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

Rostad, Christina A.; Chahroudi, Ann; Mantus, Grace; Lapp, Stacey A.; Teherani, Mehgan; Macoy, Lisa; Rostad, Bradley S.; Milla, Sarah Sarvis; Tarquinio, Keiko M.; Basu, Rajit K.; Kao, Carol; Linam, W. Matthew; Zimmerman, Matthew G.; Shi, Pei–Yong; Menachery, Vineet D.; Oster, Matthew E.; Edupuganti, Sri; Anderson, Evan J.; Suthar, Mehul S.; Wrammert, Jens; Jaggi, Preeti

doi:10.1101/2020.07.10.20150755

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…We also found that 3 out of 4 tested MIS-C patients seroconverted and had comparable levels of SARS-CoV-2 IgG antibodies to the spike protein as the children with mild SARS-CoV-2 infection and no MIS-C ( Figure 6 A). This result is in line with data from other groups studying antibody responses in MIS-C patients ( Gruber et al., 2020 ; Rostad et al., 2020 ). A possible hypothesis for why some children develop MIS-C is that prior immunity to other viruses could modulate their responses to SARS-CoV-2 infection and give rise to hyperinflammation either by antibody-mediated enhancement or other mechanisms ( Tetro, 2020 ).…”

Section: Resultssupporting

confidence: 92%

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

Consiglio

Cotugno

Sardh

et al. 2020

Cell

769

950

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

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Section: Resultssupporting

confidence: 92%

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

Consiglio

Cotugno

Sardh

et al. 2020

Cell

769

950

View full text Add to dashboard Cite

show abstract

“…We also found that 3 out of 4 tested MIS-C patients seroconverted and had comparable levels of SARS-CoV-2 IgG antibodies to the spike protein as the children with mild SARS-CoV-2 infection and no MIS-C ( Figure 6A ). This result is in line with data from other groups studying antibody responses in MIS-C patients (Gruber et al, 2020; Rostad et al, 2020). A possible hypothesis for why some children develop MIS-C is that prior immunity to other viruses could modulate their responses to SARS-CoV-2 infection and give rise to hyperinflammation either by antibody-mediated enhancement or other mechanisms (Tetro, 2020).…”

Section: Resultssupporting

confidence: 92%

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

Consiglio

Cotugno

Sardh

et al. 2020

Preprint

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SARS-CoV2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever and organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, is more similar to Kawasaki disease, but also differ from this with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests endoglin, an endothelial glycoprotein as one of several candidate targets of autoantibodies in MIS-C.

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“…But the remaining one-third of patients who were negative on both tests had come in contact with COVID-19-positive individuals [11]. Rostad et al have performed serological studies in children with MIS-C and compared the results with children who had usual COVID-19 infection, KD and hospital controls [54]. They showed that patients with MIS-C had higher levels of IgG SARS-CoV-2 receptor-binding domain.…”

Section: Laboratory Featuresmentioning

confidence: 99%

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

et al. 2020

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Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease. Keywords Multisystem inflammatory syndrome (MIS-C) • Kawasaki disease (KD) • Hyperinflammation • Coronavirus disease 2019 • Kawasaki-like disease Background Kawasaki disease (KD) is a medium vessel vasculitis of undetermined etiology usually affecting children below 5 years [1-3]. Rowley et al. had hypothesized as far back as 2004 that an unidentified respiratory infectious agent with tropism to vascular tissue, likely a virus, could be linked to the etiology of KD [4]. This putative RNA virus, presumably a ubiquitous one, resulted in persistent infection in bronchial epithelium and macrophages and was associated with intracytoplasmic inclusions [5, 6]. Rheumatology INTERNATIONAL Jayakanthan Kabeerdoss and Rakesh Kumar Pilania are the joint first authors and they contributed equally. Disclaimer We hereby state that this manuscript is original and no part of the manuscript has either been published before, or is under consideration of publication elsewhere. The definition of scientific term alluded to, in the manuscript have been duly cited.

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

Cited by 14 publications

References 21 publications

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

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