Iron-sepsis associations in population health revealed by epidemiology

Sepsis is a leading cause of death and disability worldwide, so identifying preventable risk factors is important. Iron is essential for immune function and microbial growth, and iron status varies substantially between individuals, across demographics, and is therapeutically modifiable. Here, we review the current understanding of iron status and associated risks of bloodstream infection, sepsis and severe COVID-19 highlighting relevant population-based studies and Mendelian randomisation studies. Both low and high iron status are associated with increased risk of sepsis. Low iron status is associated with sepsis, bloodstream infections and pneumonia. High iron status and mutations affecting hepcidin regulation are linked to increased risk of bloodstream infections, sepsis and COVID-19. Both iron status pathologies and sepsis are global health issues, and the epidemiological studies described indicate they may be linked. More population-scale investigations on iron status, infection and immunity, especially in areas of high iron deficiency and infectious burden are warranted.