Asthma and the Risk of SARS-CoV-2 Infection Among Children and Adolescents

Importance: More than 4 million SARS-COV-2 infections have occurred among children and adolescents in the United States. Risk factors for SARS-CoV-2 infection among children remain poorly defined. Objective: To evaluate the association between asthma and the risk of SARS-CoV-2 infection among children. Design: Retrospective cohort study Setting: A large, integrated health system in central North Carolina. Participants: Children 5 to 17 years of age with a Durham County address and at least one health care encounter in the Duke University Health System between March 1, 2017, and February 28, 2020. Exposure: Diagnosis of asthma Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection identified by PCR testing of a respiratory sample collected between March 1, 2020, and October 31, 2020. We matched children with asthma 1:1 to children without asthma using propensity scores and used Poisson regression to evaluate the association between asthma and the risk of SARS-CoV-2 infection. We assessed for effect modification of this association by inhaled corticosteroid prescription and comorbid atopic diseases. Results: Of 49,455 children, 6,515 (13%) met criteria for a diagnosis of asthma; all children with asthma were matched to a control child without asthma for a final cohort of 13,030 children. Median (interquartile range) age was 11.0 (8.0, 14.0) years, 56% were male, and 78% were non-White. A diagnosis of asthma was associated with a decreased risk of SARS-CoV-2 infection [risk ratio (RR): 0.67, 95% confidence interval (CI): 0.49-0.92]. This association tended to be stronger in children with asthma who were prescribed inhaled corticosteroids (RR: 0.60, 95% CI: 0.38-0.94) or who had comorbid atopic diseases (RR: 0.59, 95% CI: 0.39-0.88). Of the 66 children with asthma who developed SARS-CoV-2 infection, none required hospitalization for COVID-19. Conclusions and Relevance: Children with asthma had a lower risk of SARS-CoV-2 infection, particularly children prescribed an inhaled corticosteroid or with comorbid atopic diseases. Further studies are needed to explore the complex relationship between asthma, inhaled corticosteroids, and SARS-CoV-2.

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

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.

Age-related changes in the upper respiratory microbiome are associated with SARS-CoV-2 susceptibility and illness severity

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. SummaryEvaluation of nasopharyngeal microbiome profiles in children, adolescents, and young adults with a SARS-CoV-2-infected close contact identified specific bacterial species that vary in abundance with age and are associated with SARS-CoV-2 susceptibility and the presence of SARS-CoV-2-associated respiratory symptoms.

SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study

BACKGROUNDChildren 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. METHODSWe 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. RESULTSOf 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONSHispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of 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.

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches

In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.