Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.
Transl Res
; 244: 47-55, 2022 06.
Article
in English
| MEDLINE | ID: covidwho-1783792
ABSTRACT
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 risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR = 29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in antiviral immunity.
Keywords
BMI = body mass index; COVID-19 = coronavirus disease 2019; CRP = C-reactive protein; IFIH1 = interferon-induced with helicase c domain 1; IFN = interferon; IRF = interferon regulatory factor; NYU = New York University; OR = odds ratio; PRKG1 = protein kinase cGMP-dependent 1; SLE = systemic lupus erythematosus; SNP = single nucleotide polymorphism; STAT4 = signal transducer and activator of transcription 4
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
/
Lupus Erythematosus, Systemic
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Aged
/
Humans
/
Middle aged
Language:
English
Journal:
Transl Res
Journal subject:
Medicine
/
Laboratory Techniques and procedures
Year:
2022
Document Type:
Article
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