Pediatric Annals

Feature Article 

Pediatric COVID-19 Disease: A Review of the Recent Literature

Meyri Arzu Yoldas, MD; Hamit Yoldas, MD

Abstract

The first pediatric coronavirus disease 2019 (COVID-19) case was confirmed in Shenzhen, China on January 20, 2020. At the beginning of the outbreak, COVID-19 pneumonia was more common in adults than in children and adolescents, and the rate of confirmed pediatric cases was relatively lower. However, as screening tests and pathogen detection campaigns were initiated in more regions as the outbreak spread, the number of pediatric infection cases increased significantly. Currently, studies on pediatric COVID-19 are limited in the literature to case reports and case series, and a few epidemiological studies. COVID-19 has distinct characteristics in the pediatric population compared to adults; therefore, we need to better understand the characteristics of this disease in children. Discovering the characteristics of the pediatric COVID-19 disease is important for contributing to the diagnosis and treatment of the disease in this population. In this review, clinical characteristics, epidemiology, diagnosis, and management of pediatric COVID-19 pneumonia based on the recent literature are discussed. [Pediatr Ann. 2020;49(7):e319–e325.]

Abstract

The first pediatric coronavirus disease 2019 (COVID-19) case was confirmed in Shenzhen, China on January 20, 2020. At the beginning of the outbreak, COVID-19 pneumonia was more common in adults than in children and adolescents, and the rate of confirmed pediatric cases was relatively lower. However, as screening tests and pathogen detection campaigns were initiated in more regions as the outbreak spread, the number of pediatric infection cases increased significantly. Currently, studies on pediatric COVID-19 are limited in the literature to case reports and case series, and a few epidemiological studies. COVID-19 has distinct characteristics in the pediatric population compared to adults; therefore, we need to better understand the characteristics of this disease in children. Discovering the characteristics of the pediatric COVID-19 disease is important for contributing to the diagnosis and treatment of the disease in this population. In this review, clinical characteristics, epidemiology, diagnosis, and management of pediatric COVID-19 pneumonia based on the recent literature are discussed. [Pediatr Ann. 2020;49(7):e319–e325.]

At the end of December 2019, a new type of coronavirus infection emerged in Wuhan, China and spread rapidly to the rest of mainland of China and then to the rest of the world.1 On January 10, 2020 it was confirmed that the virus was isolated from the lower respiratory tract of a patient and was a novel type of coronavirus. The first pediatric case was confirmed in Shenzhen, China on January 20, 2020.2 On February 11, 2020, the infectious disease caused by this novel coronavirus was named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 was declared as pandemic by the WHO on March 12, 2020.3 At the time of this writing, the pandemic was rapidly spreading worldwide, causing a significant death toll, and having major social and economic impacts. According to the daily report published by the WHO on May 5, 2020, there were 3,517,345 confirmed cases and 243,401 deaths worldwide.4 As of the same date, according to WHO risk assessment, the general risk of death caused by the disease is still in the “very high” category at the global level.4

Initial studies on COVID-19 have focused predominantly on respiratory symptoms, which are more common in adults are rarer in children.5 At the beginning of the outbreak, COVID-19 pneumonia was more common in adults than in the pediatric age group, and the rate of confirmed pediatric cases was relatively low. However, as screening tests and pathogen-detection campaigns were initiated in more regions as the outbreak spread, the confirmed number of pediatric infection cases increased significantly.6 Recent guidelines have reported that all people, including children, are sensitive to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen.7 In addition, the fact that children exhibit certain characteristics and cannot state their own health status or contact history makes protection of this population, as well as diagnosis and treatment of the disease in this age group, more difficult.8 As in many infectious diseases, COVID-19 pneumonia affects children differently than adults, and understanding these differences will contribute to the development of treatment strategies by providing important information about the pathogenesis and management of this disease. Therefore, revealing the characteristics of the pediatric COVID-19 disease is important for contributing to the diagnosis and treatment of the disease in this population. Data about COVID-19 in children have not been fully developed, and presently there are only limited case reports and case series in the literature.9 This review discusses characteristics of the pediatric COVID-19 pneumonia in the light of the recent literature.

Why COVID-19 is Different in Children

Aging is associated with a progressive decline in normal function of the immune system, leading to weaker immune responses and disruption of the ability of an individual to give response to stimuli. Aging affects the composition effect on peripheral C4 and C8 T cell pools, and it has a negative effect on adaptive immunity, which is thought to be the leading cause of morbidity and mortality in older adults.10 CD8 T cells play a more important role than CD4 T cells in control of disease and clinical outcomes in numerous viral infections. The function of CD8 T cells is to recognize and destroy the cells infected with the virus, contributing to antiviral immunity. It has been found in COVID-19 patients that T cell counts significantly decrease with age. This was proposed as an additional hypothesis to explain the lower incidence of COVID-19 pneumonia in children.11

According to the data published by the Chinese Center for Disease Control and Prevention (CCDC) on February 11, 2020, 0.9% of COVID-19 cases are in patients age 0 to 10 years, and 1.2% are in patients age 10 to 19 years.12 One possible reason why children are less susceptible to COVID-19 is that they are less involved in activities outside of the home and in international travel, reducing their likelihood of viral contact. However, the number of pediatric cases has increased as the pandemic has spread, and even infants may be infected by COVID-19.6

The reason of relative resistance in children to some infectious diseases is not fully understood. It was argued that changes related to maturation in the axonal transport system of mice can explain the resistance against poliovirus-induced paralysis.13 It was also suggested that the COVID-19 S protein binds to angiotensin-converting enzyme 2, and children are protected against this virus because this enzyme is less mature in younger people.14 Another proposed reason is that children have a more active immune response and they do not smoke, making their respiratory tract healthier. In addition, the incidence of underlying disease is lower compared to adults.

Epidemiology

As the pandemic progressed, transmission of SARS-CoV-2 pathogen from person to person in shared living space, hospitals, and interprovincial and international settings was confirmed.15 Children are a special group due to their close contact with family members, and they are sensitive to cross infection. In a recent study, a history of transmission through family or social gatherings was found in 56% of children with COVID-19.16 Again, in an epidemiological analysis of pediatric COVID-19 patients, a confirmed history of contact with an infected adult was observed in 68% of cases.17

According to the initial data from China, children seem to be less affected by COVID-19 than adults. This is reflected both by the number of cases and disease severity. This finding has been confirmed with the data from other countries, especially Italy.18 The rate of infection is much lower in children in Europe and the United States as well.18 There are concerns that selective testing leads to these lower rates. However, data from South Korea and Iceland, where large-scale community testing has been carried out, showed lower incidence in children. No cases in children younger than age 10 years were found in the town of Vo in Italy, a place in which 70% of the population was screened. The overall infection rate in Vo is 2.6%.18

In a study investigating 8,866 COVID-19 cases, the majority of patients were between ages 36 and 65 years, and only 14 children younger than age 10 years were infected.19 In a study of 72,314 COVID-19 cases in China, Wu and McGoogan20 reported that patients age 19 years or younger accounted for just 1% of all cases. Children constituted just 2% of the confirmed cases in China,21 1.2% in Italy,22 and 5% in the US.23 So far, the youngest reported pediatric patient was age 30 hours1 and the oldest child was age 18 years.24

Transmission

Presumably, when the virus spread further during the middle of January 2020, infected adults caused transmission to their family, especially to older adults and children who are more susceptible to the infection. The possibility of contact with family members and/or other children with COVID-19 clearly indicates person-to-person transmission in most children with COVID-19. There are findings indicating that children are sensitive to SARS-CoV-2 infection, but often do not have notable symptoms. This increases the likelihood of children to facilitate transmission. Because children are crucial for viral transmission and amplification, social and public health policies should be developed (eg, prevention of interaction with elderly people) to decelerate transmission and protect susceptible groups.

Clinical Characteristics

The majority of children with COVID-19 don't develop any symptoms or have only subclinical symptoms. According to the most detailed pediatric population data reported from China, 13% of the confirmed pediatric patients have no symptoms. Considering both confirmed and suspected cases together, 32% of children aged between ages 6 and 10 years are asymptomatic.25

Clinical features are somewhat different in symptomatic children compared to adults. Children have a tendency toward milder disease. The most common admission symptoms in pediatric symptomatic cases include fever and cough, which are seen in more than half of this patient group. Upper respiratory tract symptoms such as rhinorrhea and sore throat are seen in 30% to 40% of pediatric COVID-19 patients. Diarrhea and/or vomiting are observed in about 10% of the pediatric cases, and sometimes these symptoms are the single feature at presentation.26 Prognosis of the disease is milder in the patients with confirmed diagnosis of COVID-19 compared to the suspected patients, and this suggests that COVID-19 can be milder in this age group compared to the other acute respiratory tract infections.

Symptoms

Children are less influenced by SARS-CoV-2, and according to the CCDC, only 2% of the confirmed 72,314 cases as of February 11, 2020 were age 19 years or younger.20 At the time of this writing, four case series have been reported on COVID-19 pneumonia in children.6,27,28 In a series of 20 children reported by Chen et al.,27 the most common presentation symptoms reported were low-moderate fever, cough, fatigue, headache, diarrhea and dyspnea, cyanosis, and, in more severe cases, malnutrition. Although not stated in the literature, parents who smoke, home environment, and nutritional status may also be associated with the frequency and severity of the disease. In a nine-infant series reported by Wei et al.,6 fever was reported in four patients and one infant was asymptomatic. Dong et al.28 reported a pediatric series of more than 2,000 children with suspected or confirmed COVID-19. In that study, the authors found asymptomatic infection in 13% of the virologically confirmed cases. Because testing was performed in many asymptomatic children, it was found that the rate of asymptomatic infection might be underestimated. It is understood from these series that children have milder symptoms compared to adults. As a result, children undergo less testing than adults and thus, asymptomatic or mildly symptomatic children can transmit the disease. It has been stated in a study29 that the likelihood of having COVID-19 is similar between children and adults, but pediatric patients are less likely to be symptomatic or to develop severe symptoms. Furthermore, preschool children and infants are more likely to have severe clinical symptoms than older children.29Table 1 shows the symptoms rates in children with COVID-19 pneumonia reported by several studies.

Distribution of the Most Common Symptoms in Studies of Pediatric COVID-19

Table 1:

Distribution of the Most Common Symptoms in Studies of Pediatric COVID-19

Infants Born to Mothers with COVID-19

There are numerous published case reports in the literature investigating pregnant women with COVID-19 and the outcomes of their newborn infants.30,31 So far, the general status of the mothers and infants seems good, and cord blood, amniotic fluid, and placental swabs have been negative for COVID-19. A few cases have been reported on the infants born from mothers infected with COVID-19 with high SARS-CoV-2 immunoglobulin M (IgM) levels.30 This may indicate intrauterine transmission, but swab polymerase chain reaction testing in these children was negative, and false-positive results are not infrequent in IgM testing. Newborn and young infants with positive test results have been reported; however, no disease complications have occurred and minimal respiratory support was required in these patients. Vertical transmission from the mother to the infant has not been reported yet.27 However, because infants of mothers with COVID-19 are delivered surgically and separated from their mothers rapidly, there is not clear information on intrauterine transmission.

Children with Comorbidity

Clinical data are quite limited on the effects of COVID-19 pneumonia in children with comorbidities. According to the data from a liver transplantation unit in Lombardy, Italy, COVID- 19 was detected in three patients after transplantation, all of whom experienced only mild symptoms.32 Data from the US Centers for Disease Control and Prevention show that a high proportion of pediatric COVID-19 cases requiring hospitalization have at least one comorbidity, with the most common being respiratory.33

Diagnosis

Clinical diagnosis of COVID-19 pneumonia is established with the presence of at least two symptoms (fever, respiratory symptoms, gastrointestinal symptoms, or fatigue) with laboratory test outcomes (normal-low white cell counts and increased C-reactive protein) and an abnormal chest X-ray. On the other hand, reverse transcription polymerase chain reaction (RT-PCR) test is used as the standard method in confirming the diagnosis of COVID-19.

Differential diagnoses of COVID-19 include influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, and other known viral infections.

RT-PCR

In RT-PCR testing, the preferred swab is taken from the upper respiratory tract (nasopharyngeal and oropharyngeal swabs) in children not receiving mechanical ventilation, and these samples should be transported on ice with viral transport media. In children receiving mechanical ventilation, test specimens are obtained through bronchoalveolar lavage or endotracheal aspirate.

In a study including patients diagnosed with COVID-19 confirmed by RT-PCR, the sensitivity was found as 72% for bronchoalveolar lavage, 63% for nasal swab, 32% for pharyngeal, 29% for stool, 1% for blood, and 0% for urine.34 Viral load is expected to be high in symptomatic children, and thus a single test performed with a sample taken from the upper respiratory tract can detect the virus in almost all cases.

Computed Tomography

X-rays and chest computed tomography (CT) scans have shown nonspecific findings, even in asymptomatic children. Therefore, these scans should not be routinely performed when pediatric patients have no specific clinical problem, even when a small amount of oxygen is required at the time of admission. A chest X-ray can be considered in children requiring oxygen or continuous positive airway pressure 3 days after the admission.

Lobar collapse due to bacterial pneumonia is more likely in children with dyspnea and persistent fever; however, lobar collapse, pneumothorax, or effusion have not been reported in children with COVID-19. Many studies advocate the use of CT scans, but these will not be helpful in the diagnosis or management of the disease and are not indicated. Transferring the children with COVID-19 to the room where the CT device is located will put other children at risk. On the other hand, radiographic imaging should be considered in children with an increase in the need for oxygen, respiratory distress, or respiratory support, which suggests disease progression.

The most common CT findings in pediatric series were reported as ground glass opacities (GGO) (32.7%), local patchy shadow (18.7%), bilateral patch shadow (12.3%), and interstitial abnormalities (1.2%).35 In another CT study with pediatric COVID-19 patients, bilateral involvement (50%) was higher than unilateral involvement (30%).37 In that study, the most common chest CT patterns were reported as GGO, consolidation with halo mark, fresh mesh body, and tiny nodules.36

Clinical Approach and Management

There are no drug and/or testing studies for COVID-19 specific to children in the literature. The majority of the publications include oxygen therapy and antibiotics for bacterial superinfections as initial treatment.37 Some authors recommend antiviral treatment,38 but there are no data on the effectiveness of this treatment in children with COVID-19.

Based on experience, a consensus group from China recommends discharging children with COVID-19 pneumonia when three criteria are met. These criteria include a normal body temperature over 3 days, improvement of respiratory symptoms, and negative COVID-19 tests.5

Actions for the treatment and management of pediatric patients with COVID-19 who have been hospitalized are listed in Table 2.

Management of Pediatric Patients Hospitalized with COVID-19

Table 2:

Management of Pediatric Patients Hospitalized with COVID-19

Oxygen cannulation with a flow up to 1 to 2 L/min in infants, 2 to 4 L/min in young children, and 4 to 6 L/min in older children is used for respiratory support. Children should be frequently monitored for oxygen saturation (SpO2), changes in heart rate and respiratory rate, hemodynamic parameters, and urinary output.

At the time of this writing, there is no specific antiviral drug with proven effectiveness. There are also no pediatric studies in the literature on this issue. The recommendations are based on the guidelines developed for adults. The indications for initiating virus-suppressive treatment (hydroxychloroquine or lopinavir/ritonavir) include COVID-19 patients with suspected or confirmed severe pneumonia or those who are critically ill.

Indications for hospitalization of pediatric patients with COVID-19 in the intensive care unit are listed in Table 3, and indications for intubation are listed in Table 4. The decision for intubation should be made on a case-by-case basis with the clinician's discretion.

Indications for ICU Hospitalization in Pediatric Patients with COVID-19

Table 3:

Indications for ICU Hospitalization in Pediatric Patients with COVID-19

Indications for Intubation in Pediatric Patients with COVID-19

Table 4:

Indications for Intubation in Pediatric Patients with COVID-19

Other Effects on Children

The effects of closed schools and confining children to their homes due to COVID-19 were evaluated by Wang et al.39 The authors proposed that these measures may have negative effects on the physical and mental health of children. These negative effects include longer times spent watching screens, irregular sleep, less healthy nutrition leading to weight gain, and loss of cardiorespiratory fitness due to staying indoors.39 In a study not related to COVID-19, Sprang and Sillman40 reported that putting children under quarantine and isolating them because of health-related disasters may significantly increase the risk of developing posttraumatic stress disorder.

Advice for Adults with COVID-19 Who Live with a Child

An adult infected with COVID-19 should stay in a separate room from children and wear a face mask. Family members should also stay in a separate room and keep away from the person with infection as much as possible. Only one family member should be tasked to care for the person who is COVID-19 positive. Handshaking or direct skin contact should be avoided. The hands should be washed with soap and water (for at least 20 seconds) or an alcohol-based disinfectant (for at least 30 seconds) before and after meals. Toys played with by a child should be washed as frequently as possible.

Conclusion

COVID-19 pneumonia has specific features in children that are different from those in adults. However, studies on pediatric COVID-19 are limited in the literature, and the recommendations are largely based on the findings of adult studies. Although the pediatric patient group is less sensitive to COVID-19 and has milder symptoms, pediatric cases are continuing to be reported worldwide. Therefore, there is an urgent need for further studies to be conducted on early detection, treatment, and prevention of COVID-19 in the pediatric population.

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Distribution of the Most Common Symptoms in Studies of Pediatric COVID-19

Author Location Patients, n Asymptomatic, % Fever, % Cough, % Dyspnea
Xia et al.36 Wuhan 20 0 60 65 NR
Tang et al.41 Shenzhen 36 35 42 46 0
Henry and Oliveira42 International 82 8 68 36 NR
Cai et al.37 Shanghai 10 0 80 60 0
Wang et al.17 North China 31 0 65 45 NR
Rahimzadeh et al.43 Iran 9 0 100 100 NR

Management of Pediatric Patients Hospitalized with COVID-19

<list-item>

Maintaining oxygen saturation at >92%

</list-item><list-item>

Conservative fluid management in mechanically ventilated patients

</list-item><list-item>

Symptomatic treatment with paracetamol for fever

</list-item><list-item>

Blood culture sample should be sent before beginning antimicrobials

</list-item><list-item>

Empirical antimicrobials in the cases of suspected sepsis or septic shock

</list-item><list-item>

Systemic corticosteroids are not recommended if not indicated due to other reasons

</list-item>

Indications for ICU Hospitalization in Pediatric Patients with COVID-19

<list-item>

Need for mechanical ventilation

</list-item><list-item>

Shock requiring vasopressor support

</list-item><list-item>

Worsened mental status

</list-item><list-item>

Multiorgan dysfunction syndrome

</list-item><list-item>

Indications for intubation

</list-item>

Indications for Intubation in Pediatric Patients with COVID-19

<list-item>

Severe respiratory distress

</list-item><list-item>

Inability to maintain SpO2 >90% with noninvasive oxygen support

</list-item><list-item>

PaO2/FiO2 ratio <200

</list-item><list-item>

PaO2/FiO2 ratio <300 plus hypotension requiring vasopressor support

</list-item><list-item>

Threatened airway with GCS <8

</list-item>
Authors

Meyri Arzu Yoldas, MD, is a Specialist, Department of Pediatrics. Hamit Yoldas, MD, is an Assistant Professor, Department of Anesthesiology and Reanimation. Both authors are affiliated with Bolu Abant Izzet Baysal University, Faculty of Medicine.

Address correspondence to Meyri Arzu Yoldas, MD, Department of Pediatrics, Bolu Abant Izzet Baysal University Faculty of Medicine, Gölköy Campus, 14280, Bolu, Turkey; email: m.arzuyoldas@gmail.com.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/19382359-20200615-01

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