Characteristics of patients with PCR-positive SARS-CoV-2 infection (N=403) according to severity of disease (WHO COVID-19 Clinical Progression Scale of ≥6) and univariable ordinal logistic regression ORs for more severe disease along WHO COVID-19 Clinical Progression Scale
| Mild/moderate disease n=301 (%) | Severe disease n=102 (%) | P value* | Unadjusted OR of more severe disease† | |
| Demographics | ||||
| Median age in years (IQR)‡ | 3.21 (0.31–9.87) | 6.69 (1.31–13.46) | 0.002 | – |
| Age≤30 days | 34 (11.3%) | 3 (2.9%) | 0.009 | 0.56 (0.29–1.08) |
| Age category‡ | ||||
| <1 year | 94 (31.4%) | 19 (18.6%) | 0.025 | Ref. |
| 1–4 years | 79 (26.4%) | 27 (26.5%) | 1.63 (0.98–2.70) | |
| 5–11 years | 66 (22.1%) | 23 (22.5%) | 1.66 (0.97–2.84) | |
| ≥12 years | 60 (20.1%) | 33 (32.3%) | 2.23 (1.34–3.73) | |
| Male sex | 171 (56.8%) | 56 (54.9%) | 0.826 | 0.95 (0.66–1.38) |
| Admission period | ||||
| Prior to 1 July 2020 | 16 (5.3%) | 3 (2.9%) | 0.262 | Ref. |
| Between 1 July 2020 and 31 December 2020 | 118 (39.2%) | 33 (32.3%) | 1.60 (0.61–4.22) | |
| Between 1 January 2021 and 31 May 2021 | 167 (55.5%) | 66 (64.7%) | 1.70 (0.66–4.42) | |
| Admitted in Canada | 195 (64.8%) | 71 (69.6%) | 0.442 | 0.75 (0.51–1.09) |
| Number of comorbidities | ||||
| None | 173 (57.5%) | 43 (42.1%) | 0.009 | Ref. |
| 1 comorbidity | 81 (26.9%) | 31 (30.4%) | 1.61 (1.05–2.48) | |
| Multiple (>2) comorbidities | 47 (15.6%) | 28 (27.4%) | 2.58 (1.59–4.18) | |
| Individual comorbidities§ | ||||
| Obesity | 25 (8.3%) | 25 (24.5%) | <0.001 | 4.72 (2.29–9.73) |
| Pulmonary disorders | 35 (11.6%) | 19 (18.6%) | 0.104 | 2.60 (1.59–4.24) |
| Non-asthma pulmonary disorders¶ | 12 (4.0%) | 10 (9.8%) | 0.047 | 3.11 (1.47–6.57) |
| Asthma | 23 (7.6%) | 9 (8.8%) | 0.865 | 2.01 (1.11–3.64) |
| Prematurity (<37 weeks’ gestational age) | 20 (6.6%) | 10 (9.8%) | 0.405 | 1.35 (0.68–2.66) |
| Immunosuppression | 26 (8.6%) | 5 (4.9%) | 0.284 | 0.31 (0.13–0.74) |
| Malignancy** | 15 (5.0%) | 1 (1.0%) | 0.083 | 0.07 (0.01–0.51) |
| Anaemia or haemoglobinopathy†† | 7 (2.3%) | 6 (5.9%) | 0.152 | 1.80 (0.61–5.29) |
| Sickle cell anaemia | 4 (1.3%) | 2 (2.0%) | 0.646 | 1.13 (0.25–5.24) |
| Neurological disorders‡‡ | 33 (11.0%) | 23 (22.5%) | 0.006 | 2.04 (1.22–3.41) |
| Cardiac disorders | 13 (4.3%) | 6 (5.9%) | 0.709 | 1.57 (0.69–3.59) |
| Metabolic disorders | 8 (2.6%) | 4 (3.9%) | 0.509 | 1.82 (0.55–6.04) |
| Diabetes mellitus | 3 (1.0%) | 2 (2.0%) | 0.604 | 2.38 (0.54–10.42) |
| Renal disorders | 9 (3.0%) | 5 (4.9%) | 0.357 | 1.55 (0.57–4.24) |
| Hypertension | 4 (1.3%) | 5 (4.9%) | 0.049 | 2.83 (0.84–9.53) |
| Chromosomal disorders§§ | 3 (1.0%) | 5 (4.9%) | 0.027 | 3.60 (1.02–12.63) |
| Others¶¶ | 17 (5.6%) | 8 (7.8%) | 0.578 | 1.76 (0.88–3.50) |
| Clinical features | ||||
| Fever prior to or during admission*** | 226 (81.3%) | 76 (84.4%) | 0.604 | 0.96 (0.63–1.46) |
| Cough | 147 (48.8%) | 61 (59.8%) | 0.071 | 1.93 (1.33–2.81) |
| Shortness of breath | 110 (36.5%) | 78 (76.5%) | <0.001 | 10.60 (6.83–16.45) |
| Vomiting | 91 (30.2%) | 36 (35.3%) | 0.408 | 1.01 (0.68–1.51) |
| Rhinitis | 97 (32.2%) | 28 (27.4%) | 0.437 | 0.93 (0.63–1.37) |
| Diarrhoea | 87 (28.9%) | 28 (27.4%) | 0.878 | 1.04 (0.69–1.56) |
| Abdominal pain | 80 (26.6%) | 28 (27.4%) | 0.966 | 0.80 (0.52–1.23) |
| Headache | 52 (17.3%) | 20 (19.6%) | 0.703 | 1.20 (0.75–1.94) |
| Rash | 50 (16.6%) | 19 (18.6%) | 0.753 | 0.86 (0.51–1.45) |
| Conjunctivitis | 46 (15.3%) | 22 (21.6%) | 0.189 | 1.24 (0.75–2.06) |
| Myalgia | 46 (15.3%) | 14 (13.7%) | 0.825 | 1.06 (0.64–1.76) |
| Pharyngitis | 50 (16.6%) | 10 (9.8%) | 0.131 | 0.77 (0.46–1.29) |
| Wheeze | 37 (12.3%) | 17 (16.7%) | 0.341 | 2.16 (1.34–3.49) |
| Chest pain | 27 (9.0%) | 12 (11.8%) | 0.528 | 1.39 (0.76–2.52) |
| Cracked lips | 26 (8.6%) | 12 (11.8%) | 0.461 | 1.14 (0.59–2.20) |
| Oedema of hands and feet | 19 (6.3%) | 8 (7.8%) | 0.760 | 1.25 (0.59–2.64) |
| Anosmia | 10 (3.3%) | 2 (2.0%) | 0.738 | 0.85 (0.30–2.44) |
| Seizures | 6 (2.0%) | 5 (4.9%) | 0.155 | 1.73 (0.55–5.45) |
| Coinfections | ||||
| Bacterial (positive cultures)††† | 14 (4.6%) | 10 (9.8%) | 0.097 | 2.00 (0.93–4.30) |
| Viral | 15 (5.0%) | 17 (16.7%) | <0.001 | 4.10 (2.22–7.58) |
| Bacterial and/or viral | 29 (9.6%) | 25 (24.5%) | <0.001 | 3.23 (1.94–5.39) |
| Investigations | ||||
| No chest imaging done | 89 (29.6%) | 2 (2.0%) | <0.001 | 0.12 (0.05–0.28) |
| CXR and/or CT chest normal or had findings unrelated to COVID-19 | 102 (33.9%) | 19 (18.6%) | Ref. | |
| CXR and/or CT chest abnormalities compatible with COVID-19 | 110 (36.5%) | 81 (79.4%) | 3.63 (2.32–5.67) | |
| Laboratory investigations | ||||
| Leucopenia (<4×109/L)‡‡‡ | 47 (16.5%) | 12 (11.9%) | 0.344 | 0.66 (0.39–1.11) |
| Leucocytosis (>15×109/L)‡‡‡ | 33 (11.6%) | 14 (13.9%) | 0.670 | 1.23 (0.70–2.18) |
| Neutropenia (<1.5×109/L)§§§ | 69 (24.5%) | 15 (14.8%) | <0.001 | 0.55 (0.34–0.87) |
| Normal neutrophil count§§§ | 145 (51.6%) | 37 (36.6%) | Ref. | |
| Neutrophilia§§§ | 67 (23.8%) | 49 (48.5%) | 2.59 (1.67–4.01) | |
| Thrombocytopenia (<100×109/L)¶¶¶ | 29 (10.2%) | 13 (12.9%) | 0.275 | 1.14 (0.61–2.13) |
| Normal platelet count¶¶¶ | 199 (70.1%) | 62 (61.4%) | Ref. | |
| Thrombocytosis (>450×109/L)¶¶¶ | 56 (19.7%) | 26 (25.7%) | 1.14 (0.71–1.82) | |
| CRP not done**** | 51 (16.9%) | 9 (8.8%) | 0.003 | Ref. |
| Normal CRP**** | 174 (57.8%) | 50 (49.0%) | 1.46 (0.84–2.53) | |
| CRP >50 (mg/L)**** | 76 (25.2%) | 43 (42.1%) | 2.32 (1.26–4.26) | |
| Ferritin >500 (mcg/L)†††† | 30 (26.1%) | 25 (36.8%) | 0.175 | 2.15 (1.24–3.70) |
| Albumin <29 (g/L)‡‡‡‡ | 24 (26.7%) | 22 (52.4%) | 0.007 | 3.38 (1.84–6.21) |
| Complications | ||||
| MIS-C diagnosis | 55 (18.3%) | 26 (25.5%) | 0.153 | 1.24 (0.77–1.99) |
*Comparisons between mild/moderate and severe disease performed using χ2 or Fisher’s exact test as appropriate for categorical data and Wilcoxon rank-sum test for continuous data as appropriate.
†ORs obtained from univariable ordinal logistic regression.
‡A total of two children with mild/moderate disease were missing date of birth.
§Children are listed more than once if they had more than one comorbidity.
¶Additional information is available for 14 out of 22 patients: obstructive sleep apnoea (n=5); bronchopulmonary dysplasia (n=3); pulmonary hypertension (n=2); cystic fibrosis (n=1); chronic aspiration pneumonia (n=1); subglottic stenosis (n=1); and Pierre-Robin anomaly (n=1).
**Malignancy consists of the following: acute lymphoblastic leukemia (n=11); neuroblastoma (n=2); lymphoma (n=1); rhabdomyosarcoma (n=1); and osteosarcoma (n=1).
††Anaemia and/or haemoglobinopathy consist of the following: sickle cell disease (n=6); glucose-6-phosphate dehydrogenase deficiency (n=2); anaemia of chronic disease (n=2); ovalocytosis (n=1); pancytopenia of unknown aetiology (n=1); and iron deficiency anaemia (n=1).
‡‡Additional information is available for 47 out of 56 patients: syndromic condition with global developmental delay (GDD) (n=19); autism and/or GDD of unexplained etiology (n=10); cerebral palsy (n=7); muscular dystrophy (n=3); hydrocephalus (n=2); congenital microcephaly (n=2); brain tumor (n=1); focal cortical dysplasia (n=1); encephalopathy (n=1); and epilepsy (n=1).
§§Additional information is available for 7 out of 8 patients: Trisomy 21 (n=3); unbalanced translocation (n=2); Prader-Willi syndrome (n=1); and Miller-Dieker syndrome (n=1).
¶¶Others consist of the following: gastrostomy (n=12); liver transplantation (n=2); coeliac disease (n=1); Crohn disease (n=1) failure to thrive (n=1); inflammatory bowel disease (n=1); inflammatory bowel disease and Hirschsprung disease (n=1); unclear liver disease (n=1); oesophageal atresia (n=1); scoliosis (n=2); liver cirrhosis and cholestasis (n=1); and Glanzmann thrombasthenia (n=1).
***A total of 35 children were missing data on fever prior to or during admission (23 with mild/moderate disease and 12 with severe disease) resulting in a total N of 368.
†††Children with one of the following are included: blood culture thought to be truly positive and/or positive endotracheal tube cultures treated with antibiotics for presumptive bacterial pneumonia and/or positive bacterial culture from another site treated with antibiotics.
‡‡‡A total of 17 children were missing leukocyte values (16 with mild/moderate disease and 1 with severe disease) resulting in a total N of 386.
§§§A total of 21 children were missing a neutrophil value (20 with mild/moderate disease and 1 with severe disease) resulting in a total N of 382. Cut-off values for neutrophilia are age dependent.
¶¶¶A total of 18 children were missing a platelet value (17 with mild/moderate disease and 1 with severe disease) resulting in a total N of 385.
****TA total of 60 children were missing a CRP value (51 with mild/moderate disease and 9 with severe disease) and were considered as CRP not done in the above table.
††††The highest ferritin value measured variable used and a total of 220 children were missing a value (186 with mild/moderate disease and 34 with severe disease) resulting in a total N of 183.
‡‡‡‡A total of 271 children were missing albumin values (211 with mild/moderate disease and 60 with severe disease) resulting in a total N of 132.
CRP, C-reactive protein; CXR, chest X-ray; MIS-C, multisystem inflammatory syndrome in children.