Coronavirus disease 2019 (COVID-19) originated in Wuhan, China, and spread very quickly around the world. Previous reports on COVID-19 pneumonia suggested that while pediatric patients rarely have serious consequences, the infection may be more severe in young children.1 There is little information about COVID-19 children with underlying diseases, including chromosomal or genetic abnormalities.
Inhaled ciclesonide, one of the drug candidates for COVID-19 pneumonia due to its inhibitory effect on SARS-COV-2 replication2,3 has not yet been widely used for pediatric COVID-19. This is a first report on a moderate COVID-19 child with Sotos syndrome, who was treated with ciclesonide inhalation.
Our patient was a 20-month-old Japanese boy. He was born at 34 weeks of pregnancy and diagnosed with Sotos syndrome due to a microdeletion of the NSD-1 gene. He had deafness, hypothyroidism and vesicoureteral reflux, but no congenital heart disease. He showed severe developmental delay; unable to hold his head or not speak at all. Although he often coughed while drinking water, he had no history of asthma or pneumonia. He was admitted to another hospital on day 3 of the coughing. The contacts, including his family, doctors, nurses and therapists, showed no suspicious symptoms of COVID-19. His temperature was 37.6 °C and the percutaneous oxygen saturation (SpO2) was 94% in the ambient air. A chest X-ray showed bilateral bronchopneumonia. Laboratory tests showed a slightly elevated C-reactive protein (0.54 mg/dL). He received intravenous methylprednisolone, antibiotics, pranlukast, and oxygen therapy once. A nasopharyngeal SARS-CoV-2 PCR test, performed on admission, was positive on day 4 of illness. None of his relatives had tested positive for the PCR test. On day 5 of the illness he was transferred to our hospital for further treatment. He coughed occasionally, but no fever. There was no receding breathing and no definitive abnormal lung sound, although SpO2 fell to 90% on room air during sleep.
Laboratory test results showed white blood cell count; 6,100/μL (lymphocytes 40%), C-reactive protein; 0.11 mg/dL, LDH; 319 U/L, ferritin; 68 ng/ml and d-dimer; <0.5 µg/ml.
A chest computed tomography (CT) scan revealed peribronchial consolidation and ground glass opacities (GMO) in bilateral lungs (Fig. 1a,b). Given its ability to inhibit viral replication in vivo, we introduced ciclesonide inhalation (100 g/dose, once daily) by using a spacer with a mask, after informed consent for off-label use for COVID-19 infection. was obtained from his family. We continued oxygenation (nasal O2 2 L/min) and intravenous fluid replacement therapy, followed by tube feeding. Oxygenation improved in a few days and he was able to sleep without oxygen by day 9 of the illness. Chest CT scan, evaluated on day 11 of disease, showed significant improvement in shadows, especially GMO (Fig. 1c,d).
Chest computed tomography (CT) shows peribronchial consolidation and frosted glass opacities (GMO) in bilateral lungs on day 5 of disease, before ciclesonide treatment (a, b). After ciclesonide therapy, the GMO decreased on day 11 of the disease (c, d).
We evaluated chest CT scans of the COVID-19 child with Sotos syndrome and found peribronchial consolidation and GMO in bilateral lungs. Previous study reported that the typical CT findings on the thorax of COVID-19 pneumonia were peripheral and bilateral GMO with or without consolidation on visible intralobular lines.4 Our patient’s CT findings resembled bronchopneumonia, which was not caused by the coronavirus alone. could be caused but also by micro-aspiration due to its poor swallowing function.
Ciclesonide, inhaled corticosteroid, is one of the alternative therapeutic candidates for COVID-19, due to its relatively high viral suppression effect against SARS-CoV-2.2. A previous report demonstrated the efficacy of ciclesonide inhalation for three adult patients with mild to mid-stage COVID-19 pneumonia.3 Improvement of hypoxia and GMO on CT imaging was consistently observed in this case. However, we cannot determine the effect of ciclesonide therapy, as children with COVID-19 show relatively better outcomes. In asthma and chronic obstructive pulmonary disease, there is a risk of respiratory infection when using inhaled corticosteroids.5 In our case, however, there were no complications.
In conclusion, we attempted to use inhaled ciclesonide for a moderately hypoxic COVID-19 child with Sotos syndrome. The patient recovered quickly with no side effects. Further evaluations are needed to elucidate the benefit of ciclesonide therapy for pediatric COVID-19 infection.
We thank Dr. Kazutoshi Cho of Hokkaido University and Dr. Natsuko Inazawa of Sapporo Hokushin Hospital for providing detailed information about the patient. We appreciate the helpful treatment advice provided by Dr. Fumihiro Kodama and Dr. Atsushi Nagasaka, Infectious Diseases Department of Sapporo City General Hospital.
The authors declare no conflict of interest.
Contributions from authors
TI and HS designed the therapeutic strategy and treated the patient. EK collected clinical information. TI, EK, TY, KH and HS evaluated CT scans. TI and HS wrote the manuscript. All authors have read and approved the final manuscript.
Informed consent was obtained from the patient’s family for the publication of this manuscript.