tetano
Editor, Senior Moderator
J Infect Dis
. 2024 Jun 14;229(6):1740-1749.
doi: 10.1093/infdis/jiae031. Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19
Mukundan Attur[SUP] 1 [/SUP], Christopher Petrilli[SUP] 2 [/SUP], Samrachana Adhikari[SUP] 3 [/SUP], Eduardo Iturrate[SUP] 2 [/SUP], Xiyue Li[SUP] 3 [/SUP], Stephanie Tuminello[SUP] 3 [/SUP], Nan Hu[SUP] 4 [/SUP], Aravinda Chakravarti[SUP] 2 4 [/SUP], David Beck[SUP] 2 4 [/SUP], Steven B Abramson[SUP] 2 [/SUP]
Affiliations
Background: We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Methods: IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021.
Results: Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030).
Conclusions: The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.
Keywords: IL1RN; SARS-CoV-2; genetic variation and mortality; inflammation.
. 2024 Jun 14;229(6):1740-1749.
doi: 10.1093/infdis/jiae031. Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19
Mukundan Attur[SUP] 1 [/SUP], Christopher Petrilli[SUP] 2 [/SUP], Samrachana Adhikari[SUP] 3 [/SUP], Eduardo Iturrate[SUP] 2 [/SUP], Xiyue Li[SUP] 3 [/SUP], Stephanie Tuminello[SUP] 3 [/SUP], Nan Hu[SUP] 4 [/SUP], Aravinda Chakravarti[SUP] 2 4 [/SUP], David Beck[SUP] 2 4 [/SUP], Steven B Abramson[SUP] 2 [/SUP]
Affiliations
- PMID: 38871359
- DOI: 10.1093/infdis/jiae031
Background: We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Methods: IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021.
Results: Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030).
Conclusions: The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.
Keywords: IL1RN; SARS-CoV-2; genetic variation and mortality; inflammation.