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. Obesity, Black ethnicity and being under one month old are factors that increased the risk of a child being admitted into intensive care with the condition, the report said. The findings also identify new symptoms of a severe inflammation syndrome that significantly increases the risk of children with COVID-19 needing intensive care.
Researchers are calling for the World Health Organisation‘s definition of Multisystem Inflammatory Syndrome in Children (MIS-C) to be updated to help doctors identify more children with the condition and improve their treatment.
The team led by researchers from the Universities of Edinburgh and Liverpool, Imperial College London and the Royal Hospital for Children-Glasgow, 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 ISARIC4C – a global group of clinicians working to prevent death from respiratory disease – and involved 138 hospitals across England, Wales and Scotland. The ISARIC4C COVID-19 study includes two thirds of all people admitted to hospital with the disease.
The findings suggest that it is rare for young people to end up in hospital with COVID-19. They make 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 relatively low – six in total – when compared with adult deaths.
Three children who died were new-born 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 intensive care. Experts say children most at risk of needing intensive 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.
The study also identified 52 patients who had MIS-C an inflammatory syndrome. The researchers found that these children were five times more likely to be admitted to intensive care.
The symptoms usually seen in those with MIS-C include conjunctivitis, a rash or gastro-intestinal problems such as abdominal pain, vomiting and diarrhoea.
The study found new COVID-19 symptoms in children with MIS-C. These include headaches, tiredness, muscle aches and a sore throat.
The study also found that the number of platelets – a component of the blood involved in clotting – was much lower in the blood of children with MIS-C than in those without the condition.
The combination of symptoms and low platelets may be important in identifying children with MIS-C who may become more unwell, experts say.
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.
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.”
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 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.”
Professor Fiona Watt, Medical Research Council CEO, said: “This is a significant study involving 138 hospitals across England, Wales and Scotland showing that children and teenagers are less likely than adults to develop severe COVID-19 or die from the disease. Indeed, the findings suggest it is rare for young people to end up in hospital with COVID-19.
“However, while the overall the risk for young people is lower, the added risks of obesity and ethnicity are shared with adults. We need to understand this, and also why a very small number of children are suffering from an inflammatory syndrome. Obviously, the goal is to ensure that everyone who develops COVID-19 has the most appropriate treatment.”
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).
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