Experience with previous coronavirus outbreaks indicates that there is a reduced propensity for these viruses to affect children. Among patients infected during the 2003 SARS-CoV-1 outbreak, only 6.9% were children, and there were no fatalities in patients aged <18 years. Additionally, children experienced a milder form of the disease . In the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in 2012, only 2% of the patients were children .
At the beginning of this pandemic, children seemed to be relatively spared; however, later reports from various centres described a potentially COVID-19-related severe multisystem inflammatory syndrome in children and young adults [10,11].
A study of 46 paediatric COVID-19 patients admitted to ICUs in Canada and the United States for COVID-19 found that comorbidities were prevalent in this paediatric cohort, with 50% having 1 comorbidity, 17% with 2, and 19% with 3 or more significant comorbidities . Reported comorbidities were: medically complex conditions with dependence on technological support, immune suppression, malignancy, obesity, diabetes, seizures, sickle cell disease, lung disease, congenital heart disease, and other congenital malformations.
We describe here two paediatric cases of DS who developed severe COVID-19. DS is the most common chromosomal abnormality in people worldwide; the prevalence is ≈1/1,000 live births. It is characterised by a variety of dysmorphic features, congenital malformations, and other disease conditions. During the SARS-CoV-1 outbreak, no cases of children with DS were reported. Whereas throughout the emergence of MERS-CoV, Menish et al.  described a case of a 14-year-old girl with DS having repaired ventriculoseptal defect with residual severe mitral regurgitation, history of systolic and diastolic left ventricular impairment, and pulmonary hypertension. Furthermore, she was obese (BMI 42.2) and suffering from hypothyroidism and OSA that was managed with home oxygen. On her admission, chest radiography revealed bilateral infiltrate. Nasopharyngeal swab samples tested positive for MERS-CoV. She was treated symptomatically and received nebulisation treatment, intravenous diuretics, imipenem, and oseltamivir. Her condition gradually improved and supplemental oxygen was discontinued. She was discharged after 7 days and remained in good health.
A confidence study of paediatric COVID-19 cases in 17 paediatric emergency departments in Italy taken between 3 and 27 March reported 27% of comorbidities. However, it did not report any case of children with DS .
Another retrospective cohort study at the Children’s National Hospital, Washington DC, included 177 children and young adults with clinical symptoms and laboratory-confirmed SARS-CoV-2 infection treated between 15 March and 30 April 2020 . From 177 infected patients who sought medical attention, 44 were hospitalised, and of these 35 were non- critically ill and 9 critically ill. The study found that cardiac, haematologic, neurologic, and oncologic diagnoses were more common in hospitalised children with COVID-19 compared to non-hospitalised children with the disease. Among the critically ill patients, a 7-week-old female child with DS was reported. She was admitted due to progressive tachypnoea and fever, and chest radiography revealed right-lower-lobe pneumonia. Ventilatory support with RAM cannula was administered.
Literature on COVID-19 in DS patients is unavailable thus far. De Cauwer et al. described the clinical course of 4 adults with DS during an outbreak of COVID-19. In all 4 patients, disease course was severe, warranting hospital care in 3 patients and resulting in a fatal outcome in one . The first case was a 60-year-old female with DS who was treated with oxygen and antibiotics (amoxicillin-clavulanate, initially, and meropenem, subsequently) with a favourable outcome. The second case was a 48-year-old female who was treated with oxygen, amoxicillin-clavulanate, azithromycin, and chloroquine and recovered. The third case was a 55-year-old female who was treated with oxygen, amoxicillin-clavulanate, chloroquine, and azithromycin; however, she did not respond to therapy and died in the hospital. The fourth case was a 62-year-old patient with DS who developed respiratory failure and subsequently received supportive care.
Of the total number of children 55 admitted to paediatric wards in Bergamo (February - May 2020) for COVID-19 infection, 2 children with DS and confirmed COVID-19 diagnosis had a severe course. In addition, both cases had one or more comorbidities, being cardiovascular anomalies, obesity, and/or OSA. Children with DS have a unique profile of cardiovascular disease. In addition, diverse anatomic abnormalities of the airways are considered major risk factors for respiratory infections in DS. OSA is very common in DS and can trigger pulmonary complications . In the context of COVID-19, obesity is a recognised risk factor. In a recent study, it was reported that 30.4% of children admitted for hospitalisation were obese  and that obesity is prevalent in DS  This currently presents a challenge in distinguishing the role of comorbidities in the development of COVID-19 in DS. Research studies suggest that children with trisomy 21 could be genetically vulnerable to severe infections by the SARS-CoV-2 virus .
During the COVID-19 outbreak in Italy, the incidence of paediatric emergency visits declined drastically. This observation is attributed to the closure of schools, intensifying of public hygiene measures, and the wearing of facemasks. These measures of mitigating the spread of the disease seemed to be efficient in protecting not only adults but also children during the peak period. Nevertheless, a few severe infections still occurred in children. As lockdown measures begin to ease and schools reopen in countries still battling SARS-CoV-2, it is strongly recommended that sufficient measures are implemented to protect children with DS, in particular those with comorbidities, considering the possibility of COVID-19 resurgence.