COVID-19 in Children and Adolescents

Coronavirus Infections in Children and Adolescents

Coronaviruses are enveloped single-stranded RNA viruses comprising four genera: alpha, beta, gamma, and delta. They infect humans and animals and were first described in the 1960s as causative agents of mild upper respiratory tract infections. Four human coronaviruses caused up to 35% of upper respiratory tract infections in humans: 2229E, NL63 (both alpha coronaviruses), and HKU1 and OC43 (beta coronaviruses). OC43 was thought to cause the most disease and was prevalent in children younger than 5 years. In rare instances, severe infections have been described in immunosuppressed children with NL63. These endemic human coronaviruses are often identified in coinfections with other respiratory viruses, making it difficult to determine their true role in disease. ^,

In evaluations of children with respiratory symptoms and respiratory virus testing, approximately 2% to 10% had human coronavirus. ^, Human coronavirus was also detected in 10% of asymptomatic control children. Additionally, 33% to 68% had coinfections of human coronavirus and another virus, most commonly rhinovirus or respiratory syncytial virus (RSV). ^{, ,} Human coronavirus infections were present throughout the year but peaked in the winter months in North America and Europe. ^, Clinical manifestations of human coronavirus were indistinguishable from those of other respiratory viruses. ^, In rare cases, human coronavirus could cause lower respiratory tract infection in children with underlying medical conditions.

Over the past 20 years, three new beta coronaviruses emerged and caused severe, sometimes fatal illness in humans: severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), Middle Eastern respiratory syndrome coronavirus (MERS-CoV), and, more recently, SARS-CoV-2. SARS-CoV-1 was described in 2003 in Southeast Asia and is thought to have originated from bats. It caused over 8000 cases and more than 700 deaths and had a mortality rate of 10% in adults but caused no deaths in the 135 pediatric cases reported. No further cases of SARS-CoV-1 have been reported since 2004. MERS-CoV is thought to have been transmitted from bats to camels to humans and was identified in 2012 in Saudi Arabia. It infected more than 2400 people and caused severe respiratory illness and a mortality rate of 36%. However, in children most cases of MERS-CoV infection were asymptomatic. MERS-CoV continues to occur sporadically, primarily in the Middle East.

In both SARS-CoV-1 and MERS-CoV outbreaks, children had less severe manifestations than adults and infected children were commonly identified during contact investigations of adult patients. ^, The clinical manifestations of children infected with SARS-CoV-1 or MERS-CoV were nonspecific and ranged from asymptomatic to mild, nonspecific respiratory symptoms such as fever, cough, and rhinorrhea. Some infected children developed opacities on their chest radiographs and laboratory abnormalities, including lymphopenia, thrombocytopenia, and elevated transaminases. ^,

Epidemiology of SARS-CoV-2 Infection in Children and Adolescents

SARS-CoV-2 was first recognized as the cause of the COVID-19 pandemic by the World Health Organization (WHO) in March 2020, at which time 118,000 cases had occurred in 114 countries and nearly 4300 people had died. By September 27, 2021, approximately 18 months later, there had been more than 231 million confirmed cases of COVID-19 and more than 4 million deaths globally. Our understanding of SARS-CoV-2 transmission dynamics, infectiousness, clinical manifestations, and outcomes continues to evolve during the pandemic.

Throughout the pandemic there has been great geographic variation in the burden of COVID-19. At the time of this writing, the highest number of COVID-19 cases has been reported by the United States, at more than 42 million cases, followed by India with more than 33 million cases and Brazil with 21 million cases. These three countries also report the greatest number of COVID-19–associated deaths. In contrast, by September 2021 all of Europe reported 69 million cases, Southeast Asia reported 42 million cases, and Africa reported 6 million cases. All of these numbers are underestimates because of imperfect reporting systems and limited capacity for SARS-CoV-2 testing in many parts of the world. Additionally, the true burden of infection in children is likely to be much higher, because many places preferentially tested for SARS-CoV-2 among symptomatic, hospitalized patients early in the pandemic, and these patients tended to be adult patients.

Hospitalization and mortality rates for SARS-CoV-2 have been consistently lower among children than adults. Despite variability in testing and reporting of SARS-CoV-2 infections and deaths, reports from most parts of the world show that pediatric cases account for 1% to 2% of infections documented. As of September 16, 2021, the United States reported over 5.5 million pediatric SARS-CoV-2 infections, representing 15% of all cases, 1% to 4% of total hospitalizations and less than 1% of all COVID-19 deaths. Children 5 to 11 years had lower hospitalization rates compared with younger and older children ( Fig. 14.1 ). Among 121 people younger than 21 years of age who died from SARS-CoV-2 in the United States between February and July 2020, 10% were infants younger than 1 year and 70% were between the ages of 10 and 20 years.

Although hospital admissions for COVID-19 among children and adolescents are rare, it is important to consider that COVID-19 has caused more pediatric hospitalizations than influenza. Among US adolescents, COVID-19–associated hospitalizations between October 2020 and April 2021 were almost three times higher than influenza-associated hospitalizations from three previous influenza seasons ( Fig. 14.2 ). In children, as in adults, SARS-CoV-2 infection and hospitalization rates and mortality vary by race and ethnicity. Hispanic, Black, or American Indian/Alaskan Native persons composed 75% of a US cohort of persons younger than 21 years who died from COVID. ^,

In the summer of 2021, the B.1.617.2 (delta) variant of SARS-CoV-2 emerged and spread in the United States. This fourth surge of SARS-CoV-2 coincided with off-season circulation of RSV and return to in-person school for children after summer vacation, resulting in high numbers of pediatric SARS-CoV-2 infections and hospitalizations in the United States. ^, The delta variant appears to be more transmissible than SARS-CoV-2 variants that circulated earlier in the pandemic. Although the delta variant has caused increased numbers of pediatric COVID infections, thus far it does not seem to cause more severe disease than earlier variants. Hospitalization rates and outcomes of children infected with delta variant have not been different from those seen with earlier variants. ^,

Clinical Manifestations of SARS-CoV-2 Infection in Infants and Children

As observed with the other human coronaviruses, the clinical presentation of SARS-CoV-2 is milder in young children than in adolescents and adults. It is estimated that approximately 15% to 35% of infected children can be asymptomatic. When children do exhibit symptoms, they range from mild fever, with or without respiratory symptoms (cough, rhinorrhea, congestion, sore throat), gastrointestinal symptoms (nausea, vomiting, diarrhea), and other systemic symptoms (headache, myalgias, fatigue), to acute respiratory distress syndrome and respiratory failure and death. An early report comparing 291 children to over 10,000 adults suggested that children experience fever, cough, or shortness of breath less commonly than do adults. In general, it is difficult to distinguish SARS-CoV-2 infection from other viral illnesses based on symptoms alone. SARS-CoV-2 infection also has been associated with extrarespiratory symptoms, including neurological manifestations such as loss of taste and/or smell; cerebrovascular accidents and seizures; Guillain-Barré syndrome; cutaneous findings, including chilblain-like (pernio) lesion, erythema multi­forme, and urticaria ; conjunctivitis ; myocarditis ^, ; and liver and renal dysfunction. ^, In addition, thrombotic complications are commonly seen in COVID-19 patients with critical illness. The constellation of symptoms appears to vary by age of the child, with adolescents having more respiratory, influenza-like, and sensory symptoms than younger children ( Fig. 14.3 ). ^,

Children with asymptomatic or mild COVID-19 may have mild lymphopenia and thrombocytopenia. Those with moderate to severe symptoms are more likely to have laboratory abnormalities, including lymphopenia, thrombocytopenia, coagulopathy, and elevated inflammatory markers such as C-reactive protein and procalcitonin. A wide spectrum of abnormalities can be seen on chest radiographs among children with COVID-19 pneumonia, including unilateral or bilateral infiltrates, often with peripheral and lower lung zone predominance, peribronchial thickening or opacities, ground-glass opacities, and consolidations. To date, bacterial superinfection has been seen in only a small proportion of hospitalized adults with COVID-19. ^, This is likely also true in hospitalized children, although pediatric data are still emerging.

Duration of symptoms is generally short, with symptom resolution occurring in 45% by 5 days and in 94% by 1 month in an assessment of 1000 infected children. Postacute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long-COVID, has been reported in many adults after SARS-CoV-2 infection but appears to be rare among children. Among 366 adults in California who had a positive SARS-CoV-2 infection between April and December 2020, 128 (35%) endorsed ongoing symptoms 2 months later. In contrast, in a large prospective cohort study of SARS-CoV-2–infected children in the United Kingdom in which parents reported data about their symptomatic children using a mobile application, median illness duration in positive children was 6 days and only 25 of 1379 (1.8%) experienced symptoms for at least 56 days. However, emerging data suggest that PASC may be more common in children than previously reported and warrants further study.