Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19

  1. Christina A. Rostad
  2. Ann Chahroudi
  3. Grace Mantus
  4. Stacey A. Lapp
  5. Mehgan Teherani
  6. Lisa Macoy
  7. Bradley S. Rostad
  8. Sarah S. Milla
  9. Keiko M. Tarquinio
  10. Rajit K. Basu
  11. Carol Kao
  12. W. Matthew Linam
  13. Matthew G. Zimmerman
  14. Pei-Yong Shi
  15. Vineet D. Menachery
  16. Matthew E. Oster
  17. Sri Edupuganti
  18. Evan J. Anderson
  19. Mehul Suthar
  20. Jens Wrammert
  21. Preeti Jaggi
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Abstract

Objectives

We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls.

Methods

From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Children’s Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression.

Results

All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010).

Conclusion

Quantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.

Table of Contents Summary

Children with MIS-C have high antibody titers to the SARS-CoV-2 spike protein receptor binding domain, which correlate with neutralization, systemic inflammation, and clinical outcomes.

What’s Known on This Subject

Although the clinical features of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been recently described, the serologic features of MIS-C are unknown.

What This Study Adds

In this case series, all hospitalized children with MIS-C had significantly higher SARS-CoV-2 binding and neutralizing antibodies than children with COVID-19 or Kawasaki Disease. SARS-CoV-2 antibodies correlated with metrics of systemic inflammation and clinical outcomes, suggesting diagnostic and prognostic value.

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