Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study
Authors: Dongngan T. Truong, Felicia L. Trachtenberg, Chenwei Hu, Gail D. Pearson, Kevin Friedman, Arash A. Sabati, Audrey Dionne, Matthew E. Oster, Brett R. Anderson, Joseph Block, Tamara T. Bradford, M. Jay Campbell, Laura D’Addese, Kirsten B. Dummer, Matthew D. Elias, Daniel Forsha, Olukayode D. Garuba, Keren Hasbani, Kerri Hayes, Camden Hebson, Pei-Ni Jone, Anita Krishnan, Sean Lang, Brian W. McCrindle, Kimberly E. McHugh, Elizabeth C. Mitchell, Tonia Morrison, Juan Carlos Muniz, R. Mark Payne, Michael A. Portman, Mark W. Russell, Yamuna Sanil, Divya Shakti, Kavita Sharma, J. Ryan Shea, Michelle Sykes, Lara S. Shekerdemian, Jacqueline Szmuszkovicz, Deepika Thacker, Jane W. Newburger, Kristin Burns, Victoria Pemberton, D’Andrea Egerson, Lynn Mahony, Julie Miller, Allison Crosby-Thompson, Ayesha Amarnath*, James Ambrosoli, Cassandra Artis, Kay Rubio*, Chitra Kinhikar*, Amanda Marshall, Devine Mbiydzenyuy*, Valentina Kazlova, PJ Mu*, Lozan Eyob*, Beverly Slayton, Lauren DiStefano, Jami Honig, Tiffany Bowie*, Rob Nero*, Emily Birmingham*, Robin Rowe, Melissa Joyce, Cole Gallagher*, Djenawa Bowman*, Mo Zhang, Sachin Bandari, Alissa Mooney*, Andreea Dragulescu, Christopher Lam, Rae Yeung, Beth Gamulka, Jessica Bainton, Martha Rolland, Patti Walter*, Simran Mahanta*, Thomas Giorgio, Veronique Wright, Olivia Rossi*, Numaira Khan*, Annette Baker, Lisa Jean Buckley, Jessica Jones*, LaTina Watson*, Anna Clarke*, Tor-Samuel-Aleer Leek*, Gwendolyn Orav*, Therese Giglia, Katherine Lupton, Donna Sylvester, Dana Albizem, Kristin Lanzilotta, Grace Marks, Tyler Kasmarcak, Madison Johnson*, Megan Bickford*, Edem Binka, Linda Lambert, Lilly Fagatele, Emma Joyce, Andrea Dunn, Mark Russell, Tammy Doman, Lori Harris*, Marisa Almaguer, Elise Pickering, Lauryn Dugan, Kathleen Rathge, Elizabeth Seibert*, Mary Stumpf, Jennifer Howell, Jyoti Patel, Nancy Kehlenbrink, Gloria Mitscher*, Melissa Burnett*, Kolby Sanders-Lewis, Morgan Van Dresser, Beatrice Doe-Printemps, Brooke Evans*, William T. Mahle, Lazaros Kochilas, Madison Rudow*, Susie Gentry*, Kristie Le*, Caitlen Taylor*, Kristen Sexson Tejtel, Elias Moussi*, Faridis Serrano, Sandra Pena, Ricardo Pignatelli, Asela Liu*, Kanwal Farooqi, Brett Anderson*, Amee Shah, Michael DiLorenzo, Neeka Karaminian, Katrina Golub, Chantal Sanchez*, Chanel Rojas*, Karen Martyrosyan*, Jacqueline R. Szmuszkovicz, Andrew L. Cheng, Sindhu Mohandas, Jodie K. Votava-Smith, Shuo Wang, Pierre C. Wong, Jennifer Su, Allison Garcia*, Anastasia Sarkissian*, Matthew Dam*, Javier Medina, Kavita Sharma, Catherine Ikemba, Maria Martinez*, Parvin Mohazabnia*, Delaney Evans, Wendy Rojas, Joseph Block, Stephanie Handler, Regina Cole, Jennifer Maldonado, Shubhika Srivastava, Deepika Thacker, Carol Prospero, Varsha Zadokar, Ed Williams, Michael Carr, Kathleen Van't Hof, Lauren Goodell*, Colleen Sullivan*, Jason Lu, Aaron Olson, Eyal Sagiv, Sujatha Buddhe*, Hidemi Kajimoto*, Deepthi G. Nair*, Mikayla A. Beckley*, Camilla Pedroso*, Cisco Pedroso, Kirsten Dummer, Joan Pancheri, Sherrie Bandy, Katheryn Crane*, Ashraf Harahsheh, Charles Berul, Laura Olivieri*, Jordyn Britton, Mitchell Haverty*, Alix Fetch, Christina Schott*, Sarah Litt*, Jennifer Nelson*, Dara Watkins, Suchitra Rao, Michelle Hite*, Isabel Glassmeyer*, Heather Heizer, Sonia Chavez, Todd Nowlen, Ashley Herzberg, Samantha Stack, Jade Porche*, Megan Warner*, Susan Park, Amy Johnson, Amy Ellerbe*, Kathleen Nagaran Hildebrand*, Divya Shakti*, Aimee S. Parnell, Onyekachukwu Osakwe, Michael D. Weiland, Phenique Parker*, Jeffrey A. Kertis*, Charlotte V. Hobbs, Candace M. Howard, Shivraj Savadkar, Aren E. Worrell, Madelyn R. Barr*, Heather Williams, David Gordy, Preeti Vemula*, Zachary White*, Jemylle Grace S. Morato*, Sandra Tyler, Krissie Hock, Lerraughn Morgan, Carl Owada, Mayra Lemus Rangel, Isaura Macias*, Tania Jimenez, Gautham Singh, Sanjeev Aggarwal, Charmaine Williams-Farr*, Nancy Sullivan*, Aiman Almasnaah*, Vishnu Undyala, Brian Hannah*, Mary McCall*, Emily Ward, Louisa Keith, Jacob Strelow*, Sagar Jani, Antonette Salazar, Rachel Downey, Ken Shaffer, Chesney Castleberry, Lisa Pomeroy, Rachel Amsellem, Olga Shamailova, Arlett Zelaya, Marla Johnston, Juan Carlos Muniz, Moya Chang*, Ryan Shea, Miriam Davis, Maryanne Chrisant, Danielle Katz*, Norma "Jean" Barton, Doris Alaby, Paulette Smith, Bukky Oni, Francesca Sperotto, Ed Marcus, Raquel Ferreira*, Patrick McGeoghegan, Michael Taylor, Joshua Germann, Andrew Powell, Andrew Mackie, Jogarao Gobburu, Sally Hunsberger, Patrick McQuillen, Michael Spaeder, Dianne Atkins, Craig Broberg, David J. Driscoll, Frank Evans, Sally A. Hunsberger, Liza-Marie Johnson, Thomas J. Knight, Paul Lipkin, J. Philip Saul
Journal: JAMA Pediatrics (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;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]; R 2 = 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;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.