Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children

Autor:in

Abu Hammour, Walid; Yavuz, Lemis; Jain, Ruchi; Abu hammour, khawla; Al-Hammouri, Ghalia F.; El Naofal, Maha; Halabi, Nour; Yaslam, Sawsan; Ramaswamy, Sathishkumar; Taylor, Alan; Wafadari, Deena; Alsarhan, A.; Khansaheb, Hamda; Deesi, Zulfa Omar; Varghese, Rupa Murthy; Uddin, Mohammed; Al Suwaidi, Hanan Sulaiman; Al-Hammadi, Suleiman; Alkhaja, Abdulmajeed; AlDabal, Laila Mohamed; Loney, Tom; Nowotny, Norbert; AlKhayat, Abdulla Ibrahim; Alsheikh-Ali, Alawi A.; Abou Tayoun, Ahmad

Abstrakt

IMPORTANCE Clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C) have not yet been documented. OBJECTIVE To assess the genetic and clinical characteristics of patients with MIS-C of primarily Arab and Asian origin. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter cohort study was conducted from September 1, 2020, to August 31, 2021, in the United Arab Emirates and Jordan. Forty-five patients with MIS-C and a matched control group of 25 healthy children with a confirmed SARSCoV-2 infection status were recruited. Whole exome sequencing in all 70 participants was performed to identify rare, likely deleterious variants in patients with MIS-C and to correlate genetic findings with the clinical course of illness. EXPOSURES SARS-CoV-2. MAIN OUTCOMES AND MEASURES Fever, organ system complications, laboratory biomarkers, whole exome sequencing findings, treatments, and clinical outcomes were measured. The Mann-Whitney U test was used to assess the association between genetic variants and MIS-C attributes. The Fisher exact test was used to compute the genetic burden in MIS-C relative to controls. RESULTS A total of 45 patients with MIS-C (23 [51.1%] male; 30 [66.7%] of Middle Eastern origin; mean [SD] age, 6.7 (3.6) years) and 25 controls (17 [68.0%] male; 24 [96.0%] of Middle Eastern origin; mean [SD] age 7.4 [4.0] years) participated in the study. Key inflammatory markers were significantly dysregulated in all patients with MIS-C. Mucocutaneous and gastrointestinal manifestations were each reported in 36 patients (80.0%; 95% CI, 66.1%-89.1%), cardiac findings were reported in 22 (48.9%; 95% CI, 35.0%-63.0%), and neurologic findings were reported in 14 (31.1%; 95% CI. 19.5%-45.6%). Rare, likely deleterious heterozygous variants in immune-related genes, including TLR3, TLI26, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%; 95% CI, 29.0%-56.7%), of whom 7 had multiple variants. There was higher enrichment of genetic variants in patients relative to controls (29 vs 3, P < .001). Patients with those variants tended to have earlier disease onset (7 patients [36.8%; 95% CI, 19.1%-58.9%] with genetic findings vs 2 [7.7%; 95% CI, 2.1%-24.1%] without genetic findings were younger than 3 years at onset) and resistance to treatment (8 patients [42.1%; 95% CI, 23.1%-63.7%] with genetic findings vs 3 patients [11.5%; 95% CI, 4.0%-29.0%] without genetic findings received 2 doses of intravenous immunoglobulin). CONCLUSIONS AND RELEVANCE The results of this cohort study suggest that rare, likely deleterious genetic variants may contribute to MIS-C disease. This finding paves the way for additional studies with larger, diverse populations to fully characterize the genetic contribution to this new disease entity.

CC Lizenz

CCBY

ISSN/eISSN

2574-3805 -

WoS ID

WOS:000805532900010

Repository Phaidra

o:1967