Abstract
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
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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.
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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.
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These data may inform long-term immunoprotection from reinfection in children with past SARS-CoV-2 infections or MIS-C.
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Data availability
All relevant data are included in this manuscript. Data is available upon reasonable request.
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Acknowledgements
We thank the children and their families for participating in this research and Nancy Zimmerman, Mark and Lisa Schwartz, Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support.
Funding
We acknowledge support from Massachusetts General Hospital for Children, the Ragon Institute of MGH, MIT, and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, and the March of Dimes. We also received support from an anonymous donor (financial support), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, 1U01CA260476-01, CIVIC75N93019C00052, 5K08HL143183, R01HD100022-02S2) and the Gates Foundation Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650).
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Substantial contributions to conception and design, acquisition of data or analysis and interpretation of data: M.D.B., Y.C.B., J.P.D., B.P.B., M.L., J.K., A.S.K., A.G.E., A.F., G.A., L.M.Y. Drafting the article or revising it critically for important intellectual content: M.D.B., Y.C.B., A.S.K., A.G.E., A.F., G.A., L.M.Y. Final approval of the version to be published: M.D.B., Y.C.B., J.P.D., B.P.B., M.L., J.K., A.S.K., A.G.E., A.F., G.A., L.M.Y.
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Competing interests
G.A. is a V.P. at Moderna, a founder and equity holder of Seromyx Systems, and an employee and equity holder of Leyden Labs. G.A.’s interests were reviewed and are managed by MGH and Partners HealthCare in accordance with their conflict-of-interest policies. A.G.E. reported serving as a medical advisor for Mirvie, Inc. and receiving research funding from Merck & Co. outside of the scope of the submitted work. No other disclosures were reported. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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Informed consent, and where appropriate, assent, was verbally obtained from participants and/or parents/guardians involved in the study. The study was approved by the Institutional Review Board of Massachusetts General Brigham (IRB #2020P000955, approved 12/14/20).
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Burns, M.D., Bartsch, Y.C., Davis, J.P. et al. Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children. Pediatr Res 94, 1327–1334 (2023). https://doi.org/10.1038/s41390-023-02627-w
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DOI: https://doi.org/10.1038/s41390-023-02627-w
