Emerging and underrecognized viral triggers of autoimmune inflammatory rheumatic disease flares

Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus-autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations.