Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses

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Data sharing: The data obtained as part of this study are available from the corresponding author upon reasonable request.

Objectives

As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical.

Study design: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital (MGH) were offered enrollment in the MGH Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.

Results

A total of 192 children (mean age 10.2 +/- 7 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met criteria for MIS-C. Only 25 (51%) of children with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were non-specific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower ACE2 expression (P=0.004). IgM and IgG to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein were increased in severe MIS-C (P<0.001), with dysregulated humoral responses observed.

Conclusion

This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms, and immune dysregulation is implicated in severe post-infectious MIS-C.

Supported by the National Heart, Lung, and Blood Institute (5K08HL143183 to L.Y.), the Cystic Fibrosis Foundation (YONKER18Q0 to L.Y.), the National Institute of Child Health and Human Development (K08 HD094638 [to A.N.] and R01HD100022 [to A.E.]), Mark and Lisa Schwartz (to J.L.), the National Institute of Diabetes and Digestive and Kidney Diseases (DK039773, DK072381 [to J.B.] and DK104344 [to A.F.]), the National Institute of Allergy and Infectious Disease (K24AI141036 to I.B.), the Centers for Disease Control and Prevention (U01CK000490 to E.R.), and the Department of Pediatrics and the Department of Obstetrics/Gynecology at Massachusetts General Hospital (to L.Y. and A.E.). The authors declare no conflicts of interest.

As schools plan for re-opening, debates around the role children play in the COVID-19 pandemic persist. Concerns have been raised as to whether allowing children to congregate in the classroom will fuel the spread of the pandemic. On an individual level, families are worried how SARS-CoV-2 infection could affect their children and family. Particular concern is elevated for families belonging to low socio-economic classes, where the prevalence of SARS-CoV-2 infection is higher, and where multi-generational co-habitation is the norm, increasing the risk of transmitting the infection to vulnerable grandparents and older adults(1).

The manner in which children contribute to the spread of SARS-CoV-2 is unclear. Children are less likely to become seriously ill from SARS-CoV-2(2); however, asymptomatic carriers, including children, can spread infection and carry virus into their household.3 Children infected with SARS-CoV-2 tend to have milder symptoms with significantly lower mortality than is seen in adult infection(4). It has been hypothesized that children have reduced incidence of COVID-19 because ACE2 expression in the nasopharynx increases with age(5); however ACE2 expression has not been studied in the upper airways of children infected with SARS-CoV-2. Understanding infectious burden and potential for transmissibility within the pediatric population is critical for developing both short- and long-term responses, including public health policies, to the current pandemic.

Although an acute SARS-CoV-2 infection tends to be mild or symptom-free in most pediatric cases, some children develop a multisystem inflammatory syndrome (MIS-C)(

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Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City.