Roberta L DeBiasi1, Ashraf S Harahsheh2, Hemalatha Srinivasalu3, Anita Krishnan2, Matthew P Sharron4, Kavita Parikh5, Karen Smith5, Michael Bell4, Drew Michael6, Meghan Delaney7, Joseph Campos7, Eric Vilain8, Jonathan LoTiempo8, Jaclyn N Kline9, Tova Ronis3, Suvankar Majumdar10, Eleanor Sadler11, Susan R Conway4, Charles L Berul2, Sangeeta Sule3, Rebeca Lahoz12, Emily Ansusinha12, Jay Pershad13, Vanessa Bundy14, Elizabeth Wells15, James E Bost16, David Wessel17. 1. Divisions of Pediatric Infectious Diseases, Children's National Hospital; Divisions of Cardiology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences; Departments of Microbiology,Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences. Electronic address: rdebiasi@childrensnational.org. 2. Divisions of Cardiology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 3. Divisions of Rheumatology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 4. Divisions of Critical Care Medicine, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 5. Divisions of Hospitalist Medicine, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 6. Divisions of Laboratory Medicine and Pathology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences; Departments of Pathology, The George Washington University School of Medicine and Health Sciences; Departments of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences. 7. Divisions of Laboratory Medicine and Pathology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 8. Departments of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences; Center for Genetic Medicine Research, Children's Research Institute, Washington DC. 9. Divisions of Emergency Medicine, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 10. Divisions of Hematology Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 11. Divisions of Pharmacy, Children's National Hospital. 12. Divisions of Pediatric Infectious Diseases, Children's National Hospital. 13. Divisions of Emergency Medicine, Children's National Hospital. 14. Divisions of Immunology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 15. Divisions of Neurology, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences. 16. Divisions of Biostatistics, Children's National Hospital. 17. Divisions of Cardiology, Children's National Hospital; Divisions of Critical Care Medicine, Children's National Hospital; Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences.
Abstract
OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with Multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March-September 2020 at Children's National, a quaternary freestanding Children's Hospital in Washington DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were overrepresented in the MIS-C cohort, with Black children at highest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill MIS-C (55% vs. 28%; p=0.04) including systolic myocardial dysfunction (39% vs. 3%; p=0.001), and valvular regurgitation (33% vs. 7%; p=0.01). Median cycle threshold (Ct) was 31.8 (27.95--35.1 IQR) in MIS-C cases, significantly higher (indicating lower viral load) than in primary SARS-CoV-2 infection. Cytokines siL2R, IL10, and IL-6 were higher in MIS-C compared with controls. Cytokine analysis revealed sub-phenotype differences between critically ill vs. noncritically ill (IL-2, sIL2R, IL-10, Il-6); PCR positive vs. negative (TNF-α, IL10, IL-6), and presence vs. absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing MIS-C with primary COVID patients. Treatment was well tolerated, and no children died. CONCLUSION: This study establishes a well-characterized large cohort of MIS-C treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long term follow up will provide opportunity for future insights into MIS-C and its sequelae.
OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with Multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March-September 2020 at Children's National, a quaternary freestanding Children's Hospital in Washington DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were overrepresented in the MIS-C cohort, with Black children at highest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill MIS-C (55% vs. 28%; p=0.04) including systolic myocardial dysfunction (39% vs. 3%; p=0.001), and valvular regurgitation (33% vs. 7%; p=0.01). Median cycle threshold (Ct) was 31.8 (27.95--35.1 IQR) in MIS-C cases, significantly higher (indicating lower viral load) than in primary SARS-CoV-2 infection. Cytokines siL2R, IL10, and IL-6 were higher in MIS-C compared with controls. Cytokine analysis revealed sub-phenotype differences between critically ill vs. noncritically ill (IL-2, sIL2R, IL-10, Il-6); PCR positive vs. negative (TNF-α, IL10, IL-6), and presence vs. absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing MIS-C with primary COVIDpatients. Treatment was well tolerated, and no children died. CONCLUSION: This study establishes a well-characterized large cohort of MIS-C treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long term follow up will provide opportunity for future insights into MIS-C and its sequelae.
Authors: Ashraf S Harahsheh; Anita Krishnan; Roberta L DeBiasi; Laura J Olivieri; Christopher Spurney; Mary T Donofrio; Russell R Cross; Matthew P Sharron; Lowell H Frank; Charles I Berul; Adam Christopher; Niti Dham; Hemalatha Srinivasalu; Tova Ronis; Karen L Smith; Jaclyn N Kline; Kavita Parikh; David Wessel; James E Bost; Sarah Litt; Ashley Austin; Jing Zhang; Craig A Sable Journal: Cardiol Young Date: 2021-08-05 Impact factor: 1.023
Authors: Susan R Conway; Christopher A Lazarski; Naomi E Field; Mariah Jensen-Wachspress; Haili Lang; Vaishnavi Kankate; Jessica Durkee-Shock; Hannah Kinoshita; William Suslovic; Kathleen Webber; Karen Smith; Jeffrey I Cohen; Peter D Burbelo; Anqing Zhang; Stephen J Teach; Trisha Ibeh; Meghan Delaney; Roberta L DeBiasi; Michael D Keller; Catherine M Bollard Journal: Front Immunol Date: 2022-01-18 Impact factor: 7.561