Background
At the end of 2019, a sudden outbreak of novel coronavirus pneumonia in Wuhan, China, brought a series of calamities to both Chinese society and global communities [
1]. The International Committee on Taxonomy of Viruses (ICTV) names the new coronavirus as severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), and World Health Organization (WHO) designates the pandemic disease caused by SARS-Cov-2 as coronavirus disease 2019 (COVID-19) [
2,
3]. Although COVID-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) are all caused by coronavirus and can be manifested with severe respiratory distress, COVID-19 has its own epidemiological and clinical features [
4]. In adults, COVID-19 has the characteristics of a long incubation period, strong infectivity, atypical clinical symptoms, and high mortality in the elderly [
5‐
7]. In view that people at any age are susceptible to COVID-19 and it has spread widely around the world, COVID-19 may affect human health for a long period of time [
1,
6,
7]. Therefore, understanding of the epidemiological and clinical features of COVID-19 will help to control the spread and improve the curative rate of this pandemic disease.
Compared to adults, there are relatively few studies on pediatric COVID-19 [
8‐
10]. In particular, the epidemiological and clinical characteristics of COVID-19 in children aged 0–14 years are yet to be fully defined. With the current rapid worldwide spread of SARS-CoV-2 infection, the number of pediatric patients with COVID-19 is expected to increase significantly or has already been rising remarkably [
9]. Therefore, defining the epidemiological and clinical features of the disease in large cohorts of pediatric patients is an urgent need. In this report, we conducted a retrospective review of COVID-19 features in 341 pediatric patients with ages between 0 and 14 years with the overall goal of providing data that could help in the development of guidelines for the prevention and treatment of pediatric COVID-19.
Discussion
The current rapid global spread of SARS-CoV-2 infection prioritizes our intense efforts to identify effective preventive strategies and develop optimal medical management. Although there is relatively ample information available for adult COVID-19 patients, our knowledge and analysis of the epidemiology and clinical characteristics of pediatric COVID-19 is quite limited. In this context, we performed a retrospective review of COVID-19 in children under 14 years old to assess the epidemiological and clinical features of the pediatric COVID-19. This systematic review of pediatric patients with COVID-19 showed that children with COVID-19 were mainly infected via family clustering and had a long incubation period. The majority of patients infected by SARS-CoV-2 presented as asymptomatic or mild/moderate disease. The most frequent clinical manifestations were fever and cough. Children with COVID-19 had rare comorbid conditions and few severe complications. The medical management for the pediatric COVID-19 patients mainly included supportive therapy and antiviral treatment. In general, the pediatric patients with COVID-19 had a good prognosis.
Pediatric patients acquired COVID-19 by a clear route of transmission that included close contact with family members with COVID-19 or a history of exposure to epidemic areas, or both. In our study, 66% of the pediatric patients were diagnosed after their family members were confirmed to be infected with SARS-CoV-2. In particular, two neonates were infected with SARS-CoV-2, followed by their mothers being confirmed with COVID-19. Although previous studies including 19 newborns have downplayed the possibility of maternal-fetal vertical transmission of SARS-CoV-2 [
15,
16], we cannot rule out such a potential risk. A study reported by Zeng et al. also found that 3 of 33 newborns born to pregnant women infected with SARS-CoV-2 were diagnosed with COVID-19 [
17]. Irrespective of insufficient evidence of vertical transmission, there was definitely a high neonatal risk of SARS-CoV-2 infection if a mother contracted COVID-19. Furthermore, our study indicates that the source of infection could not be traced for some cases of pediatric COVID-19. The epidemiological profiles of 1.9% of children included remain unknown since they had never visited any epidemic zone, contacted anyone from an epidemic zone, or been around anyone with a definitive COVID-19 diagnosis. That may add a new layer of complexity for the transmission of COVID-19 in children and may highlight the importance of strategies such as minimizing close contact with strangers even for children.
Our study also demonstrates that the median and interquartile range of the incubation period for pediatric COVID-19 were 9 days and 6–13 days, compared to 4 days and 2–7 days for adults with COVID-19. This difference might be explained by the fact that children’s immune system is far from mature and may respond to pathogens differently to adults. Furthermore, younger children, especially at pre-school age, may not clearly describe their own health conditions and contact history, which could contribute to the delay in seeking medical attention and making the diagnosis. Regardless of underlying causes, the result that the incubation period of COVID-19 was longer in children than it was in adults might implicate that parents should monitor children more closely when the family members have COVID-19, and a long medical observation period for children exposed to SARS-CoV-2 should be warranted.
The prevalence of pediatric asymptomatic infection was estimated at 5.9% in this study, which was higher than 1% in the study by Wu et al. on adult patients [
14]. Unexpectedly, some cases of asymptomatic children had abnormal radiologic findings. The percentage of asymptomatic children with abnormal chest radiographic presentation was as high as 30%. Although an abnormal chest radiograph did not predict the symptoms and severity of pediatric COVID-19 patients, the presence of pulmonary lesions in asymptomatic patients may suggest the need for medication to reduce pulmonary inflammation. At present, there is no report of pulmonary imaging lesions in asymptomatic adult patients. The presenting clinical symptoms of pediatric COVID-19 were often atypical. Fever and cough were the main symptoms that could be accompanied by gastrointestinal symptoms such as nausea, vomiting and diarrhea, and other symptoms like sneezing, stuffy nose, sore throat, dizziness, headache, myalgia, and conjunctivitis. COVID-19 symptoms in children generally followed a similar pattern in adults, albeit much less severe and more atypical [
6]. In this study, we found that pediatric patients had fewer underlying diseases and complications than adult patients. One child with COVID-19 was comorbid with congenital heart disease, and severe complication such as heart failure, myocardial injury, or liver injury was observed in one, six, or three children, respectively. The underlying diseases of adult COVID-19 patients included hypertension, diabetes, and coronary heart disease while many patients, especially severe patients, may have the complications of septic shock, acute respiratory distress syndrome, and acute kidney injury, etc.
Although there are no clear guidelines for the treatment of pediatric COVID-19, our study suggests that the treatment measures for pediatric COVID-19 patients were not as complex as that of adult COVID-19 patients, but even relatively simple. The treatment modalities for children with COVID-19 were mainly composed of antiviral therapy, traditional Chinese medicine, empirical antibiotic treatment, nutritional support therapy, and symptom reliefs. The time from the onset to recovery in children with COVID-19 was 6 to 39 days, with a median of 16 days and an interquartile of 13 to 21 days. The prognosis of children with COVID-19 was decent. However, we still cannot relax the stringency of monitoring of affected children, and we should be alert to the possibility of aggravation caused by delayed treatment. The critical patient included in this study is likely to result from delayed treatment [
13]. It may be worth noting that there is a significant patient overlap between this study and the one recently reported by Dong et al. [
9] due to the fact that both studies used the same pool of pediatric COVID-19 cases. However, what our study adds is the detailed clinical findings including clinical symptoms, therapeutic management, and prognosis of pediatric COVID-19 in addition to analysis of the epidemiological characteristics of COVID-19 in children that have also been defined by the prior study [
9].
This study has several limitations. The research only covered a brief 2-month period with observational design and retrospective nature. The data was obtained from local China health authorities thus unable to compare the epidemiological and clinical data from US and European studies in children with COVID-19. We were also unable to correlate viral burden with clinical severity due to the limitation of SARS-CoV-2 virus nucleic acid test per se. Lastly, our study encountered a problem of missing some clinical information, particularly detailed treatment strategies. However, it should be recognized that due to the low incidence of COVID-19 in children, our analysis is in the forefront to clarify the epidemiological and clinical lack of knowledge on pediatric COVID-19. Moreover, to our knowledge, the sample size of this study represents a relatively large and comprehensive survey of the characteristics of children with COVID-19.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.