Estudo de CNVs em indivíduos com síndrome inflamatória multissistêmica pediátrica associada à COVID-19 (SIM-P)

Abstract

Pediatric Multisystemic Inflammatory Syndrome (SIM-P) is characterized by an exacerbated and delayed inflammatory response that occurs, on average, from two to four weeks after contact with SARS-CoV2 in the population aged 0 to 19 years. Its frequency is considered rare, but with the potential for death due to the severity of the clinical manifestations. The search for genetic variants that confer predisposition to SIM-P should involve the evaluation of the entire human genome or its coding regions (exome). The identification of genetic variants that are determinant for Y-PS-M is fundamental to better understand the genetic architecture of the disease and to define prevention strategies to detect individuals at high risk of developing the disease, as well as the treatment to partially restore the deficient immune response. Objective: Identify Copy Number Variants (CNVs) potentially involved in MIS-C. Methodology: The present study is descriptive in nature, with a convenience sample consisting of 21 children and adolescents (0-19 years of age). The data were organized in Excel 2013 and the statistical analysis was performed using the SPSS program, version 2.8.0 through descriptive and inferential analysis, with the data described by the medians and interquartile ranges. Clinical and laboratory information from individuals diagnosed with MIS-C after SARS-CoV-2 infection were used. The patients came from 03 (three) hospitals in the Northeast region of Brazil. Whole exome sequencing was performed using the Illumina platform (San Diego, CA, USA) with analysis of CNVs in 445 candidate genes. Results: We identified 43 pathogenic or likely pathogenic CNVs in 18 of the 21 patients. These CNVs are present in 30 genes associated with inborn immune errors or described related to SARS-CoV2 infection. Discussion: Most of these CNVs were considered secondary finds for being in heterozigose and associated with diseases with a standard of recessive inherited autosomal. However, eight of the patients showed signs of CNVs, that, according to the zygosity in evidence and the standard of inherited associated phenotypes, can be clinically relevant for SIM-P. These variants are present in the genes IFNGR1, CFHR3, CSF3R, CFHR4, DOCK8, ICOS, SRP72. Conclusion: The identification of these genetic markers enables a better understanding of susceptibility to MIS-C after COVID and can be applied for the development of targeted therapies.