The symptoms in children with COVID-19 infection have been well described in the literature [9,10,11,12,13,14,15,16,17,18]. Our results are consistent with these previous reports. For example, the clinical symptoms from our study versus the recent study with the most pediatric patients are similar : fever, 64% versus 41.5%; cough, 44% versus 48.5%; diarrhea, 6% versus 8.8%; and fatigue, 4% versus 7.6%. Results including ours indicate that COVID-19 symptoms in children follow a similar pattern in adults, albeit much less severe.
Our results of abnormal laboratory findings for children infected with COVID-19 contrast with recently published ones [15, 22,23,24]. For example, our results for lymphopenia compared to Zheng et al. are 16% versus 40% . Their normal reference values for lymphocytes were (2.1–5.7) × 109/L (< 3 years), (1.4–4.2) × 109/L (4–6 years), and (1.1–3.2) × 109/L (≥ 6 years). To date, this is the only paper that has explicitly listed the normal ranges for children of different age ranges . Thus, the differences between ours and those in the literature are most likely due to different normal ranges used for children of different ages or the small number of children who participated in their studies.
Like clinical symptoms, the laboratory findings in COVID-19-positive pediatric patients can vary from adult patients. Guan et al.  noted that 731 (82%) of 890 adult patients had lymphopenia, whereas only eight (16%) children had lymphopenia in this study. Similarly, 481 (61%) of 793 adult patients were found to have an elevated C-reactive protein. In contrast, only ten (20%) children in this study had elevated C-reactive protein. Some laboratory findings were consistent between children and adult groups: leukopenia 38% versus 36% and thrombocytopenia 14% versus 18%. The mechanism behind the observations is unknown and might provide an explanation for the differences between pediatric and adult patients.
The most common pattern of chest CT is ground-glass opacities, followed by local patchy shadowing and then local bilateral patchy shadowing, which is consistent with published data [9,10,11,12,13,14,15,16,17,18]. Our study indicates that chest CT manifested with a predominance of lesions in the subpleural area (41 [95%] of 43) and in lower lung lobes (28 [65%] of 43), especially in the posterior segment (22 [78%] of 28), an area with a relatively dense amount of bronchioles, blood vessels, and alveoli. To the best of our knowledge, these are the first quantitative results on the locations of chest CT lesions for COVID-19 children . COVID-19 is less severe in children than in adults, and the children infected with COVID-19 were at the early stages of the disease when admitted to the hospital. The fact that an overwhelming percentage of pediatric patients had lesions in the subpleural area suggests this site is the first target for the COVID-19 virus.
The current gold standard for the diagnosis of COVID-19 is PCR. However, it has been documented that patients with a negative PCR result cannot be definitively ruled out for COVID-19 infection [11, 26]. Our results are consistent with the literature. Among the 50 hospitalized children with positive PCR results, five of them (10%) had negative initial PCR results but showed positive results in subsequent tests. Moreover, 26 patients in group C never had a positive PCR result but had histories of contact with COVID-19 patients. Most of them exhibited clinical symptoms such as fever (81%) and cough (73%). Although they received a negative PCR result at least twice, all 26 patients had similar CT patterns to the PCR-positive COVID-19 patients in group A. Twenty-one (81%) had ground-glass opacities (GGO). Seven (27%) had local patchy shadowing. Five (19%) had bilateral patchy shadowing. Furthermore, our Fisher exact analysis indicated that there was no significant difference in CT image characteristics and lesion location between groups A and C. Although a positive CT alone cannot rule out the possibility of other causes of virus-induced pneumonia [11, 26], all 26 children were hospitalized and given immediate antiviral and supportive therapy. Whether or not a child presents with pneumonia is one of the key considerations for clinical management, and it is crucial to start treatment as early as possible, considering that many deaths in the adult population are due to complications resulting from severe pneumonia [3,4,5,6,7].
It has been well documented that chest CT is a powerful tool to identify and characterize pneumonia for COVID-19 adult patients [25,26,27,28]. However, there is no publication to study its usefulness in evaluating clinical recovery for children with COVID-19 infection. To determine whether CT is necessary, we investigated the data of 23 patients who had been discharged after effective treatment and had at least two CT scans. All patients had normal body temperatures for more than 3 days at the time of discharge, clinical symptoms disappeared, and PCR tests all returned negative twice at 24-h intervals. Of the 23 children, eight patients did not receive CT scans within the 2 days before their discharge. However, in their most recent CT scan performed in the hospital, most children either still had lesions (50%), or more developed lesions since the previous scan (37%). The remaining 15 discharged children had a CT obtained within 2 days of discharge. Again, ten patients had lesions that were not completely absorbed (67%), two were the same (13%), and lesions in another two became worse (13%). These results indicate that CT may not be better than symptoms in evaluating recovery. Our Cox regression analysis further showed that there was no association between changes in CT lesions and clinical outcomes. The results are consistent with the knowledge that clinical improvement predates radiographic improvement by weeks for children with community-acquired pneumonia.
When deciding whether to use CT on children, the harmful effects that radiation may have on a growing body must be considered. Hong et al., in a study of 12,068,821 children aged 0 to 19 years, found a statistically significant increase in cancer in children exposed at least once to diagnostic low-dose ionizing radiation after adjusting for age and sex [29, 30]. Based on our data, we do not recommend using CT for determining clinical recovery unless it is necessary to evaluate the status of pneumonia. For comparison, the current criteria for discharging adult patients infected with COVID-19 in China are (1) normal body temperature for 3 days, (2) two negative PCR tests at 24-h intervals, (3) resolution of clinical symptoms (these three are the current criteria for discharging pediatric patients in this hospital), plus (4) a chest imaging requirement: pulmonary imaging must show significant absorption of lesions. To date, there are no child-specific discharge criteria for COVID-19 in China.
Our study had a few limitations. First, this study has a small sample size and was conducted at a single-center in Wuhan, China, located at the center of the outbreak. The clinical severity of pediatric patients outside Wuhan may be less severe. Indeed, it is reported that there is a lower death rate of adult patients outside Wuhan areas. Second, long-term follow-up was not done because of the short time for data collection.