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Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children
Madeleine D Burns1,2, Yannic C Bartsch3,4, Jameson P Davis1,2
1Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA.
Insights
Children’s immune systems mature after COVID-19 and MIS-C, showing resolving inflammation and varied antibody responses. These findings may inform long-term protection against reinfection in pediatric post-infectious cohorts.
Area of Science:
- Pediatric immunology
- Virology
- Infectious diseases
Background:
- While most children have mild SARS-CoV-2 infections, some develop Multisystem Inflammatory Syndrome in Children (MIS-C).
- The long-term immune profiles in children after acute COVID-19 and MIS-C remain largely unknown.
Purpose of the Study:
- To deeply profile the humoral immune responses and circulating cytokines in children following acute COVID-19 and MIS-C.
- To understand the lasting immune signatures in pediatric post-infectious cohorts.
Main Methods:
- Blood samples were collected from 21 children and young adults (aged 2 months-20 years) at acute presentation and 6-month follow-up.
- Humoral immune responses and circulating cytokines were analyzed using deep profiling techniques.
Main Results:
- Pro-inflammatory cytokine levels resolved by 6 months post-infection in both COVID-19 and MIS-C groups.
- Humoral immune profiles matured after acute COVID-19, with decreasing IgM, increasing IgG, and enhanced antibody-dependent monocyte activation.
- Anti-Spike IgG1 levels diminished over time in the MIS-C cohort.
Conclusions:
- Pediatric immune profiles mature after both COVID-19 and MIS-C, indicating a diversified anti-SARS-CoV-2 antibody response.
- Resolving inflammation and recalibrated humoral responses characterize the mature immune signature.
- Heightened antibody-activated responses in convalescent COVID-19 may offer long-term immunoprotection against reinfection.
Background:
Although most children experience mild symptoms during acute SARS-CoV-2 infection, some develop the severe post-COVID-19 complication, Multisystem Inflammatory Syndrome in Children (MIS-C). While acute presentations of COVID-19 and MIS-C have been well immunophenotyped, little is known about the lasting immune profile in children after acute illness.
Methods:
Children 2 months-20 years of age presenting with either acute COVID-19 (n = 9) or MIS-C (n = 12) were enrolled in a Pediatric COVID-19 Biorepository at a single medical center. We deeply profiled humoral immune responses and circulating cytokines following pediatric COVID-19 and MIS-C.
Results:
Twenty-one children and young adults provided blood samples at both acute presentation and 6-month follow-up (mean: 6.5 months; standard deviation: 1.77 months). Pro-inflammatory cytokine elevations resolved after both acute COVID-19 and MIS-C. Humoral profiles continue to mature after acute COVID-19, displaying decreasing IgM and increasing IgG over time, as well as stronger effector functions, including antibody-dependent monocyte activation. In contrast, MIS-C immune signatures, especially anti-Spike IgG1, diminished over time.
Conclusions:
Here, we show the mature immune signature after pediatric COVID-19 and MIS-C, displaying resolving inflammation with recalibration of the humoral responses. These humoral profiles highlight immune activation and vulnerabilities over time in these pediatric post-infectious cohorts.
Impact:
The pediatric immune profile matures after both COVID-19 and MIS-C, suggesting a diversified anti-SARS-CoV-2 antibody response after resolution of acute illness. While pro-inflammatory cytokine responses resolve in the months following acute infection in both conditions, antibody-activated responses remain relatively heightened in convalescent COVID-19. These data may inform long-term immunoprotection from reinfection in children with past SARS-CoV-2 infections or MIS-C.
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