Study population
A detailed dataset was returned for 682 cases, of which 678 were included in the final analysis. Reasons for exclusion were duplication in reporting (n=3) and age ≥ 18 years (n=1). The age of the children ranged from 7 days to 17.9 years with a median of 12.2 years (interquartile range (IQR) 5.0 – 14.6) (Table 1). Most of the children were Caucasian (532 [78.5%]), followed by Arabic (29 [4.3%]), Hispanic (27 [4.0%]), Black (18 [2.7%]) and Asian (10 [1.5%]). Ethnicity was unknown for 62 (9.1%) children. Numbers of reported children over time are shown in Figure 1 and stratified to age group in supplementary data Figure S1. Geographical and temporal distribution of SARS-CoV-2 cases in Swiss cantons (political states) are shown in supplementary data Figure S2.
Hospitalisation and management
Overall, 126 (19%) children were hospitalised of which 14 (11.1%) were admitted for other reasons than infection with SARS-CoV-2. A total of 16 (12.7%) children required ICU admission for the following reasons: hemodynamic instability (n=8), respiratory failure (n=4), prematurity (n=1), coma (n=1), cardiovascular arrest (n=1), neurogenic shock (n=1). One adolescent with a mild upper respiratory tract illness was admitted to ICU for a non-COVID-19-related reason (neurogenic shock after an accident). Ethnicity of the children admitted to ICU were Caucasian (n=8), Black (n=4), Hispanic (n=3), and unknown (n=1). Oxygen was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) hospitalised cases. Complications were reported in 28 (22.2%) hospitalised children with cardiovascular complications being most frequent (10 [7.9%]). A total of 48 children were retrospectively analysed for potential PIMS-TS of which 17 children were identified as cases based on available data (eight non-ICU admitted, nine ICU admitted). Three deaths were recorded.
Overall, most children (646 [95.3%]) did not receive medication. Specific treatment was given to 10 (1.8%) of non-hospitalised, 15 (13.6%) of hospitalised and 12 (75.0%) of ICU-admitted children. Among hospitalised children (non-ICU admitted), six (5.5%) received corticosteroids, two (1.8%) each hydroxychloroquine and intravenous immunoglobulins and one (0.9%) tocilizumab. Among ICU-admitted children nine (56.3%) received biologicals (anakinra [n=7], tocilizumab [n=2]), seven (43.8%) each corticosteroids, intravenous immunoglobulins and two (12.5%) hydroxychloroquine. No further treatment including remdesivir was given (supplementary data Questionnaire). The median duration of hospitalisation for non-ICU admitted children was 3.0 (IQR 2.0 - 4.0) days and for children admitted to ICU 14 (IQR 4.75 – 15.25) days (supplementary data Figure S3).
Comorbidities
A total of 106 (15.6%) children had pre-existing medical conditions, the most common comorbidities were reported in the following groups: respiratory (45 [42.5%]), endocrinology (15 [14.2%]), haemato-oncology (12 [11.3%]) and cardiovascular (10 [9.4%]) (details are listed in Table 2). Hospitalised children had significantly more comorbidities than non-hospitalised children (p-value < 0.01). Five (31.3%) children admitted to ICU had pre-existing comorbidities: three children had asthma/bronchitis, a neonate had apnoea of prematurity (born at 29 weeks gestational age) and a 2-month-old infant had isolated microcephaly with a normal cerebral ultrasound and no evidence of Cytomegalovirus in urine. Children requiring admission to ICU did not have more frequently pre-existing medical conditions compared to non-ICU hospitalised children. The univariable regression analysis showed that children ≥ 2 years of age were less likely to be hospitalised and comorbidities increased the risk of hospitalisation in both the uni- and the multivariable analysis (Table 3).
Symptoms
Overall, fever was the most frequent symptom observed among children with COVID-19 (305 [45.3%]) (Table 1). In children aged less than 2 years, fever, cough, and rhinorrhoea were the most common symptoms and in adolescents between 10 and 18 years of age, fever, cough and headache were more commonly reported (a detailed distribution of symptoms according to age group is presented in Figure 2). Fever and rash were more common in hospitalised compared with non-hospitalised children ((96 [76.2%] vs 209 [38.1%], p-value <0.001) and (16 [12.8%] vs 6 [1.1%], p-value <0.001), respectively. In contrast, anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value 0.001). Children admitted to ICU more often had abdominal pain (5 [33.3%] vs 11 [10.0%], p-value 0.034) and rash (5 [33.3%] vs 11 [10.0%], p-value 0.034) than non-ICU hospitalised children. A heatmap with a co-occurrence matrix for symptoms showed three clusters of symptoms representing three different clinical phenotypes (Figure 3). The first cluster represents an upper respiratory tract illness with fever, cough, rhinorrhoea, and pharyngitis, the second a gastrointestinal illness with abdominal pain, diarrhoea and vomiting, and the third cluster corresponds to more constitutional symptoms with headache, myalgia and asthenia.
Complications
A total of 28 (4.1%) children with SARS-CoV-2 infection developed complications, this was more frequent in hospitalised than non-hospitalised children (p-value <0.001). The most frequent complications/non-pulmonary organ manifestations were cardiovascular in 11 (1.6%) children, including coronary artery dilatation (n=4), elevation of cardiac enzymes (n=3), hypotensive shock (n=3), myocarditis (n=1), vasculitis (n=3). Bacterial co-infection was reported in 10 (1.5%) children, exclusively in hospitalised children. Further complications were: pancytopenia (n=5), kidney failure (n=4), seizures (n=3), encephalopathy (n=1), polyradiculoneuritis (n=1) and myopathy (n=1).
In hospitalised cases three (2.4%) deaths were reported during the study period. A 10-month-old infant with severe brain oedema, signs of hypoxic-ischemic encephalopathy and cerebral haemorrhages presenting with vomiting without fever, respiratory distress (with evidence of respiratory illness on chest radiography) and status epilepticus. A 2-month-old infant with cardiorespiratory arrest secondary to cerebral haemorrhage presenting with pale stools, haematochezia, haematemesis and hepatosplenomegaly with abnormal liver function. A 6-year-old with an Epstein-Barr Virus (EBV)-associated hemophagocytic lymphohistiocytosis developed cerebral bleeding due to coagulation deficiency caused by liver failure. He presented with abdominal pain, fever and abnormal liver function two weeks after a SARS-CoV-2 infection and was initially suspected to have PIMS-TS.
Diagnosis
Diagnosis was mostly confirmed by a single nasopharyngeal PCR (620 [96.3%]). Of the 40 children in whom serology was done, 35 (87.5%) were positive. Five (55.6%) ICU-admitted patients had positive serology with negative PCR. A chest radiography was done in 47 (6.9%) children and showed unilateral and bilateral changes in six (12.8%) and 16 (34.0%) cases, respectively. Echocardiography was done in 47 (6.9%) children, abnormal findings were identified in eight (21.6%) children (coronary dilatation (n=4), reduced left ventricle ejection fraction (n=3), dyskinesia (n=1)), all of them were hospitalised. Other diagnostic tests included abdominal ultrasound (21 [3.1%]) and thoracic CT-scan (10 [1.5%]) (further details in supplementary data Table S1).
Transmission
In total, 309 children (45.6%) had a family member with a confirmed or suspected SARS-CoV-2 infection (supplementary data Figure S4). Community-acquired infection (including school and day-care) was confirmed or suspected in 86 (12.7%) children. In one third of children, the primary case was unknown 284 (41.9%).