Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Immunologic Research
Published in: Immunologic Research 4/2020

Open Access 01-08-2020 | SARS-CoV-2 | Interpretive Synthesis Review Article

COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy

Authors: Carlo Perricone, Elena Bartoloni, Roberto Bursi, Giacomo Cafaro, Giacomo Maria Guidelli, Yehuda Shoenfeld, Roberto Gerli

Published in: Immunologic Research | Issue 4/2020

Login to get access

Abstract

SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still’s disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.
Literature
1.
2.
3.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.CrossRefPubMedPubMedCentral
4.
Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136:95–103.PubMedPubMedCentral
5.
Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76:16–32.PubMedPubMedCentral
6.
Wang WK, Chen SY, Liu IJ, Kao CL, Chen HL, Chiang BL, et al. Severe acute respiratory syndrome research Group of the National Taiwan University College of Medicine/NTU Hospital. Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome. Clin Infect Dis. 2004;39:1071–5.PubMed
7.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–3.PubMedPubMedCentral
8.
Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5:562–9.PubMed
9.
Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34:1.PubMed
10.
Xu YH, Dong JH, An WM, Lv XY, Yin XP, Zhang JZ, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Inf Secur. 2020;80:394–400.
11.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529–39.PubMedPubMedCentral
12.
Tanaka T, Kishimoto T. The biology and medical implications of interleukin-6. Cancer Immunol Res. 2014;2:288–94.PubMed
13.
Xu XJ, Tang YM. Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells. Cancer Lett. 2014;343:172–8.PubMed
14.
Xiaoling Xu, Mingfeng Han, Tiantian Li, et al. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv: 202003.00026v1; TOCIVID-19.
15.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH across speciality collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–4.PubMedPubMedCentral
16.
Karakike E, Giamarellos-Bourboulis EJ. Macrophage activation-like syndrome: a distinct entity leading to early death in sepsis. Front Immunol. 2019;10:55.PubMedPubMedCentral
17.
18.
Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002;99:3505–16.PubMed
19.
Zandman-Goddard G, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev. 2007;6:457–63.PubMed
20.
Zandman-Goddard G, Orbach H, Agmon-Levin N, Boaz M, Amital H, Szekanecz Z, et al. Hyperferritinemia is associated with serologic antiphospholipid syndrome in SLE patients. Clin Rev Allergy Immunol. 2011;44:23–30.
21.
Da Costa R, Szyper-Kravitz M, Szekanecz Z, Csepany T, Danko K, Shapira Y, et al. Ferritin and prolactin levels in multiple sclerosis. Isr Med Assoc J. 2011;13:91–5.PubMed
22.
Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:385–400.PubMed
23.
Bennett TD, Hayward KN, Farris RW, Ringold S, Wallace CA, Brogan TV. Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients. Pediatr Crit Care Med. 2011;12:e233–6.PubMed
24.
Garcia PC, Longhi F, Branco RG, Piva JP, Lacks D, Tasker RC. Ferritin levels in children with severe sepsis and septic shock. Acta Paediatr. 2007;96:1829–31.PubMed
25.
Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;10:387–92.PubMed
26.
Grangé S, Buchonnet G, Besnier E, Artaud-Macari E, Beduneau G, Carpentier D, et al. The use of ferritin to identify critically ill patients with secondary hemophagocytic lymphohistiocytosis. Crit Care Med. 2016 Nov;44(11):e1045–53.PubMed
27.
Lachmann G, Knaak C, Vorderwülbecke G, la Rosée P, Balzer F, Schenk T, et al. Hyperferritinemia in critically ill patients. Crit Care Med. 2020;48(4):459–65.PubMed
28.
Betancur JF, Navarro EP, Echeverry A, Moncada PA, Cañas CA, Tobón GJ. Hyperferritinemic syndrome: Still's disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients. Clin Rheumatol. 2015;34:1989–92.PubMed
29.
Birndt S, Schenk T, Heinevetter B, Brunkhorst FM, Maschmeyer G, Rothmann F, et al. Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry. J Cancer Res Clin Oncol. 2020;146:1065–77.PubMedPubMedCentral
30.
31.
Ruscitti P, Cipriani P, Ciccia F, Di Benedetto P, Liakouli V, Berardicurti O, et al. H-ferritin and CD68(+) /H-ferritin(+) monocytes/macrophages are increased in the skin of adult-onset Still’s disease patients and correlate with the multi-visceral involvement of the disease. Clin Exp Immunol. 2016;186:30–8.PubMedPubMedCentral
32.
Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D'Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013;11:185.PubMedPubMedCentral
33.
Carcillo JA, Simon DW, Podd BS. How we manage hyperferritinemic sepsis-related multiple organ dysfunction syndrome/macrophage activation syndrome/secondary hemophagocytic lymphohistiocytosis histiocytosis. Pediatr Crit Care Med. 2015;16:598–600.PubMedPubMedCentral
34.
Schaffner M, Rosenstein L, Ballas Z, Suneja M. Significance of hyperferritinemia in hospitalized adults. Am J Med Sci. 2017;354:152–8.PubMed
35.
Saeed H, Woods RR, Lester J, Herzig R, Gul Z, Monohan G. Evaluating the optimal serum ferritin level to identify hemophagocytic lymphohistiocytosis in the critical care setting. Int J Hematol. 2015;102(2):195–9.PubMed
36.
La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133:2465–77.PubMed
37.
Wang H, Xiong L, Tang W, Zhou Y, Li F. A systematic review of malignancy-associated hemophagocytic lymphohistiocytosis that needs more attentions. Oncotarget. 2017;8:59977–85.PubMedPubMedCentral
38.
Danhaive O, Caniglia M, Devito R, Piersigilli F, Corchia C, Auriti C. Neonatal liver failure and haemophagocytic lymphohistiocytosis caused by a new perforin mutation. Acta Paediatr. 2010;99:778–80.PubMed
39.
Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol. 2015;90:220–4.PubMed
40.
41.
Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M, et al. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet. 2014;46:1135–9.PubMedPubMedCentral
42.
Sepulveda FE, de Saint Basile G. Hemophagocytic syndrome: primary forms and predisposing conditions. Curr Opin Immunol. 2017;49:20–6.PubMed
43.
Lehmberg K, Sprekels B, Nichols KE, Woessmann W, Müller I, Suttorp M, et al. Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol. 2015;170:539–49.PubMed
44.
Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA, Paessler M, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest. 2011;121:2264–77.PubMedPubMedCentral
45.
Choi YB, Yi DY. Fatal case of hemophagocytic lymphohistiocytosis associated with group B streptococcus sepsis: a case report. Medicine (Baltimore). 2018;97:e12210.
46.
Sağlam B, Albayrak M, Acar A, Yıldız A, Maral S, Tığlıoğlu M, et al. Q fever as a rare cause of hemophagocytic lymphohistiocytosis: case report. Transfus Apher Sci. 2020;28:102747.
47.
Miyoshi Y, Yoshioka S, Gosho H, Miyazoe S, Suenaga H, Aoki M, et al. A neonatal case of coxsackievirus B3 vertical infection with symptoms of hemophagocytic lymphohistiocytosis. ID Cases. 2020;20:e00738.PubMedPubMedCentral
48.
Gavand PE, Serio I, Arnaud L, Costedoat-Chalumeau N, Carvelli J, Dossier A, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 103 episodes in 89 adult patients. Autoimmun Rev. 2017;16:743–9.PubMed
49.
Mărginean MO, Molnar E, Chinceşan MI. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in a small child: a case report. Medicine (Baltimore). 2020;99:e18759.
50.
Chuang HC, Lay JD, Hsieh WC, Wang HC, Chang Y, Chuang SE, et al. Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome. Blood. 2005;106:3090–6.PubMed
51.
Hsieh YC, Wu TZ, Liu DP, Shao PL, Chang LY, Lu CY, et al. Influenza pandemics: past, present and future. J Formos Med Assoc. 2006;105:1–6.PubMed
52.
Mao H, Liu Y, Sia SF, Peiris JSM, Lau YL, Tu W. Avian influenza virus directly infects human natural killer cells and inhibits cell activity. Virol Sin. 2017;32:122–9.PubMedPubMedCentral
53.
Brisse E, Wouters CH, Andrei G, Matthys P. How viruses contribute to the pathogenesis of hemophagocytic lymphohistiocytosis. Front Immunol. 2017;8:1102.PubMedPubMedCentral
54.
Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130:2728–38.PubMedPubMedCentral
55.
Gauiran DTV, Cheng PVCY, Pagaduan CRP, Santos MCM. Autoimmune-associated hemophagocytosis and myelofibrosis in a newly diagnosed lupus patient: case report and literature review. Case Rep Hematol. 2019;2019:3879148.PubMedPubMedCentral
56.
Agmon-Levin N, Rosário C, Katz BS, Zandman-Goddard G, Meroni P, Cervera R, et al. Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS). Lupus. 2013;22:1327–35.PubMed
57.
Zandman-Goddard G, Orbach H, Agmon-Levin N, Boaz M, Amital H, Szekanecz Z, et al. Hyperferritinemia is associated with serologic antiphospholipid syndrome in SLE patients. Clin Rev Allergy Immunol. 2013;44:23–30.PubMed
58.
59.
60.
Singer M. The new sepsis consensus definitions (Sepsis-3): the good, the not-so-bad, and the actually-quite-pretty. Intensive Care Med. 2016;42:2027–9.PubMed
61.
Knaak C, Schuster FS, Spies C, Vorderwülbecke G, Nyvlt P, Schenk T, et al. Hemophagocytic lymphohistiocytosis in critically ill patients. Shock. 2020;53(6):701–9.PubMed
62.
63.
Ruscitti P, Cipriani P, Di Benedetto P, Liakouli V, Berardicurti O, Carubbi F, et al. H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome. Clin Exp Immunol. 2018;191:220–8.PubMed
64.
Ruddell RG, Hoang-Le D, Barwood JM, Rutherford PS, Piva TJ, Watters DJ, et al. Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology. 2009;49:887–900.PubMed
65.
Li R, Luo C, Mines M, Zhang J, Fan GH. Chemokine CXCL12 induces binding of ferritin heavy chain to the chemokine receptor CXCR4, alters CXCR4 signaling, and induces phosphorylation and nuclear translocation of ferritin heavy chain. J Biol Chem. 2006;281:37616–27.PubMed
66.
Recalcati S, Invernizzi P, Arosio P, Cairo G. New functions for an iron storage protein: the role of ferritin in immunity and autoimmunity. J Autoimmun. 2008;30:84–9.PubMed
67.
Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biochim Biophys Acta. 1800;2010:760–9.
68.
Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica. 2020;105:260–72.PubMedPubMedCentral
69.
ten Kate J, Drenth JP, Kahn MF, van Deursen C. Iron saturation of serum ferritin in patients with adult onset Still's disease. J Rheumatol. 2001;28:2213–5.PubMed
70.
71.
Jia Z, Liming Y, Ren Z, Wu L, Wang J, Guo J, et al. Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 2019;47:6538–50.PubMedPubMedCentral
72.
73.
74.
75.
76.
77.
Rigamonti L, Ariotti S, Losana G, Gradini R, Russo MA, Jouanguy E, et al. Surface expression of the IFN-gamma R2 chain is regulated by intracellular trafficking in human T lymphocytes. J Immunol. 2000;164:201–7.PubMed
78.
Weiss G, Goossen B, Doppler W, Fuchs D, Pantopoulos K, Werner-Felmayer G, et al. Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. EMBO J. 1993;12:3651–7.PubMedPubMedCentral
79.
Brock JH, Mulero V. Cellular and molecular aspects of iron and immune function. Proc Nutr Soc. 2000;59:537–40.PubMed
80.
Regis G, Bosticardo M, Conti L, De Angelis S, Boselli D, Tomaino B, et al. Iron regulates T-lymphocyte sensitivity to the IFN-gamma/STAT1 signaling pathway in vitro and in vivo. Blood. 2005;105:3214–21.PubMed
81.
Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, et al. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res. 2008;18:290–301.PubMed
82.
83.
Lachmann G, Knaak C, von Haefen C, Paeschke N, Meisel C, Nyvlt P, et al. Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients (HEMICU): a prospective observational study protocol. BMJ Open. 2019;9:e032695.PubMedPubMedCentral
84.
Møller HJ. Soluble CD163. Scand J Clin Lab Inv. 2012;72:1–13.
85.
Vishwanath P, Prashant A, Nataraj SM, Kotekar N, Doddamani P. Can soluble CD163 predict outcome of patients with acute respiratory distress from mechanical ventilation? A pilot study. Indian J Crit Care Med. 2013;17:355–8.PubMedPubMedCentral
86.
Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119.PubMedPubMedCentral
87.
Schaer D, Schleiffenbaum B, Kurrer M, Imhof A, Bächli E, Fehr J, et al. Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome. Eur J Haematol. 2005;74:6–10.PubMed
88.
Behrens EM, Beukelman T, Paessler M, Cron RQ. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol. 2007;34:1133–8.PubMed
89.
Sakumura N, Shimizu M, Mizuta M, Inoue N, Nakagishi Y, Yachie A. Soluble CD163, a unique biomarker to evaluate the disease activity, exhibits macrophage activation in systemic juvenile idiopathic arthritis. Cytokine. 2018;110:459–65.PubMed
90.
Colafrancesco S, Priori R, Alessandri C, Astorri E, Perricone C, Blank M, et al. sCD163 in AOSD, a biomarker for macrophage activation related to hyperferritinemia. Immunol Res. 2014;60:177–83.PubMed
91.
Nishino A, Katsumata Y, Kawasumi H, Hirahara S, Kawaguchi Y, Yamanaka H. Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus. Lupus. 2019;28:986–94.PubMed
92.
Gao Z, Wang Y, Wang J, Zhang J, Wang Z. Soluble ST2 and CD163 as potential biomarkers to differentiate primary hemophagocytic lymphohistiocytosis from macrophage activation syndrome. Mediterr J Hematol Infect Dis. 2019;11:e2019008.PubMedPubMedCentral
93.
Shimizu M, Mizuta M, Okamoto N, Yasumi T, Iwata N, Umebayashi H, et al. Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Pediatric Rheumatol Online J. 2020;18:2.
94.
Isaacs JD, Harari O, Kobold U, Lee JS, Bernasconi C. Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis. Athritis Res Ther. 2013;15:R204.
95.
Schulert GS, Minoia F, Bohnsack J, Cron RQ, Hashad S, KonE’-Paut I, et al. Effect of biologic therapy on clinical and laboratory features of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis. Arthritis Care Res. 2018;70:409–19.
96.
Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci. 1998;850:191–201.PubMed
97.
Le Lan C, Loréal O, Cohen T, et al. Redox active plasma iron inC282Y/C282Y hemochromatosis. Blood. 2005;105(11):4527–31.PubMed
98.
99.
Traoré HN, Meyer D. The effect of iron overload on in vitro HIV-1 infection. J Clin Virol. 2004;(Suppl 1):S92–8.
100.
van Asbeck BS, Georgiou NA, van der Bruggen T, Oudshoorn M, Nottet HS, Marx JJ. Anti-HIV effect of iron chelators: different mechanisms involved. J Clin Virol. 2001;20:141–7.PubMed
101.
Georgiou NA, van der Bruggen T, Oudshoorn M, Nottet HS, Marx JJ, van Asbeck BS. Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin. J Infect Dis. 2000;181:484–90.PubMed
102.
Romeo AM, Christen L, Niles EG, Kosman DJ. Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: ribonucleotide reductase maturation as a probe of intracellular iron pools. J Biol Chem. 2001;276:24301–8.PubMed
103.
Crowe WE, Maglova LM, Ponka P, Russell JM. Human cytomegalovirus-induced host cell enlargement is iron dependent. Am J Physiol Cell Physiol. 2004;287:C1023–30.PubMed
104.
Bayraktar Y, Koseoglu T, Somner C, Kayhan B, Temizer A, Uzunalimoglu B, et al. The use of deferoxamine infusions to enhance the response rate to interferon-alpha treatment of chronic viral hepatitis B. J Viral Hepat. 1996;3:129–35.PubMed
105.
Mateos F, González C, Dominguez C, Losa JE, Jimenez A, Pérez-Arellano JL. Elevated non-transferrin bound iron in the lungs of patients with Pneumocystis carinii pneumonia. J Inf Secur. 1999;38:18–21.
106.
Arantes JM, Francisco AF, de Abreu Vieira PM, Silva M, Araújo MSS, de Carvalho AT, et al. Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect. Exp Parasitol. 2011;128:401–8.PubMed
107.
Lehmann C, Islam S, Jarosch S, Zhou J, Hoskin D, Greenshields A, et al. The utility of iron chelators in the management of inflammatory disorders. Mediat Inflamm. 2015;2015:516740.
108.
Visseren FLJ, Verkerk MSA, van der Bruggen T, Marx JJM, van Asbeck BS, Diepersloot RJA. Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with chlamydia pneumoniae or influenza A. Eur J Clin Investig. 2002;32(Suppl 1):84–90.
109.
Kazmierski WM, Wolberg G, Wilson JG, Smith SR, Williams DS, Thorp HH, et al. Iron chelates bind nitric oxide and decrease mortality in an experimental model of septic shock. Proc Natl Acad Sci U S A. 1996;93:9138–41.PubMedPubMedCentral
110.
Wang S, Liu C, Pan S, Miao Q, Xue J, Xun J, et al. Deferoxamine attenuates lipopolysaccharide-induced inflammatory responses and protects against endotoxic shock in mice. Biochem Biophys Res Commun. 2015;465:305–11.PubMed
111.
Adams PC. Chelation therapy for secondary iron overload: is the primary effect less iron or less liver fibrosis? Gastroenterology. 2011;141:1142–3.PubMed
112.
Adel N, Mantawy EM, El-Sherbiny DA, El-Demerdash E. Iron chelation by deferasirox confers protection against concanavalin A-induced liver fibrosis: a mechanistic approach. Toxicol Appl Pharmacol. 2019;382:114748.PubMed
113.
Mohammed A, Abd Al Haleem EN, El-Bakly WM, El-Demerdash E. Deferoxamine alleviates liver fibrosis induced by CCl4 in rats. Clin Exp Pharmacol Physiol. 2016;43:760–8.PubMed
114.
Darwish SF, El-Bakly WM, El-Naga RN, Awad AS, El-Demerdash E. Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: impact on interferon therapy. Biochem Pharmacol. 2015;98:231–42.PubMed
115.
Sobbe A, Bridle KR, Jaskowski L, de Guzman CE, Santrampurwala N, Clouston AD, et al. Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox. J Gastroenterol Hepatol. 2015;30:638–45.PubMed
116.
Tamura K, Uneda K, Azushima K, Wakui H, Haruhara K. Possible therapeutic impact of the iron chelation on renal fibrosis. Hypertens Res. 2015;38:455–6.PubMed
117.
Ikeda Y, Ozono I, Tajima S, Imao M, Horinouchi Y, Izawa-Ishizawa Y, et al. Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction. PLoS One. 2014;9:e89355.PubMedPubMedCentral
118.
Li LF, Huang CC, Liu YY, Lin HC, Kao KC, Yang CT, et al. Hydroxyethyl starch reduces high stretch ventilation-augmented lung injury via vascular endothelial growth factor. Transl Res. 2011;157:293–305.PubMed
119.
Huang LT, Chou HC, Wang LF, Chen CM. Tissue plasminogen activator attenuates ventilator-induced lung injury in rats. Acta Pharmacol Sin. 2012;33:991–7.PubMedPubMedCentral
120.
Zhu W, Huang Y, Ye Y, Wang Y. Deferoxamine preconditioning ameliorates mechanical ventilation-induced lung injury in rat model via ROS in alveolar macrophages: a randomized controlled study. BMC Anesthesiol. 2018;18:116.PubMedPubMedCentral
121.
122.
Metadata
Title
COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy
Authors
Carlo Perricone
Elena Bartoloni
Roberto Bursi
Giacomo Cafaro
Giacomo Maria Guidelli
Yehuda Shoenfeld
Roberto Gerli
Publication date
01-08-2020
Publisher
Springer US
Published in
Immunologic Research / Issue 4/2020
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-020-09145-5

Other articles of this Issue 4/2020

Immunologic Research 4/2020 Go to the issue

Review

Hyperprogressive disease in patients with advanced renal cell carcinoma: a new pattern of post-treatment cancer behavior

Brief report

A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report

Original Article

Granulomatous inflammation in lymph nodes of the head and neck—a retrospective analysis of causes in a population with very low incidence of tuberculosis

Original Article

Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4

Original Article

Association of genetic polymorphism of BCL-2 (rs2279115) with susceptibility to HCV-related hepatocellular carcinoma