Clinical Management of Pediatric COVID-19: An International Perspective and Practical Guide

Clinical Management of Pediatric COVID-19: An International Perspective and Practical Guide provides the most current international research and clinical characteristics of pediatric patients with SARS-CoV-2 infection. Coverage ranges from epidemiology including origin, route of transmission, incubation period, mortality and susceptibility risk factors; to pathogenesis, including difference between the adult and pediatric populations. Diagnosis is covered with special attention to the difference between adult and pediatric patients as well as the differences between newborns, children and adolescents. The book presents current complications, including multisystemic inflammatory syndrome as well as treatment therapies including antiviral and immunomodulatory therapies for this age group.

Finally, immunization efficacy and safety are examined. This is the perfect reference to provide guidance to pediatricians on the diagnosis and treatment of SARS-CoV-2, as well as a valuable source of the latest research about the pediatric population for further study.

• Provides the latest findings on the clinical characteristics of pediatric patients with SARS-CoV-2 infection
• Elucidates the differences between pediatric COVID-19 and its adult counterpart, outlining the correct clinical course for infants, children and adolescents
• Covers both recent clinical practice as well as current research specific to the pediatric population

• Language: English
• Publisher: Academic Press
• Release date: Jan 13, 2023
• ISBN: 9780323950602

Book preview

Preface

By the time I am editing this book, it has already been more than 2years since the outbreak of COVID-19. The pandemic has not ended, and new variants continue to emerge. A large body of studies has been done—from virology and epidemiological research to therapeutics. We have learned that the elderly and those with certain comorbidities are at high risk of SARS-CoV-2 infection and morbidity. We have also learned that the underage has a milder clinical course compared to adults. Consequently, we should ask ourselves, are pediatrics with COVID-19 overlooked because children are generally believed to fare better?

There are already several books covering different aspects of COVID-19. While some of them may have addressed children with COVID-19, there is a need to have a piece of work entirely dedicated to pediatric COVID-19—a book that highlights key findings and serves as a reference for clinicians and medical students in pediatrics. I hope this book satisfies this need.

Gathering contributors for this book was not an easy task at all as most of us including academics and clinicians are busy during the pandemic. This also means that getting the drafts done on the scheduled time was also problematic. Luckily, with Pat's help, Elsevier provided multiple platforms for manuscript submission, streamlining the process and making my life easier.

Each chapter is aimed to be a review study of a specific topic. Although a single title cannot cover all existing literature, our contributors carefully selected studies and presented key findings of clinical importance and presented. A wide range of topics on pediatric COVID-19 is covered. The first two chapters are set to provide background materials of the disease. The virology and epidemiology of SARS-CoV-2 such as the origin of the disease, route of transmission, and key epidemiologic metrics are discussed in Chapter 1. The pathogenesis of SARS-CoV-2 is discussed in Chapter 2 with a focus on the host–pathogen interaction, including tissue tropism, viral replication, and mechanism of dissemination, and how these factors interact in different age groups.

Chapters 3–6 focus on the clinical aspects of pediatric COVID-19. Chapter 3 is more descriptive with the aim to highlight signs and symptoms commonly seen in pediatrics. COVID-19-related complications such as multisystemic inflammatory syndrome in children are discussed in Chapter 4. Diagnosis of COVID-19 including laboratory tests and imaging is addressed in Chapter 5. Existing treatments are then discussed in Chapter 6.

The last two chapters focus on other topics—immunization and long COVID-19 in Chapters 7 and 8, respectively.

Lastly, I would like to thank all contributors for their effort, Pat Gonzalez of Elsevier for managing the book project and Stacy Masucci of Elsevier for inviting me to be the editor of the book. Without them, this book can never be published. I would also like to thank our reviewers Sarah Messiah, Luyu Xie, and Olivia Kapera of the University of Texas Health Science Center, Arthur Vengesai of Midlands State University, and other anonymous reviewers for their helpful and enlightening comments. Last but not least, I would like to thank my sister, Davily Leung, a graphic designer, for the cover image.

Char Leung

Chapter 1: Epidemiology and virology of SARS-CoV-2

Char Leung ¹ , ²       ¹School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom      ²Department of Health Sciences, University of Leicester, Leicester, United Kingdom

Abstract

This chapter addresses the basic virological and epidemiologic characteristics of severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 is a member of the seven human coronaviruses and is one of the three coronaviruses that cause acute respiratory distress syndrome in humans, along with Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV. It is an airborne virus although vertical transmission is suspected. Existing evidence shows that children play a small role in the transmission and that newborns have a higher risk of mortality.

Keywords

Epidemiology; SARS-CoV-2; Virology

Introduction

Commonly known as COVID-19, the coronavirus disease 2019 is a viral respiratory disease caused by severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV. It was first identified in Wuhan, the capital of Hubei province in China, in December 2019 when a series of pneumonia cases were reported. The early phase of the outbreak in Wuhan is not well understood. Existing literature indicates that the first patient became symptomatic on December 1, 2019 [1]. A day before the closedown of the Market, the Wuhan Health Commission confirmed 27 cases of COVID-19 on December 31, 2019 [2]. According to the Chinese Center for Disease Control and Prevention, 33 environmental samples collected in the Huanan Seafood Wholesale Market in January 2020 were polymerase chain reaction (PCR) positive for SARS-CoV-2. In particular, 94% (31/33) of these samples were collected in the area where wildlife animals were heavily traded [3], suggesting the Market as the origin of SARS-CoV-2 [4]. The daily release of COVID-19 cases by Chinese health authorities did not start until January 10, 2020 when the number of cases increased to 41. The first case of COVID-19 outside China was reported on January 13, 2020, in Thailand where a 61-year-old woman traveling from Wuhan was detected with fever at the Suvarnabhumi Airport in Bangkok on January 8, 2020. As of end of January, more than 10,000 COVID-19 cases were confirmed in Wuhan, and the virus has spread to 22 countries. Meanwhile, the World Health Organization (WHO) declared the COVID-19 pandemic the sixth Public Health Emergency of International Concern.

Virological characteristics of human coronaviruses

Commonly known as coronaviruses, Cornidovirineae or Coronaviridae, is a group of enveloped positive-strand RNA viruses. The two terms refer to the suborder and family in virus taxonomy, respectively, according to the International Committee on Taxonomy of Viruses (ICTV). Because Coronaviridae is the only family under Cornidovirineae as of 2021, the two terms have been used interchangeably. There are currently a total of 46 species of virus under Cornidovirineae, of which 19 and 10 have bats and birds as reservoir/host, respectively [5–8].

SARS-CoV-2 is one of the seven coronaviruses pathogenic to humans, the others being SARS-CoV (or SARS-CoV-1), MERS-CoV, OC43, NL63, 229E, and HKU1. According to the taxonomy by the ICTV, these viruses fall under the family of Coronaviridae that consists of the subfamilies Letovirinae and Orthocoronavirinae. Viruses of the latter can be further divided into 4 genera; Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus. Viruses of the latter two genera are not pathogenic to humans. NL63 and 229E are Alphacoronaviruses, whereas OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2 are Betacoronavirus.

Coronaviruses cause common colds

Human coronaviruses that produce mild upper respiratory diseases are OC43 first identified in 1965 in the United Kingdom [9], 229E in 1966 in the United States [10], NL63 in 2004 in the Netherlands [11], and HKU1 in 2005 in Hong Kong [12]. It has been proposed that NL63 and 229E originate from bat reservoirs, whereas OC43 and HKU1 are more likely to have speciated from rodent-associated viruses [13]. These coronaviruses constitute the second most common causative agent of all common colds, accounting for 10%–15%, after rhinoviruses [14]. It has been estimated that approximately 1 in 10 hospitalized children with respiratory tract infection is infected with at least one of these coronaviruses [15], the more recently discovered ones NL63 and HKU1 in particular [16,17]. The prevalence of infections among children is lowest in early summer, and the seasonal patterns can vary over time and between countries [18]. Studies have shown that many children and infants have been exposed to these strains although their seroprevalence varies over time and geographically [19–23].

Coronaviruses causing acute respiratory distress syndrome

Similar to SARS-CoV-2, SARS-CoV, and MERS-CoV can cause acute respiratory distress syndrome (ARDS). SARS-CoV emerged in Shunde of Foshan in China in November 2002 [24] and was first identified in Hong Kong in March 2003 [25]. The virus was believed to originate from bats and transmitted to humans through civets that were consumed as food. The data of 1425 SARS-CoV cases in Hong Kong suggest a case-fatality rate of 13% for patients younger than 60 years of age but 43% for those aged 60 years or above, In addition, approximately 25% of patients with SARS-CoV developed severe respiratory failure [26]. Children generally had a milder clinical course, and no deaths were reported [27]. MERS-CoV emerged in a hospital in Jordan in April 2012 [28] and was first isolated from a 60-year-old Saudi Arabian man admitted to the hospital in June 2012 [29]. While the virus is believed to originate from bats, patients could be infected by consuming and have close contact with camels infected with the virus. As the deadliest human coronavirus, the case-fatality rate of MERS-CoV is estimated to be 33%, based on 2562 confirmed cases [30]. Children with MERS-CoV appeared to have a lower mortality rate than adults [31] and were less likely to have a severe clinical course [32]. The phylogenetic tree of these viruses is shown in Fig. 1.1.

Severe acute respiratory syndrome–associated coronavirus 2

The structure of SARS-CoV-2 is shown in Fig. 1.2 and the genome organization in Fig. 1.3. Under the electronic microscope, the virus particle (also called the virion) is spherical in shape with spikes on the surface and has a diameter between 60 and 140nm[33]. Each spike has a length of about 9–12nm and is a glycosylated protein with two subunits, namely S1 and S2.

The S1 subunit forms the top part of the spike, largely consisting of the amino-terminal domain and the receptor binding domain (RBD) that attache the virus to the host cell surface receptor known as the angiotensin-converting enzyme 2 (ACE2), an enzyme abundantly expressed on airway epithelial cells (type II pneumocytes and alveolar macrophages, for example [34]) and small intestinal epithelial cells) [35]. The RBD comprises the core and the receptor-binding motif (RBM). The latter is relatively less preserved than the former during viral evolution as it must evolve to sustain sufficient affinity to engage the ACE2. Biochemical data have confirmed the difference in five residues in the SARS-CoV-2 RBM, namely Y455L, L486F, N493Q, D494S, and T501N, that strengthened the binding affinity compared with that of SARS-CoV [36]. Given its role in host cell entry, the RBD is the target of 90% of the neutralizing antibody and vaccines [37]. Unfortunately, most mutations have occurred in the RBD, potentially escaping immune response and undermining vaccine efficacy. Details of SARS-CoV-2 mutations can be found in