Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium.

Sperotto, Francesca; Gutiérrez-Sacristán, Alba; Makwana, Simran; Li, Xiudi; Rofeberg, Valerie N; Cai, Tianxi; Bourgeois, Florence T; Omenn, Gilbert S et al. · EClinicalMedicine · 2023

retrospective_cohort · Level III

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Abstract

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. 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 <i>Alpha</i> as reference. Meta-analysis was used to pool data across sites. Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the <i>Alpha</i> era, 111 (19%) in the <i>Delta</i> era, and 104 (17%) in the <i>Omicron</i> era. Compared with patients admitted in the <i>Alpha</i> era, those admitted in the <i>Delta</i> 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<sup>9</sup>/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 <i>Omicron</i> versus <i>Alpha</i> 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<sup>9</sup>/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 <i>Delta</i> versus <i>Alpha</i> eras (-1.3 days [95% CI -2.3, -0.4]). Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in <i>Delta</i> and <i>Omicron</i> eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. None.