Covid-19 in the End an Endothelial Disease

Thomas F. Lüscher, MD, FRCP Professor of Cardiology, Imperial College and Director of Research, Education

and Development, Royal Brompton and Harefield Hospital, London, UK

Chairman, Center for Molecular Cardiology, University Zurich, Switzerland

Covid-19 – in the End an Endothelial Disease

Biomarkers & Personalized

Medicine in Cardiology

2021

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

On December 30th Dr. Li Wenliang warns of

a new Corona Virus causing Pneumonia

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

Lung CT Presentation of Covid-19

Typical Features: Multiple bilateral lobular and subsegmental areas of

groundglass opacity or consolidationa, crazy-paving pattern, air bronchograms,

reverse halo/perilobular pattern.

Atypical features: interlobular or septal thickening (smooth or irregular),

thickening of the adjacent pleura, subpleural involvement, pleural effu-sion,

pericardial effusion, bronchiectasis, cavitation, pneumothorax,

lymphadenopathy, round cystic changes.

Lin

Yan

g Eu

r. H

eart

J. 2

02

0

Endothelitis with Covid-19 at Autopsy

Varg

a et

al.

Lanc

et A

pril

17, 2

020

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

Interleukin-6 and serum Amyloid A levels at the site of coronary occlusion and in the

peripheral blood

Interleukin-1a Interleukin-1b

Inte

rleu

kin-

1 Inc

reas

e (%

)

Inte

rleu

kin-

6 (U

/ml)

Baseline Hypoxia

Reperfusion

Y. A

la e

t al.

Agen

ts &

Act

ion

1992

;37:

134-

138

Interleukin-6 and serum Amyloid A levels at the site of coronary occlusion and in the

peripheral blood

Thrombus and Cellular Inflammation at the Site of Plaque Rupture

Immunohistochemistry: CD68 Positive Macrophages (A), IL-6 Positive Staining (B)

Maier, Altwegg et al. Circulation 2005

TF VIIa

Prothrombin Thrombin

Fibrinogen Fibrin

VIIIa

IXa

XII XIIa

XI XIa

IX IXa

Xa X

Ste 2011

vWF

TXA2

ADP

GpIIb/IIIa

PAR-1

Thrombusbildung und Protektion

Aspirin?

Clopidogrel?

Prasugrel?

Ticagrelor?

TNF

(10 ng/mL,

6x10-10 mol/L)

NaCl

(5x10-2 mol/L)

LiCl

(5x10-2 mol/L)

- + + +

- - + -

- - - +

Tissue factor

Tumor Necrosis Factor induces Tissue Factor

in Human Endothelial Cells

47KDa

Western blotting

Eto and Lüscher Circulation 2005

H1

TNF-R

TLR-4 Il-1-R

Histamine

TNF-α

Il-1β

LPS

PAR

Thrombin

KDR

VEGF

CD40

CD40-L

Serotonin

5-HT2a

Inflammation begets Coagulation

TF-bearing

microparticles

asTF

TF pool

Cytoplasm Nucleus

Induction of Tissue Factor Expression

J. Steffel, T.F. Lüscher, F. C. Tanner. Circulation 2005

Eto et al. 2002

Prolonged Incubation with Thrombin

inhbits Endothelim-depedent Relaxations

eNOS

ECE-1

Thrombin (4U/ml, 24h) - + + -

C3 Exoenzyme - - + +

eNOS

ECE-1

Thrombin Regulates Endothelial NOS and ECE-1Expression:

Role of RhoA/ROCK Pathway

Eto et al. Circ. Res. 2001

Thrombin (4U/ml, 24h) - + + -

Y-27632 - - + +

C e l l M e m b r a n e

C y t o s o l

T h r o m b i n

R h o - G D P R h o - G T P

I n a c t i v e A c t i v e

R h o - K i n a s e

eNOS Expression

Tissue Factor

Y - 2 7 6 3 2

Thrombin and Rho/Rho-Kinase Pathway

Antivirals Cytokine inhibitors (IL-6, IL-1)

Corticosteroids

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

Myocardial Injury

• Myocarditis

• Heart Failure

• Hypoxia

• VTE or PE

Myocardial Ischemia

• NSTEMI

• STEMI

• Takotsubo

Cardiac Troponin and Outcome of Acute Covid-19 Infection

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

Admission for Myocardial Infarction During Covid-19 Pandemic in Italy Number of Patients admitted in the 12-19 March Week

Vascular Effects of Angiotensin 1-7

1.Un (un-)expected Pandemic

2.A Lung Disease

3.Only a Lung Disease?

4.Covid-19 is in the end an Endothelial Disease

5.Covid-19 and Cardiac Injury and Disease

6.CV Collateral Damage of Covid-10

7.Post Covid Disease

Many thanks for your attention!