학술논문
Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
MAJOR ARTICLE
MAJOR ARTICLE
Document Type
Clinical report
Author
Lapp, Stacey A.; Abrams, Joseph; Lu, Austin T.; Hussaini, Laila; Kao, Carol M.; Hunstad, David A.; Rosenberg, Robert B.; Zafferani, Marc J.; Ede, Kaleo C.; Ballan, Wassim; Laham, Federico R.; Beltran, Yajira; Hsiao, Hui-Mien; Sherry, Whitney; Jenkins, Elan; Jones, Kaitlin; Horner, Anna; Brooks, Alyssa; Bryant, Bobbi; Meng, Lu; Hammett, Teresa A.; Oster, Matthew E.; Bamrah-Morris, Sapna; Godfred- Cato, Shana; Belay, Ermias; Chahroudi, Ann; Anderson, Evan J.; Jaggi, Preeti; Rostad, Christina A.
Source
Open Forum Infectious Diseases. March 2022, Vol. 9 Issue 3
Subject
Language
English
ISSN
2328-8957
Abstract
Following the onset of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel multisystem inflammatory syndrome in children (MIS-C) was first [...]
Background. The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. Methods. We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID- 19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. Results. Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-[gamma]). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization [greater than or equal to] 8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]). Conclusions. MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-[gamma]. Keywords. children; COVID-19; cytokines; MIS-C; PIMS; SARS-CoV-2; serology.
Background. The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. Methods. We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID- 19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. Results. Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-[gamma]). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization [greater than or equal to] 8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]). Conclusions. MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-[gamma]. Keywords. children; COVID-19; cytokines; MIS-C; PIMS; SARS-CoV-2; serology.