tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2022 Feb 24;9(3)
fac070.
doi: 10.1093/ofid/ofac070. eCollection 2022 Mar.
Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
Stacey A Lapp[SUP] 1 2 [/SUP], Joseph Abrams[SUP] 3 [/SUP], Austin T Lu[SUP] 1 2 [/SUP], Laila Hussaini[SUP] 1 2 [/SUP], Carol M Kao[SUP] 4 [/SUP], David A Hunstad[SUP] 4 [/SUP], Robert B Rosenberg[SUP] 5 6 [/SUP], Marc J Zafferani[SUP] 5 6 [/SUP], Kaleo C Ede[SUP] 6 7 [/SUP], Wassim Ballan[SUP] 6 8 [/SUP], Federico R Laham[SUP] 9 [/SUP], Yajira Beltran[SUP] 9 [/SUP], Hui-Mien Hsiao[SUP] 1 2 [/SUP], Whitney Sherry[SUP] 1 2 [/SUP], Elan Jenkins[SUP] 1 2 [/SUP], Kaitlin Jones[SUP] 2 [/SUP], Anna Horner[SUP] 1 2 [/SUP], Alyssa Brooks[SUP] 1 2 [/SUP], Bobbi Bryant[SUP] 3 10 [/SUP], Lu Meng[SUP] 3 11 [/SUP], Teresa A Hammett[SUP] 3 [/SUP], Matthew E Oster[SUP] 1 2 3 [/SUP], Sapna Bamrah-Morris[SUP] 3 [/SUP], Shana Godfred-Cato[SUP] 3 [/SUP], Ermias Belay[SUP] 3 [/SUP], Ann Chahroudi[SUP] 1 2 [/SUP], Evan J Anderson[SUP] 1 2 12 [/SUP], Preeti Jaggi[SUP] 1 2 [/SUP], Christina A Rostad[SUP] 1 2 [/SUP]
Affiliations
Abstract
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-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥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-γ.
Keywords: COVID-19; MIS-C; PIMS; SARS-CoV-2; children; cytokines; serology.
. 2022 Feb 24;9(3)
doi: 10.1093/ofid/ofac070. eCollection 2022 Mar.
Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
Stacey A Lapp[SUP] 1 2 [/SUP], Joseph Abrams[SUP] 3 [/SUP], Austin T Lu[SUP] 1 2 [/SUP], Laila Hussaini[SUP] 1 2 [/SUP], Carol M Kao[SUP] 4 [/SUP], David A Hunstad[SUP] 4 [/SUP], Robert B Rosenberg[SUP] 5 6 [/SUP], Marc J Zafferani[SUP] 5 6 [/SUP], Kaleo C Ede[SUP] 6 7 [/SUP], Wassim Ballan[SUP] 6 8 [/SUP], Federico R Laham[SUP] 9 [/SUP], Yajira Beltran[SUP] 9 [/SUP], Hui-Mien Hsiao[SUP] 1 2 [/SUP], Whitney Sherry[SUP] 1 2 [/SUP], Elan Jenkins[SUP] 1 2 [/SUP], Kaitlin Jones[SUP] 2 [/SUP], Anna Horner[SUP] 1 2 [/SUP], Alyssa Brooks[SUP] 1 2 [/SUP], Bobbi Bryant[SUP] 3 10 [/SUP], Lu Meng[SUP] 3 11 [/SUP], Teresa A Hammett[SUP] 3 [/SUP], Matthew E Oster[SUP] 1 2 3 [/SUP], Sapna Bamrah-Morris[SUP] 3 [/SUP], Shana Godfred-Cato[SUP] 3 [/SUP], Ermias Belay[SUP] 3 [/SUP], Ann Chahroudi[SUP] 1 2 [/SUP], Evan J Anderson[SUP] 1 2 12 [/SUP], Preeti Jaggi[SUP] 1 2 [/SUP], Christina A Rostad[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35237703
- PMCID: PMC8883592
- DOI: 10.1093/ofid/ofac070
Abstract
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-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥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-γ.
Keywords: COVID-19; MIS-C; PIMS; SARS-CoV-2; children; cytokines; serology.