Autoimmunity in the era of immune checkpoint inhibitors: the evolving epidemiology of autoimmune diseases and the possible impact of COVID-19.

Immune checkpoint inhibitors (ICIs) have markedly improved the prognosis of previously fatal malignancies, as evidenced by substantial gains in overall and progression-free survival in multiple clinical trials. The mechanism of action of ICIs is based on altering the immune response while the reported side effects display clear autoimmune features. Designated as immune-related adverse events (irAEs) affect nearly every organ system, including the gastrointestinal tract, liver, and thyroid gland, and share features with autoimmune disorders of the same organs. The severity of irAEs ranges from mild to life-threatening reactions. Many cases require systemic corticosteroids, hospitalization, and in many instances the discontinuation of ICI therapy. In this review, we present the history of ICIs, their indications, and the reported irAEs in a systematic manner. We then focus on the autoimmune nature of these side effects, with particular attention to the epidemiology of autoimmune diseases, including their female preponderance in certain age groups. In the final sections, we discuss how irAEs may be altering the epidemiology of autoimmune disease and address the possible effect of COVID-19 as a potential trigger.