Epidemiology
Around the world, children make up a minority of confirmed cases of COVID-19, usually contributing to between 1 – 5% of total case numbers. Concerns exist that low case rates reflect selective testing of only the most unwell, however data from South Korea and subsequently Iceland which have undertaken widespread community testing, have also demonstrated significantly lower case numbers in children. This has also been seen in the Italian town of Vo, which screening 70% of its population and found 0 children <10 years positive, despite a 2.6% positive rate in the general population.
More detailed information has emerged into childhood severity of COVID-19. A large number of children may be asymptomatic, but the true proportion is unknown. Critical illness is very rare (~1%). In Chinese and USA CDC data, infants appear most likely to be hospitalised, although rates of PICU admission do not appear to be significantly different as yet.
To date, deaths remain extremely rare in children from COVID-19.
Transmission
Precise details regarding paediatric transmission cannot be confirmed without widespread sero-surveillance, however important trends are emerging. Low case numbers in children suggest a more limited role than was initially feared. Contact tracing data from Asia, the USA, Europe and Israel have all demonstrated a significantly lower attack rate in children than adults, including testing of asymptomatic household contacts on both PCR and serology. Coupled with low case numbers would suggest that children are less likely to acquire the disease. The role of children in passing the disease to others is unknown, in particular given unknown numbers of asymptomatic cases. Notably, the China/WHO joint commission could not recall episodes during contact tracing where transmission occurred from a child to an adult. Studies of multiple family clusters have revealed children were unlikely to be the index case, in Guangzhou, China, Israel, the USA, Switzerland and internationally. Limited data on positive cases in schools have not demonstrated significant transmission. A SARS-CoV2 positive child in a cluster in the French alps did not transmit to anyone else, despite exposure to over 100 people.
Several studies have now shown that SARS-CoV-2 can be detected by PCR in the stool of affected children for several weeks after symptoms have resolved. Studies have confirmed there can also be live virus found in the stool of infected individuals. How much virus is present, and the extent to which faecal-oral transmission may be possible is yet to be confirmed.
Clinical features
A significant proportion of children with COVID-19 do not appear to develop any symptoms, or have subclinical symptoms. In the absence of widespread community or serological testing, it is uncertain what this proportion is. The most detailed paediatric population data from China showed 13% of confirmed cases had no symptoms (cases detected by contact tracing). Considering both confirmed and suspected cases, 32% of children aged 6-10yrs were asymptomatic. Data from Italian emergency departments found 21% of SARS-CoV-2 positive children to be asymptomatic. Importantly, these studies did not follow up children to determine if they later developed symptoms, so the true proportion of asymptomatic children is unknown.
Clinical features in symptomatic children are somewhat different to adults. Children tend to have more mild illness. The most common presenting features are cough and fever, occurring in over half of symptomatic patients. Upper respiratory tract symptoms such as rhinorrhoea and sore throat are also relatively common, occurring in 30-40% of patients. It is not uncommon for children to have diarrhoea and/or vomiting (around 10% of cases), even in some cases as their sole presenting features. Several case series of rashes resembling chill blains (often occurring on feet/toes) have been reported from Europe, contemporaneously associated with the COVID-19 outbreak but with few cases simultaneously confirmed to be infected
Blood tests also show slightly different features to adults. Lymphocytopaenia is relatively rare in children, with the majority having normal or sometimes raised lymphocyte counts. Inflammatory markers such as CRP and Procalcitonin are often raised but only very mildly. Slight elevations in liver transaminases appear to be common.
Radiographic features in children are also somewhat different to their adult counterparts. Chest X-rays are often normal, and many CT chest scans are also normal. When present abnormalities are often less severe, however a reasonable number of children have bilateral pneumonia. Changes may be found on CT even in asymptomatic children. Common features in abnormal CT scans include mild, bilateral ground glass opacities, but with less peripheral predominance than is reportedly found in adults.
There appears to be little in the way of clinical signs in children to differentiate COVID-19 from other childhood respiratory virus infections.
More recently, a hyperinflammatory syndrome resembling Kawasaki shock, which appears to be a delayed immune response to COVID-19 has been described. It is known as PIMS-TS in Europe and MIS-C in the USA. Published reports from London, Italy and France in a cohort of children with evidence of past COVID-19 infection have presented with early symptom of abdominal pain, vomiting and diarrhoea, with persistent high-grade fever and commonly progression on to shock with cardiac involvement. High inflammatory markers, myocarditis, macularpapular rashes and non-suppurative conjunctivitis are common. Respiratory involvement is notably absent. Investigations are underway to ascertain a link and mechanism of disease.
Consistent with adult literature, children from a Black, Asian and Minority Ethnic (BAME) background seem to be at higher risk of severe disease from acute COVID-19 infection, and are significantly overrepresented in case reports of PIMS-TS
Newborns
A large number of cases of infants born to mothers with COVID-19 have now been reported, including several hundreds from the UK. Mothers and their babies in general appear to do well. There is a small but notable increase in the rates of preterm birth, and signals of increase in rates of foetal loss/stillborn delivery. As yet, cord blood, amniotic fluid and placental swabs persistently testing negative for SARS-CoV-2. There have been a few cases of infants delivered to mothers with COVID-19, who had elevated SARS- CoV-2 IgM. This may indicate intrauterine transmission, however swab PCR from these children has been negative and false positives with IgM tests are not uncommon. When tested, breast milk has usually been negative for SARS-CoV-2, but there have been a small number of instances where it has tested positive. It is unclear if this positive result reflects live, infectious virus, and whether the source was the mother or infants who subsequently also test positive for the virus. The vast majority of newborns have not acquired COVID-19 themselves. There have been case reports of newborns and very young infants testing positive including several within 12 hours of age, however they have mostly not suffered any complications of the disease and required minimal respiratory support.
Children with comorbidities
There is a growing body of evidence reflecting a small increased risk of children with comorbidities to be hospitalised or need intensive care from COVID-19. Studies from PICU admissions in the US and Italy found the majority have some comorbidities, most commonly respiratory or complex neurodisability – groups for whom there is a background increased risk of complications from all respiratory viruses. The rates of complications from SARS-CoV-2 infection do not appear disproportionate to those from other respiratory viruses from this early data. Children with malignancy or immunosuppression are slightly overrepresented in admission and PICU data, however reports indicate that the majority of children with these conditions still largely suffer mild illness. A study from London did not find children with comorbidities to be at significantly increased risk of severe disease.
Conclusion
COVID-19 appears to affect children less often, and with less severity, including frequent asymptomatic or subclinical infection. There is evidence of critical illness, but it is rare. The role of children in transmission is unclear, but consistent evidence is demonstrating a lower likelihood of acquiring infection, and lower rates of children bringing infections into households. Changes in laboratory or radiographic parameters are slightly different to adults, and changes usually mild. There is some evidence of vertical transmission to neonates, however it is unclear is this is perinatal or intrauterine. Evidence suggests both infected mothers and infants are no more severely affected than other groups. There does not appear to be significant increased risk for children with immunosuppression, but further data is needed. Children with respiratory and complex neurodisability appear more likely to suffer complications, however not obviously more than would be expected from infection with other respiratory viruses.
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