Association of blood group B and of rare variants affecting immune system with multisystem inflammatory syndrome in children in an Italian cohort.
Multisystem inflammatory syndrome in children (MIS-C) is an uncommon delayed complication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children, whose cause remains unknown. The aim of this study was to investigate the role of genetic predisposition to COVID-19 and dysregulated inflammatory response in the development of MIS-C in Italian children.
Eighteen individuals were enrolled: 12 with classical MIS-C and 6 with a Kawasaki-SARS-CoV-2-related disease (KD). The frequency distribution of the main common risk variants underpinning COVID-19 susceptibility (ABO tagging SNPs) and severity (five GWAS-prioritized loci) was compared between patients and children with COVID-19 without MIS-C and with adult controls (n = 79 and n = 2,848, respectively). Whole exome sequencing (WES) was performed in the MIS-C cohort to examine the frequency of rare damaging variants in a panel of 207 immune-related genes as compared to that of local controls (n = 266).
Blood group B alleles conferred an increased risk of MIS-C independently of sex, ethnicity, the presence of COVID-19, and blood group A [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.04-8.5; p = 0.04], with a larger impact on the KD subphenotype (OR 6.8; 95% CI 1.7-35.1; p = 0.007). A total of 49 rare damaging variants, 4 classified as pathogenic, were prioritized in 39 immune-related genes; all patients harbored at least one variant.
These results not only support a role of blood group B as a risk factor for MIS-C development in children with COVID-19, possibly through modulation of the coagulability and microvascular dysfunction, but also support an immune-genetic basis for this condition.
Eighteen individuals were enrolled: 12 with classical MIS-C and 6 with a Kawasaki-SARS-CoV-2-related disease (KD). The frequency distribution of the main common risk variants underpinning COVID-19 susceptibility (ABO tagging SNPs) and severity (five GWAS-prioritized loci) was compared between patients and children with COVID-19 without MIS-C and with adult controls (n = 79 and n = 2,848, respectively). Whole exome sequencing (WES) was performed in the MIS-C cohort to examine the frequency of rare damaging variants in a panel of 207 immune-related genes as compared to that of local controls (n = 266).
Blood group B alleles conferred an increased risk of MIS-C independently of sex, ethnicity, the presence of COVID-19, and blood group A [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.04-8.5; p = 0.04], with a larger impact on the KD subphenotype (OR 6.8; 95% CI 1.7-35.1; p = 0.007). A total of 49 rare damaging variants, 4 classified as pathogenic, were prioritized in 39 immune-related genes; all patients harbored at least one variant.
These results not only support a role of blood group B as a risk factor for MIS-C development in children with COVID-19, possibly through modulation of the coagulability and microvascular dysfunction, but also support an immune-genetic basis for this condition.
Authors
Ronzoni Ronzoni, Di Pietro Di Pietro, Lombardi Lombardi, Miano Miano, Minoia Minoia, Baselli Baselli, Filocamo Filocamo, Torcianti Torcianti, Malvestiti Malvestiti, Bosis Bosis, Prati Prati, Valenti Valenti
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