Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children

Madeleine D Burns; Yannic C Bartsch; Jameson P Davis; Brittany P Boribong; Maggie Loiselle; Jaewon Kang; Abigail S Kane; Andrea G Edlow; Alessio Fasano; Galit Alter; Lael M Yonker

doi:10.1038/s41390-023-02627-w

Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children

Pediatr Res. 2023 Oct;94(4):1327-1334. doi: 10.1038/s41390-023-02627-w. Epub 2023 May 12.

Authors

Madeleine D Burns^#^{1

2}, Yannic C Bartsch^#^{3

4}, Jameson P Davis^{1

2}, Brittany P Boribong^{1

2

3}, Maggie Loiselle^{1

2}, Jaewon Kang⁴, Abigail S Kane^{1

2}, Andrea G Edlow^{3

5

6}, Alessio Fasano^{1

2

3}, Galit Alter^{3

4}, Lael M Yonker^{7

8

9}

Affiliations

¹ Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA.
² Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA.
⁴ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
⁵ Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA, USA.
⁷ Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA. Lyonker@mgh.harvard.edu.
⁸ Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, USA. Lyonker@mgh.harvard.edu.
⁹ Harvard Medical School, Boston, MA, USA. Lyonker@mgh.harvard.edu.

^# Contributed equally.

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: 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.

MeSH terms

Acute Disease
Antibodies, Viral
COVID-19* / complications
COVID-19* / diagnosis
Child
Cytokines
Humans
SARS-CoV-2
Systemic Inflammatory Response Syndrome / diagnosis
Young Adult

Substances

Cytokines
Antibodies, Viral

Supplementary concepts

pediatric multisystem inflammatory disease, COVID-19 related