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Exploring the complex relationship between systemic lupus erythematosus and coronavirus disease 2019: genetic

Xiaoli Xu1,2, An-Tian Chen3, Yantao Ding1,2

  • 1Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Journal of Global Health
|July 11, 2025
PubMed

Insights

Systemic lupus erythematosus (SLE) may protect against COVID-19 infection and severity. Key cytokines like IL-6, TNF, and IL-10 are involved, suggesting a complex relationship needing further study.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Shared genetic loci between severe COVID-19 and SLE are reported, but causality is debated.
  • Understanding the interplay between autoimmune diseases and viral infections is crucial.

Purpose of the Study:

  • To investigate the genetic correlation between SLE and COVID-19 infection/severity.
  • To determine the causal effect of SLE on COVID-19 susceptibility using Mendelian randomization.
  • To identify key molecular pathways and genes involved in the SLE-COVID-19 relationship.

Main Methods:

  • Genome-wide association studies (GWAS) data from European populations.
  • Linkage Disequilibrium Score Regression (LDSC) for genetic correlation.
  • Mendelian Randomization (MR) analysis for causal inference.
  • Enrichment and Protein-Protein Interaction (PPI) analyses for pathway identification.

Main Results:

  • Significant genetic correlation found between SLE and COVID-19 severity (rg=0.340, P=0.001).
  • No significant genetic correlation with COVID-19 infection.
  • SLE showed a protective causal effect against COVID-19 infection (OR=0.986) and severity (OR=0.955) in Europeans and East Asians.
  • Interleukin-6 (IL-6), Tumor Necrosis Factor (TNF), and Interleukin-10 (IL-10) identified as key connecting cytokines.

Conclusions:

  • SLE may confer a protective effect against COVID-19 infection and severity.
  • IL-6, TNF, and IL-10 are central to the observed relationship.
  • SLE patients did not exhibit increased severe COVID-19 outcomes, possibly due to behavioral factors.
Abstract

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