Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study
Authors: Truong Dongngan T. , Trachtenberg Felicia L. , Hu Chenwei , Pearson Gail D. , Friedman Kevin , Sabati Arash A. , Dionne Audrey , Oster Matthew E. , Anderson Brett R. , Block Joseph , Bradford Tamara T. , Campbell M. Jay , D’Addese Laura , Dummer Kirsten B. , Elias Matthew D. , Forsha Daniel , Garuba Olukayode D. , Hasbani Keren , Hayes Kerri , Hebson Camden , Jone Pei-Ni , Krishnan Anita , Lang Sean , McCrindle Brian W. , McHugh Kimberly E. , Mitchell Elizabeth C. , Morrison Tonia , Muniz Juan Carlos , Payne R. Mark , Portman Michael A. , Russell Mark W. , Sanil Yamuna , Shakti Divya , Sharma Kavita , Shea J. Ryan , Sykes Michelle , Shekerdemian Lara S. , Szmuszkovicz Jacqueline , Thacker Deepika , Newburger Jane W. ,   MUSIC Study Investigators, Burns Kristin , Pemberton Victoria , Egerson D’Andrea , Mahony Lynn , Miller Julie , Crosby-Thompson Allison , Amarnath* Ayesha , Ambrosoli James , Artis Cassandra , Rubio* Kay , Kinhikar* Chitra , Marshall Amanda , Mbiydzenyuy* Devine , Kazlova Valentina , Mu* PJ , Eyob* Lozan , Slayton Beverly , DiStefano Lauren , Honig Jami , Bowie* Tiffany , Nero* Rob , Birmingham* Emily , Rowe Robin , Joyce Melissa , Gallagher* Cole , Bowman* Djenawa , Zhang Mo , Bandari Sachin , Mooney* Alissa , Dragulescu Andreea , Lam Christopher , Yeung Rae , Gamulka Beth , Bainton Jessica , Rolland Martha , Walter* Patti , Mahanta* Simran , Giorgio Thomas , Wright Veronique , Rossi* Olivia , Khan* Numaira , Baker Annette , Buckley Lisa Jean , Jones* Jessica , Watson* LaTina , Clarke* Anna , Leek* Tor-Samuel-Aleer , Orav* Gwendolyn , Giglia Therese , Lupton Katherine , Sylvester Donna , Albizem Dana , Lanzilotta Kristin , Marks Grace , Kasmarcak Tyler , Johnson* Madison , Bickford* Megan , Binka Edem , Lambert Linda , Fagatele Lilly , Joyce Emma , Dunn Andrea , Russell Mark , Doman Tammy , Harris* Lori , Almaguer Marisa , Pickering Elise , Dugan Lauryn , Rathge Kathleen , Seibert* Elizabeth , Stumpf Mary , Howell Jennifer , Patel Jyoti , Kehlenbrink Nancy , Mitscher* Gloria , Burnett* Melissa , Sanders-Lewis Kolby , Van Dresser Morgan , Doe-Printemps Beatrice , Evans* Brooke , Mahle William T. , Kochilas Lazaros , Rudow* Madison , Gentry* Susie , Le* Kristie , Taylor* Caitlen , Sexson Tejtel Kristen , Moussi* Elias , Serrano Faridis , Pena Sandra , Pignatelli Ricardo , Liu* Asela , Farooqi Kanwal , Anderson* Brett , Shah Amee , DiLorenzo Michael , Karaminian Neeka , Golub Katrina , Sanchez* Chantal , Rojas* Chanel , Martyrosyan* Karen , Szmuszkovicz Jacqueline R. , Cheng Andrew L. , Mohandas Sindhu , Votava-Smith Jodie K. , Wang Shuo , Wong Pierre C. , Su Jennifer , Garcia* Allison , Sarkissian* Anastasia , Dam* Matthew , Medina Javier , Sharma Kavita , Ikemba Catherine , Martinez* Maria , Mohazabnia* Parvin , Evans Delaney , Rojas Wendy , Block Joseph , Handler Stephanie , Cole Regina , Maldonado Jennifer , Srivastava Shubhika , Thacker Deepika , Prospero Carol , Zadokar Varsha , Williams Ed , Carr Michael , Van't Hof Kathleen , Goodell* Lauren , Sullivan* Colleen , Lu Jason , Olson Aaron , Sagiv Eyal , Buddhe* Sujatha , Kajimoto* Hidemi , Nair* Deepthi G. , Beckley* Mikayla A. , Pedroso* Camilla , Pedroso Cisco , Dummer Kirsten , Pancheri Joan , Bandy Sherrie , Crane* Katheryn , Harahsheh Ashraf , Berul Charles , Olivieri* Laura , Britton Jordyn , Haverty* Mitchell , Fetch Alix , Schott* Christina , Litt* Sarah , Nelson* Jennifer , Watkins Dara , Rao Suchitra , Hite* Michelle , Glassmeyer* Isabel , Heizer Heather , Chavez Sonia , Nowlen Todd , Herzberg Ashley , Stack Samantha , Porche* Jade , Warner* Megan , Park Susan , Johnson Amy , Ellerbe* Amy , Nagaran Hildebrand* Kathleen , Shakti* Divya , Parnell Aimee S. , Osakwe Onyekachukwu , Weiland Michael D. , Parker* Phenique , Kertis* Jeffrey A. , Hobbs Charlotte V. , Howard Candace M. , Savadkar Shivraj , Worrell Aren E. , Barr* Madelyn R. , Williams Heather , Gordy David , Vemula* Preeti , White* Zachary , Morato* Jemylle Grace S. , Tyler Sandra , Hock Krissie , Morgan Lerraughn , Owada Carl , Lemus Rangel Mayra , Macias* Isaura , Jimenez Tania , Singh Gautham , Aggarwal Sanjeev , Williams-Farr* Charmaine , Sullivan* Nancy , Almasnaah* Aiman , Undyala Vishnu , Hannah* Brian , McCall* Mary , Ward Emily , Keith Louisa , Strelow* Jacob , Jani Sagar , Salazar Antonette , Downey Rachel , Shaffer Ken , Castleberry Chesney , Pomeroy Lisa , Amsellem Rachel , Shamailova Olga , Zelaya Arlett , Johnston Marla , Muniz Juan Carlos , Chang* Moya , Shea Ryan , Davis Miriam , Chrisant Maryanne , Katz* Danielle , Barton Norma "Jean" , Alaby Doris , Smith Paulette , Oni Bukky , Sperotto Francesca , Marcus Ed , Ferreira* Raquel , McGeoghegan Patrick , Taylor Michael , Germann Joshua , Powell Andrew , Mackie Andrew , Gobburu Jogarao , Hunsberger Sally , McQuillen Patrick , Spaeder Michael , Atkins Dianne , Broberg Craig , Driscoll David J. , Evans Frank , Hunsberger Sally A. , Johnson Liza-Marie , Knight Thomas J. , Lipkin Paul , Saul J. Philip 
Published: January 2025

Importance

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective

To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] &amp;lt;55%), coronary artery aneurysms (z score ≥2.5), and noncardiac involvement through 6 months after MIS-C.

Design, Setting, and Participants

This cohort study enrolled participants between March 2020 and January 2022 with a follow-up period of 2 years. Participants were recruited from 32 North American pediatric hospitals, and all participants met the 2020 Centers for Disease Control and Prevention case definition of MIS-C.

Exposure

MIS-C after COVID-19 infection.

Main Outcomes and Measures

Outcomes included echocardiography core laboratory (ECL) assessments of LVEF and maximum coronary artery z scores (zMax); data collection on cardiac and noncardiac sequelae during hospitalization and at 2 weeks, 6 weeks, and 6 months after discharge; and age-appropriate Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health Instruments at follow-up. Descriptive statistics, linear regression models, and Kaplan-Meier analysis were used.

Results

Of 1204 participants (median [IQR] age, 9.1 [5.6-12.7] years; 724 male [60.1%]), 325 self-identified with non-Hispanic Black race (27.0%) and 324 with Hispanic ethnicity (26.9%). A total of 548 of 1195 participants (45.9%) required vasoactive support, 17 of 1195 (1.4%) required extracorporeal membrane oxygenation, and 3 (0.3%) died during hospitalization. Of participants with echocardiograms reviewed by the ECL (n = 349 due to budget constraints), 131 of 322 (42.3%) had LVEF less than 55% during hospitalization; of those with follow-up, all but 1 normalized by 6 months. Black race (vs other/unknown race), higher C-reactive protein level, and abnormal troponin level were associated with lowest LVEF (estimate [SE], −3.09 [0.98]; R2 = 0.14; P =.002). Fifteen participants had coronary artery z scores of 2.5 or greater at any time point; 1 participant had a large/giant aneurysm. Of the 13 participants with z scores of 2.5 or greater during hospitalization, 12 (92.3%) had normalized by 6 months. Return to greater than 90% of pre–MIS-C health status (energy, sleep, appetite, cognition, and mood) was reported by 711 of 824 participants (86.3%) at 2 weeks, increasing to 548 of 576 (95.1%) at 6 months. Fatigue was the most common symptom reported at 2 weeks (141 of 889 [15.9%]), falling to 3.4% (22 of 638) by 6 months. PROMIS Global Health parent/guardian proxy median T scores for fatigue, global health, and pain interference improved significantly from 2 weeks to 6 months (fatigue, 56.1 vs 48.9; global health, 48.8 vs 51.3; pain interference, 53.0 vs 43.3; P &amp;lt; .001) and by the 6-week visit were at least equivalent to prepandemic population norms.

Conclusions and Relevance

Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.