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

Yonker, Lael M.; Neilan, Anne M.; Bartsch, Yannic; Patel, Ankit B.; Regan, James; Arya, Puneeta; Gootkind, Elizabeth; Park, Grace; Hardcastle, Margot; St. John, Anita; Appleman, Lori; Chiu, Michelle L.; Fialkowski, Allison; De la Flor, Denis; Lima, Rosiane; Bordt, Evan A.; Yockey, Laura J.; D’Avino, Paolo; Fischinger, Stephanie; Shui, Jessica E.; Lerou, Paul H.; Bonventre, Joseph V.; Yu, Xu G.; Ryan, Edward T.; Bassett, Ingrid V.; Irimia, Daniel; Edlow, Andrea G.; Alter, Galit; Li, Jonathan Z.; Fasano, Alessio

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.