Main Article Content
Thalassemia, SARS-COV-2 infection, Covid-19, risk factors
We’re all flying blind regarding coronavirus, but it’s fair to think if thalassemic patients are particularly vulnerable to SARS-COV-2 infection or are at potential higher risk of complications from COVID-19 than normal population, specially when they become older. The frustrating thing is that, right now, this virus is still new. It only came to the attention of the World Health Organization at the end of December. Very few cases in thalassemia have so far been reported; is this due to lack of testing or a true lack of infection/susceptibility? However, we believe that more data should be collected to better characterise the impact of SARS-CoV-2 infection in patients with thalassemias. Therefore, a multicenter registry and the collection of comprehensive data from both positive COVID-19 thalassemia major and non-transfusion dependent thalassemia are necessary to clarify debated issues. In the meantime an early and vigilant monitoring along with high quality supportive care are needed in thalassemic patients at high risk for SARS-CoV-2 infection.
2. Gralinski LE, Menachery VD. Return of the Coronavirus: 2019-nCoV. Viruses. 2020;12:E135. doi:10. 3390/v12020135.
3. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-3. doi:10.1038/s41586-020-2012-7.
4. Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020; 27:325–328.
5. Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol. 2016; 3:237–61.
6. Lan J, G JW, Yu JF, Shan SS, Zhou H, Fan SL, et al. Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor. 2020. https://www.biorxiv.org/content/ 10.1101/ 2020.02. 19.956235v1.
7. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637.
8. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
9. Tao C, Di W, Huilong C, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020; 368:m1091 BMJ 2020; 368 doi: https://doi.org /10. 1136/bmj.m1091 (Published 26 March 2020).
10. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020. China CDC Weekly.2020;2:10.
11. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020.
12. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020. doi:10.1016/S0140-6736(20)30183-5.
13. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. doi:10.1016/j.ijantimicag.2020.105949.
14. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11. Published 2010 May 21.doi:10.1186/1750-1172-5-11.
15.Krittayaphong R, Viprakasit V, Saiviroonporn P, et al. Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data. Blood Cells Mol Dis. 2017;66:24–30.
16. De Sanctis V, Soliman AT, Daar S, et al. A Concise Review on the Frequency, Major Risk Factors and Surveillance of Hepatocellular Carcinoma (HCC) in β-Thalassemias: Past, Present and Future Perspectives and the ICET-A Experience. Mediterr J Hematol Infect Dis. 2020;12(1): e2020006. Published 2020 Jan 1. doi:10.4084/MJHID.2020.006.
17. Hamed AA, Elguindy W, Elhenawy YI, Ibrahim RH. Early Cardiac Involvement and Risk Factors for the Development of Arrhythmia in Patients With β-Thalassemia Major. J Pediatr Hematol Oncol. 2016;38:5–11.
18. De Sanctis V, Soliman AT, Canatan D, et al. Thyroid Disorders in Homozygous β-Thalassemia: Current Knowledge, Emerging Issues and Open Problems. Mediterr J Hematol Infect Dis. 2019;11(1):e2019029. Published 2019 May 1. doi:10.4084/MJHID.2019.029.
19. De Sanctis V, Soliman AT, Canatan D, et al. An ICET-A survey on occult and emerging endocrine complications in patients with β-thalassemia major: Conclusions and recommendations. Acta Biomed. 2019;89:481–489.
20. Motta I, De Amicis MM, Pinto VM, et al. SARS-CoV-2 infection in beta thalassemia: preliminary data from the Italian experience [published online ahead of print, 2020 Apr 20]. Am J Hematol. 2020;10.1002/ ajh.25840. doi:10.1002/ajh.25840.
21. Chang L, Yan Y, Wang L. Coronavirus Disease 2019: Coronaviruses and Blood Safety, Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.02.003.
22. Canatan D, De Sanctis V.The medical concerns of patients with thalassemias at the time of COVID-19 outbreak: The personal experience and the international recommendations. Acta Biomed. 2020; Vol. 91, N. 2: DOI: 10.23750/abm.v91i2.9533.
23. Cappelini MD, Eleftheriou P, Piga A, Porter J, Taher A, Telfer P. THE COVID–19 PANDEMIC AND HAEMOGLOBIN DISORDERS. A contribution of Thalassaemia International Federation to its global patients’ community. 2020; version III (updated):1-15.
24. Rachmilewitz EA, Weizer-Stern O, Adamsky K, et al. Role of iron in inducing oxidative stress in thalassemia: Can it be prevented by inhibition of absorption and by antioxidants? Ann N Y Acad Sci.2005;1054:118-123.
25. Walter PB, Fung EB, Killilea DW, et al. Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol. 2006;135: 254-263.
26. Ghatreh-Samani M, Esmaeili N, Soleimani M, Asadi-Samani M, Ghatreh-Samani K, Shirzad H. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging? Cent Eur J Immunol. 2016;41:116–124.
27. Pfeifer W, Degasperi G, Almeida M, et al. Vitamin E supplementation reduces oxidative stress in beta thalassaemia intermedia. Acta Haematol.2008;120: 225-231.
28. Villalba JM, Navarro F, Gomez-Diaz C, et al. Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane. Mol Aspects Med.1997; 18: S7-13.
29. Giakoumis A. A Useful Health & Nutrition Short Guide for the COVID-19 Pandemic. Thalassemia International Federation publication. Version 2.30 march 2020. https://thalassaemia. org.cy/news/a-useful-health-nutrition-short-guide-for-the-covid.
30. Moshtaghi-Kashanian GR, Gholamhoseinian A, Hoseinimoghadam A, Rajabalian S. Splenectomy changes the pattern of cytokine production in beta-thalassemic patients. Cytokine.2006;35:253–257.
31. Boettler T, Newsome PN, Mondelli MU, et al. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. JHEP Rep. 2020;2(3):100113. doi:10.1016/j.jhepr.2020.100113.
32. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61:1385–1396.
33. Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA. 2020. https://doi.org/10.1001/jamacardio.2020.0950.
34. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus- infected pneumonia in wuhan, China. JAMA. 2020. https://doi.org/ 10.1001 /jama. 2020.1585.
35. Ngim CF, Lee MY, Othman N, Lim SM, Ng CS, Ramadas A. Prevalence and Risk Factors for Cardiac and Liver Iron Overload in Adults with Thalassemia in Malaysia. Hemoglobin. 2019;43:95–100.
36. Pepe A, Meloni A, Rossi G, et al. Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicentre study by a multi-parametric approach. Eur Heart J Cardiovasc Imaging. 2018;19:299–309.
37.Casale M, Meloni A, Filosa A, et al. Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study. Circ Cardiovasc Imaging. 2015;8 (8): e003230. doi:10.1161/ CIRCIMAGING.115.003230.
38. Seldrum S, Pierard S, Moniotte S, et al. Iron overload in polytransfused patients without heart failure is associated with subclinical alterations of systolic left ventricular function using cardiovascular magnetic resonance tagging. J Cardiovasc Magn Reson. 2011;13(1):23.Published 2011 Apr 26. doi:10.1186/1532-429X-13-23.
39. Puig-Domingo M, Marazuela M, Giustina A.COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology. Endocrine. 2020; 68:2–5.
40. Ferlita S, Yegiazaryan A, Noori N, et al. Type 2 Diabetes Mellitus and Altered Immune System Leading to Susceptibility to Pathogens, Especially Mycobacterium tuberculosis. J Clin Med. 2019;8(12):2219. Published 2019 Dec 16. doi:10.3390/jcm8122219.
41. Critchley JA, Carey IM, Harris T et al. Glycemic control and risk of infections among people with type 1 or type 2 diabetes in a large primary care cohort study. Diabetes Care. 2018;41:2127–35.
42.De Sanctis V, Soliman AT, Elsedfy H, et al. The ICET—a survey on current criteria used by clinicians for the assessment of central adrenal insufficiency in thalassemia: analysis of results and recommendations. Mediterr J Hematol Infect Dis. 2016;8(1):e2016034.
43. Soliman AT, Yassin M, Majuid NM, Sabt A, Abdulrahman MO, De Sanctis V. Cortisol response to low dose versus standard dose (back-to-back) adrenocorticotrophic stimulation tests in children and young adults with thalassemia major. Indian J Endocrinol Metab. 2013;17:1046–1052.
44.Huang KE, Mittelman SD, Coates TD, Geffner ME, Wood JC. A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing. J Pediatr Hematol Oncol. 2015;37:54–59.
45. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory medicine. 2020. https://doi.org/10.1016/ S2213-2600(20)30076-X.
46. Gharagozloo M, Mehran Karimi M, Amirghofran Z. Double-faced cell-mediated immunity in β-thalassemia major: stimulated phenotype versus suppressed activity. Ann Hematol.2009; 88:21–27.
47. Weiss G. Iron and immunity: a double-edged sword. Eur J Clin Invest.2002;32:70–78.
48. Walker EM Jr, Walker SM. Effects of iron overload on the immune system. Ann Clin Lab Sci.2000;30:354–365.
49. Cunningham-Rundles S, Giardina PJ, Grady RW, Califano C, McKenzie P, De Sousa M.Effect of transfusional iron overload on immune response. J Infect Dis. 2000;182:S115–S1121.
50. Ezer U, Gülderen F, Culha VK, Akgül N, Gürbüz. Immunological status of thalassemia syndrome. Pediatr Hematol Oncol.2002:19:51–58.
51. Liu W, Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. 2020, Preprint. https://doi.org/10.26434/ chemrxiv. 11938173.v6.