The role of the JAK/STAT pathway in the pathogenesis and treatment of post-COVID autoimmune syndromes

The coronavirus disease 2019 (COVID-19) pandemic has not only resulted in acute respiratory illness but has also led to a growing population of individuals affected by persistent, debilitating symptoms, collectively known as post-COVID syndrome or “Long COVID”. This condition presents with a variety of manifestations, including fatigue, joint pain, cognitive disturbances, and dysautonomia, often mimicking autoimmune and neuroinflammatory disorders. Recent research highlights the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway as a central mediator in the inflammatory cascade triggered by SARS-CoV-2 infection. This review explores the dual role of the JAK/STAT pathway in both the acute phase of COVID-19 and its potential contribution to post-infectious autoimmune phenomena. We summarize the current understanding of JAK inhibitors (JAKi) as therapeutic agents for mitigating hyperinflammation during active infection and examine their emerging role in the management of post-COVID syndromes, particularly in cases with pulmonary involvement and features overlapping with fibromyalgia and chronic fatigue syndrome. Moreover, we discuss the safety profile of JAKi, their impact on vaccine immunogenicity, and the implications of autoantibody formation targeting the autonomic nervous system. Understanding the immunopathological mechanisms underpinning post-COVID may not only inform therapeutic strategies but also illuminate broader pathways involved in chronic autoimmune conditions.