The coronavirus disease 2019 (COVID‐19) is an emerging infectious disease, caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2). COVID‐19 was first reported in December 2019 in Wuhan, the capital of Hubei province, China.
The World Health Organization declared COVID‐19 a public health emergency of international concern on 30 January 2020, and recognized it as a pandemic on 11 March.
More than 9 million people worldwide have tested positive for COVID-19 and over 489000 people have died of coronavirus, including over 126,381 in the United States, according to data compiled by Johns Hopkins University.
Less Common in Children
COVID‐19 appears to be less common in children than adults. Early data from the Chinese Center for Disease Control (CDC) showed that 2.1% of 44.672 patients with laboratory‐confirmed COVID‐19 as of 11 February 2020, were children up to 10 years old.
As of 2 April, among the 149 760 laboratory‐confirmed cases in the Unites States, 1.7 percent were children aged <18 years, which make up 22% of the U.S. population.
In Europe, children and adolescents made up a small proportion of the 266 393 cases reported to the European Surveillance System‐European CDC (1.1%: <10 years, 2.5%: 10‐19 years).
The number of studies in children is still limited, and most of them were case series or case reports with a small number of patients.
Epidemiological Characteristics
Of 551 children with laboratory‐confirmed COVID‐19, 311 were males (57%). The patients' age ranged from 1 day to 17.5 years old, and 216 (48%) were children under 5 years of age. At least seven cases were neonates aged up to 28 days.
Household exposure was most common, with a pooled mean prevalence of 87%. Thirty‐four patients (1%) had unknown exposure information.
Three small case series with a total of 26 patients reported the incubation period, with a median (range) of 7 days (2‐10 days), 5 days (3‐12 days), and 7.5 days (1‐16 days), respectively.
Clinical and Radiological Findings
The most common symptoms and signs in children with laboratory‐confirmed COVID‐19 were fever 53%, cough 39%, and sore throat/pharyngeal erythema 14%. However, it was found that 18% of cases were asymptomatic.
The most common radiographic and computed tomography (CT) findings were patchy consolidations (33 %) and ground glass opacities (28%), but 36% of patients had normal CT images.
Previously healthy children with COVID‐19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID‐19 case. Children with COVID‐19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.
Treatment
Antiviral agents were given to 74% of children with laboratory‐confirmed COVID‐19. Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died.
There is currently no approved treatment for COVID‐19 in adults as well as in children. However, among 381 pediatric cases in this review with available data on treatments, 74% were treated with at least one antiviral drug, and inhaled IFN‐α was the most commonly used antiviral agent.
IFN‐α exerts its antiviral effect mainly by inducing the expression of antiviral proteins and activating cellular immunity. Several multi‐center studies from China have shown that inhaled IFN‐α can reduce viral load, alleviate symptoms, and shorten disease duration in children with viral infections, including bronchiolitis and viral pneumonia. The Chinese Experts Consensus Statement on Diagnosis, Treatment, and Prevention of COVID‐19 in Children has listed nebulized IFN‐α as a choice of treatment.
This may explain high prevalence of children with COVID‐19 treated with inhaled IFN‐α. There is at least one ongoing randomized trial to assess the efficacy and safety of inhaled IFN‐α in children with COVID‐19.
Prognosis
Children with COVID‐19 seem to have less severe disease and better prognosis than adults. Of 551 pediatric cases with laboratory‐confirmed COVID‐19 included in this review, only nine had severe/critical disease.
Six patients needed invasive mechanical ventilation, and one of them died. All of these six patients had major underlying medical condition. Among a nationwide case series of 2135 pediatric patients with COVID‐19 (728 laboratory‐confirmed cases) reported to the Chinese CDC, 55.4% were classified as asymptomatic or mild, 38.8% were classified as moderate, and 5.8% were classified as severe/critical.
The proportion of severe and critical cases was 10.6%, 7.3%, 4.2%, 4.1%, and 3.0% for the age group of <1, 1 to 5, 6‐10, 11 to 15, and ≥16 years, respectively. One 14‐year‐old boy died, but it is not clear whether this adolescent had underlying condition.
In the U.S. cohort of pediatric COVID‐19 cases, children aged <1 year accounted for the highest percentage (15%‐62%) of hospitalization among 745 cases with known hospitalization status. Among 345 cases with information on underlying conditions, 23% had at least one health problem, such as chronic lung disease (including asthma), cardiovascular disease, and immunosuppressive conditions.
Seventy‐seven percent of hospitalized patients, including six patients admitted to an ICU, have one or more underlying condition. Three deaths were reported in the U.S. cohort of 2572 pediatric cases. These results may suggest that patient's age and underlying medical condition are possible host factors associated with susceptibility to COVID‐19, disease severity, and prognosis in pediatric patients.
Implications for Clinical Practice and Research
Previously healthy children with COVID‐19 usually have mild symptoms and good prognosis. The diagnosis is generally suspected from history of household exposure to COVID‐19 case. For these patients, the management should focus on symptomatic and supportive care. In mild cases, unnecessary laboratory and imaging evaluation and unproven treatment should be avoided.
More attention should be given to children with COVID‐19 and major underlying medical conditions. These patients are more likely to have severe or critical disease and poor prognosis.
Currently available evidence regarding COVID‐19 in children is mainly descriptive and anecdotal, and many questions remain unanswered.
What are the risk factors for COVID‐19 in children? Why do children seem to be less affected by COVID‐19?
What is the role of radiological imaging in the diagnosis and assessment of children with COVID‐19, and is there any advantage of CT scan over plain X‐ray?
What are the effective treatments for children with COVID‐19?
Could the WHO algorithm for the management of acute respiratory infections in children be applicable to patients with mild‐ to moderate COVID‐19, especially in low‐middle‐income countries?
What are the prognosis factors for children with COVID‐19? What is the clinical implication of prolonged fecal shedding of SARS‐CoV‐2 RNA in children with COVID‐19?
Further prospective multicenter studies are needed to answer these questions.
In conclusion, children of all ages can get COVID‐19, although they appear to be affected less commonly than adults.
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