVID-19 drugs with

ACE inhibitors
ARBs Hydroxychloroquine
Thiazolidinediones Azithromycin
Lopinavir–ritonavir
Remdesivir?

Fig. 2 | Bidirectional interaction between cardiovascular diseases and COVID-19. Cardiovascular comorbidities such
as hypertension and coronary artery disease are associated with high mortality in patients with coronavirus disease 2019
(COVID-19). Drugs used to reduce cardiovascular risk such as angiotensin-converting enzyme (ACE) inhibitors and
Thank You