Cardiovascular aspects of

COVID-19 in children
Najib Advani
COVID-19 in children
• End of 2019: novel coronavirus was identified in Wuhan as the cause
of a cluster of pneumonia
• February 2020: WHO -> COVID-19
• 11 March: WHO -> pandemic
• In children usually mild, rarely severe ?
• 15% of lab confirmed cases (Wu et al 2020)
• April 2020 reports from UK COVID-19 condition similar to Kawasaki ->
MIS-C (Multisystem Inflammatory Syndrome in Children)
Clinical findings of COVID-19

• Symptoms of COVID-19 maybe similar in children and adults

but the frequency of symptoms varies
• Most common: fever or chills and cough
• Respiratory system is the dominant issue but cardiovascular is one of
the most significant complication
• Cardiovascular abnormalities : arrhythmias, myocarditis, pericarditis,
cardiogenic shock, heart failure, sudden death
• Cardiovascular involvement is more frequent and severe in MIS-C
MIS-C Multiple inflammatory syndrome mimicking KD (Kawa-
COVID-19)
• Cilinical features resembling Kawasaki disease
• Occurs around 4 weeks following COVID-19 infection
• Positive COVID RT PCR or serology or history of close contact with COVID19 patient
• Lower platelets
• Lower lymphocytes
• More frequent and severe myocarditis
• More frequent and severe abdominal pain
• Ferritin, D dimer, CRP increase >
• Cytokine storm, shock
• More frequent in areas where KD incidence is low (Pouletty, 2020)
Three subgroups of MIS-C (CDC, 570 patients) :

1. MIS-C without overlap with acute COVID-19 or Kawasaki

disease (KD) (35%)

Nearly all had cardiovascular and gastrointestinal involvement,

and one-half had ≥4 additional organ systems involved.

More likely to have shock, cardiac dysfunction, and markedly

elevated CRP and ferritin.

Nearly all had positive SARS-CoV-2 serology (with or without

positive PCR).
Pouletty 2020
2. MIS-C overlapping with severe acute COVID-19 (30%)

Many presented with respiratory involvement, including cough,

shortness of breath, pneumonia, and acute respiratory distress
syndrome.

Most children had positive SARS-CoV-2 PCR without seropositivity. The

mortality rate was higher compared with the other two subgroups (5.3
versus 0.5 and 0 %, respectively).

Older than those with KD-like features, more commonly have

comorbidities
3. MIS-C overlapping with KD (35%)
Younger than the other two groups (median age 6 vs 9 and 10 years,
respectively).
More common rash and mucocutaneous involvement and less commonly had
shock or myocardial dysfunction.
Approximately two-thirds of patients had positive SARS- CoV-2 serology with
negative PCR, and one-third were positive on both tests
MISC %
MISC %
MISC
Myocarditis

• An inflammatory disease of the heart characterized by inflammatory infiltrates

and myocardial injury without an ischaemic cause (Esfandiarei 2008)
• Increasing evidence that myocarditis can develop after COVID-19
• Acute myocardial injury in COVID-19 may be due to
- Direct viral myocardial injury
- Inflammatory response (cytokine storm)
- Severe hypoxemia due to pneumonia
- Side effects of therapy
Moss and Adam’s Heart
Disease in….2016
Myocarditis

• Myocardial injury affects all age from neonates to adolescent, increase morbidity
(ICU admission, inotropic support, mechanical ventilation)
• Cardiotropic viruses directly attack cardiac cells at initial phase, followed by a
secondary inflammatory response à further cardiac damage
• May also occur after mRNA COVID-19 vaccine, mild form (> 1000 reports, AAP)
• Acute lung injury and ARDS à right heart strain, RV dilation and dysfunction
while mechanical ventilation may worsen cardiac function
Myocarditis

• SARS-CoV-2 gains entry into human cells by binding its spike protein
to the membrane protein angiotensin converting enzyme 2 (ACE2)
• ACE2 can be found on the ciliated columnar epithelial cells
respiratory tract, type II pneumocytes and cardiomyocytes
• Up to 7% of COVID-19 related deaths were atributable to myocarditis
(estimate, Wu 2020)
Zareef et al 2020
Myocarditis

• Clinical presentation: from asymptomatic to fulminant fatal courses with severe

dyspnea, pulmonary edema, cardiogenic shock and death
• Viral myocarditis: fatigue, reduced physical capacity, tachycardia and tachypnea
• Typical symptoms :
- tachycardia, extrasystole
- tachypnea
- chest pain
- pallor, cool extremities
- hepatomegaly, edema
Myocarditis

- hypotension, oliguria
- lethargy, somnolence, irritable
- fever, hypothermia
• Auscultation :
- regurgitation pansystolic murmur at apex
- gallop rhythm
Myocarditis

Laboratory
• Anemia
• CRP, ESR
• Metabolic acidosis ec heart failure
• NT-proBNP, CK-MB, LDH
Myocarditis

ECG
- Sinus tachycardia
- Ventricular tachycardia
- Extrasystoles
- AV block grade I-III, BBB, prolonged QT interval
- ST depression, if there is pericardial effusion: ST elevation
- T wave flattening or inversion
- Low voltage

CXR: cardiomegaly
Myocarditis

Echocardiography
• Not reliable to distinguish acute myocarditis vs dilated cardiomyopathy
• Enlarged LV and possibly RV
• Poor ventricular function, reduced Ejection Fraction and Fraction of Shortening
• Regional wall motion abnormalities
• Mitral and or tricuspid regurgitation
• Possibly pericardial effusion
Myocarditis

CMR (Cardiac Magnetic Resonance Imaging)

• Non invasive gold standard for evaluation of ventricular volumes and function
• Hallmark of CMR: tissue characterization : edema’ hyperemia, fibrosis or scarring
of ventricular myocardium
• Major imaging advantages over echocardiography, require breath holding

EMB (Endomyocardial Biopsy)

• Gold standard for diagnosis of myocarditis
• Tissue evaluation
• Invasive (cath), shifted to a better CMR
• Not routinely used
Cardiac Arrhythmias

• Although not frequent but not uncommon in critically ill children with
COVID-19 and MISC
• Clinical presentation varies from mild symptoms :fatigue and dyspnea to
chest pain or chest tightness or excertion
• Both ventricular and atrial arrhytmias may occur
• Cause of arrythmia
- Direct injury to cardiomyocyte
- Infection of pericardium causing massive edema
- Re- entrant
- Ischaemia (rare in children)
Cardiac Arrhythmias

• - myocarditis
- electrolyte imbalance
- hypoxia
- drugs : hydroxychloroquine, azithromycin : prolong QTc interval
Management
- Supportive
- Control underlying clinical condition
- Electrolyte repletion
- Anti arrhythmic therapy
Thrombotic events

• Underlying etiology is multifactorial

• Esp in ICU admitted patients
• Mechanical ventilation -> prolongs immobilization and venous stasis
à coagulopathy
Zareef et al 2020
Covid in children with pre-existing heart disease

• Children with CHD are vulnerable to a potential clinical deterioration

if bilateral pneumonia or ARDS occurs
• Especially non-corrected complex cardiac defect, pulmonary
hypertension
• Children with complete and successful surgical correction and
without the need of medication : managed as healthy children
Pediatric Cardiologist consult or referral if :

• Elevation of NT pro BNP, Troponin

• Features of Kawasaki disease /MIS-C
• Features of myocarditis
• Cardiogenic shock
• ECG abnormalities
• Heart failure
• History of congenital or acquired heart diseases
Brugada syndrome, Long QT syndrome, PH
Conclusion

• As this new pandemic of COVID-19 continues to unfurl, a variety of cardiac

manifestations have become evident
• There is still scarce data about the role of cardiovascular involvement in children
• Even COVID-19 is less in children but clinicians should be aware of cardiac
complications such as myocarditis, arrhythmias, cardiac thrombus, which may be
fatal
• All children(previously healthy or with pre-existing heart disease) with COVID-19
requiring hospitalization should undergo a cardiac workup and close
cardiovascular monitoring to identify and treat timely life-threatening cardiac
complications
• We must be vigilant about the potential adverse effects and interactions of
existing therapies