INTRODUCTION

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, People's Republic of China, which was reported in a cluster of patients with pneumonia of unknown cause and who were epidemiologically linked to a seafood and wet animal wholesale market.1 Infection with SARS-CoV-2 can lead to COVID-19 in some individuals; COVID-19 was declared a public health emergency in early 2020.2 As of February 10, 2023, more than 755 million cases of COVID-19 and more than 6.8 million associated deaths were reported worldwide.2

Early in the Wuhan outbreak, it was apparent that a small percentage (ie, <1%) of SARS-CoV-2 cases were in children younger than 10 years.3 However, as the pandemic progressed, the proportion of infections in children and adolescents increased.4 Compared with the characteristics seen in adults, a milder clinical course and common asymptomatic infections were observed in children,3,5–7 although severe illness can occur.8,9 Cough is the most common symptom of COVID-19 reported in the majority of adults (80%), with fever and shortness of breath reported in 71% and 43% of patients, respectively.10 Among children, however, fever is the most common symptom (reported in approximately 50%–60% of children).6,10

SARS-CoV-2 is predominantly spread via direct or indirect contact with respiratory droplets from an infected person, although studies indicate that infection may occur from airborne aerosolized virus particles and viral shedding from other bodily fluids.11,12 Both asymptomatic and presymptomatic infection can occur with SARS-CoV-2 (ie, from individuals who never display symptoms and from those in the period between becoming infected and displaying symptoms, respectively).13 The prevalence of asymptomatic infections and mildly symptomatic cases in pediatrics, therefore, have implications regarding the transmission of SARS-CoV-2 among children and from children to adults.7

Children are known to be involved in transmission during other respiratory viral epidemics and from bacterial pathogens colonizing the upper respiratory tract, such as Streptococcus pneumoniae.14–17 Studies of influenza A epidemics in the United States and Japan and on respiratory syncytial virus epidemics in the United States support the important role children play in viral transmission and propagation of epidemics.14–16 Children were also thought to be important reservoirs of infection during the spread of the 2009 influenza pandemic.18

The role of pediatric populations in SARS-CoV-2 transmission is likely affected by a combination of exposure (likelihood of exposure to the virus), susceptibility (likelihood of infection and developing COVID-19), and transmissibility (likelihood of transmitting the virus to others).19 As the transmission potential of children infected with SARS-CoV-2 can help guide control measures for managing the pandemic,3,7 the purposes of this review are to assess SARS-CoV-2 infection in children and to ascertain their role in transmission by considering the exposure, susceptibility, and transmissibility of pediatric populations to SARS-CoV-2.

METHODS

A PubMed search was initially conducted on November 25, 2020, using the following search terms: (coronavirus OR Severe acute respiratory syndrome OR covid-19 OR nCoV OR COVID OR SARS OR MERS OR middle east respiratory syndrome) AND (Child OR Children OR childhood OR preschool OR infant OR babies OR baby OR neonates OR pediatrics OR pediatric OR paediatrics OR paediatric) AND (transmission). The following filters were applied: Abstract; in the last 1 year; Humans; English, French, German, Italian, or Spanish language. Two authors reviewed the title and abstract of the retrieved publications to identify the articles of interest describing transmission of SARS-CoV-2 in children. Given the rapidly evolving nature of the COVID-19 pandemic and the frequent publication of new data, additional articles were added as they were identified after the initial search date. In addition, with the emergence of a number of SARS-CoV-2 variants of concern (VOCs),20 further searches conducted up to February 7, 2023, incorporated the additional search terms: (Alpha or Beta OR Delta OR Gamma OR Omicron OR B.1.1.7 OR B.1.351 OR B.617.2 OR P.1 OR B.1.529).

RESULTS

This narrative review includes original research articles; retrospective, surveillance, modeling, and case studies; case series; systematic reviews; and meta-analyses. Narrative reviews were generally not included, and precedence was given to systematic reviews and meta-analyses. Herein, themes and observations identified on infection in children and the role of children in transmission among the selected articles are summarized.

Exposure of Children to SARS-CoV-2

A key point of exposure of pediatric populations to SARS-CoV-2 is thought to be school settings, which has been associated with outbreaks among students and staff.21,22 Accordingly, school closures were instituted beginning early in the pandemic as an approach to prevent exposure of children and adolescents to SARS-CoV-2 and ultimately to curb the spread of the virus to households and the community,23 particularly before the availability of preventative vaccines. However, the impact of school closures on preventing illnesses in children and their family members has been difficult to quantify as data on its effectiveness in reducing the spread of COVID-19 are limited and conflicting, with a variety of recommendations that warrant further and timely studies.24,25 For instance, a German retrospective observational study found that the risk of infection for students increased compared with the general population when schools were open and fully attended, while mask wearing and limited student numbers decreased this risk.26 Notably, the findings were dependent on the predominant VOC.26 The potential benefits of school closures on reducing the exposure of pediatric populations should also be considered in the context of potential detrimental effects of these mitigation measures. For example, the closure of schools had numerous negative effects on children and adolescents, with potential long-term negative impacts on health and well-being, especially among younger children and those from lower-income families, with disabilities, or of color.27–31

In pregnant individuals, SARS-CoV-2 infection may also expose the baby to the virus; however, the role and frequency of vertical and perinatal transmission are debated.32–36 Initial reports in the pandemic were based on cohort studies and small data sets, with varying frequencies of vertical and perinatal infection provided.32–36 However, in a recent systematic review of SARS-CoV-2 positivity rates of 14,518 exposed babies born to mothers with SARS-CoV-2 infection, which included publications to August 2021, a low frequency of mother-to-child transmission via in utero, intrapartum, and early postnatal exposure was found (<2%).37 Maternal factors associated with SARS-CoV-2 infection in newborns included severe COVID-19, while vaginal delivery, breastfeeding, and mother−baby contact after birth were not.37 Overall, vertical or perinatal transmission seems to occur infrequently37 and horizontal transmission during the neonatal period can be minimized by careful hygiene and mask wearing by the mother and other caregivers.33,34

Susceptibility of Children to SARS-CoV-2 Infection

Early in the pandemic, infection rates observed in children were low compared with rates in adults, with a systematic review noting at that time that children represented 1% to 5% of cases.5 In an Italian study conducted from March to April 2020 that tested 214 adult and pediatric patients hospitalized for noninfectious conditions, approximately 1% of children versus 9% of adults tested positive for SARS-CoV-2.38 Similarly, a French study of nasopharyngeal samples from 4050 patients in February–March 2020 found the percentage of individuals positive for SARS-CoV-2 was lower in children (0% in 0- to 1-year-olds, 1.1% in 15-year-olds, and 3.6% in 5- to 10-year-olds) compared with that in individuals older than 18 years (6.5%).39 A study in Wuhan, China, in February 2020 of 85 households with members infected with SARS-CoV-2 found that children comprised only 1.5% of infections.40 During the COVID-19 outbreak on the Diamond Princess cruise ship in February 2020, 619 of 3711 people (17%) were infected, 318 (51%) of whom were asymptomatic.41 Age-stratified data of passengers showed that 6 of 39 children (15%) and adolescents 19 years or younger and 1 of 16 children (6%) younger than 10 years were infected, and 4 of 6 and 1 of 1, respectively, were asymptomatic.41

As the pandemic progressed through 2020, infection rates increased among younger age groups, including children, adolescents, and young adults.42 For instance, the US Centers for Disease Control and Prevention (CDC) examined the age distribution of COVID-19 cases in the United States from May to August 2020 and reported that the percentage of all cases represented by 0- to 19-year-olds increased from 7.4% in May 2020 to 15.5% in August 2020.43 By December 14, 2020, children and adolescents younger than 18 years comprised 10.2% of COVID-19 cases in the United States.44 Notably, older pediatric populations were disproportionately affected. Among nearly 280,000 cases of COVID-19 in US school-aged children, the incidence among 12- to 17-year-old adolescents from March to September 2020 was nearly twice that of younger children (5–11 years old).45

More recently, the emergence of highly transmissible variants has changed the age distribution of SARS-CoV-2 infections, with seroprevalence among pediatric populations increasing over time depending on the specific pandemic wave and the associated predominant VOC.46 In the United States, at the end of August 2021, infections in children and adolescents younger than 18 years comprised more than 45% of all infections; notably approximately 99% of these infections were the Delta variant.4,47 At that time, 16- to 17-year-old adolescents had the highest infection rates of all age groups (206 per 100,000 population), followed by 12- to 15-year-olds (200 per 100,000 population).4 In the United Kingdom, infection rates of the Delta variant in May and June 2021 were found to be predominantly driven by infections among 5- to 12-year-old children and young adults (18–24 years old).48 The Omicron variant seems to be substantially more transmissible than the Delta variant.49 In February 2022, seroprevalence in 0- to 17-year-olds in the United States was approximately 75%, an increase from approximately 45% since December 2021.50 These data highlight the highly transmissible nature of the Delta and Omicron variants, particularly among children, and their dynamic effects on the epidemiology of infection.46,50

The literature suggests that children are less susceptible to or have subclinical SARS-CoV-2 infection,51–54 which highlights the difficulty in identifying children positive for infection unless identified through routine testing, contact tracing, or evident signs of infections.55–57 A study of household data from Bnei Brak, Israel, found that children were not only less susceptible to infection but had lower infectivity (63%) than that of adults.52 Children with and without symptoms can carry high viral loads of SARS-CoV-2,58 although the data are variable. In 1 study, despite the observation of asymptomatic and subclinical infection, the viral load of SARS-CoV-2 seemed to be similar among pediatric and adult populations.59 In contrast, a study conducted in 2020 reported significantly lower viral loads in younger than 12-year-old children compared with adults.60 Similarly, in a review of clinical records of symptomatic and asymptomatic patients in China during January 2022 who tested positive for the Omicron variant, nasopharyngeal polymerase chain reaction cycle threshold values of adult patients were higher than that of pediatric patients 13 years or younger, suggesting that viral loads with contemporary VOCs are also lower in pediatric populations.61

COVID-19 is also mostly associated with mild or moderate disease in children, with severe disease associated with an underlying condition and generally most frequent in infants, although temporal and geographic variations may be observed.8,45,55,56,62–66 Underlying reasons for children generally having milder COVID-19 are debated.19 As reviewed by Zimmerman and Curtis,67 viral load was proposed as a contributory factor determining decreased risk of severe COVID-19 in pediatrics. However, evidence to support this hypothesis is contradictory, as described previously.59–61,67 It is thought that the underlying explanation for the age gradient in severity of disease is multifactorial and likely includes rapid engagement of the mucosal immune system among pediatric populations, as well as host factors, infection history, immune status, and associated pathogens.19,67,68

A notable exception to the mild course of disease in pediatrics is multisystem inflammatory syndrome in children (MIS-C), a rare but serious condition that, as of January 30, 2023, had affected more than 9300 children and adolescents and caused 76 deaths in the United States alone.69 Data from a Swedish population-based study of more than 2 million children found that male sex, age 5 to 11 years, or having foreign-born parents, asthma, obesity, or a life-limiting condition were associated with increased MIS-C risk.70 Further underlying risk factors and the role of transmission in developing MIS-C are not well elucidated, although it has been suggested that vulnerability increases during periods of extensive community transmission of SARS-CoV-2.71 Notably, studies from Europe and Australia, Israel, and the United States have respectively found that the number of cases,72–74 incidence,75 and percentage of hospitalized cases76 of MIS-C have generally progressively decreased in pediatric populations over subsequent pandemic waves (ie, Alpha, Delta, and Omicron), which are respectively associated with increased transmissibility.77,78 The authors noted that potential reasons for these findings include viral and host immunity changes, including by previous infection and vaccination, although conflicting results were reported.72–76 Support for the protective effect of vaccination against MIS-C includes Danish (in 0- to 17-year-olds) and US (in 5- to 18-year-olds) studies, which reported 84% to 94% vaccine efficacy for preventing MIS-C during periods of Delta and Delta and Omicron predominance, respectively.79,80 Conversely, other studies were unable to decipher the relative contribution of vaccination on MIS-C epidemiology and outcomes,72–74,76 and further study is required.

Transmissibility of SARS-CoV-2 in Children

Studies and reports from 2020 suggested that SARS-CoV-2 infections in children were generally associated with household clusters, school settings, contact with a known infected person, or exposure in epidemic areas.39,44,53–55,63,81–86 However, the literature varies, and transmission in children may be more substantial than originally estimated.87 It is currently thought that the predominant role of children in transmission of SARS-CoV-2 is in household and school settings,19,88 although the relative contribution of each setting to transmission is debated.

In a systematic review of studies published to March 2021 and that analyzed intrafamilial and institutional spread of COVID-19 of pediatric index cases, children 18 years and younger were found to have a small contribution to transmission risk, particularly to other children (child-to-child and child-to-adult transmission rate of 5.7% and 26.4%, respectively), including in school and childcare settings, although nearly half of child-to-child transmission was associated with secondary school environments,89 which is consistent with previous reports finding greater transmission in secondary versus primary schools.90 In the systematic review, household transmission was suggested to be the greatest source of child-to-adult (47.0% transmission rate) and child-to-child transmission (50.3% transmission rate).89 Conversely, a systematic review and meta-analysis covering publications to April 2022 evaluated pediatric COVID-19 cases in family clusters, estimated secondary attack rates, and compared SARS-CoV-2 transmissibility by age group.91 The contribution of child index cases to household transmission was found to be small, suggesting that children were unlikely to be the main SARS-CoV-2 source in familial clusters.91 Finally, a systematic review that included reports published to March 2021 found that SARS-CoV-2 transmission was not amplified in schools but was more closely associated with the level of community transmission.92

Differences in transmissibility between adults and children may be attributed to the viral incubation period in these 2 populations. For instance, a meta-analysis of literature published between December 2019 and February 2022 found that the incubation period of SARS-CoV-2 was higher in those younger than 18 years (8.82 days) compared with the general population (6.65 days).93 Another consideration is variation in transmission risk by VOC, with the transmission risk among children and from children to adults appearing to be higher with the Delta and Omicron variants compared with earlier strains.88,94,95 For instance, in a population-based study of Japanese children 3 years and younger conducted between July 2020 and April 2022, the secondary transmission risk of the Delta and Omicron variants was significantly higher than that of the Alpha variant, corresponding to a 3 to 4 and 8 to 10 times higher transmissibility of the Delta and Omicron variants, respectively, compared with the Alpha variant.94

Another consideration is the potential contribution to SARS-CoV-2 transmission of the fecal-oral route/prolonged fecal shedding of virus by children. Early reports from Chinese studies of children with confirmed SARS-CoV-2 detected viral RNA in feces up to 20 days after respiratory specimens became negative.96–98 In addition, a systematic review of studies published to January 2022 found that compared with adults, children with COVID-19 have a longer duration of gastrointestinal viral shedding (28–42 days in 60% of pediatric cases vs 9–18 days in literature reports in adults).99 Another systematic review of studies published up to October 2021 reported that the pooled prevalence of fecal RNA in children with COVID-19 was 86%.100 Although there is currently no direct evidence of viral transmission from feces and further study is required, late shedding of virus in feces as a source of transmission in children should be considered, and caregivers of infected children should take precautionary hygiene measures.82,96,99

DISCUSSION

The SARS-CoV-2 transmission potential of children is an important consideration, as it can help guide control measures for managing the COVID-19 pandemic, protect vulnerable populations, and ensure that effective mitigation measures are used. As summarized in Figure 1, our review found that pediatric populations contribute to SARS-CoV-2 transmission through a combination of exposure, susceptibility, and transmissibility.

FIGURE 1:

The contribution of pediatric population on the transmission of SARS-CoV-2.

Beginning early in the pandemic, children were generally considered less susceptible than older populations to COVID-19, including to severe outcomes. However, the susceptibility of children may have been underestimated because children are more likely to be asymptomatically infected with SARS-CoV-2 and because mitigation measures, such as school closures, may have decreased the exposure of children to SARS-CoV-2 and hence diminished measures of susceptibility to COVID-19.19 With children and adolescents mixing in crowded classrooms and educational spaces, schools are a key point of exposure to SARS-CoV-2 for many pediatric populations. Along within household settings, schools also play a predominant role in the transmission of SARS-CoV-2 between children and from children-to-adults.

Because of the importance of schools in the transmission of SARS-CoV-2, mitigation measures including school closures were implemented beginning early in the pandemic to decrease the spread of SARS-CoV-2 to households and the community, particularly before the availability of COVID-19 vaccines for adults and pediatric age groups. However, it has been difficult to quantify whether this approach successfully curbed COVID-19 case numbers without detrimentally affecting the long-term health and well-being of children.

Ensuring the safety of in-person learning has therefore been a priority in many countries and regions. Public health recommendations, including hand washing, respiratory hygiene, physical distancing, and correct use of masks, are important and have been encouraged to reduce transmission within households and in educational and congregate settings.42,54,83,90,101,102 The CDC updated guidelines for COVID-19 prevention in schools, including a focus on COVID-19 vaccination as the leading public health strategy.103 The focus of vaccination is supported by data from the United States, which found increased seroprevalence during September 2021–February 2022, among children and adolescents, the groups with the lowest vaccination coverage (28% of 5- to 11-year-olds and 59% in 12- to 17-year-olds; compared with 69% of 18- to 49-year-olds, 80% of 50- to 64-year-olds, and 90% of those 65 years or older).50 Other mitigation strategies to reduce transmission include universal and correct wearing of masks in all children 2 years or older; good ventilation, physical distancing; hand washing and respiratory etiquette; cleaning and maintenance of healthy facilities; and contact tracing, and isolation; monitoring community transmission; testing (both diagnostic and screening); and layering of prevention strategies to protect those who are not fully vaccinated.103 Although routine screening is no longer recommended, screening can be considered for high-risk activities (eg, close-contact sports, choir), at key times of year (eg, prom, tournaments), and when returning from breaks. The CDC no longer recommends quarantine for students, teachers, or staff who are exposed to COVID-19. Individuals who are exposed to COVID-19 should wear well-fitting masks while in school, should get tested, and are advised to stay home and isolate if they develop symptoms or test positive for SARS-CoV-2.103,104 Schools that choose to continue to require quarantine for people exposed to COVID-19 may also continue to implement “Test to Stay” (TTS), which combines contact tracing and serial testing to allow some students, teachers, and staff who have had close contact with someone with COVID-19 to continue in-person learning rather than being quarantined; asymptomatic students who participate in TTS and develop symptoms or test positive for SARS-CoV-2 should follow the above recommendations for individuals exposed to COVID-19 who are not participating in TTS.103,105 Support for the effectiveness of this approach was recently reported, with a study showing the incidence of SARS-COV-2 infections was lower for students attending TTS schools compared with students attending schools not implementing TTS (ie, >8000 days of in-person instruction saved).106

Our understanding of SARS-CoV-2 infection and transmission in children has been challenging, as the characteristics in this population often differ to that of other common respiratory diseases, including the generally mild clinical course, development of MIS-C, variable epidemiology and pathogenesis with VOCs, and identification of transmission chains with SARS-CoV-2. The characteristics of SARS-CoV-2 infection among children may be attributed to their immune response to the virus, the presence of generally fewer comorbidities in children compared with adults, stronger innate immune systems, previous exposure to benign coronaviruses, and the differential expression of angiotensin-converting enzyme 2 in pediatrics.107,108 It has been suggested that mild infections may also be less transmissible in children, because of a lack of coughing or sneezing, for example, although direct evidence of this is minimal.24,51 In addition, viral incubation time in pediatric populations and the transmissibility potential of the particular variant may be contributory.88,93–95 Further study is needed to fully understand the characteristics of children that contribute to disease pathogenesis, immunity, and transmission in this population to clarify risk factors and improve preventative and therapeutic strategies.107

A limitation of this narrative review is that because of the large number of publications in this field, the authors reviewed titles and abstracts for relevance before considering the full article; therefore, some relevant articles may not be included. Another limitation is that some of the articles reported small studies or case studies and may not be representative.

CONCLUSIONS

Early in the pandemic, SARS-CoV-2 seemed to infect children and adolescents less frequently than adults; however, with the emergence of VOCs, infection rates in this group have risen considerably. Compared with adults, children tend to have a milder course of disease. Vaccination of all eligible individuals alongside public health measures including physical distancing, correct and universal mask use, and adequate hygiene are recommended to prevent the spread of COVID-19 in schools. Our understanding of SARS-CoV-2 infection and transmission in children continues to evolve; however, more extensive and outcome-specific studies are warranted to understand how children contribute to the spread of COVID-19 and the differences in clinical manifestation of COVID-19 between adults and children, and the impact of existing and new variants of concern.

ACKNOWLEDGMENTS

The authors thank Sheena Hunt, PhD, Philippa Jack, PhD, and Tricia Newell, PhD, of ICON (Blue Bell, PA) for editorial/medical writing support.

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