No genetic causal association between systemic lupus erythematosus and COVID-19

Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, = 0.040) and COVID-19 infection (OR = 0.988, = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, = 0.664), hospitalized COVID-19 (OR = 0.872, = 0.109), and COVID-19 infection (OR = 0.943, = 0.811) on SLE were found. The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.