Ferritin – from iron, through inflammation and autoimmunity, to COVID-19

Abstract

While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.

Risk Factors Associated with Mortality among Patients with COVID-19: Analysis of a Cohort of 1213 Patients in a Tertiary Healthcare Center

“…Ferritin promotes the release of proinflammatory mediators and increases the inflammatory burden, resulting in a vicious circle. Ferritin achieves this by activation of NF-ԟB, leading to a positive regulation of ferritin gene transcription [ 32 ]. In our study, its impact appears not to have been very significant on the risk of death.…”

Light and heavy ferritin chain expression in the liver and kidneys of Wistar rats: aging, sex differences, and impact of gonadectomy

“…The role of iron in kidney diseases has recently been emphasised, and more precise localisation of ferritin throughout the kidney may tell us more about its functions in (pato)physiology ( 5 , 25 , 26 , 27 , 28 ). However, protein expression in organs detected by western blotting in our study has yet to be confirmed by in situ distribution in order to reveal a more precise expression pattern.…”

“…Our findings have shown strong ferritin staining of interstitial cells irregularly present in all kidney zones. We assume that it could be associated with macrophages ( Figures 6 and 7, c and d ), as macrophages have recently been recognised as a new source of serum ferritin ( 25 , 28 ). This could be relevant for our positive findings of ferritin in aged rats.…”

Alteration of Inflammatory Parameters and Psychological Post-Traumatic Syndrome in Long-COVID Patients

“…We highlighted that beyond the first three months after contagion, individuals who recovered from SARS-CoV-2 infection are characterized by the persistence of a systemic inflammatory state and are at high risk for developing somatization, depression, anxiety, and sleep disturbances. In particular, we found out that the median baseline serum LDH and ferritin levels were significantly higher three months after SARS-CoV-2 infection [ 16 ]. Interestingly enough, ferritin value was strongly correlated with sleep disorders, independently of gender.…”