Study details clinical characteristics of UK paediatric cohort admitted to hospital with COVID-19
A study in the British Medical Journal confirms that children and young people have lower rates of severe coronavirus disease 2019 (COVID-19) than adults, with researchers noting that severe illness was "rare" and death "exceptionally rare" in a large prospective cohort in the UK. However, factors that raised the likelihood of a child being admitted to critical care with the condition included age under 1 month old, age between 10 to 14 years, and black ethnicity, while older age and non-white ethnicity were associated with multisystem inflammatory syndrome in children (MIS-C) temporarily related to COVID-19.
For their analysis, investigators identified 651 subjects under 19 years of age with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who were recruited to the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study between January 17 and July 3, 2020. The paediatric cohort accounted for 0.9% of all patients in ISARIC CCP-UK, which is an ongoing prospective cohort study in acute care hospitals in England, Wales, and Scotland.
The median age of patients was 4.6 years (interquartile range 0.3-13.7), and 35% (225/651) were under 12 months old. Males accounted for 56% (367/650). Ethnicity was recorded in a majority of the cases, with 57% (330/576) being white, 12% (67/576) South Asian, and 10% (56/576) black. At least one comorbidity was recorded in 42% (276/651) of patients. The most common presenting symptoms were fever, cough, shortness of breath, nausea, and vomiting, and researchers also identified a systemic mucocutaneous-enteric cluster of symptoms, which encompassed symptoms for the WHO MIS-C criteria.
In the study, 18% (116/632) of the children admitted to hospital needed critical care, among whom 8% (47/597) received inotropic support, 9% (57/619) were given non-invasive ventilation, and 9% (58/620) were on invasive mechanical ventilation. By contrast, the critical care admission rate was 10% in a North American cohort of children admitted to hospital and 13% in a cohort study across 25 European countries. "This rate may be elevated in our study owing to hospitals with dedicated paediatric research teams being more likely to provide paediatric critical care," the authors, led by Olivia V Swann, Royal Hospital for Sick Children, Paediatric Infectious Diseases, Edinburgh, UK, noted.
On univariable analysis, children with comorbidities were more likely to be admitted to critical care than those without (odds ratio (OR) 1.73, 95% CI: 1.15 to 2.60; P=0.008), but this no longer reached significance in the multivariable model (OR 1.42, CI: 0.89 to 2.28; P=0.141). Comorbidities most commonly associated with critical care admission on univariable analysis were prematurity (50% [15/30] of critical care admissions vs 18% [30/165] of standard care admissions; P=0.001), respiratory comorbidities (10% [12/115] vs 4% [21/491]; P=0.019), cardiac comorbidities (11%[13/115] vs 5% [25/493]; P=0.018), and obesity (6% (7/115) vs 2% (10/487); P=0.028).
On multivariable analysis, admission to critical care was associated with age under 1 month (OR 3.21, CI 1.36 to 7.66; P=0.008), age 10-14 years (OR 3.23, CI: 1.55 to 6.99; P=0.002), and black ethnicity (OR 2.82, CI: 1.41 to 5.57; P=0.003).
The authors found that the all cause in-hospital case fatality rate for children and young people was "strikingly low" at 1% (6/627), compared with 27% (18 803/69 516) in the whole ISARIC CCP-UK cohort of all ages (0-106 years) over the same time period. Researchers noted that all six children who died "had profound comorbidity."
Children who met the WHO preliminary definition for MIS-C were older than those who did not (median age 10.7 (8.3-14.1) vs 1.6 (0.2-12.9) years; P<0.001) and were more likely to be of non-white ethnicity (64% (29/45) vs 42% (148/355); P=0.004). Further, MIS-C was associated with obesity (10% (5/51) vs 2% (6/385); P=0.005), but not with any other comorbidity.
Children with MIS-C were also five times more likely to be admitted to critical care (73% (38/52) vs 15% (62/404); P<0.001). In addition to the WHO preliminary case definition features (fever, rash, conjunctivitis, and gastrointestinal symptoms), children with MIS-C were more likely to present with fatigue (51% [24/47] vs 28% [86/302]; P=0.004), headache (34% [16/47] vs 10% [26/263]; P<0.001), myalgia (34% [15/44] vs 8% [21/270]; P<0.001), sore throat (30% [14/47] vs 12% [34/284]; P=0.003), and lymphadenopathy (20% [9/46] vs 3% [10/318]; P<0.001) and to have a platelet count of less than 150 × 109/L (32% [16/50] vs 11% [38/348]; P<0.001) than those who did not have MIS-C. No deaths occurred in the MIS-C group.
"It is becoming apparent that MIS-C can present both in children with acute SARS-CoV-2 infection and in the post-acute or convalescent phase of infection," the authors said, citing a case series of 565 children with MIS-C across North America that used latent class analysis to identify three classes of the condition. "Class 1 predominantly comprises patients who were antibody-positive and PCR-negative for SARS-CoV-2, with multiple systems involved, a strong association with cardiac complications, and a greater likelihood of having received intravenous immunoglobulin and corticosteroids. These class 1 patients resemble the post-acute group in our analysis….Class 2 [is described] as children who were predominantly PCR-positive with more respiratory involvement, and these resemble the acute group in our analysis."
They also discussed the distinct cluster presenting with systemic mucocutaneous-enteric symptoms (rash, conjunctivitis, diarrhoea, vomiting, and abdominal pain) in addition to headache, myalgia, sore throat, fatigue, and lymphadenopathy, which overlapped closely with the WHO preliminary case definition. "The significant associations between MIS-C and fatigue, headache, myalgia, sore throat, and lymphadenopathy in our cohort may be useful in refining the [WHO preliminary] case definition. In addition, the association of MIS-C with platelet count less than 150 × 109/L and low lymphocyte counts agrees with previous reports. These important findings may assist in differentiating this syndrome from other illnesses, particularly Kawasaki disease in which platelet counts are typically elevated," they said.
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