Heart Disease Associated with COVID-19 in Children

: Introduction: Heart disease in children associated with COVID-19 is described during acute infection or in the context of the Multisystem inflammatory syndrome in children (MIS-C), and in patients with and without previous heart disease. It has different manifestations: asymptomatic, with alterations in complementary tests (elevated troponins, arrhythmias, imaging changes), up to severe forms: myocardial infarction, heart failure, cardiogenic shock, sudden death. We report a schoolgirl who had severe COVID-19, with cardiac, digestive, and respiratory manifestations. Clinical case: 10-year-old girl, carrier of disabling chronic disease. In the course of severe COVID-19, she added shock and respiratory failure, elevated inflammatory markers, increased troponins, and dilated cardiac cavities, with functional compromise of the left ventricle. She received non-invasive ventilatory assistance, antibiotics, and systemic corticosteroids. Cardiac manifestations reversed, with a decrease in inflammatory parameters. Discussion: The heart is frequently affected in COVID-19. Cardiac injury may be due to: viral replication, systemic inflammatory response, respiratory failure, or myocardial stress. The severity will depend on the extent of the damage and the inflammatory response. Cardiac involvement is more common in those who meet MIS-C criteria. Most recover cardiac function. The case report contributes to the knowledge of SARS-CoV-2 infection, and the severe forms of presentation with cardiac involvement in children highlight the need to advance in primary prevention by vaccines in the pediatric population. on day 14 was negative. Hemodynamics remained stable. Electrocardiogram: sinus tachycardia. Echocardiogram: moderate cardiomegaly, LVEF 48%, mild pericardial effusion Treatment: angiotensin converting enzyme inhibitors and low molecular weight heparin (isocoagulation). She did not receive vasoactive drugs. Troponin decreased to 206.7 ng/L on day 17.


Introduction
In Uruguay, the SARS-CoV-2 virus infection reached a maximum incidence of 149.5 cases/100,000 inhabitants. Children under 15 years of age have a cumulative incidence of 5908.6/100,000 [1].
COVID-19 in children usually has an asymptomatic course, or with mild symptoms. Among the severe forms, the Multisystem inflammatory syndrome in children (MIS-C) stands out [2,3].
We report a school age girl, who carries a disabling chronic disease, that suffers a severe COVID-19, with cardiac, respiratory and digestive manifestations.

Clinical Case
A 10-year-old girl, hospitalized in January 2021, from a region with a Harvard index of 38.03. Carrier of merosin deficient congenital muscular dystrophy (Gene LAMA2): joint deformity and retractions, severe scoliosis, swallowing disorder and chronic malnutrition. Without cardiac compromise. She also has chronic lung disease that requires non-invasive ventilatory support (NIV) during sleep but not receiving it.
She was diagnosed with SARS-CoV-2 infection, by a household contact, with mild symptoms: scant cough, without fever. Confirmed by Real Time Polymerase Chain Reaction (RT-PCR). During day 10 of illness added vomiting and severe abdominal pain. No diarrhea, fever, or respiratory symptoms. Malaise and decrease in diuresis.
Initial hemodynamic stabilization was achieved with positioning, oxygen therapy, and fluid intake. A dose of antibiotics was indicated.
She was admitted to the intensive care unit (ICU). NIV with double-level positive pressure was required for respiratory improvement. Troponins increased to 662.6 ng / L. RT-PCR for SARS-CoV-2 on day 14 was negative. Hemodynamics remained stable. Electrocardiogram: sinus tachycardia. Echocardiogram: moderate cardiomegaly, LVEF 48%, mild pericardial effusion Treatment: angiotensin converting enzyme inhibitors and low molecular weight heparin (isocoagulation). She did not receive vasoactive drugs. Troponin decreased to 206.7 ng/L on day 17.
Remained in the ICU for 72 hours, and discharged from hospital after 12 days, on the 21st day of illness, with decreased inflammatory markers, negative troponins, and normal echocardiogram. Vasodilators and anticoagulants were suspended, acetylsalicylic acid was indicated. SARS-CoV-2 antibodies were positive 29 days after diagnosis.

Discussion
The clinical case presented was a COVID-19 disease with myocarditis, pericarditis and pneumonia in a girl with underline disease (merosin deficient congenital muscular dystrophy) with chronic lung disease.
The pediatric population represents 2% to 5% of confirmed cases of SARS-CoV-2 infection [4]. In reports of the Centers for Disease Control and Prevention of the United States, in February 2021, 1.9% of the cases were children between 0 and 4 years old, and 9.4% between 5 and 17 years [8].
The risk in children with comorbidities of suffering severe COVID-19 is not well established [9]. It's described that carriers of cardiac, respiratory, or immunological disorder, are more susceptible to develop severe disease [5].
Cardiac involvement is reported in the course of SARS-CoV-2 infection, in acute phase or with MIS-C [4,10]. Up to 34% of the children admitted to the ICU in Spain had cardiac involvement, the majority with MIS-C criteria [4].
This communication presents a patient with severe chronic lung disease, carrier of myopathy, without heart disease, who had a severe form of COVID-19. She presented with shock, elevated inflammatory markers and cardiac involvement, between days 10 and 14 of infection, in apyrexial, without criteria for MIS-C. Elevated troponins, moderate cardiomegaly, decreased LVEF, and the presence of pericardial effusion elucidate the cardiac injury.
This clinical presentation of COVID-19 with rapid resolution of the cardiac and lung affectation in children with underlying diseases is reported. The girl didn't meet criteria for MIS-C.
The heart is the second target organ for SARS-CoV-2 virus, after the lungs. Cardiac involvement without MIS-C criteria is described. It can manifest with markers of myocardial injury or with structural and functional damage [11]. It's proposed that cardiac injury can be produced by: viral replication in the myocardium, secondary to systemic inflammatory response, or respiratory failure and myocardial stress in the setting of severe disease [6,10,11]. The severity will depend on the extent of damage and levels of inflammatory mediators. In published reviews, improvement in LVEF is observed together with a decrease in troponins and interleukin-6 [11].
In the review published in February 2021 by Feldstein et al, clinical characteristics and outcome of patients under 21 years of age with severe COVID-19 and MIS-C are compared. Cardiac involvement was observed in both groups, more frequently in those who met MIS-C criteria [12]. In patients with severe COVID, depress LVEF was observed in 5.4% of patients that underwent echocardiography evaluation [12].
Our patient presented non-severe and reversible myocardial dysfunction, with recovery of LVEF and troponin values, associated with a decrease in inflammatory markers.
Patients with severe SARS-CoV-2 infection present immune dysregulation, with an imbalance between host response and virus evasion mechanisms [13]. The kinetics of the immune response and the triggering of pro-inflammatory pathways lead to a phenomenon of "hyperinflammation" or "cytokine storm" [13].
Early diagnosis and prompt initiation of anti-inflammatory treatment is crucial for the success, speed, and recovery of cardiac involvement [4].
This patient received treatment with hydrocortisone and methylprednisolone, which could have influenced her evolution. Due to their anti-inflammatory action, corticosteroids are recognized as adjuvants for the cytokine storm associated with COVID-19. Observational studies show inconclusive results and moderate clinical benefit [13].
Regarding its genetic disease, the variety of muscular dystrophy that it presents can associate cardiac anomalies, but when it is installed, it is irreversible [14].

Conclusions
This patient presented a severe COVID-19, with reversible cardiac involvement, with LVEF recovery and normalization of injury markers after 21 days of confirmed infection.
Understanding the role of inflammation in the pathogenesis of this entity allows the early recognition of symptoms and the opportunity of treatment, which conditions the patient's outcome.
Case reports contribute to the knowledge of severe SARS-CoV-2 infection, and cardiac involvement in children. This highlights the need to advance in primary prevention by vaccines in the pediatric population.