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COVID‐19 epidemic: Disease characteristics in children

Abstract In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children.

fragment. Zhou et al 5 used cryo-electron microscopy to analyze the full-length structure of the SARS-CoV-2 receptor, namely, ACE-2, for the first time, which will be helpful in developing inhibitors to block entry of the virus into cells. On 21 February 2020, Thi et al proposed that active SARS-CoV-2 can be produced and transformed based on viral genetic structure, which is important in understanding and predicting development trends of the virus and the disease. 6 On 3 March 2020, Tang et al 7 described the genome evolution of 103 new coronaviruses and found that SARS-CoV-2 has evolved into two subtypes, L and S, and the virus strain has 149 mutation points more common in the early stages of the Wuhan outbreak; as such, it is speculated that it is more infectious and capable of spreading.
COVID-19 was predominantly more prevalent among adults more than or equal to 15 years of age in the early stages of the outbreak, and the proportion of confirmed cases among children was relatively small. Since then, however, more regions have launched pathogen detection campaigns and, because younger children cannot wear masks and have not taken other special preventive and control measures, the number of child infection cases has increased significantly, especially in younger age groups and, therefore, should be given high attention. 8 On 2 February 2020, the PRC issued a notice on "doing a good job in the prevention and control of pneumonia outbreaks in children and pregnant women with new coronavirus infection," which clearly states that children are susceptible to SARS-CoV-2 due to the immaturity of their immune systems. 1 The latest guidelines also make it clear that all individuals, including children, are generally susceptible to SARS-CoV-2. 9 Furthermore, children exhibit certain particularities and cannot clearly describe their own health status or contact history, which has contributed to the severe challenge of protecting, diagnosing, and treating this population. 10 Due to the increasing global spread of SARS-CoV-2, China is now facing the risk of transmission of imported cases, which poses new challenges for the prevention and control of the COVID-19 epidemic among Chinese children. At the same time, children with other (ie, comorbid) diseases (such as congenital heart, lung and airway diseases, malnutrition, and tumors, etc) are vulnerable to infection with SARS-CoV-2; more specifically, "prone to severe illness." 11 The present article reviews the epidemiological characteristics of COVID-19 in children.  13 and, as of 26 February 2020, the total number of confirmed cases in Wuhan, China was 490. 14 Two children with COVID-19 were diagnosed in Germany on 4 February 2020 1 and a 5-year-old child in the Philippines was also diagnosed. 15 Canada reported the first confirmed case of COVID-19, who still carries the virus after rehabilitation and discharge, and is a possible communicator. 16 Zou et al 17 analyzed the relationship between viral load and symptoms of infection in 18 patients with COVID-19, and found that the pattern of viral nucleic acid excretion in those with SARS-CoV-2 infection was similar to that of influenza and that the viral load determined in asymptomatic patients was similar to that of those with symptoms, which indirectly suggested potential transmission capacity in asymptomatic or mild cases with COVID-19. Current studies have shown that the incubation period of SARS-CoV-2 is 1 to 14 days, and most commonly 3 to 7 days. 9 However, Guan et al 18 described a patient with an incubation period of up to 24 days.

| EPIDEMIC STATUS
Subsequently, Bai et al 19 reported a patient with an incubation period of up to 19 days, who was also the first asymptomatic infection in China. Children, generally, have low immunity and some exhibit a long incubation period after SARS-CoV-2 infection. Therefore, children should try to avoid contact with complex populations to avoid being infected by potential spreaders.
COVID-19 is an acute, self-limiting disease; nevertheless, patients can die, with a mortality rate of 2%, 20 and have also been reported in critically ill children. 21 Compared with the current COVID-19 epidemic, during the outbreak of SARS-CoV, the number of confirmed in children cases (4 months to 17 years of age) worldwide was less than 0.02% of the total number of cases (no deaths were confirmed in children), and children with severe cases accounted for ∼7.9%, and the vast majority of these had a history of family exposure or adult contacts, while a few had a history of travel in affected areas and a history of exposure in the hospital. Of the 1621 confirmed cases of MERS-CoV reported globally, children less than 19 years of age accounted for ∼2.2%.
Of the 14 pediatric cases (8 months to 16 years of age), nine (64%) were children infected after home exposure, but all were asymptomatic: five (36%) were in the hospital and at home, with a history of internal exposure were symptomatic infections, of whom two (14.3%) exhibited mild respiratory symptoms, three  As the outbreak spread, it was gradually confirmed that SARS-CoV-2 could be transmitted from person to person in places such as homes or hospitals, and even from city to city, and country to country. Children are a very special group, largely due to close family contacts, and may be susceptible to cross-infection. According to existing epidemiological data, 56% (34/61) of children with COVID-19 demonstrated clear evidence of transmission through family gatherings. 23 China's first newborn COVID-19 patient was diagnosed at 17 days of age, first confirmed in the family nursing staff, followed by the parents, who were also diagnosed with COVID-19. 24 A 5-day-old neonatal COVID-19 patient, whose mother was also confirmed to be infected with SARS-CoV-2, and a newborn with suspected disease from cesarean delivery was confirmed to be infected with SARS-CoV-2 36 hours after birth, followed by his mother who was diagnosed with COVID-19 shortly after giving birth. 25 On 26 January 2020, a 3-month-old baby and its parents in Hubei Province, China, were both confirmed to be infected with SARS-CoV-2. 26 On 19 January 2020, a hospital in Shanghai, China, admitted a 7-year-old boy diagnosed with SARS-CoV-2 infection, whose father was diagnosed with COVID-19 earlier than the child. 27 On 11 January 2020, a case of asymptomatic infection was found in a 10- year-old boy in Shenzhen, Guangdong, China, whose parents, grandparents, and grandparents all developed fever, diarrhea, cough, and other symptoms, and were diagnosed with COVID-19 earlier than the boy. 28 According to the epidemic situation described by Anhui Provincial Health Commission on 28 and 29 January 2020, a family of six in Huangshan city, Anhui, China, was confirmed to have COVID-19, including an 8-month-old baby and a 10-year-old child. 1 These cases were found in family clusters. Wei et al 8 performed a study on nine infant COVID-19 patients, revealing that they all had at least one family member who had been infected with SARS-CoV-2 earlier, among which seven infants lived in Wuhan, China or had family members who had traveled to Wuhan. The parents of a 6-month-old baby in Singapore were infected with SARS-CoV-2. After the parents were diagnosed, the baby was initially asymptomatic but was admitted to the hospital due to close contact. The baby was diagnosed with SARS-CoV-2 the day after admission. 29 The average incubation period for COVID-19 in children is ∼6.5 days, which is longer than the 5.4 days reported in adults. The average number of secondary infections transmitted within the family was 2.43. The duration of nasal and pharyngeal detoxification in children is 6 to 21 days (average 12 days). 30 An epidemiological analysis of 31 children with COVID-19 in six provinces (autonomous region) of northern China found that 21 (68%) had contact with an adult with confirmed disease. One (3%), who had contact with asymptomatic Wuhan return Township staff (without nucleic acid testing), became ill after 5 days, and 28 of these 31 children (90%) were clustered in families. 31

| Patients with COVID-19 exhibit characteristics of exposure to infection in the foci
According to available epidemiological data, 43% of children with COVID-19 (26/61) exhibited characteristics of infection from epidemic exposure. 23

| Age and sex distribution characteristics of COVID-19 patients
Patients with COVID-19 are distributed among all age groups. A study investigating 8866 cases of COVID-19 reported that the majority of patients were 36 to 65 years of age, with only 14 children less than 10 years of age diagnosed with the disease. 33 In an investigation of 72 314 cases, Wu et al 34 reported that children less than or equal to 9 and 10 to 19 years of age accounted for 1% of the total number cases, respectively. The youngest of the confirmed child cases to date was merely 30 hours of age, and the oldest was 18 years. 1 Studies have reported a higher incidence in men than in women (0.31/100 000 vs 0.27/100 000, respectively). 33 In a study involving nine children with COVID-19 less than 1 year of age, seven were girls 8 ; however, it was not possible to determine whether girls or boys were more susceptible  increased to greater than 1 around 3 January 2020, and peaked at 8 to 15 January, but fell again to less than 1 after 16 January 2020.
However, the researchers believe that this did not necessarily indicate a decline in the transmission capacity of the virus, but may have been related to a delay in reporting epidemiological data. 33 According to a study involving 1099 patients, Bai et al 19 reported that there was asymptomatic transmission of infected patients without excluding the existence of "super-disseminators." The Korean government confirmed a "super-spread incident" on 20 February 2020, in which a surge of 53 cases in a single-day was reported, of which 43 individuals from a church in Daegu were diagnosed. 42 In response to this epidemic, a new virus was found in the clinical front line before it spread, which is of great importance to early detection of pathogens and the implementation of effective prevention and control measures. Success in containing the SARS-CoV-2triggered epidemic was largely due to the country's immediate measures at the beginning of the first spread of COVID-19, a very important "golden window" for disease control. A second-generation epidemic will be exponentially larger. Therefore, the application of modern diagnostic technology can more effectively grasp the "golden window" period for infectious disease prevention and control. 43

| SARS-CoV-2 infection is widespread
3.4.1 | SARS-CoV-2 can be transmitted by respiratory droplets, close contact, aerosols, and through the conjunctiva They found that ACE2 was not only expressed in lung AT2 cells, but also in upper esophageal and stratified epithelial cells, as well as intestinal epithelial cells in the ileum and colon. Therefore, intestinal symptoms of SARS-CoV-2 may be associated with invasion of intestinal epithelial cells expressing ACE2. 46 In an earlier report from Wuhan, China, 2% to 10% of patients with COVID-19 experienced gastrointestinal symptoms such as diarrhea, abdominal pain, and vomiting.
Patients with SARS-CoV-2 infection who were transferred to the intensive care unit exhibited a higher frequency of abdominal pain than those with SARS-CoV-2 infection who did not require intensive care, and 10% of patients with COVID-19 experienced diarrhea and nausea symptoms in the 1 to 2 days before the onset of fever and respiratory symptoms. 49 A study from the USA reported detected SARS-CoV-2 RNA in the feces of a patient. 50

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There is no direct evidence that SARS-CoV-2 can be transmitted vertically from mother to child Since the Wuhan Children's Hospital diagnosed COVID-19 in an infant at 30 hours of age on 5 February 2020, it has been argued that SARS-CoV-2 may be transmitted vertically from the mother to the child. 1 Based on the potential mechanism of vertical transmission to the fetus, potential susceptible cell subsets of SARS-CoV-2 may not exist at the maternal-fetal interface, and the results show that there is no evidence of vertical transmission of SARS-CoV-2 to the fetus. 52 Chen et al 53 tested for the presence of SARS-CoV-2 in amniotic fluid, umbilical cord blood, and neonatal pharynx swab and breast milk samples at first lactation and detected no virus. All patients in the study were in the late stages of pregnancy; as such, evidence of intrauterine vertical transmission was insufficient. Nevertheless, the possibility of early or midgestational vertical transmission could not be determined. In addition, the study did not collect vaginal mucosal samples or birth canal shedding samples; therefore, it was not possible to analyze whether SARS-CoV-2 infection could be transmitted during vaginal delivery. 53 It is also uncertain whether breastfeeding leads to vertical transmission from mother to child. There is no direct evidence of vertical mother-to-child transmission; however, newborns can be infected through close contact.
Zhu et al 54 considered neonates to be at high risk for SARS-CoV-2 infection if they met the following criteria: the mother experienced persistent fever before, during, or after childbirth, and routine laboratory investigations revealed a decrease in lymphocyte ratio; chest CT revealed lung infiltration, based on viral nucleic acid test results and epidemiological history suggesting that the mother is a confirmed/highly suspected case (remove other viral and bacterial infections, mycoplasma infections, puerperal fever, breast swelling, mastitis, and other obstetric conditions); newborn whose mother has clinical manifestations or epidemiological history of infection, but not sufficiently suspicious to definitively diagnose; newborns with a history of infection epidemiology, including those from community sources and obstetric mother-infant same-room sources, family members or caregivers, and visitors who are training and, at the same time, perform hospital cleaning and disinfection to ensure that newborns admitted for separate treatment are not exposed to infection risk. 1 3.5 | Changes in incidence during the timeline Before 23 January 2020, the incidence of COVID-19 increased exponentially, which basically corresponded to the spring transportation period, and the growth of suspected cases was slightly lower than that of diagnosed cases for 2 to 3 days. 33 According to incomplete statistics, as of 24:00 hours on 31 January 2020, China reported a total of 74 confirmed cases involving children. 23 As of 15 February 2020, incomplete statistics reported 300 cumulatively confirmed cases involving children nationally (excluding Hubei region). 13 Thirty days after the report of the first confirmed case of COVID-19, the epidemic spread to the entire country (the first confirmed imported COVID-19 patient in Guangdong province on 19 January 2020, was the first confirmed patient outside Hubei province 35 ). The first epidemic peak occurred between 24 and 26 January 2020, and then gradually decreased from 1 February 2020. 35 Shen et al 55 evaluated the role of the Wuhan "limit inflow and outflow" strategy in controlling the epidemic through mathematical models. The study predicted that "limit inflow and outflow" could reduce all cases of infection and by nearly 70%, assuming that all individuals wore a mask after "limit inflow and outflow" and that masks could reduce the risk for infection by 90%.
Limit inflow and outflow, the establishment of the Raytheon Mountain, SHE ET AL.

| 5
Fire God Mountain, and Fang Cabin Hospitals, delayed resumption of work, suspension of classes, 56 and enhanced etiological detection in various places all affected changes in morbidity.

| COVID-19 mortality rate
According to preliminary statistics, the mortality rate among were negative at the time of throat swab virus nucleic acid testing, were children: two at 9 days after illness; and three at 12 days after illness. Two critically ill patients had a history of underlying disease, and one was after congenital heart disease 7 months with moderate malnutrition; the one other had bilateral hydronephrosis and left kidney stones. Of the 134 confirmed cases of disease in children, if chest imaging was used as the basis for the diagnosis of pneumonia, 36 patients exhibited the common type (26.9%, including seven cases, were subclinical); two cases were critically ill (1.5%); nine cases were completely asymptomatic with normal lung imaging and asymptomatic infection (6.7%); and 87 cases were mild (64.9%). 27 The data show that the prevalence of disease in children less than or equal to 18 years of age is relatively low, accounting for ∼2.4% of all reported cases, 59  Among these 10 children with COVID-19, body temperature, routine blood tests, and chest computed tomography tests showed that, compared with adults, children with COVID-19 were less ill and exhibited less obvious symptoms, and were not typical. 51 Although the incidence of critical illness in children is low, the current incidence is sufficient to alert pediatricians. In is important to identify children with COVID-19, especially those with underlying/comorbid disease (s), and to treat them early.
In summary, special attention should be devoted to children