Ferritin in COVID-19 infection and its diagnostic significance

Hridya Harimohan, Manojan Kannan Kandiyil, Sreekanth Kavitha Sivaraman


COVID-19 caused by SARS-CoV-2 (severe acute respiratory syndrome corona virus-2) is the major health issue facing the entire world at present. There are several pathological mechanism associated with the infection which aggravates to significant morbidity and mortality among the population. Of the several complications, hypercoagulation due to fibrin clot formation is one of the complications often seen in patients suffering from COVID-19 infection. The link of iron with hypercoagulation and related events are always a matter of discussion in the scientific world. Yet another cause of disseminated intravascular coagulation seen in these patients is cytokine storm, which occurs due to release of pro inflammatory signaling molecules as a result of increased inflammation due to depletion of iron stores. The viral attack can destroy the hemoglobin; release the iron content by separating it from the heme. This free iron in the blood will be able to produce free radicals which can convert fibrinogen into fibrin clots. More over iron could elicit oxidative stress which can subsequently lead to increased erythrocyte viscosity and thrombosis. Further ferritin, the iron storing protein will actively get released and can lose its inner iron content leading to increased free iron in circulation. It was evident that iron overload was one of the critical factor which determines the immunological processes leading to a type of cell death referred as ferroptosis. This review discussed with the mechanism involved in the release of iron and cytokine storm along with the diagnostic significance of ferritin in COVID-19 infection.



COVID-19, SARS-CoV-2, Hypercoagulation, Ferritin, Cytokine storm, Ferroptosis

Full Text:



Liu W, Li H. COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. Cambridge: Cambridge Open Press; 2020.

Sun Y, Chen P, Zhai B, Zhang M, Xiang Y, Fang J, et al. The emerging role of ferroptosis in inflammation. Biomed Pharmacother. 2020;127:110108.

Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56.

Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113(1):45-57.

Skevaki C, Fragkou PC, Cheng C, Xie M, Renz H. Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus. J Infect. 2020;81(2):205-12.

Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383(23):2255-73.

Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085-94.

Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368(6490):473-4.

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19-preliminary report. N Engl J Med. 2020;383(19):1813-26.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel corona virus in Wuhan, China. Lancet. 2020;395(10223):497-506.

Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z, et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int J Infect Dis. 2020;95:332-9.

Valle DMD, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-43.

Ahmed S, Ahmed ZA, Siddiqui I, Rashid NH, Mansoor M, Jafri L. Evaluation of serum ferritin for prediction of severity and mortality in COVID-19-a cross sectional study. Ann Med Surg. 2021;63:102163.

Vargas-Vargas M, Cortés-Rojo C. Ferritin levels and COVID-19. Rev Panam Salud Publica. 2020;44(72):1-2.

Perricone C, Bartoloni E, Bursi R, Guidelli GCGM, Shoenfeld Y, Gerli R. COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy. Immunol Res. 2020;68(4):213-24.

Nemeth E, Ganz T. the role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3):78-86.

Gropper SS, Smith JL. Advanced nutrition and human metabolism. 6th ed. Belmont, CA: Wadsworth; 2013: 481.

Gulec S, Anderson GJ, Collins JF. Mechanistic and regulatory aspects of intestinal iron absorption. Am J Physiol Gastrointest Liver Physiol. 2014;307(4):397-409.

Mims MP, Prchal JT. Divalent metal transporter 1. Hematology. 2005;10(4):339-45.

Wallace DF. The regulation of iron absorption and homeostasis. Clin Biochem Rev. 2016;37(2):51-62.

Kawabata H. Transferrin and transferrin receptors update. Free Radic Biol Med. 2019;133:46-54.

Kakhlon O, Cabantchik ZI. The labile iron pool: characterization, measurement, and participation in cellular processes. Free Radic Biol Med. 2002;33(8):1037-46.

Collins JF, Prohaska JR, Knutson MD. Metabolic crossroads of iron and copper. Nutr Rev. 2010;68(3):133-47.

Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell. 2010;142(1):24-38.

Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med. 2005;352(17):1741-4.

Kim J, Wessling-Resnick M. The role of iron metabolism in lung inflammation and injury. J Allergy Ther. 2012;3(4):1-14.

Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: a new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev. 2020;19(7):102573.

Lipinski B, Pretorius E. Iron-induced fibrin in cardiovascular disease. Curr Neurovasc Res. 2013;10(3):269-74.