Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C)

• Published in: Pediatrics (Evanston) 2020-12, Vol.146 (6), p.1
• Main Authors: Rostad, Christina A, Chahroudi, Ann, Mantus, Grace, Lapp, Stacey A, Teherani, Mehgan, Macoy, Lisa, Tarquinio, Keiko M, Basu, Rajit K, Kao, Carol, Linam, W Matthew, Zimmerman, Matthew G, Shi, Pei-Yong, Menachery, Vineet D, Oster, Matthew E, Edupuganti, Srilatha, Anderson, Evan J, Suthar, Mehul S, Wrammert, Jens, Jaggi, Preeti
• Format: Article
• Language: English
• Subjects: Adolescent; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Blood Sedimentation; Case-Control Studies; Child; Child, Preschool; Children; Confidence intervals; Coronaviridae; Coronavirus Nucleocapsid Proteins - blood; Coronavirus Nucleocapsid Proteins - immunology; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 Serological Testing; Diagnosis, Differential; Erythrocyte sedimentation rate; Female; Hospitalization; Humans; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulins; Infant; Infant, Newborn; Inflammation; Length of Stay; Male; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - blood; Mucocutaneous Lymph Node Syndrome - diagnosis; Mucocutaneous Lymph Node Syndrome - immunology; Multisystem inflammatory syndrome in children; Neutralization Tests; Nucleocapsids; Pediatrics; Phosphoproteins - blood; Phosphoproteins - immunology; Prospective Studies; Regression Analysis; SARS-CoV-2 - immunology; Serology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - blood; Spike Glycoprotein, Coronavirus - immunology; Systemic Inflammatory Response Syndrome - blood; Systemic Inflammatory Response Syndrome - diagnosis; Systemic Inflammatory Response Syndrome - immunology; Young Adult
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2020-018242

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. From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C ( = 10), symptomatic COVID-19 ( = 10), and KD ( = 5) and hospitalized controls ( = 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. All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies ( = 0.956; < .001), nucleocapsid protein antibodies ( = 0.846; < .001), and neutralizing antibodies ( = 0.667; < .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; < .001), children with KD (geometric mean titer 124; 95% confidence interval 91-170; < .001), and hospitalized controls (geometric mean titer 85; < .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 ( = 0.512; < .046) and with hospital ( = 0.548; = .014) and ICU lengths of stay ( = 0.590; = .010). 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.