Humoral signatures of protective and pathological SARS-CoV-2 infection in children
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Published on: June 5, 2021
Yannic C Bartsch1, Chuangqi Wang2, Tomer Zohar1,2
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Insights
Children with COVID-19 show distinct immune responses compared to adults. Some children develop multisystem inflammatory syndrome (MIS-C) due to specific IgG antibodies, offering insights into COVID-19 severity.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- The SARS-CoV-2 pandemic causes varied disease severity, from asymptomatic cases in children to severe respiratory failure in adults.
- Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication of SARS-CoV-2 infection.
- Understanding differing immune responses in children versus adults is crucial for COVID-19 pathogenesis insights.
Purpose of the Study:
- To investigate the immune mechanisms underlying differential COVID-19 clinical phenotypes in children.
- To compare SARS-CoV-2 specific immune responses between children with mild COVID-19, adults with mild/severe disease, and children with MIS-C.
Main Methods:
- Systems serology was employed to analyze antibody responses in pediatric and adult COVID-19 cohorts.
- Functional assays assessed IgG and IgA responses, including phagocyte and complement activation.
- Neutrophil and monocyte activation by antibodies were also evaluated.
Main Results:
- Children with acute mild COVID-19 exhibited functional IgG responses similar to adults with mild disease.
- Adults with severe COVID-19 showed expanded IgA and neutrophil responses.
- Children who developed MIS-C had distinct, highly inflammatory monocyte-activating IgG antibodies post-infection.
Conclusions:
- SARS-CoV-2 IgG antibody profiles differ significantly between acute mild COVID-19 in children and MIS-C.
- Specific IgG and IgA responses may explain varying COVID-19 severity and complications in children.
- These findings provide critical insights into pediatric COVID-19 immune responses and MIS-C pathogenesis.
Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.
