As the pandemic continues to evolve, more cases of COVID-19 in pediatric patients are being detected. A 12-year-old boy with HbSC disease alpha-thalassemia trait presented to a pediatric emergency room with fever and weakness. His vital signs were notable for fever, tachypnea, and tachycardia. His physical exam was concerning for increased work of breathing. He tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR although his hemoglobin level remained near his baseline. His chest radiograph showed a retrocardiac opacity concerning for evolving acute chest syndrome. He decompensated quickly requiring invasive mechanical ventilation and exchange transfusion. He received hydroxychloroquine, broad-spectrum antibiotics, and enoxaparin for DVT prophylaxis. Despite showing clinical signs of improvement, he became acutely hypoxemic and suffered a cardiac arrest. We believe this to be an unusual case of a pediatric patient with HbSC disease and COVID-19. We outline clearly the course of illness and treatments trialed, which can prove beneficial to providers facing similar challenges as this virus continues to strike areas around the world. Although children have significantly better outcomes than adults, providers must remain vigilant while treating any patient with a hemoglobinopathy in the setting of severe COVID-19.
Children infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generally fare better than adults but may suffer critical illness [
A 12-year-old male with HbSC disease alpha-thalassemia trait, with mild sickle-related complications including no history of splenectomy, presented to a tertiary hospital in the spring of 2020 with acute respiratory failure in the setting of a positive PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was evaluated in the emergency department (ED) one day prior to hospital admission for nausea, subjective fever, and left lower quadrant tenderness. However, he was afebrile, well appearing, and had a hemoglobin level near his baseline (10.6 g/dL). Based on this, he did not meet hospital testing criteria for SARS-CoV-2 at that time so he was discharged home. The following day, he developed fever, weakness, and pallor at which time he was referred back to the ED. He was noted to be febrile (39.2°C), tachycardic (116 beats/minute), and tachypneic (36 breaths/minute) with an oxygen saturation of 97%. His physical exam was notable for labored breathing. The patient tested positive for SARS-CoV-2 by nasopharyngeal PCR testing. The initial chest radiograph was notable for a retrocardiac opacity, and he received ceftriaxone and doxycycline (azithromycin was on shortage) for empiric management of acute chest syndrome (ACS). The patient required rapid escalation of respiratory support with noninvasive bilevel positive airway pressure before transfer to the PICU.
On arrival to the PICU, the patient was in respiratory extremis and emergently intubated by anesthesia using COVID-19 airway precautions: rapid sequence intubation, negative pressure room, N-95 mask, gown, gloves, eye protection, bouffant, and video laryngoscopy. Despite lack of data, hydroxychloroquine was initiated (600 mg enteral every 12 hours) following confirmation of a normal QTc, and he was started on deep vein thrombosis prophylaxis with enoxaparin (30 mg subcutaneous every 12 hours).
The patient met criteria for severe acute chest syndrome [
The patient met criteria for mild pediatric acute respiratory distress syndrome (pARDS) with a positive SARS-CoV-2 test, bilateral infiltrates consistent with acute pulmonary disease, and a PaO2 to FiO2 (
Chest radiograph one day prior (a) and at day of arrest (b).
Routine labs obtained the morning of the arrest are shown in Table
Notable lab values. Peak (or nadir) noted as clinically relevant and values on day of arrest.
Lab | Peak (nadir) | Day of arrest | Reference (units) |
---|---|---|---|
Procalcitonin (on presentation, not repeated) | 0.31 | — | ≤0.08 (ng/mL) |
C-reactive protein | 127 | — | 0.00-10.00 (mg/L) |
Ferritin (on presentation, not repeated) | 250 | — | 30.0-400.0 (ng/mL) |
D-dimer | >20.00 | 18.21 | ≤0.80 ( |
Fibrinogen | 458 | 458 | 191–430 (mg/dL) |
International normalization ratio | 1.7 | 1.3 | 0.9–1.1 |
Partial thromboplastin time | 52.8 | 44.8 | 23.9–34.7 (seconds) |
White blood cell count | 26.9 | 23.54 | 3.84–9.84 (×10-3/ |
Band | 24% | 0% | 0–0 (%) |
Lymphocytes | 6% (nadir) | 11.1% | 16.4-52.7 (%) |
Neutrophils | 77% | 76.4% | 32.5–74.5 (%) |
Monocytes | 3% (nadir) | 11.1% | 4.4–12.3 (%) |
Eosinophils | 0.1% | 0% | 0.0–4.0 (%) |
Basophils | 1% | 0.1 | 0.0–0.7 (%) |
Hemoglobin | 8 (nadir) | 8 | (g/dL) |
Platelets | 36 (nadir) | 126 | 175–332 (×103/ |
Partial thromboplastin time | 52.8 | 44.8 | 23.9–34.7 seconds |
Creatinine (baseline 0.66) | 1.6 | 1.33 | 0.60-1.00 mg/dL |
Interleukin-18 | 757 | — | 89-540 pg/mL |
CXCL9 | 136 | — | ≤121 pg/mL |
Interleukin-6 | 78.7 | — | ≤5 pg/mL |
Interleukin-10 | 59 | — | ≤18 pg/mL |
Creatine kinase | 950 | — | 64.0-499.0 U/L |
Troponin-T | 6 | — | ≤22 ng/L |
In the early afternoon he became hypoxemic in the setting of an acute drop in tidal volumes delivered by the ventilator. Despite manual ventilation with evidence of good chest rise and 100% oxygen administration, the patient’s oxygen saturations remained in the 70% range. Repeated inline suctioning and increased ventilator settings did not resolve the hypoxemia, and the patient became increasingly bradycardic; chest compressions were initiated once less than 60 beats per minute. Per local CPR protocol for COVID-19 patients, the patient remained on the ventilator while receiving compressions to avoid aerosolization of respiratory secretions. Despite chest compressions, bilateral needle thoracostomy (no rush of air noted), and multiple doses of epinephrine administration, the patient did not regain pulses. The family requested no autopsy. During the early stages of the pandemic, limited invasive postmortem investigations were done. No postmortem imaging was performed.
Early case series of adult patients with sickle cell disease and COVID-19 report mild disease, and centers with significant sickle cell populations report minimal severe pediatric presentations supporting the hypothesis that sickle cell disease is not generally considered a risk factor for severe COVID-19 [
Alpha-thalassemia trait appears to have a protective effect in the setting of HbSS disease with regard to red blood cell metrics [
This patient died of acute hypoxemic respiratory failure, but without an autopsy, it is difficult to determine the exact mechanism. Let us hypothesize that our patient died from refractory hypoxemia secondary to severe V/Q mismatch in the setting of severe COVID-19 inflammatory response leading to purulent, thick secretions of the alveoli and airway. Copious secretions may have occluded the endotracheal tube or prevented adequate gas exchange at the alveolar level despite increased ventilator settings. Pulmonary emboli are less likely given the patient was receiving prophylactic anticoagulation. Fat emboli are a possible source given his underling hematological diagnosis but would require autopsy for confirmation. Tension pneumothorax is unlikely given the lack of tachycardia, hypotension, or evacuation of air with needle chest decompression. Early in the pandemic, our institution was not offering high-frequency oscillatory ventilation or extracorporeal membrane oxygenation in SARS-CoV-2-positive pediatric patients although it is unclear if either procedure would have altered the course for this child.
A dedicated approach to the management of children at risk for severe ACSin the setting of COVID-19 is necessary. Guideline-based care includes remdesivir for patients not mechanically ventilated and a short course of steroids for severe or critical COVID-19 [
Although children have significantly better outcomes than adults with COVID-19, pediatric intensivists must remain vigilant. This report of a pediatric death in a patient with HbSC and alpha-thalassemia trait with severe COVID-19 following an exchange transfusion underscores the risk of pediatric death when treating any patient with a hemoglobinopathy during the SARS-CoV-2 pandemic [
The essential data are provided in the manuscript. There is no additional data or material.
No written consent has been obtained from the patient or family as there is no patient identifiable data included in this case report.
The authors have no relevant conflicts of interest to disclose.
Joshua E. Motelow and Stacie Kahn are the co-first authors.
We appreciate Dr. Cindy Neunert’s review of the manuscript and constructive feedback. J.E.M. is supported by the National Institutes of Health (TL1TR001875).