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

• Published in: Nature 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
• Language: English
• 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30357-w

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