key: cord-0872097-clhbtjr9
authors: Joshi, Krittika; Kaplan, Daniel; Bakar, Adnan; Jennings, John F.; Hayes, Denise A.; Mahajan, Siddharth; Misra, Nilanjana; Mitchell, Elizabeth; Sweberg, Todd M.; Taylor, Matthew D.; Capone, Christine A.
title: Cardiac dysfunction and shock in pediatric patients with COVID-19
date: 2020-06-18
journal: JACC Case Rep
DOI: 10.1016/j.jaccas.2020.05.082
sha: e4413bd3164d09568611c5161c22d1f67bae8c43
doc_id: 872097
cord_uid: clhbtjr9

Abstract The 2019 novel coronavirus (COVID-19) has been reported to cause significant morbidity in adults with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe three cases of previously healthy children presenting with shock and COVID-19 related cardiac inflammation.

The pandemic caused by the 2019 novel coronavirus (COVID-19) continues to inflict significant morbidity and mortality around the world. Most pediatric infections have been reported to be mild.

Cardiovascular complications of COVID-19 have been reported in adult literature, but pediatric data is lacking. With Northwell IRB approval we describe three previously healthy children admitted to the pediatric intensive care unit (PICU) for COVID-19 related shock and evidence of cardiac injury.

A 13-year-old previously healthy obese male presented to the emergency department (ED) with five days of fever, headache and abdominal pain, two days of diarrhea and one day of shortness of breath. On initial presentation, he was afebrile, tachycardic (119 beats per minute (bpm)), hypotensive (76/35 mmHg), and tachypneic (56 breaths per minute) with oxygen saturations of 94% on room air.

On examination he had mild crackles at lung bases, a regular heart rhythm with a gallop, hepatomegaly, and delayed capillary refill time of four seconds. A norepinephrine infusion was started for fluid refractory hypotension along with supplemental oxygen therapy via non-rebreather.

Initial laboratory results showed a leukocytosis with neutrophil predominance and bandemia, as well as significant elevation in inflammatory markers that have been associated with COVID-19 (C-Reactive Protein, procalcitonin, lactate dehydrogenase, triglycerides, ferritin, d-dimer, and fibrinogen).

The high-sensitivity troponin T (hsTnT) was elevated to 389 ng/L (<6-14 ng/L). The patient also had acute kidney injury (AKI) and mild transaminitis. He had a metabolic acidosis with an initial lactate of 6.4mmol/L. Nasopharyngeal PCR testing for COVID-19 returned positive and a respiratory viral panel was negative. An initial chest X-ray showed a left basal opacity, with no cardiomegaly.

He was admitted to the PICU, where bedside cardiac ultrasound showed moderately decreased function (fractional shortening (FS) 18%) with no pericardial effusion. Due to increasing lactate levels, he was intubated, placed on a ventilator, sedated and chemically paralyzed. Epinephrine and milrinone infusions were initiated. He was treated with tocilizumab, an interleukin-6 inhibitor, and intravenous immunoglobulin (IVIG) on PICU day 1 and transthoracic echocardiogram (TTE) showed improvement in left ventricular function with a FS of 32% and left ventricular ejection fraction (LVEF) of 49%.

Remdesivir, an anti-viral that inhibits COVID-19 replication, and IV methylprednisolone were started on PICU day 2.

His course was complicated by brief episodes of atrial tachycardia. By PICU day 4, he was off inotropic infusions and extubated to non-invasive ventilation, and by PICU day 5, he was weaned to room air with downtrending inflammatory markers and troponin levels. A repeat echocardiogram on PICU day 5 showed improved function (FS 45% and LVEF 65%) and he was discharged on PICU day 11 after completing his remdesivir course.

A 6-year-old male with history of mild persistent asthma presented to the ED with six days of fever, pharyngitis, myalgia, and abdominal pain, and one day of diarrhea and shortness of breath. On initial presentation, he was afebrile, tachycardic (130 bpm), hypotensive (71/34 mmHg), and tachypneic (40 breaths per minute) with oxygen saturations of 97% on room air. On examination, he had good air entry bilaterally, with a III/VI systolic murmur appreciated at the left upper sternal border.

A norepinephrine infusion was started for fluid refractory hypotension.

Initial laboratory results showed a leukocytosis with neutrophil predominance and bandemia as well as significant elevation in inflammatory markers that have been associated with COVID-19. He had a normal lactate level, but was noted to have AKI as well as a mild transaminitis. His hsTnT was elevated to 116 ng/L (<6-14 ng/L). A rapid test for COVID-19 returned positive and respiratory viral PCR panel was negative.

He was admitted to the PICU on room air. Contemporaneous TTE showed low-normal LVEF of 56%, FS 29%, mild mitral regurgitation and holodiastolic reversal of flow in the descending aorta.

Epinephrine infusion was added at this time due to continued hypotension. He was treated with a five-day course of hydroxychloroquine, as well as IV tocilizumab. By 36 hours of admission all inotropic support had been weaned off and his AKI had resolved. He was discharged on PICU day 3.

His inflammatory markers trended down at discharge and his ECHO showed LVEF of 57%, FS 35%.

A 13-year-old female with a known small mid-muscular ventricular septal defect presented to the ED with nine days of intermittent fever, headache, and cough and five days of abdominal pain and diarrhea. On initial presentation she was febrile (39.4°C), tachycardic (119 bpm), normotensive (117/68 mmHg), and mildly tachypneic (18 breaths per minute) with oxygen saturations of 100% on room air. On examination, she was awake, alert, had good air entry with diminished breath sounds at the bases, normal heart sounds, mild epigastric abdominal tenderness, and normal peripheral perfusion with brisk capillary refill. For tachycardia, she received a 10 cc/kg fluid bolus with minimal improvement in heart rate. Initial laboratory results showed an elevated white blood cell count with a left shift and bandemia. She also had a significant elevation in inflammatory markers that have been associated with COVID-19. The patient had normal renal function. Her hsTnT was 43 ng/L (<6-14 ng/L). Nasopharyngeal PCR testing for COVID-19 returned positive and a respiratory viral panel was negative.

She was admitted to the pediatric ward where she received additional fluid boluses for worsening tachycardia (134 bpm) and hypotension (85/45 mmHg). Given the abnormal hsTnT and persistent tachycardia, a TTE was performed which showed moderately decreased left ventricular systolic function with LVEF of 40%, FS of 21% with mild MR, holodiastolic flow reversal in the descending aorta, and a small pericardial effusion. She was transferred to the PICU, started on a milrinone infusion, and continued treatment with hydroxychloroquine. By PICU day 2, her inflammatory markers and hsTnT had improved. A repeat echocardiogram on PICU day 3 showed improved LVEF to 54%, FS of 28%, and milrinone was discontinued. She was discharged on PICU day 4.

Studies suggest a milder clinical course in children, with very few requiring intensive care (1).

There is currently limited data regarding cardiovascular and myocardial involvement in pediatric patients with COVID-19 although anecdotal reports of a shock-like presentation with features of Kawasaki disease with myocarditis exist (2). We present three pediatric patients admitted to intensive care with shock and evidence of cardiac injury ( Table 1 ).

The mechanism for COVID-19 related cardiac injury and shock is unclear. One proposed theory is cytokine mediated myocardial inflammation (3) . Cytokine release appears to be a major causative Currently there are no established treatment recommendations for cardiac injury and inflammation related to COVID-19 infection. Steroids and IVIG have been described as treatments in adult COVID-19 myocarditis with unclear benefit (6) . Both IVIG and steroids were utilized to treat Patient 1, our patient with the most severe clinical presentation. Tocilizumab, an interleukin-6 inhibitor was used in Patients 1 and 2 per an institutional guideline (7) . Antiviral therapies were also used.

These cases demonstrate that COVID-19 infection can cause severe illness in previously healthy children. Shock and cardiac dysfunction can be a significant component of illness independent of lung disease. Further studies are ultimately needed to determine the optimal treatment for these patients.

Long-term follow-up is important to understand the pathophysiology and long-term prognosis of children with cardiac injury resulting from COVID-19. As this case series goes to press, our hospital has admitted more than 100 children with COVID-19 related illnesses, including more than 30 children with various cardiac manifestations of COVID-19. Of these children admitted with cardiac manifestations, a large proportion have required intensive care. We anticipate addressing this growing patient population in more detail in future manuscripts, and hope that this case series will raise awareness of a particular subset of cardiac dysfunction and shock associated with COVID-19.

To recognize that pediatric COVID-19 may present with evidence of shock and cardiac dysfunction independent of lung disease.

To review the different mechanisms of cardiac injury in pediatric patients with COVID-19. 

SARS-CoV-2 Infection in Children

COVID-19 and the Heart

SARS-CoV-2 and viral sepsis: observations and hypotheses. The Lancet

Myocardial localization of coronavirus in COVID-19 cardiogenic shock: COVID-19 does not spare the heart

Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)

The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality