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Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C)
Christina A Rostad1,2, Ann Chahroudi1,3,2, Grace Mantus1,2
1Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia.
Insights
Children with multisystem inflammatory syndrome in children (MIS-C) exhibit significantly higher SARS-CoV-2 antibody titers than those with COVID-19, Kawasaki disease, or controls. Serological responses in MIS-C correlate with disease severity and duration.
Area of Science:
- Pediatric Immunology
- Infectious Diseases
- Viral Serology
Background:
- Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition linked to SARS-CoV-2 infection.
- Distinguishing MIS-C from other pediatric inflammatory conditions like Kawasaki disease (KD) is crucial for appropriate management.
- Understanding the specific serological profile of MIS-C can aid in diagnosis and risk stratification.
Purpose of the Study:
- To compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological responses in children with MIS-C versus those with COVID-19, KD, and healthy controls.
- To evaluate the correlation between SARS-CoV-2 antibody titers and clinical parameters in MIS-C.
- To assess the potential role of quantitative serology in diagnosing MIS-C.
Main Methods:
- Prospective identification and blood sample collection from hospitalized children with MIS-C, COVID-19, KD, and controls.
- Quantitative measurement of SARS-CoV-2 specific antibodies (IgM, IgG, neutralizing) using ELISAs and live-virus assays.
- Statistical comparison of antibody titers and correlation analyses with clinical data.
Main Results:
- Children with MIS-C demonstrated significantly higher SARS-CoV-2 RBD IgG antibody titers compared to all other groups (P < .001).
- MIS-C patients had detectable RBD IgM antibodies, indicating recent infection, and strong correlations between various SARS-CoV-2 antibody types.
- RBD IgG titers correlated with inflammatory markers (ESR) and length of hospital/ICU stay.
Conclusions:
- Quantitative SARS-CoV-2 serology can help diagnose MIS-C and differentiate it from similar pediatric conditions.
- Serological profiles may assist in stratifying risk for adverse outcomes in children with MIS-C.
- Elevated SARS-CoV-2 antibody titers are a key feature distinguishing MIS-C.
Objectives:
We aimed to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological responses in children hospitalized with multisystem inflammatory syndrome in children (MIS-C) compared with those with coronavirus disease 2019 (COVID-19), those with Kawasaki disease (KD), and hospitalized pediatric controls.
Methods:
From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C (n = 10), symptomatic COVID-19 (n = 10), and KD (n = 5) and hospitalized controls (n = 4) at Children's Healthcare of Atlanta. With institutional review board approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin M and immunoglobulin G (IgG), full-length spike IgG, and nucleocapsid protein antibodies using quantitative enzyme-linked immunosorbent assays and SARS-CoV-2 neutralizing antibodies using live-virus focus-reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses.
Results:
All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R 2 = 0.956; P < .001), nucleocapsid protein antibodies (R 2 = 0.846; P < .001), and neutralizing antibodies (R 2 = 0.667; P < .001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer 6800; 95% confidence interval 3495-13 231) than children with COVID-19 (geometric mean titer 626; 95% confidence interval 251-1563; P < .001), children with KD (geometric mean titer 124; 95% confidence interval 91-170; P < .001), and hospitalized controls (geometric mean titer 85; P < .001). All children with MIS-C also had detectable RBD immunoglobulin M antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with the erythrocyte sedimentation rate (R 2 = 0.512; P < .046) and with hospital (R 2 = 0.548; P = .014) and ICU lengths of stay (R 2 = 0.590; P = .010).
Conclusions:
Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.
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