key: cord-0782493-jgr0iuir authors: Simpson, Megan; Collins, Catherine; Nash, Dustin B.; Panesar, Laurie E.; Oster, Matthew E. title: COVID-19 Infection in Children with Pre-existing Heart Disease date: 2020-07-27 journal: J Pediatr DOI: 10.1016/j.jpeds.2020.07.069 sha: 892360bd50a26bb5b914d23ca905794894a339dd doc_id: 782493 cord_uid: jgr0iuir nan mortality [1] . We share our early multicenter experience with children admitted from March 27 th , 2020 to April 27 th , 2020 with a history of congenital heart disease who were hospitalized with COVID-19 as diagnosed by SARS-CoV-2 polymerase chain reaction (PCR). The pertinent details for each case are summarized in the Table. Case 1 An ex-35-week, 3-month-old male with trisomy 21, and unrepaired complete atrioventricular canal (CAVC) defect with marginally compensated heart failure on maximal medical therapy of furosemide, chlorothiazide, and digoxin presented with tachycardia, tachypnea and hypoxemia in the setting of two days of fever and irritability. His chest radiograph (CXR) was concerning for bilateral scattered atelectasis and hyperinflation. Venous blood gas demonstrated hypercarbia of 51 mmHg. He was SARS-CoV-2 positive by PCR on admission. He had no known sick contacts. He was given broad spectrum antibiotics for 24 hours. He required up to 8L high-flow nasal cannula of respiratory support, and weaned off respiratory support on hospital day 4. He was discharged on hospital day 6. He remained stable as an outpatient until his planned readmission 4 weeks after discharge for complete surgical repair. One week after his surgical repair he had hypercarbic respiratory failure of unclear etiology. Post-operative catheterization was notable for a mildly elevated pulmonary vascular resistance with a pulmonary blood flow to systemic blood flow ratio of 1.7:1 in the setting of a residual VSD. He subsequently had his VSD closed and was discharged home on overnight oxygen and sildenafil. At 95 days after initial discharge he remained stable as an outpatient. A 3-month-old female with trisomy 21 and unrepaired CAVC defect with compensated heart failure maintained on furosemide, spironolactone, carvedilol presented with respiratory distress and hypoxemia. Her CXR was concerning for pneumonia and pulmonary edema (Figure1; available at www.jpeds.com). Echocardiogram at baseline showed mild to moderate common AV valve regurgitation with mildly dilated and hypertrophied right ventricle. Echocardiogram after admission showed severe left atrioventricular valve regurgitation, otherwise stable. She had an elevated brain natriuretic peptide (BNP), and C-reactive protein (CRP). On admission a standard respiratory viral panel was negative. SARS-CoV-2 PCR testing sent on hospital day 13 using the respiratory viral sample obtained on admission was positive. She had no known sick contacts. She was diagnosed with worsening heart failure with acute respiratory failure and required aggressive diuresis, milrinone and mechanical ventilation. A dexmedetomidine infusion was started due to persistent narrow-complex tachycardia to the 200's to improve diastolic filling. After a 10 day course of Remdesivir she was persistently SARS-CoV-2 positive by PCR, and received 5 convalescent plasma infusions with subsequent negative SARS-CoV-2 PCR testing. Her hospital course was complicated by staphylococcal scalded skin syndrome, acute kidney injury (AKI) secondary to heart failure, and medical necrotizing enterocolitis. She was extubated on hospital day 33 to non-invasive positive pressure ventilation. She remained inpatient, on milrinone until surgical repair on hospital day 54. On hospital day 111 she was off respiratory support, with compensated heart failure on oral therapy. A 6-month-old male with a history of anomalous left coronary artery from the pulmonary artery surgically repaired at 2-months-of-age with moderate post-operative supravalvar aortic stenosis, and severe left ventricular dysfunction with compensated heart failure maintained on enalapril, digoxin, carvedilol, furosemide, and aspirin presented with hypoxemia in the setting of two days of fever, decreased oral intake, and increased work of breathing. His CXR showed cardiomegaly, ground-glass opacity consistent with pneumonia, and He required intubation and substantial ventilatory support due to acute respiratory distress syndrome. During intubation he developed bradycardia and ventricular tachycardia requiring epinephrine and cardiopulmonary resuscitation. Epinephrine and milrinone infusions were started for decompensated heart failure. Inhaled nitric oxide was added for pulmonary hypertension with rapid improvement in oxygenation. He received tocilizumab and remdesivir. During hospital day 5-14 his inflammatory markers improved, and he weaned off epinephrine. Milrinone was continued until after extubation and initiation of enalapril. On hospital day 20 he was successfully extubated. He was discharged home on hospital day 35 on an enteral heart failure regimen, Lovenox, and full oral feeds. At 58 days after discharge he remained stable as an outpatient. An ex-36-week 6-month-old male with a history of left ventricular non-compaction and dilated cardiomyopathy with depressed biventricular function with compensated heart failure maintained on captopril, carvedilol, digoxin, aspirin, furosemide, and spironolactone presented with emesis and diarrhea in the setting of one day of fever, increased work of breathing, cough, nasal congestion, and decreased oral intake. He required intravenous fluid resuscitation during admission. Home captopril and furosemide were held initially due to hypovolemia. He received empiric intravenous antibiotics for 48 hours. He was discharged home on hospital day 4 no longer on furosemide, but otherwise on his home regimen. He was re-admitted two weeks later with fever, diarrhea, rash and tachypnea requiring intravenous fluid resuscitation. His SARS-CoV-2 PCR remained positive. He was discharged home after two days; 81 days after his initial hospital discharge he was stable as an outpatient. A 9 month-old-male with a history of trisomy 21, obstructive sleep apnea, hypothyroidism, tetralogy of Fallot, right dominant CAVC with parachute left AV valve, and pulmonary hypertension who had surgical repair at 3-months-of-age with placement of Melody Valve in the left atrioventricular valve position and compensated heart failure on furosemide, sildenafil, and oxygen at night presented with intermittent cough, increased work of breathing and hypoxemia in the setting of two days of fever. His CXR was concerning for pulmonary edema and pneumonia (Figure 2 ; available at www.jpeds.com). He had an elevated CRP. N-terminal-pro-hormone BNP was elevated, however improved from baseline. ST-segment-changes were noted on telemetry, with reassuring electrocardiogram and serum troponin. He was SARS-CoV-2 positive by PCR on admission with a known sick contact in his mother who had symptoms of COVID-19 infection prior to his admission. She did not receive SARS-CoV-2 testing. After admission he required escalation to 10L high-flow nasal cannula of respiratory support. He was started on empiric intravenous antibiotics for 48 hours, and intravenous diuretics. Over the next week he was able to wean on respiratory support and diuretics until he was on his home regimen. He was discharged home on hospital day 8. He was readmitted one month after discharge for hypoxemia secondary to fluid overload. He improved with intravenous diuresis, and required a maximum of 2L nasal cannula. His SARS-CoV-2 PCR remained positive. He was discharged home on hospital day 6 on his home regimen. The patient died 2.5 months after his initial hospital discharge. His cause of death was thought to be related to his residual cardiac disease. An obese 18-year-old female with metabolic syndrome, type II diabetes, chronic hypertension and a cardiac history of hypertrophic cardiomyopathy maintained on metoprolol presented with fever and respiratory distress. She remained on mechanical ventilation, vasoactive support, anti-arrhythmic agents and on renal replacement therapy for AKI until she had recurrence of ventricular tachycardia and died on hospital day 31. An obese 19-year-old female with type II diabetes mellitus, stage II chronic kidney disease, mild intermittent asthma and a cardiac history of double inlet left ventricle with Fontan palliation followed by cardiac transplant 8 years ago presented with five days of diarrhea, decreased appetite with poor oral intake for four days, and loss of taste for three days. She was maintained on atorvastatin, lisinopril, cellcept, tacrolimus prior to presentation. Creatinine was elevated concerning for AKI. NT-proBNP was elevated. She was SARS- She required intravenous fluid resuscitation for hypovolemia. Her mycophenolate mofetil was halved while she was actively infected with COVID-19; she remained on tacrolimus. Her creatinine improved however did not return to baseline. She was discharged on hospital day 9 on her home regimen with the exception of lisinopril which was held due to her AKI. At 72 days after hospital discharge she was stable as an outpatient. In this series of hospitalized patients with pre-existing cardiac conditions, we observed that new or worsening heart failure was common. Each of these cases is believed to represent acute COVID-19 infection, and not Multisystem Inflammatory Syndrome in Children [3] . Four of the 7 patients presented with acute congestive heart failure: one with de novo acute heart failure (case 6), and three with acutely decompensated chronic heart failure (case 2, case 3, case 5). In one case (case 2), the decompensated heart failure was initially believed to be progression of the child's underlying disease, thus delaying diagnosis. The cases with the most severely decompensated cardiac function demonstrated cardiogenic shock requiring inotropes (case 2, case 3, case 6), and in one case venoarterial ECMO (case 6). In addition to heart failure, new cardiac arrhythmias and evidence of myocardial inflammation were noted. Four of the seven patients developed cardiac arrhythmias or new electrocardiogram abnormalities with no prior history of arrhythmias (case 2, case 3, case 6, case 7). Three of these also had the longest clinical courses (case 2, case 3, case 6). Two also had evidence of acute myocardial inflammation vs. acute myocardial injury with elevated troponins (case 3, case 6), one of whom had accompanying ST-segment changes on electrocardiogram concerning for acute coronary syndrome vs. myocarditis with arrhythmia eventually leading to death (case 6). Consistent with prior reports of severe acute COVID-19 in children, the majority of our cases were less than one year of age [2, 4] . Three of the 5 patients had CAVC defect and trisomy 21 (case 1, case 2, case 5). Currently there are no pharmacotherapies for COVID-19 or its associated cardiovascular disease that have high-quality data supporting clinical efficacy. Although awaiting the results of several clinical trials currently underway, intravenous immunoglobulin, convalescent plasma, hydroxyurea, remdesivir, and tocilizumab are currently being used in a case-by-case basis in both adults and children. Three of our patients received 2 or more of these therapies with varying results. COVID-19 was community acquired for all 7 of our patients. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units Center for Disease Control and Prevention Health Alert Network. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19) [Internet]. United States: CDCHAN Center for Disease Control and Prevention Morbidity and Mortality Weekly Report Coronavirus Disease 2019 in Children -United States United States: CDCMMWR