key: cord-0807097-ctowz2j8
authors: Imai, Kazunori; Matsushima, Asako; Saitoh, Shinji
title: Characteristics and considerations in the medical treatment of COVID‐19 in children
date: 2020-10-15
journal: Acute Med Surg
DOI: 10.1002/ams2.597
sha: a0895c2b7fed307cdfe8eb42651997ec7291d944
doc_id: 807097
cord_uid: ctowz2j8

It is rare for children to be in serious condition or die from Coronavirus disease 2019 (COVID‐19) caused by the 2019 novel coronavirus (SARS‐CoV‐2) except for those with underlying diseases such as chronic lung disease (including asthma), cardiovascular disease, and immunosuppressive disease. Recently, patients with hyperinflammatory shock have been identified among children who are confirmed to have or are suspected of having SARS‐CoV‐2 infection. The presenting signs and symptoms are characterized by prolonged fever, abdominal pain, and cardiac involvement without any signs of pneumonia on chest computed tomography. However, it is uncertain at this time whether SARS‐CoV‐2 infection affects this syndrome. Compared to adults, quite a few children are asymptomatic even when infected with SARS‐CoV‐2, which could make these children serious sources of infection at home or in medical institutions. Considering these characteristics, it is important to take appropriate precautions during medical examinations and perform infection control in emergency departments to save the lives of both the children and adult patients. Most healthy children are suffering huge stress due to restrictions against going outside and school closures as social means to control infection. It is possible that children are socially isolated when they come to the emergency department, and they might require mental or social support even if they are only complaining about their physical condition. Healthcare providers are required to examine the children’s circumstances carefully and cooperate with workers in other professions appropriately.

In December 2019, an infection caused by a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China. The infection was named novel coronavirus disease 2019 . Later, SARS-CoV-2 infection spread throughout the world, but early reports confirmed few infections in pediatric patients, whereas more than half of those infected were over 60 years of age. Therefore, it was pointed out that children may not be infected with SARS-CoV-2 or that they may experience very slight symptoms. 1 Since then, there have been reports of pathological conditions and epidemiology in children, and the characteristics of COVID-19 in children have become clear.

We summarized the characteristics of COVID-19 in children and the important points in pediatric emergency care during the COVID-19 pandemic based on literature and epidemiological data published as of June 10, 2020. We searched for papers on the PubMed web database as of June 10, 2020, using the search terms COVID-19, SARS-CoV-2, and children, and investigated survey reports, systematic reviews, and case reports that seemed to be clinically significant. For case reports, the reports with larger numbers of cases were prioritized and adopted. In addition, in view of the fact that social policies are changing over time, epidemiologic data published by public institutions such as the Japanese Ministry of Health, Labor and Welfare and the World Health Organization, and guidelines posted on the websites of related academic societies such as the Japanese Association for Acute Medicine and the Japan Pediatric Society were also examined.

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According to reports from each country, pediatric patients account for 0-5% of COVID-19 patients diagnosed by PCR and are considered to be rare. [2] [3] [4] In Japan, 17,051 patients were confirmed to be COVID-19 positive by PCR, except for those returning by charter flights and those confirmed in airport quarantine or on the cruise ship Diamond Princess. Among these 17,501 patients, 284

(1.7%) are under the age of 10, and 418 are in their teens (Figure 1 ). 5 The rate of PCR testing for COVID-19 varies from country to country, but the proportion of children with COVID-19 in Japan compared to that in other countries is not significantly different. Among children, patients have been reported in a wide range of age groups from 0 to late teens, and it appears that there is no difference in morbidity depending on age (Table 1) . [6] [7] [8] [9] ② Transmission route From China, it was reported that in 28 pediatric patients with confirmed COVID-19 aged 1 month to 17 years of age, all belonged to a family cluster of infections or had extensive contact with infected persons. 10 In contrast, a follow-up report of 392 co-family members who were in contact with 105 confirmed COVID-19 patients found a 16.3% incidence of secondary transmission within the family. The secondary attack rate was 4% in children younger than 18 years of age, significantly lower than that of adults at 17.1%. 11 It has been pointed out that the transmission route of SARS-CoV-2 may include aerosol transmission in addition to droplet/contact infection. 12, 13 Initially, the incubation period was reported to be about 5-6 days and that the amount of excreted virus was at its maximum immediately after

This article is protected by copyright. All rights reserved the symptoms appeared. 14, 15 However, it was more recently reported that the excretion of virus increases over the 2-3 days before disease onset and peaks 0.7 days before onset. 16 Even in children, it was reported that asymptomatic infants whose mother was diagnosed as having COVID-19 had nasopharyngeal excretion with a viral load similar to that of the mother. 17 Children infected with SARS-CoV-2 have been shown to potentially excrete large amounts of virus in the long term, even when asymptomatic, and may be a potential source of infection.

Due to the effects of school closures worldwide, childhood infections are currently centered around secondary infections within the family. However, there is concern that the number of infected children may increase with the reopening of schools and that infection may also spread through asymptomatic children.

In a meta-analysis of 3600 COVID-19 patients, fever (83.3%), cough (60.3%), and malaise (38.0%) were the most common clinical symptoms. 18 However, 5.8% of patients were also reported to be asymptomatic. Although there are no specific findings for COVID-19 in children, the incidence of individual symptoms tends to be lower than that in adults ( Table 2 ). [6] [7] [8] [9] In addition, it was also reported that among 171 pediatric patients with COVID-19, 27 (15.8%) were asymptomatic, and pneumonia could not be detect by radiological examination. 7 Compared to adults, children are less likely to develop symptoms when infected with SARS-CoV-2, and the rate of asymptomatic passage may be higher than that of adults.

This article is protected by copyright. All rights reserved It was reported that the sensitivities of PCR tests and computed tomography (CT) scans at the first visit in confirming COVID-19 infection in adults were 84.6% and 97.2%, respectively. 19 CT examination findings are characterized by interstitial shadows called ground-glass opacification (GGO) that appear on the dorsal and peripheral sides of the lung field. 20, 21 In addition, as characteristic findings in children, GGO that appears as a lighter shadow in a more localized area that does not straddle a lung lobe 22 and infiltrative shadows with a halo have been reported. 23 Among 15 patients under 15 years of age with confirmed COVID-19, 7 of 8 asymptomatic patients (4 at initial diagnosis, 3 during follow-up) had GGO. 24 From the above, it is possible that more sensitive diagnosis can be made in children by combining PCR with CT.

Hematological findings do not show any specific findings of COVID-19 in children but only nonspecific changes associated with viral infection. 7 Therefore, it is difficult at present to diagnose SARS-CoV-2 infection from the results of blood tests alone.

Thus, tests with high sensitivity and specificity for SARS-CoV-2 infection are limited, disease severity in pediatric patients rarely increases, and there is no effective treatment at this time.

Therefore, PCR testing should be performed in children only if there is a history of concentrated contact and symptomatic infection, mass infection, or pneumonia or respiratory distress of unspecified cause. Testing for asymptomatic and mild patients is not recommended. 25

The mortality rate of patients of all ages due to COVID-19 is reported to be 5.6% worldwide. 5 The severity of 44,672 COVID-19 patients confirmed by PCR from China was reported; severe pneumonia with respiratory failure was present in 14%, respiratory failure/septic shock/organ

This article is protected by copyright. All rights reserved failure occurred in 5%, and death in 2.3% (no deaths of patients under 9 years old). 2 In Japan, the total number of deaths was 920 (5.4%), and no deaths under the age of 19 were reported ( Figure   1 ). 5 Table 3 shows the severity of pediatric patients confirmed to have COVID-19 by PCR and the number of deaths. From China, it was reported that of 171 pediatric patients aged 15 and younger, 3 patients (1.8%) who had underlying disease required management in the intensive care unit (ICU), and one who had intussusception died. 7 It was also reported that of 731 children under the age of 18, 12.9% were asymptomatic, 43.1% had respiratory symptoms, 41% pneumonia, 2.5% hypoxemia, and 0.4% acute respiratory distress syndrome or organ failure. 9 Furthermore, in the United States, it was reported that of 745 children with COVID-19 under the age of 18, 147 (19.7%) were hospitalized, 15 (2.0%) were admitted to the ICU, and 3 (0.4%) died. 6 Ninety-five infants under the age of one were included , with 59 hospitalized and 5 admitted to the ICU. Of these patients, the medical history and course of symptoms were available in 295. Thirty-seven children were hospitalized, of whom 28 (77%) had one or more underlying diseases such as chronic lung disease (including asthma), cardiovascular disease, and immunosuppression, but only 30 outpatients (12%) had underlying disease.

For severely ill children, a report of 48 admissions to pediatric ICUs in the United States and Canada (median age 13 years) found underlying disease in 40 of them (24 of 40 patients had 2 or more comorbidities) 26 . The most common comorbidity was immunosupression/malignancy (11 patients 

This article is protected by copyright. All rights reserved required a ventilator, and one required extracorporeal membrane oxygenation (ECMO). Eleven patients suffered organ failure of two or more organs, and 2 died.

The rates of COVID-19-induced morbidity and mortality in children are very low compared to those in adults, but it should be noted that there are a certain number of pediatric patients who experience severe illness and require ICU management, especially in those with underlying diseases.

In the United Kingdom in April 2020, some children with confirmed or suspected COIVD-19

showed rapid vasodilatory shock with fever, skin rash, conjunctivitis, peripheral edema, pain in the extremities, and prominent gastrointestinal symptoms despite the absence of pneumonia. 27 It was speculated that SARS-CoV-2 was associated with Kawasaki Disease (KD), KD shock syndrome (KDSS), and toxic shock syndrome (TSS). As of June 2020, this disease state has been defined as multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) by the US Centers for Disease Control and Prevention (CDC) and pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIM-TS) by the European CDC. 28, 29 The accumulation of cases has begun. 

Symptoms were mainly non-specific, such as fever (100%), vomiting (45%), diarrhea (52%), skin rash (52%), and conjunctival hyperemia (45%). Only 12 (20%) had respiratory symptoms. Blood tests showed marked elevations of inflammatory markers such as C-reactive protein and ferritin, and 29 of the 58 (50%) were in cardiogenic shock accompanied by elevation of myocardial escape enzyme. Of the 58, 13 met the American Heart Association definition of KD, with 8 (14%) having dilated coronary arteries.

In a report of 35 people who met the MIS-C definition (median age, 10 years old), 88% had a confirmed SARS-CoV-2 infection by PCR or serology with a pharyngeal swab. 31 Left ventricular ejection fraction decreased to less than 30% in 33% of cases, catecholamine administration was required in 80%, and induction of ECMO was required in 28%. Dilation of the coronary arteries was observed in 17% of cases.

In the patients with this condition, the age at illness and the proportion of African, Hispanic, and Caribbean races is higher than those of patients with KD. In addition, few of the cases satisfy the classic KD symptoms mainly in regard to digestive symptoms, and the main pathological cardiac condition is deterioration of left ventricular function rather than changes in the coronary arteries.

Thus, contrary to the initial consideration, characteristics differences from KD have been reported. [30] [31] [32] Many of the patients had a SARS-CoV-2 infection or a history of infection, but there are some who developed this condition a few weeks after the infection was confirmed by PCR, or who already had an elevated serum IgG level at the time of consultation. 33 Whether this condition is directly related to SARS-CoV-2 or is a secondary condition resulting from the immune reaction induced by SARS-CoV-2 infection remains unknown. It will be necessary to collect cases and analyze pathological conditions in the future.

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According to the American Heart Association provisional guidelines, aerosol-generating procedures in emergency medicine include chest compressions, manual ventilation, tracheal intubation and extubation, tracheal suction, high-flow nasal oxygen, non-invasive positive pressure ventilation, tracheostomy, and inhalation therapy with a nebulizer. 34 Especially, resuscitation is recommended to be performed in a negative-pressure private room.

The Japanese Society of Pediatric Allergy and Clinical Immunology recommends the use of a metered dose inhaler (MDI) with a spacer in place of a nebulizer for the treatment of asthma, considering the potential transmission of aerosol-borne infections. 35 When an infant infected with SARS-CoV-2 is hospitalized and a family member is also infected, the family member may need hospitalization/treatment depending on the medical condition. In many hospitals, even if the family is non-infected, the family cannot enter the infected ward where the child is hospitalized. Infants and children often require full-fledged life support, and it is difficult

This article is protected by copyright. All rights reserved to control their behavior. Therefore, if family members cannot help, there is a high risk of causing infection or nosocomial infection in medical personnel who provide care. 38 For this reason, the Japanese Academy of Pediatrics provides specific guidelines for the practice of COVID-19 treatment in children. 38 For example, if the child's illness is mild, he/she will be treated at home. However, if the child needs to be hospitalized, the parents are allowed to take care of their child in the ward.

There is a strong concern that in addition to restrictions on going out due to the spread of infection and restrictions on daily activities, the loss of social ties due to school closure changes the life rhythm of "healthy" children, which can have negative psychological and physical effects on them. 39 Children who are isolated from infection are reported to have a four-fold greater risk of post-traumatic stress syndrome than those not isolated. 40 It has also been pointed out that the mental and financial anxiety of parents who should be caring for their children may lead to domestic violence and child abuse. 41, 42 It is feared that restrictions on going out and school closure will keep these problems hidden in the home and isolate the affected children even more.

In pediatric emergency care, it is important not only to cure the illness of the child but also to encourage the family and society to advocate for and improve the environment for the child. 43 Healthcare workers must consider that a child who is presenting with physical symptoms may need psychological support or may be socially isolated and that the visit to the emergency department may be the child's only social contact point. In addition, it is important to observe the

This article is protected by copyright. All rights reserved behavior of the patient and his/her family at the time of medical examination and to deal with it by coordinating with multiple healthcare professionals such as social workers as necessary. Table 3 . Summary of studies on the severity of pediatric COVID-19 † Severe: patients who were treated in the ICU or required mechanical ventilation or extracorporeal membrane oxygenation.

‡ Moderate: patients who were treated in a general ward. §Mild: patients who had symptoms of acute respiratory tract infection but did not require hospitalization. N.D., not described. 

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