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Thursday 4 March 2021

Letter – Selenium supplementation may improve COVID-19 survival in sickle cell disease.




Further to Ulfberg and Stehlik’s letter of Sept 29th, further evidence supports the role of selenium in COVID-19 virulence.[1]

In their pre-print analysis by machine learning of Medicare patients Dun et al. found that the leading comorbidity associated with COVID-19 mortality, adjusted for age and race, was sickle cell disease (aOR, 1.73; 95% CI, 1.21-2.47), followed by chronic kidney disease (aOR, 1.32; 95% CI, 1.29-1.36).[2]

Both SCD and kidney disease can lower selenium levels by decreasing tubular selenium resorption, and are associated with deficient selenium status.[3,4]

Selenium status or intake has been correlated with COVID-19 outcomes, including mortality and recovery rates, in four patient groups in China, Germany, South Korea, and southern India.[5,6,7,8] SARS-CoV-2, like other RNA viruses, sequesters selenium causing selenium levels to drop during infection.[6,9] SARS-CoV-2 may infect cells in bone marrow, suppressing red blood cell formation.[10] Selenium status is inversely associated with haemolysis in SCD, and selenium may both inhibit haemolysis and enhance erythropoiesis in SCD.[3,11]

Selenium is required for the actions of both vitamin D and dexamethasone.[12,13] Selenite infusion is safe, including in critically ill and dialysis patients, and selenium supplementation has had favourable effects in other RNA virus infections.[14,15,16]

It should be noted that vitamin C and magnesium are also commonly deficient nutrients and are required for the activation of vitamin D3 by hydroxylation.[17,18,19] Deficiency of ascorbate has been associated with COVID-19 and COVID-19 outcomes in hospital populations.[20]

Selenium, supplemented if necessary with its cofactors in vitamin D metabolism, is proposed to be an important protective factor in the general population, but has the potential to reduce mortality from SARS CoV-2 infection in the sickle cell disease population to an even greater extent.


[1] Ulfberg, J., & Stehlik, R. (2020). Finland’s handling of selenium is a model in these times of coronavirus infections. British Journal of Nutrition, 1-2. doi:10.1017/S0007114520003827

 
[2] Dun C, Walsh CM, Bae S et al. A Machine Learning Study of 534,023 Medicare Beneficiaries with COVID-19: Implications for Personalized Risk Prediction. medRxiv 2020.10.27.20220970; doi: https://doi.org/10.1101/2020.10.27.20220970


[3] Delesderrier E, Cople-Rodrigues CS, Omena J, et al. Selenium Status and Hemolysis in Sickle Cell Disease Patients. Nutrients. 2019;11(9):2211. Published 2019 Sep 13. doi:10.3390/nu11092211

[4] Iglesias P, Selgas R, Romero S, Díez JJ. Selenium and kidney disease. J Nephrol. 2013 Mar-Apr;26(2):266-72. doi: 10.5301/jn.5000213. Epub 2012 Sep 18. PMID: 23023721.


[5] Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1297–1299, https://doi.org/10.1093/ajcn/nqaa095

[6] Moghaddam A, Heller RA, Sun Q et al. L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients 2020, 12, 2098.

[7] Im, JH et al. Nutritional status of patients with coronavirus disease 2019 (COVID-19) Int J Infectious Diseases, August 11, 2020

[8] Majeed, M et al. An Exploratory Study of Selenium Status in Normal Subjects and COVID-19 Patients in South Indian population: Case for Adequate Selenium Status: Selenium Status in COVID-19 Patients. Nutrition. Available online 11 November 2020, 11105

[9] Wang, Y et al. SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, ER stress and DNA synthesis. Preprint, 2020/07/31. 10.1101/2020.07.31.230243


[10] Reva, I., et al. Erythrocytes as a Target of SARS CoV-2 in Pathogenesis of Covid-19. Archiv EuroMedica. 2020. doi.org/10.35630/2199-885X/2020/10/3.1


[11] Jagadeeswaran R, Lenny H, Zhang H et al. The Impact of Selenium Deficiency on a Sickle Cell Disease Mouse Model. Blood 2018; 132 (Supplement 1): 3645. doi: https://doi.org/10.1182/blood-2018-99-111833

[12] Schütze N, Fritsche J, Ebert-Dümig R, et al. The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite. Biofactors. 1999;10(4):329-338. doi:10.1002/biof.5520100403

[13] Rock C, Moos PJ. Selenoprotein P regulation by the glucocorticoid receptor. Biometals. 2009;22(6):995-1009. doi:10.1007/s10534-009-9251-2

[14] Zhao Y, Yang M, Mao Z, et al. The clinical outcomes of selenium supplementation on critically ill patients: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98(20):e15473. doi:10.1097/MD.0000000000015473

[15] Manzanares W, Lemieux M, Elke G, Langlois PL, Bloos F, Heyland DK. High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care. 2016;20(1):356. Published 2016 Oct 28. doi:10.1186/s13054-016-1529-5

[16] Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr. 2015;6(1):73-82. Published 2015 Jan 15. doi:10.3945/an.114.007575


[17] Cantatore FP, Loperfido MC, Magli DM, Mancini L, Carrozzo M. The importance of vitamin C for hydroxylation of vitamin D3 to 1,25(OH)2D3 in man. Clin Rheumatol. 1991 Jun;10(2):162-7. doi: 10.1007/BF02207657. PMID: 1655350.

[18] Dai Q, Zhu X, Manson JE, et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018;108(6):1249-1258. doi:10.1093/ajcn/nqy274

[19] Cooper ID, Crofts CAP, DiNicolantonio JJ, et al. Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management. Open Heart. 2020;7(2):e001356. doi:10.1136/openhrt-2020-001356

[20] Carr, A.C.; Rowe, S. The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19. Nutrients 2020, 12, 3286.

[3] Delesderrier E et al. Selenium Status and Hemolysis in Sickle Cell Disease Patients. Nutrients. 2019;11(9):2211. Published 2019 Sep 13. doi:10.3390/nu11092211

[4] Iglesias P et al. Selenium and kidney disease. J Nephrol. 2013 Mar-Apr;26(2):266-72. doi: 10.5301/jn.5000213. Epub 2012 Sep 18. PMID: 23023721.

 [5] Zhang J et al. Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1297–1299, https://doi.org/10.1093/ajcn/nqaa095

[6] Moghaddam A et al. L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients 2020, 12, 2098.

[7] Im, JH et al. Nutritional status of patients with coronavirus disease 2019 (COVID-19) Int J Infectious Diseases, August 11, 2020

[8] Majeed, M et al. An Exploratory Study of Selenium Status in Normal Subjects and COVID-19 Patients in South Indian population: Case for Adequate Selenium Status: Selenium Status in COVID-19 Patients. Nutrition. Available online 11 November 2020, 111053

 

[9] Wang, Y et al. SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, ER stress and DNA synthesis. Preprint, 2020/07/31. 10.1101/2020.07.31.230243

 

[10] Reva, I., et al. Erythrocytes as a Target of SARS CoV-2 in Pathogenesis of Covid-19. Archiv EuroMedica. 2020. doi.org/10.35630/2199-885X/2020/10/3.1

 

[11] Jagadeeswaran R et al. The Impact of Selenium Deficiency on a Sickle Cell Disease Mouse Model. Blood 2018; 132 (Supplement 1): 3645. doi: https://doi.org/10.1182/blood-2018-99-111833