An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease

Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were de...

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Published inNature communications Vol. 13; no. 1; p. 2687
Main Authors Ghosh, Pradipta, Katkar, Gajanan D., Shimizu, Chisato, Kim, Jihoon, Khandelwal, Soni, Tremoulet, Adriana H., Kanegaye, John T., Bocchini, Joseph, Das, Soumita, Burns, Jane C., Sahoo, Debashis
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.05.2022
Nature Publishing Group
Nature Portfolio
Subjects
13/51
38/91
631/553/1833
692/699/255
Artificial Intelligence
Child
Children
Computational Biology - methods
Computer applications
Coronaviruses
COVID-19
COVID-19 - complications
COVID-19 - genetics
COVID-19 - immunology
Cytokine storm
Cytokines
Disorders
Eosinopenia
Gene Expression Profiling
Gene sequencing
Heart
Humanities and Social Sciences
Humans
Immune response
Immune system
Immunity - physiology
Immunopathogenesis
Infections
Interleukin 1
Interleukin 15
Kawasaki disease
Laboratories
Mucocutaneous lymph node syndrome
Mucocutaneous Lymph Node Syndrome - genetics
Mucocutaneous Lymph Node Syndrome - immunology
multidisciplinary
Multisystem inflammatory syndrome in children
Pandemics
Parameters
Pediatrics
Phenotypes
SARS-CoV-2
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Signatures
Systemic Inflammatory Response Syndrome - genetics
Systemic Inflammatory Response Syndrome - immunology
Thrombocytopenia
Viral diseases
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Abstract Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA -centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity. Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity
AbstractList Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA -centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity. Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity
Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity
Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity
Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA -centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.
Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.
ArticleNumber 2687
Author Tremoulet, Adriana H.
Burns, Jane C.
Ghosh, Pradipta
Kim, Jihoon
Shimizu, Chisato
Bocchini, Joseph
Das, Soumita
Sahoo, Debashis
Khandelwal, Soni
Kanegaye, John T.
Katkar, Gajanan D.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35577777$$D View this record in MEDLINE/PubMed
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Issue 1
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License 2022. The Author(s).
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Snippet Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the...
Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the...
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pubmedcentral
proquest
crossref
pubmed
springer
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 2687
SubjectTerms 13/51
38/91
631/553/1833
692/699/255
Artificial Intelligence
Child
Children
Computational Biology - methods
Computer applications
Coronaviruses
COVID-19
COVID-19 - complications
COVID-19 - genetics
COVID-19 - immunology
Cytokine storm
Cytokines
Disorders
Eosinopenia
Gene Expression Profiling
Gene sequencing
Heart
Humanities and Social Sciences
Humans
Immune response
Immune system
Immunity - physiology
Immunopathogenesis
Infections
Interleukin 1
Interleukin 15
Kawasaki disease
Laboratories
Mucocutaneous lymph node syndrome
Mucocutaneous Lymph Node Syndrome - genetics
Mucocutaneous Lymph Node Syndrome - immunology
multidisciplinary
Multisystem inflammatory syndrome in children
Pandemics
Parameters
Pediatrics
Phenotypes
SARS-CoV-2
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Signatures
Systemic Inflammatory Response Syndrome - genetics
Systemic Inflammatory Response Syndrome - immunology
Thrombocytopenia
Viral diseases
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Title An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
URI https://link.springer.com/article/10.1038/s41467-022-30357-w
https://www.ncbi.nlm.nih.gov/pubmed/35577777
https://www.proquest.com/docview/2664961760
https://search.proquest.com/docview/2665561001
https://pubmed.ncbi.nlm.nih.gov/PMC9110726
https://doaj.org/article/5eee4b462ba34ab699957ddce673e064
Volume 13
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