COVID-19 less deadly and causes milder symptoms in children — UK study

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Children and teenagers are less likely than adults to develop severe COVID-19 or die from the disease, according to the world’s largest study of hospital patients with COVID-19. However, the report found that obesity, Black ethnicity and being under one month old increased the risk of a child being admitted into intensive care.

The findings also identify new symptoms of Multisystem Inflammatory Syndrome in Children (MIS-C) – a rare condition thought to be linked to COVID-19.

The team led by researchers from the Universities of Liverpool, Edinburgh, and Imperial College London, recruited 651 children and young people aged 19 years or less who had been admitted to hospital with COVID-19.

The study is led by ISARIC – a global collaboration working to prevent death from outbreaks of severe respiratory and emerging infections– and involved 138 hospitals across England, Wales and Scotland. The study includes two thirds of all people admitted to hospital with the disease.

The report finds that it is rare for young people to end up in hospital with COVID-19, with children and young people making up less than one per cent of participants in the ISARIC study.

The typical age of children hospitalised was five-years-old. Some 42% of patients had at least one other condition, the most common included neurological conditions and asthma. The number of children and young people who died from COVID-19 was very low – six in total – when compared with approximately 18,000 adult deaths in the same period. Three children who died were newborn babies born with other severe health problems. The other three children were aged 15 to 18 years old and also had profound health issues.

Some 18% of hospitalised children and young people were admitted to critical care. Experts say children most at risk of needing critical care were those under one month old and those aged 10 to 14 years old. Similar to adults, obesity and Black ethnicity were also found to be risk factors for critical care admission.

The study also identified 52 patients who had MIS-C and found that these children were five times more likely to be admitted to critical care. The symptoms usually seen in those with MIS-C include conjunctivitis, a rash, gastrointestinal problem such as abdominal pain, vomiting and diarrhoea. The study found new covid-19 symptoms in children with MIS-C, including headaches, tiredness, muscle aches and a sore throat.

The researchers are now calling for the WHO’s definition of MIS-C to be updated to help doctors identify more children with the condition and improve their treatment.
Professor Calum Semple, professor in child health and outbreak medicine and consultant respiratory paediatrician at the University of Liverpool, said: “The diligent work of our colleagues working in child health and the NIHR Clinical Research Network across the UK has led to this report which is the largest and most detailed description of COVID-19 and MIS-C in children and young people. We have provided new understanding about MIS-C which will help manage this rare but serious condition, but parents can now be reassured that severe COVID-19 is very rare in children.”

Dr Olivia Swann, lead author and clinical lecturer in paediatric infectious diseases at the University of Edinburgh, said: “Researchers often want to call attention to large numbers of patients in their studies, however, we want to highlight that children made up only a fraction of a percent of all COVID-19 admissions across the UK in our study and that severe disease was rare.”

Dr Louisa Pollock, consultant in paediatric infectious disease at the Royal Hospital for Children – Glasgow, said: “Parents should be reassured by this study which confirms very few children were seriously affected by COVID-19. As children return to school, and over the winter months, it is important we continue to monitor COVID-19 in children.”

This research was funded by UK Research and Innovation (UKRI) and by the Department of Health and Social Care through the National Institute for Health Research (NIHR) as part of the UK Government’s COVID-19 rapid research response.

Abstract
Objective: To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).
Design: Prospective observational cohort study with rapid data gathering and near real time analysis.
Setting: 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).
Participants: 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.
Main outcome measures: Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.
Results: Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.
Conclusions: Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).

Authors
Olivia V Swann, Karl A Holden, Lance Turtle, Louisa Pollock, Cameron J Fairfield, Thomas M Drake, Sohan Seth, Conor Egan, Hayley E Hardwick, Sophie Halpin, Michelle Girvan, Chloe Donohue, Mark Pritchard, Latifa B Patel, Shamez Ladhani, Louise Sigfrid, Ian P Sinha, Piero L Olliaro, Jonathan S Nguyen-Van-Tam, Peter W Horby, Laura Merson, Gail Carson, Jake Dunning, Peter J M Openshaw, J Kenneth Baillie, Ewen M Harrison, Annemarie B Docherty, Malcolm G Semple

University of Liverpool material BMJ abstract

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