Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium
Francesca Sperotto, Alba Gutiérrez‐Sacristán, Simran Makwana, Xiudi Li, Valerie Rofeberg, Tianxi Cai, Florence T. Bourgeois, Gilbert S. Omenn, David A. Hanauer, Carlos Sáez, Clara-Lea Bonzel, Emily M. Bucholz, Audrey Dionne, Matthew D. Elias, Noelia García Barrio, Tomás González González, Richard Issitt, Kate F. Kernan, Jessica Laird, Sarah E. Maidlow, Kenneth D. Mandl, Taha Mohseni Ahooyi, Cinta Moraleda, Michele Morris, Karyn Moshal, Miguel Pedrera‐Jiménez, Mohsin A. Shah, Andrew M. South, Anastassia Spiridou, Deanne M. Taylor, Guillaume Verdy, Shyam Visweswaran, Xuan Wang, Zongqi Xia, Joany M. Zachariasse, James R. Aaron, Atif Adam, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, M Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew M. Atz, Paul Avillach, Vidul Ayakulangara Panickan, Paula S. Azevedo, Rafael Badenes, James Balshi, Ashley Batugo, Brendin R. Beaulieu‐Jones, Brett K. Beaulieu‐Jones, Douglas S. Bell, Antonio Bellasi, Riccardo Bellazzi, Vincent Benoît, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, Clara-Lea Bonzel, John Booth, Silvano Bòsari, Florence T. Bourgeois, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William Bryant, Mauro Bucalo, Emily M. Bucholz, Anita Burgun, Tianxi Cai, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz‐Rojo, Arianna Dagliati, Mohamad Daniar
Abstract
Background Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 10 9 /uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 10 9 /uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding None.