Purpose of review: The aim of this study was to evaluate the relationship between infection with SARS-CoV-2 and autoimmunity. Recent findings: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS-CoV-2). Although most of the infected individuals are asymptomatic, a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. Evidence suggests that some medications used to treat autoimmune rheumatologic diseases might have therapeutic effect in patients with severe COVID-19 infections, drawing attention to the relationship between COVID-19 and autoimmune diseases. COVID-19 shares similarities with autoimmune diseases in clinical manifestations, immune responses and pathogenic mechanisms. Robust immune reactions participate in the pathogenesis of both disease conditions. Autoantibodies as a hallmark of autoimmune diseases can also be detected in COVID-19 patients. Moreover, some patients have been reported to develop autoimmune diseases, such as Guillain--Barré syndrome or systemic lupus erythematosus, after COVID-19 infection. It is speculated that SARS-CoV-2 can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. The infection risk and prognosis of COVID-19 in patients with autoimmune diseases remains controversial, but patient adherence to medication regimens to prevent autoimmune disease flares is strongly recommended. Summary: We present a review of the association between COVID-19 and autoimmune diseases, focusing on similarities in immune responses, cross-reactivity of SARS-CoV-2, the development of autoimmune diseases in COVID-19 patients and the risk of COVID-19 infection in patients with preexisting autoimmune conditions.

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health¹. This is compounded by the limited efficacy of available treatments¹ and high failure rates during drug development², highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis^3–6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures⁷, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.