Interleukin-38 promoter variants and risk of COVID-19 among Iraqis.

Coronavirus disease-19 (COVID-19) has recently emerged as a respiratory infection with a significant impact on health and society. The pathogenesis is primarily attributed to a dysregulation of cytokines, especially those with pro-inflammatory and anti-inflammatory effects. Interleukin-38 (IL-38) is a recently identified anti-inflammatory cytokine with a proposed involvement in mediating COVID-19 pathogenesis, while the association between IL38 gene variants and disease susceptibility has not been explored. Therefore, a pilot study was designed to evaluate the association of three gene variants in the promoter region of IL38 gene (rs7599662 T/A/C/G, rs28992497 T/C and rs28992498 C/A/T) with COVID-19 risk. DNA sequencing was performed to identify these variants. The study included 148 Iraqi patients with COVID-19 and 113 healthy controls (HC). Only rs7599662 showed a significant negative association with susceptibility to COVID-19. The mutant T allele was presented at a significantly lower frequency in patients compared to HC. Analysis of recessive, dominant and codominant models demonstrated that rs7599662 TT genotype frequency was significantly lower in patients than in HC. In terms of haplotypes (in order: rs7599662, rs28992497 and rs28992498), frequency of CTC haplotype was significantly increased in patients compared to HC, while TTC haplotype showed significantly lower frequency in patients. The three SNPs influenced serum IL-38 levels and homozygous genotypes of mutant alleles were associated with elevated levels. In conclusion, this study indicated that IL38 gene in terms of promoter variants and haplotypes may have important implications for COVID-19 risk.

Evaluation of interleukin-38 levels in serum of patients with coronavirus disease 2019.

Interleukin-38 (IL-38) has recently been considered as a cytokine with anti-inflammatory properties in viral respiratory infections, particularly coronavirus disease 19 (COVID-19), but the evidence has not been well elucidated. Therefore, a case-control study was conducted to determine IL-38 serum levels in 148 patients with COVID-19 (45 moderate, 55 severe, and 48 critical) and 113 controls. Results demonstrated that IL-38 levels did not show significant differences between patients and controls (68.7 [interquartile range: 62.7-75.6] vs. 67.7 [58.0-82.6] pg/ml; probability = 0.457). Similarly, patients stratified by disease severity, age group, gender, or chronic disease showed no significant differences between IL-38 levels in each stratum. Whereas, overweight/obese patients had a significantly lower median of IL-38 compared to normal-weight patients. Further, IL-38 showed significantly higher levels in the age group ≥50 years of patients with critical illness than in the age group <50 years. Female patients with severe disease also showed significantly elevated levels of IL-38 compared to male patients. In conclusion, the study indicated that serum IL-38 levels were not affected by COVID-19 infection, but the distribution of patients according to disease severity, age, gender, and body mass index may better reveal the role of IL-38 in disease pathogenesis.