key: cord-1022240-ythil22o authors: Cui, Xiaojian; Zhang, Tongqiang; Zheng, Jiafeng; Zhang, Jiayi; Si, Ping; Xu, Yongsheng; Guo, Wei; Liu, Zihui; Li, Wenliang; Ma, Jia; Dong, Cuicui; Shen, Yongming; Cai, Chunquan; He, Sijia title: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients date: 2020-06-02 journal: J Med Virol DOI: 10.1002/jmv.26023 sha: 25e3201179463491ed9f56493d77e3cdfc763853 doc_id: 1022240 cord_uid: ythil22o There is a current outbreak of coronavirus disease 2019 (COVID‐19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID‐19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence‐based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID‐19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission. suspected cases of children with COVID-19, which explored that children infected with nCoV showed less severe symptoms than adults; however, infants and toddlers were vulnerable to a moderate and severe infection. This study noted one death of a 14-year-old child with COVID-19 and found that 5.9% of cases were severe, compared with 18.5% of adults experiencing severe symptoms. 10 Given the above cases, the induction factor for the discrepancy of clinical manifestations among children and adults remains to be determined. In this review, we included 2597 pediatric patients with COVID-19, comprising 1185 confirmed and 1412 suspected cases that were reported recently. The analysis of demographic, clinical, laboratory, and imaging characteristics will help to understand the natural history of COVID-19 transmission in children, which would otherwise contribute to limit the threat of this human pandemic. In this study, 2597 cases of children with COVID-19 were collected from 24 articles, 8, 9, comprising 1185 confirmed cases and 1412 suspected cases ( Table 1 ). The COVID-19 cases were confirmed with positive SARS-CoV-2 nucleic acid in nasal and pharyngeal swab specimens or blood samples. However, if a child tested negative for SARS-CoV-2 RNA test, but had any two of abnormal conditions in clinical symptoms, laboratory tests, and chest X-ray imaging, the case was defined as a suspected case. 9 Meanwhile, all the suspected children had exposed to COVID-19 patients within the last 2 weeks. 9 All children had completed the vaccines recommended by the childhood immunization program. Among them, age information was available from 2517 cases. Most of them (2492 cases) followed the age distribution as follows: less than 1 year: 446 (17.9%), 1 to 5 years: 593 (23.8%), 6 to 10 years: 626 (25.1%), 11 to 15 years: 492 (19.7%), and more than 15 years: 335 (13.4%). The age distribution of another 25 cases was grouped by using different criteria, 32 and the related information is presented in Table 1 . Gender information was available from 2566 cases, and the male/ female ratio was 1453 to 1113 ( Table 1) . The illness severity of COVID-19 was defined on the basis of the clinical characteristics, laboratory testing results, and chest radiographs, including asymptomatic infection, mild, moderate, severe, and critical. 9 According to our analysis of the 2597 cases (Table 1), 198 had an asymptomatic infection (7.6%), 1181 had mild illness (45.5%), 1079 had moderate illness (41.5%), 113 had severe illness (4.4%), 23 were critically ill (0.9%), and 3 could not survive (0.1%). Among them, 2558 children (98.5%) have an epidemiological link to the adult patients or an exposure to Wuhan or other epidemic areas. We also summarized the incubation period of 18 cases collected from seven articles; 16 (88.9%) of them showed symptoms within 2 to 10 days of exposure, 14, 20, 22, 23, 27 whereas the symptom onset occurred within 19 25 and 24 days, 21 respectively, for other two cases (11.1%). The clinical information from 452 children with COVID-19 in 23 articles was collected and analyzed ( one case of 1-year-old boy with congenital heart diseases 32 ; and the last one was a premature infant with an acute respiratory distress syndrome (ARDS). 29 It was reported that the first severe COVID-19 child in China initially had gastrointestinal symptoms and unobvious early respiratory symptoms, which then progressed to ARDS, septic shock, and acute renal failure rapidly; however, there were no underlying diseases. 31 The clinical manifestations of neonates were atypical. For the five cases, three of them (60%) suffered from fever and vomiting, two of them (40%) had diarrhea, and one of them (20%) had cough. 24 11 which indicated that the inflammatory reaction is serious. The chest X-ray or CT manifestation of infants (17 days, 3, 6, and 9 months old) is not typical, and its mechanism is worth further studying. 13 proposed that the median time from the symptom onset in patients to the diagnosis of SARS-CoV-2 infection was 2 days (0-42 days) (Table 5) . Meanwhile, some other studies also concluded that the time to diagnose SARS-CoV-2 infection mainly ranged within 1 to 5 days, but longer time cannot be excluded for some unexpected cases ( adults. 8, 9, 14, 18, 19 However, no comprehensive data are available on the impact of COVID-19 on children. It is reasonable to consider that they might be at an increased risk of severe disease, even death. 34 In this review, we collected 2597 cases and reported the demographic, clinical, laboratory and imaging characteristics of COVID-19 in children. Of the cases, most children had exposure to household members with confirmed COVID-19. Illness among pediatric cases appeared to be mild, as only 4.4% had severe and 0.9% had critical illness. Correspondingly, 14% had severe and 5% had critical illness in adults. 35 The primary symptoms in children are similar to those in adults, 36-39 but they have lower incidence rates: fever occurred in 82% to 98.6% of adults but in 43.1% of children, and cough occurred in 59.4% to 82% of adults but in 43.4% of children. Respiratory symptoms in children were mild, as 12.6% cases had tachypnea/ shortness of breath, which occurred in 31% of adult cases. 38 Other studies also reported that 55% of adult patients developed dyspnea 36 and 17% patients developed ARDS, which were rarely observed in children. However, the digestive tract symptom appeared more common in children, as diarrhea occurred in 6.6% of pediatric patients from our analysis, but in 2% to 3.8% of adult cases from some clinical studies [36] [37] [38] The different patterns of clinical features in respiratory system and digestive tract might result from the maturity and functional discrepancy of SARS-CoV-2 receptor ACE2 between children and adults. 40 However, more studies are still required to prove this hypothesis. There is a lack of particular laboratory findings on COVID-19 until now. However, some indicators presented in different patterns between children and adults should be considered. Lymphopenia is the most common lab finding in adults with COVID-19, which was found in as many as 70.3% to 83% of hospitalized patients. [36] [37] [38] [39] But in children, lymphopenia was only observed in 9.8% cases. PCT increased in 40.8% pediatric patients in our review, but it appeared normal in some other cases. 28 It is worth pointing out that 0 to 0.05 ng/mL of PCT is the normal range for laboratory testing. there was a report that a 10-year-old boy with an asymptomatic infection showed ground-glass opacities on CT scan. 33 Another report of 31 children with SARS-CoV-2 infection showed that three cases had no clinical manifestations, but had typical chest imaging manifestations. All these findings suggested that chest imaging changes may occur earlier than clinical symptoms, and they also showed the value of chest imaging in early infection recognition and diagnosis of children with COVID-19. 13 Given the much higher proportion of asymptomatic cases (7.6%) in children than that in adults (1%), 35 A novel coronavirus from patients with pneumonia in China A pneumonia outbreak associated with a new coronavirus of probable bat origin A new coronavirus associated with human respiratory disease in China The novel Chinese coronavirus (2019-nCoV) infections: Challenges for fighting the storm World Health Organization. WHO Director-General's statement on IHR Emergency Committee on Novel Coronavirus (2019-nCoV) World Health Organization. Coronavirus disease (COVID-19) Pandemic World Health Organization. Coronavirus disease (COVID-2019) situation reports SARS-CoV-2 infection in children Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020:e20200702 Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases Novel coronavirus infection in 34 children in Shenzhen: clinical and epidemiological characteristics Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features Analysis of CT features of 15 children with The different clinical characteristics of corona virus disease cases between children and their families in China-the character of children with COVID-19 Clinical features and chest CT findings of coronavirus disease 2019 in infants and young children Novel coronavirus infection in hospitalized infants under 1 year of age in China Detection of Covid-19 in children in early Clinical features of pediatric patients with COVID-19: a report of two family cluster cases SARS-CoV-2 infection with gastrointestinal symptoms as the first manifestation in a neonate 2019 novel coronavirus infection in 1 children Clinical analysis of 1 case of 2019 novel coronavirus pneumonia in Yunnan Province Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase First case of severe childhood novel coronavirus pneumonia in China Clinical characteristics of children with coronavirus disease 2019 in Hubei, China A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster COVID-19 infection in children Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention Clinical features of patients infected with 2019 novel coronavirus in Wuhan Clinical characteristics of Covid-19 in China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan Procalcitonin: the marker of pediatric bacterial infection Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Liver injury in COVID-19: management and challenges Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection CT imaging of the 2019 novel coronavirus (2019-nCoV) pneumonia Evolution of CT manifestations in a patient recovered from 2019 novel coronavirus (2019-nCoV) pneumonia in Wuhan Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2 Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing A well infant with coronavirus disease 2019 (COVID-19) with high viral load Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients The authors decare that there are no conflict of interests.