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COVID-19 and ECMO support after neonatal congenital heart surgery: a case report

Coronavirus disease 2019 causes respiratory and systemic disease and has led to a sudden epidemic affecting people of all ages. Patients with congenital heart disease represent a high-risk population. In this article, we present a newborn who required extracorporeal membrane oxygenation support for acute respiratory failure in the early postoperative period due to exposure to severe acute respiratory syndrome coronavirus 2 after aortic arch repair and ventricular septal defect closure. To the best of our knowledge, this patient represents the first neonatal case of severe acute respiratory syndrome coronavirus 2 infection after congenital heart surgery and is the youngest patient to need extracorporeal membrane oxygenation support.


Introduction
Coronavirus disease 2019, the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first announced in an adult in China on 17 November 2019, and the World Health Organization (WHO) classified the epidemic of SARS-CoV-2 as an emergency of international concern on January 30, 2020 (1,2).
Babies with congenital heart disease (CHD) continue to be born at the rate of 1 in 100 live births during the pandemic, and approximately 25% of these are considered to have critical CHD requiring surgery or other interventions in the first year of life (3). A history of cardiac surgery may be associated with the risk of hospitalization in an intensive care unit (ICU), intubation and mechanical ventilation, particularly more severe form of the disease in newborns and children (4).
In this report, we present the management of a SARS-CoV-2 infection in newborns after successful repair of the aortic arch and ventricular septal defect (VSD) closure surgery. We performed this operation approximately 6 months after the epidemic was declared. Although extracorporeal membrane oxygenation (ECMO) support was applied twice due to respiratory failure, the patient died due to multiorgan failure. To our knowledge, this patient was the first newborn to receive ECMO support for SARS-CoV-2 infection after congenital heart surgery.
Consent was obtained from the family for the publication of this study.

Case Report
A full-term 16-day-old newborn boy weighing 3.5 kg was admitted to our department with an absence of femoral pulses and suspected coarctation of the aorta. Echocardiography (ECHO) revealed aortic arch hypoplasia with important aortic coarctation (35-40 mmHg gradient with diastolic extension), the diameter of the proximal transverse arch was 4,9 m (z-score -3,27), the diameter of the distal transverse arch was 4 mm (z score -2,62), and the diameter of the isthmus was 2,8 mm (z-score -4,29). She also had a restrictive muscular outlet ventricular septal defect with no evidence of left ventricular volume overload, a bicuspid aortic valve with mild stenosis, left aortic arch, and systemic pulmonary hypertension. There were no abnormalities in the patient's preoperative laboratory values, and she did not have a fever or cough preoperatively. The patient underwent surgery with a median sternotomy, and cardiopulmonary bypass (CPB) was performed. During arch repair, selective antegrade cerebral perfusion (ASCP) was initiated, and del Nido cardioplegia was given. The aortic arch incision was started from the descending aorta and extended to the midportion of the ascending aorta, and the aortic arch was reconstructed with the anterior patch augmentation technique using an autologous pericardial patch. The VSD was closed with the pericardial patch via right atriotomy. After weaned from ECMO after 6 days of support. Since oxygen saturation decreased and respiratory functions deteriorated 7 days after weaning from ECMO, the support was applied again. After 18 days of care, including hydroxychloroquine and favipiravir therapy, the RT-PCR test for SARS-CoV-2 was negative; however, there was no significant improvement in the patient's clinical condition. During this period, the patient's sternum being open also made the patient vulnerable to infections in addition to COVID-19. Candida parapsilosis mediastinitis occurred, and Sterotrophomonas maltophilia was found to have reproduced in blood culture obtained during the second ECMO support. Unfortunately, the patient was unable to survive and died on ECMO due to sepsis and multiorgan failure despite extended antibiotic therapy on postoperative day 28.

Discussion
It is necessary to understand that although the majority of children are not seriously affected, there may be a subset of group children for whom COVID-19 can progress rapidly, leading to respiratory function deterioration (5). Our patient is the youngest patient ever reported with a progression of SARS-CoV-2 to severe disease requiring ECMO support after cardiac surgery.
The respiratory deterioration in this case is important for understanding SARS-CoV-2 disease in newborns undergoing cardiac surgery. Our patient, who developed a rapid respiratory disorder in the early postoperative period, required ECMO support within the next 24 hours despite lung protective ventilation and high PEEP therapy.
Current evidence shows that excessive inflammation, oxidation and an extreme immune reaction play significant roles in the pathogenesis of COVID-19 (6). Direct myocardial damage via angiotensin-converting enzyme 2, viral pneumonia, acute respiratory distress syndrome (ARDS), acute lung injury, hypoxia-induced myocardial damage, CPB-related systemic inflammatory response syndrome, and pulmonary hypertension related to CHD may contribute to the inflammation course (6). Moreover, these events cause a cytokine storm and result in ARDS (6). The immunity of the patient has a major influence on COVID-19 severity, and those with low immune function, such as neonates, may be more susceptible, especially after CPB (6). According to the Extracorporeal Life Support Organization (ELSO) registry, as of 5 December 2020, ECMO support has been used in 3543 confirmed SARS-CoV-2 patients, and the in-hospital mortality is 45% (7). Thrombosis and bleeding complications are well-known risks of ECMO support. Some studies have indicated a 70% incidence of bleeding and a 37% incidence of thrombosis complications in children supported by ECMO (8). However, the experience with ECMO and the corresponding literature are limited with regard to SARS-CoV-2 (9). Kaushik et al. reported a 5-year-old male patient who underwent ECMO support with carotid artery cannulation due to SARS-CoV-2 multisystem inflammatory syndrome (9).
Unfortunately, right anterior and middle cerebral artery infarction occurred on ECMO day 6, and finally, the patient succumbed to the disease The cause of stroke in the present case may be multifactorial and could include SARS-CoV-2-associated thromboembolic complications or the carotid artery cannulation strategy. A single centre reported a 5% incidence of acute ischaemic stroke in 221 patients with SARS-CoV-2, and in addition, the incidence of ECMOassociated stroke in children is known to be between 5.6% and 7.8% (10,11).
In our case, the ARDS findings were first observed on the 3rd postoperative day, and the respiratory functions of the patient deteriorated rapidly. Given that the thromboembolic complications associated with SARS-CoV-2 could increase, venoarterial ECMO support was applied with central cannulation. Perhaps for this reason, we did not observe thromboembolic neurological complications, which may produce symptoms such as anisocoria or a decrease in NIRS values over a total of 17 days of ECMO support.
CPB circuit complications during cardiac surgery are another critical issue in COVID-19. A multicentre study showed that the rate of coagulation complications (4.1% versus 0.2%) and oxygenator gas exchange complications (2 % versus 0.2%) during adult cardiac surgery were higher in patients who tested positive for COVID 19 than negative ones (12).
ECMO support in ARDS due to COVID-19 is associated with high mortality. Henry et al. Although the rate of survival with veno-arterial ECMO was 25% (1 of 4 patients), that with veno-venous was 51% (49 of 96 patients). These studies show that ECMO may faciliatate salvage, and provides a sensible rescue strategy.

Conclusion
Because little is known about the clinical course and progression of SARS-CoV-2 infection in newborns after cardiac surgery, the duration of ECMO support, cannulation and anticoagulation strategy, and the recovery timetable for guiding treatment are unclear. Our case emphasizes the clinical course of this disease leading to mortality, as well as the difficulties in managing ARDS and ECMO in the context of SARS-CoV-2 syndrome, especially in newborns who undergo cardiac surgery.

Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008, and has been approved by the institutional committees.