{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:14:56Z","timestamp":1790651696775,"version":"4.1.0"},"reference-count":82,"publisher":"Rockefeller University Press","issue":"8","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001873"],"award-info":[{"award-number":["UL1TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI100119"],"award-info":[{"award-number":["U01AI100119"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI168634"],"award-info":[{"award-number":["U01AI168634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23AI141686"],"award-info":[{"award-number":["K23AI141686"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM145440-01"],"award-info":[{"award-number":["T32GM145440-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD020056"],"award-info":[{"award-number":["S10OD020056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD030282"],"award-info":[{"award-number":["S10OD030282"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P30AI1045008"],"award-info":[{"award-number":["2P30AI1045008"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P30CA016520"],"award-info":[{"award-number":["2P30CA016520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,7]]},"abstract":"<jats:p>SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.<\/jats:p>","DOI":"10.1084\/jem.20221518","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T02:20:59Z","timestamp":1680920459000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-0382","authenticated-orcid":true,"given":"Ksenia","family":"Rybkina","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Irving Medical Center 1 Department of Microbiology and Immunology, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-0741","authenticated-orcid":true,"given":"Joseph N.","family":"Bell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-4119","authenticated-orcid":true,"given":"Marissa C.","family":"Bradley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-6004","authenticated-orcid":true,"given":"Teddy","family":"Wohlbold","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-3034","authenticated-orcid":true,"given":"Marika","family":"Scafuro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-7825","authenticated-orcid":true,"given":"Wenzhao","family":"Meng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pennsylvania 3 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, , Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3769-0047","authenticated-orcid":true,"given":"Rebecca C.","family":"Korenberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9313-4590","authenticated-orcid":true,"given":"Julia","family":"Davis-Porada","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Irving Medical Center 1 Department of Microbiology and Immunology, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0450-9387","authenticated-orcid":true,"given":"Brett R.","family":"Anderson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-1604","authenticated-orcid":true,"given":"Rachel J.","family":"Weller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3913-3869","authenticated-orcid":true,"given":"Joshua D.","family":"Milner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1796-8320","authenticated-orcid":true,"given":"Anne","family":"Moscona","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Irving Medical Center 1 Department of Microbiology and Immunology, , New York, NY, USA"},{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3866-9220","authenticated-orcid":true,"given":"Matteo","family":"Porotto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-9211","authenticated-orcid":true,"given":"Eline T.","family":"Luning Prak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pennsylvania 3 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, , Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-1886","authenticated-orcid":true,"given":"Kalpana","family":"Pethe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-7733","authenticated-orcid":true,"given":"Thomas J.","family":"Connors","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Vagelos College of Physicians and Surgeons 2 Department of Pediatrics, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-9183","authenticated-orcid":true,"given":"Donna L.","family":"Farber","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia University Irving Medical Center 1 Department of Microbiology and Immunology, , New York, NY, USA"},{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Columbia Irving University Medical Center 4 Department of Surgery, , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"2023050313582520600_bib1","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41591-020-0913-5","article-title":"A serological assay to detect SARS-CoV-2 seroconversion in humans","volume":"26","author":"Amanat","year":"2020","journal-title":"Nat. Med."},{"key":"2023050313582520600_bib2","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1016\/S2213-2600(21)00085-0","article-title":"Delayed-onset myocarditis following COVID-19","volume":"9","author":"Bajaj","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"2023050313582520600_bib3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s11262-006-0064-x","article-title":"Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1\/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy: A review","volume":"33","author":"Becker","year":"2006","journal-title":"Virus Genes"},{"key":"2023050313582520600_bib4","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1161\/CIRCULATIONAHA.120.050147","article-title":"Addition of corticosteroids to immunoglobulins is associated with recovery of cardiac function in multi-inflammatory syndrome in children","volume":"142","author":"Belhadjer","year":"2020","journal-title":"Circulation"},{"key":"2023050313582520600_bib5","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: Software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat. Methods"},{"key":"2023050313582520600_bib6","doi-asserted-by":"publisher","first-page":"3862","DOI":"10.4049\/jimmunol.164.7.3862","article-title":"Induction of functional IL-8 receptors by IL-4 and IL-13 in human monocytes","volume":"164","author":"Bonecchi","year":"2000","journal-title":"J. Immunol."},{"key":"2023050313582520600_bib7","doi-asserted-by":"publisher","first-page":"841126","DOI":"10.3389\/fimmu.2022.841126","article-title":"Autoantibodies against proteins previously associated with autoimmunity in adult and pediatric patients with COVID-19 and children with MIS-C","volume":"13","author":"Burbelo","year":"2022","journal-title":"Front. Immunol."},{"key":"2023050313582520600_bib8","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1038\/s41591-020-1054-6","article-title":"Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection","volume":"26","author":"Carter","year":"2020","journal-title":"Nat. Med."},{"key":"2023050313582520600_bib9","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.3390\/cells10082143","article-title":"Single-cell transcriptomics reveals Core regulatory programs that determine the heterogeneity of circulating and tissue-resident memory CD8+ T cells","volume":"10","author":"Chen","year":"2021","journal-title":"Cells"},{"key":"2023050313582520600_bib10","doi-asserted-by":"publisher","first-page":"25254","DOI":"10.1073\/pnas.2010722117","article-title":"Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023050313582520600_bib11","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1001\/jama.2020.10374","article-title":"Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York city","volume":"324","author":"Cheung","year":"2020","journal-title":"JAMA"},{"key":"2023050313582520600_bib12","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S2352-4642(22)00027-X","article-title":"Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: A multicentre observational study","volume":"6","author":"Cloete","year":"2022","journal-title":"Lancet Child Adolesc. Health"},{"key":"2023050313582520600_bib13","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.cell.2020.09.016","article-title":"The Immunology of multisystem inflammatory syndrome in children with COVID-19","volume":"183","author":"Consiglio","year":"2020","journal-title":"Cell"},{"key":"2023050313582520600_bib14","doi-asserted-by":"publisher","first-page":"793197","DOI":"10.3389\/fimmu.2021.793197","article-title":"SARS-CoV-2-Specific T cell responses are stronger in children with multisystem inflammatory syndrome compared to children with uncomplicated SARS-CoV-2 infection","volume":"12","author":"Conway","year":"2022","journal-title":"Front. Immunol."},{"key":"2023050313582520600_bib15","doi-asserted-by":"publisher","first-page":"e615","DOI":"10.1016\/S2665-9913(21)00223-X","article-title":"Steroids or intravenous immunoglobulin as first line in MIS-C in LMICs","volume":"3","author":"Crosby","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"2023050313582520600_bib16","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"2023050313582520600_bib17","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf4063","article-title":"Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection","volume":"371","author":"Dan","year":"2021","journal-title":"Science"},{"key":"2023050313582520600_bib18","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1126\/science.abf4896","article-title":"Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets","volume":"371","author":"de Vries","year":"2021","journal-title":"Science"},{"key":"2023050313582520600_bib19","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s00247-022-05521-5","article-title":"Ventricular function and tissue characterization by cardiac magnetic resonance imaging following hospitalization for multisystem inflammatory syndrome in children: A prospective study","volume":"53","author":"DiLorenzo","year":"2023","journal-title":"Pediatr. Radiol."},{"key":"2023050313582520600_bib20","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.1172\/JCI140970","article-title":"Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2","volume":"130","author":"Diorio","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2023050313582520600_bib21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn8057","article-title":"Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection","volume":"14","author":"Evans","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"2023050313582520600_bib22","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2021-051155","article-title":"Longitudinal outcomes for multisystem inflammatory syndrome in children","volume":"148","author":"Farooqi","year":"2021","journal-title":"Pediatrics"},{"key":"2023050313582520600_bib23","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1056\/NEJMoa2021680","article-title":"Multisystem inflammatory syndrome in U.S. Children and adolescents","volume":"383","author":"Feldstein","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023050313582520600_bib24","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals","volume":"181","author":"Grifoni","year":"2020","journal-title":"Cell"},{"key":"2023050313582520600_bib25","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.cell.2020.09.034","article-title":"Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C)","volume":"183","author":"Gruber","year":"2020","journal-title":"Cell"},{"key":"2023050313582520600_bib26","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1126\/science.abc6027","article-title":"Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients","volume":"369","author":"Hadjadj","year":"2020","journal-title":"Science"},{"key":"2023050313582520600_bib27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211381","article-title":"TIM3+ TRBV11-2 T cells and IFN\u03b3 signature in patrolling monocytes and CD16+ NK cells delineate MIS-C","volume":"219","author":"Hoste","year":"2022","journal-title":"J. Exp. Med."},{"key":"2023050313582520600_bib28","doi-asserted-by":"publisher","first-page":"7219","DOI":"10.3390\/ijms23137219","article-title":"T cells in multisystem inflammatory syndrome in children (MIS-C) have a predominant CD4+ T helper response to SARS-CoV-2 peptides and numerous virus-specific CD4- CD8- double-negative T cells","volume":"23","author":"Hsieh","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2023050313582520600_bib29","doi-asserted-by":"publisher","first-page":"e178","DOI":"10.1097\/PCC.0000000000002598","article-title":"Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 in a Children\u2019s hospital in New York city: Patient characteristics and an institutional protocol for evaluation, management, and follow-up","volume":"22","author":"Jonat","year":"2021","journal-title":"Pediatr. Crit. Care Med."},{"key":"2023050313582520600_bib30","first-page":"726","article-title":"Pheatmap: Pretty heatmaps","volume":"1","author":"Kolde","year":"2012","journal-title":"R package version"},{"key":"2023050313582520600_bib31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043603","article-title":"A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates","volume":"7","author":"Krammer","year":"2012","journal-title":"PLoS One"},{"key":"2023050313582520600_bib32","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1016\/j.celrep.2017.08.078","article-title":"Human tissue-resident memory T cells are defined by Core transcriptional and functional signatures in lymphoid and mucosal sites","volume":"20","author":"Kumar","year":"2017","journal-title":"Cell Rep."},{"key":"2023050313582520600_bib33","doi-asserted-by":"publisher","first-page":"109106","DOI":"10.1016\/j.clim.2022.109106","article-title":"SARS-CoV-2-specific T cell responses in patients with multisystem inflammatory syndrome in children","volume":"243","author":"Lam","year":"2022","journal-title":"Clin. Immunol."},{"key":"2023050313582520600_bib34","doi-asserted-by":"publisher","first-page":"5942","DOI":"10.1172\/JCI141113","article-title":"Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children","volume":"130","author":"Lee","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2023050313582520600_bib35","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2023050313582520600_bib36","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.ccc.2013.03.012","article-title":"Toxic shock syndrome: Major advances in pathogenesis, but not treatment","volume":"29","author":"Low","year":"2013","journal-title":"Crit. Care Clin."},{"key":"2023050313582520600_bib37","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMc2005073","article-title":"SARS-CoV-2 infection in children","volume":"382","author":"Lu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023050313582520600_bib38","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"2023050313582520600_bib39","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1126\/science.aad2035","article-title":"Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes","volume":"352","author":"Mackay","year":"2016","journal-title":"Science"},{"key":"2023050313582520600_bib40","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.43151","article-title":"Characteristics, outcomes, and severity risk factors associated with SARS-CoV-2 infection among children in the US national COVID cohort collaborative","volume":"5","author":"Martin","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"2023050313582520600_bib41","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.023251","article-title":"Longitudinal assessment of cardiac outcomes of multisystem inflammatory syndrome in children associated with COVID-19 infections","volume":"11","author":"Matsubara","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"2023050313582520600_bib42","doi-asserted-by":"publisher","first-page":"e138","DOI":"10.1055\/s-0040-1713678","article-title":"Pathological role of angiotensin II in severe COVID-19","volume":"4","author":"Miesbach","year":"2020","journal-title":"TH Open"},{"key":"2023050313582520600_bib43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13073-021-00918-7","article-title":"Maintenance of the human memory T cell repertoire by subset and tissue site","volume":"13","author":"Miron","year":"2021","journal-title":"Genome Med."},{"key":"2023050313582520600_bib44","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh1516","article-title":"Polyclonal expansion of TCR Vbeta 21.3(+) CD4(+) and CD8(+) T cells is a hallmark of Multisystem Inflammatory Syndrome in Children","volume":"6","author":"Moreews","year":"2021","journal-title":"Sci Immunol"},{"key":"2023050313582520600_bib45","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s00281-016-0558-0","article-title":"The host immune response in respiratory virus infection: Balancing virus clearance and immunopathology","volume":"38","author":"Newton","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"2023050313582520600_bib46","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92801","article-title":"A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage","volume":"2","author":"Norlander","year":"2017","journal-title":"JCI Insight"},{"key":"2023050313582520600_bib47","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jaci.2020.10.008","article-title":"COVID-19-associated multisystem inflammatory syndrome in children (MIS-C): A novel disease that mimics toxic shock syndrome-the superantigen hypothesis","volume":"147","author":"Noval Rivas","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023050313582520600_bib48","doi-asserted-by":"publisher","first-page":"941009","DOI":"10.3389\/fimmu.2022.941009","article-title":"Multisystem inflammatory syndrome in children and long COVID: The SARS-CoV-2 viral superantigen hypothesis","volume":"13","author":"Noval Rivas","year":"2022","journal-title":"Front. Immunol."},{"key":"2023050313582520600_bib49","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1056\/NEJMc2007617","article-title":"Children with covid-19 in pediatric emergency departments in Italy","volume":"383","author":"Parri","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023050313582520600_bib50","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd5487","article-title":"Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients","volume":"12","author":"Pierce","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"2023050313582520600_bib51","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1067\/mai.2001.118600","article-title":"IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism","volume":"108","author":"Pope","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023050313582520600_bib52","doi-asserted-by":"publisher","first-page":"5148","DOI":"10.1128\/JVI.00164-09","article-title":"Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy","volume":"83","author":"Porotto","year":"2009","journal-title":"J. Virol."},{"key":"2023050313582520600_bib53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151520","article-title":"The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children","volume":"131","author":"Porritt","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2023050313582520600_bib54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI146614","article-title":"HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children","volume":"131","author":"Porritt","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2023050313582520600_bib55","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.immuni.2021.04.003","article-title":"Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children","volume":"54","author":"Ramaswamy","year":"2021","journal-title":"Immunity"},{"key":"2023050313582520600_bib56","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/s41590-021-01051-8","article-title":"SARS-CoV-2 immune repertoire in MIS-C and pediatric COVID-19","volume":"22","author":"Ravichandran","year":"2021","journal-title":"Nat. Immunol."},{"key":"2023050313582520600_bib57","doi-asserted-by":"publisher","first-page":"12306","DOI":"10.1073\/pnas.1915681117","article-title":"TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection","volume":"117","author":"Reilly","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023050313582520600_bib58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186998","article-title":"Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells","volume":"12","author":"Reiss","year":"2017","journal-title":"PLoS One"},{"key":"2023050313582520600_bib59","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1016\/S0140-6736(20)31094-1","article-title":"Hyperinflammatory shock in children during COVID-19 pandemic","volume":"395","author":"Riphagen","year":"2020","journal-title":"Lancet"},{"key":"2023050313582520600_bib60","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1182\/bloodadvances.2019000853","article-title":"Postvaccination graft dysfunction\/aplastic anemia relapse with massive clonal expansion of autologous CD8+ lymphocytes","volume":"4","author":"Ritz","year":"2020","journal-title":"Blood Adv."},{"key":"2023050313582520600_bib61","doi-asserted-by":"publisher","first-page":"e574","DOI":"10.1016\/S2665-9913(21)00139-9","article-title":"Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: A cohort study","volume":"3","author":"Rodriguez-Smith","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"2023050313582520600_bib62","doi-asserted-by":"publisher","first-page":"6104054","DOI":"10.1155\/2017\/6104054","article-title":"IL-10: A multifunctional cytokine in viral infections","volume":"2017","author":"Rojas","year":"2017","journal-title":"J. Immunol. Res."},{"key":"2023050313582520600_bib63","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1038\/s41591-022-01724-3","article-title":"Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19","volume":"28","author":"Sacco","year":"2022","journal-title":"Nat. Med."},{"key":"2023050313582520600_bib64","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1056\/NEJMc2119641","article-title":"Plasma neutralization of the SARS-CoV-2 omicron variant","volume":"386","author":"Schmidt","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"2023050313582520600_bib65","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41584-021-00709-9","article-title":"Multisystem inflammatory syndrome in children and Kawasaki disease: A critical comparison","volume":"17","author":"Sharma","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"2023050313582520600_bib66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004503","article-title":"VDJtools: Unifying post-analysis of T cell receptor repertoires","volume":"11","author":"Shugay","year":"2015","journal-title":"PLOS Comput. Biol."},{"key":"2023050313582520600_bib67","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00571-21","article-title":"Rapid and flexible platform to assess anti-SARS-CoV-2 antibody neutralization and spike protein-specific antivirals","volume":"6","author":"Stelitano","year":"2021","journal-title":"MSphere"},{"key":"2023050313582520600_bib68","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nm.1929","article-title":"Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10","volume":"15","author":"Sun","year":"2009","journal-title":"Nat. Med."},{"key":"2023050313582520600_bib69","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.immuni.2021.03.005","article-title":"Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19","volume":"54","author":"Szabo","year":"2021","journal-title":"Immunity"},{"key":"2023050313582520600_bib70","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1038\/s41467-019-12464-3","article-title":"Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease","volume":"10","author":"Szabo","year":"2019","journal-title":"Nat. Commun."},{"key":"2023050313582520600_bib71","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aas9673","article-title":"Location, location, location: Tissue resident memory T cells in mice and humans","volume":"4","author":"Szabo","year":"2019","journal-title":"Sci. Immunol."},{"key":"2023050313582520600_bib72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030538","article-title":"Rapid screening for entry inhibitors of highly pathogenic viruses under low-level biocontainment","volume":"7","author":"Talekar","year":"2012","journal-title":"PLoS One"},{"key":"2023050313582520600_bib73","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.3367200","article-title":"Immunarch: An R package for painless bioinformatics analysis of T-cell and B-cell immune repertoires.","volume":"10","author":"Team","year":"2019","journal-title":"Zenodo"},{"key":"2023050313582520600_bib74","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1038\/sj.leu.2403202","article-title":"Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 concerted action BMH4-CT98-3936","volume":"17","author":"van Dongen","year":"2003","journal-title":"Leukemia"},{"key":"2023050313582520600_bib75","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1093\/bioinformatics\/btu138","article-title":"pRESTO: A toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires","volume":"30","author":"Vander Heiden","year":"2014","journal-title":"Bioinformatics"},{"key":"2023050313582520600_bib76","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf7570","article-title":"Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19","volume":"6","author":"Vella","year":"2021","journal-title":"Sci. Immunol."},{"key":"2023050313582520600_bib77","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1016\/S0140-6736(20)31103-X","article-title":"An outbreak of severe kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study","volume":"395","author":"Verdoni","year":"2020","journal-title":"Lancet"},{"key":"2023050313582520600_bib78","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1001\/jamapediatrics.2022.0945","article-title":"Incidence rates and clinical outcomes of SARS-CoV-2 infection with the omicron and delta variants in children younger than 5 Years in the US","volume":"176","author":"Wang","year":"2022","journal-title":"JAMA Pediatr."},{"key":"2023050313582520600_bib79","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41590-020-00826-9","article-title":"Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum","volume":"22","author":"Weisberg","year":"2021","journal-title":"Nat. Immunol."},{"key":"2023050313582520600_bib80","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"2023050313582520600_bib81","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149633","article-title":"Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier","volume":"131","author":"Yonker","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2023050313582520600_bib82","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/jmv.25587","article-title":"Clinical and Th1\/Th2 immune response features of hospitalized children with human rhinovirus infection","volume":"92","author":"Yuan","year":"2020","journal-title":"J. Med. Virol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20221518\/1451998\/jem_20221518.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20221518\/1451998\/jem_20221518.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T09:59:34Z","timestamp":1683107974000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/220\/8\/e20221518\/214087\/SARS-CoV-2-infection-and-recovery-in-children"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":82,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20221518","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]},"article-number":"e20221518"}}