Interferon Pathway Lupus Risk Alleles Modulate Risk of Death from Acute COVID-19

Ilona Nln¹, Ruth Fernandez Ruiz², Theresa Wampler Muskardin³, Stephanie Tuminello², Mukundan Attur², Eduardo Itturate², Christopher Petrilli², Steven B. Abramson⁴, Aravinda Chakravarti² and Timothy Niewold¹, ¹Colton Center for Autoimmunity NYU School of Medicine, New York, NY, ²NYU Grossman School of Medicine, New York, NY, ³Colton Center for Autoimmunity, NYU School of Medicine, New York, NY, ⁴New York University School of Medicine, New York, NY

Meeting: ACR Convergence 2021

Keywords: COVID-19, genetics, interferon, Lupus

Session Information

Date: Sunday, November 7, 2021

Title: Genetics, Genomics & Proteomics Poster (0517–0533)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common alleles contribute to the genetic high IFN trait. In this study, we examine whether these common gain-of-function alleles in the type I IFN pathway are associated with protection from mortality in acute COVID-19.

Methods: We studied IFN pathway SLE risk genes in patients with acute COVID-19 admitted to NYU Langone hospitals (751 European-American and 398 African-American ancestry). The samples were genotyped using low depth sequencing and imputation, and we analyzed data from the following SNPs: IRF5 (rs2004640, rs3807306, rs10488631, rs2280714), IRF7/PHRF (rs1131665, rs4963128), IRF8 (rs17445836, rs12444486), and PRKG1 (rs7897633). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome.

Results: We observed specific IRF5 haplotypes that are protective against SLE risk were associated with increased risk of mortality in acute COVID-19 patients in European-American ancestry (OR=3.74, p=0.015). Alleles of PRKG1 were also associated with mortality from COVID-19 in the European-American ancestry cohort (OR=1.80, p=0.0057), and this risk factor was particularly strong in younger patients (OR=29.2, p=0.01 in ages 45-54). IRF8 genotype at rs1244486 was associated with protection from mortality in COVID-19 in African-American subjects aged 65 and older (OR=0.34, p=0.04).

Conclusion: We find that a number of type I IFN pathway genes associated with risk of SLE also modulate risk of death during acute COVID-19. Similar to their associations with SLE, these alleles are variably associated with COVID-19 mortality across ancestral backgrounds, suggesting ancestral differences in the genetic regulation of the IFN pathway. These data confirm the critical role of the IFN pathway in our defense against viral infections, and support the idea that some common SLE risk alleles exert protective effects in anti-viral immunity.

Disclosures: I. Nln, None; R. Fernandez Ruiz, None; T. Wampler Muskardin, None; S. Tuminello, None; M. Attur, None; E. Itturate, None; C. Petrilli, None; S. Abramson, None; A. Chakravarti, None; T. Niewold, None.

To cite this abstract in AMA style:

Nln I, Fernandez Ruiz R, Wampler Muskardin T, Tuminello S, Attur M, Itturate E, Petrilli C, Abramson S, Chakravarti A, Niewold T. Interferon Pathway Lupus Risk Alleles Modulate Risk of Death from Acute COVID-19 [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/interferon-pathway-lupus-risk-alleles-modulate-risk-of-death-from-acute-covid-19/. Accessed .

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-pathway-lupus-risk-alleles-modulate-risk-of-death-from-acute-covid-19/