BACKGROUND: Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. RESULTS: Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have asthma (p=0.005), and more likely to have an infected sibling contact (p=0.001) than uninfected children. Children ages 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs. 48%; p=0.01) or adolescents (29% vs. 60%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p<0.0001), gastrointestinal (27% vs. 9%; p=0.002), and sensory symptoms (42% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.01]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.

Background Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. Methods We conducted a prospective cohort study of children and adolescents (&lt;21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. Results Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p&lt;0.0001), less likely to have asthma (p=0.005), and more likely to have an infected sibling contact (p=0.001) than uninfected children. Children ages 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs. 48%; p=0.01) or adolescents (29% vs. 60%; p&lt;0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p&lt;0.0001), gastrointestinal (27% vs. 9%; p=0.002), and sensory symptoms (42% vs. 9%; p&lt;0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.01]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. Conclusions Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.

Children are less susceptible to SARS-CoV-2 and typically have milder illness courses than adults. We studied the nasopharyngeal microbiomes of 274 children, adolescents, and young adults with SARS-CoV-2 exposure using 16S rRNA gene sequencing. We find that higher abundances of Corynebacterium species are associated with SARS-CoV-2 infection and SARS-CoV-2-associated respiratory symptoms, while higher abundances of Dolosigranulum pigrum are present in SARS-CoV-2-infected individuals without respiratory symptoms. We also demonstrate that the abundances of these bacteria are strongly, and independently, associated with age, suggesting that the nasopharyngeal microbiome may be a potentially modifiable mechanism by which age influences SARS-CoV-2 susceptibility and severity.

Background Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity. Methods We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (&lt;21 years of age) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms. Results Nasopharyngeal microbiome composition varied with age (PERMANOVA, p&lt;0.001, R 2=0.06) and between SARS-CoV-2-infected individuals with and without respiratory symptoms (PERMANOVA, p=0.002, R 2=0.009). SARS-CoV-2-infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (odds ratio: 0.38, 95% confidence interval: 0.18–0.81). Using generalized joint attributed modeling, we identified nine bacterial taxa associated with SARS-CoV-2 infection and six taxa that were differentially abundant among SARS-CoV-2-infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age. Conclusions We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.

Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.