Corona Virus Disease 2019, a growing threat to children?

In Wuhan, the original place of COVID-19 outbreak, the first infected-child case was diagnosed on January 28, 2020, 8 days later than the first infected-child case reported city of Shenzhen, 1000 km far away from Wuhan. However, it does not mean that children in Wuhan were not suffering COVID-19 during the epidemic-period, nor the symptoms of infection occur later than the other areas. The possible causes for the delayed diagnosis of children in Wuhan are the overstrict diagnostic criteria and the shortage of testing reagent in the early stage. Afterwards, the number of children confirmed increased dramatically as the relaxation of the diagnostic criteria and the opening of nucleic acid tests for suspected cases of childhood on January 28, 2020, with 5 cases confirmed on the same day. Most children cases had mild symptoms, similar to other seasonal viral infections. Therefore, it has not attracted parents’ enough attention. We noticed that most of the children were diagnosed during the epidemiological screening, with an exposure history to the familial clustering infection. It is a dangerous situation. The severity of children’s infection has been ignored, furthermore, the asymptomatic infection in children may become a potential source of infection, which needs to be taken seriously.

Compared to infected adults, the condition of infected children is significantly milder, with faster recovery, shorter virus shedding time and better prognosis. By far, only 2 critical cases have been reported, of which one was a child of 7 months old with congenital heart disease. The other patient was 13 months old with bilateral hydronephrosis and calculus of left kidney. Both cases progressed rapidly to respiratory failure after onset, requiring support of invasive mechanical ventilation. It demonstrates that children with underlying diseases are tended to progress to severe and critical cases, so we should pay high attention to such group and strengthen supervision for them. In the laboratory tests part, blood cell count and procalcitonin (PCT) were basically normal, C-reactive protein (CRP) was normal or slightly increased. Some cases need two or even three tests to be confirmed. It suggests that although positive viral nucleic acid test is the “gold standard”, clinical “false negative” children are also the potential source of infection. For clinical suspected cases, a continuous and repeated samples collection are need to improve the accuracy⁵.

Another urgent issue we are facing is how to perform antiviral therapy. Up to date, no effective anti-SARS-CoV-2 drug has been successfully confirmed in clinic practice. Since the outbreak of the SARS-CoV-2, interferons (IFN), Lopinavir/Ritonavir, Arbidol and even Oseltamivir have been recommended for clinical trials. IFN has been shown little effect in a variety of respiratory viral infections, the latter three are for influenza or HIV infection. Remdesivir is effective in a few cases of adult⁶, but there still lacks evidence-based clinical evidence for children. Since most children with respiratory viral infection merely have mild symptoms and can be self-healed, we consider that antiviral drugs should not be used routinely, unless in critical cases. The goals of treatment should be to alleviate symptoms and maintain the immune balance.

The epidemic characteristics of the COVID-19 in children are not yet clear, which poses a serious challenge to pediatric medical workers. Follow aspects should be pay special attention: Firstly, most children are asymptomatic or have mild symptoms. Even if there are no symptoms, children from families with clustered infections should be screened for SARS-CoV-2 to eliminate potential sources of infection⁷. Secondly, to date, two critical cases in children have been identified. Both cases progressed rapidly. So, in epidemic season, children with underlying diseases should be protected by isolation as soon as possible. Thirdly, pregnant women infected in late pregnancy and newborns delivered by infected mothers. It is important to clarify the transmission route of mother-to-child vertical transmission or postnatal exposure in neonatal infection. According to our current limited data, in 21 pregnant women with confirmed infection in late pregnancy (8 cases were etiologically diagnosed, 13 cases were clinically diagnosed by chest CT), the amniotic fluid, placenta samples of mothers and pharyngeal swabs of newborns were collected⁸. The pharyngeal swabs were collected again the next day, all these samples showed negative results for nucleic acid test. The pharyngeal swab nucleic acid tests of 14 neonates were also negative on day 5 and 10 of their hospitalization. No evidence of mother-to-child vertical transmission was found. Finally, powerful broad-spectrum antibiotics and corticosteroids should be avoided⁹. In the period of COVID-19 outbreak, the incidence and fatality rate of severe cases in Hubei province, especially in Wuhan city, are significantly higher than that in other regions of China, which may be influenced by improper use of antibiotics and corticosteroids. Premature use and excessive coverage of antibiotics and corticosteroids may result in secondary infection¹⁰.

In summary, SARS-CoV-2 is generally susceptible to people of all ages. Most of the infections in children are familial clusters with mild clinical symptoms. Early isolation should be performed to protect children with underlying diseases, and it is necessary to enhance the protection during delivery and isolate the newborns immediately after delivery.