Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission
Gijs Du Laing, Mirko Petrovic, Carl Lachat, Marthe De Boevre, Georg J Klingenberg, Qian Sun, Sarah De Saeger, Jozefien De Clercq, Louis Ide, Linos Vandekerckhove, Lutz Schomburg
Nutrients, doi:10.3390/nu13103304
Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L −1 ) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L −1 ) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The analytical measurements and research in the lab of LS are supported by the Deutsche Forschungsgemeinschaft (DFG), Research Unit FOR-2558 "TraceAge" (Scho 849/6-2), and CRC/TR 296 "Local control of TH action" (LocoTact, P17).
Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of JPH Ghent and UZ Gent (BC-07492, approved on 23 March 2020). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: LS holds shares in selenOmed GmbH, a company involved in Se status assessment and supplementation. The other authors declare no competing interest.
References
Alexander, Tinkov, Strand, Alehagen, Skalny et al., Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19, Nutrients,
doi:10.3390/nu12082358Alfthan, Eurola, Ekholm, Venalainen, Root et al., Effects of nationwide addition of selenium to fertilizers on foods, and animal and human health in Finland: From deficiency to optimal selenium status of the population, J. Trace Elem. Med. Biol,
doi:10.1016/j.jtemb.2014.04.009Beck, Handy, Levander, Host nutritional status: The neglected virulence factor, Trends Microbiol
Beck, Nelson, Shi, Van Dael, Schiffrin et al., Selenium deficiency increases the pathology of an influenza virus infection, FASEB J,
doi:10.1096/fj.00-0721fjeBeck, Shi, Morris, Levander, Rapid genomic evolution of a non-virulent coxsackievirus B3 in seleniumdeficient mice results in selection of identical virulent isolates, Nat. Med,
doi:10.1038/nm0595-433Berger, Manzanares, Micronutrients early in critical illness, selective or generous, enteral or intravenous?, Curr. Opin. Clin. Nutr. Metab. Care,
doi:10.1097/MCO.0000000000000724Braunstein, Kusmenkov, Zuck, Angstwurm, Becker et al., Selenium and Selenoprotein P Deficiency Correlates with Complications and Adverse Outcome After Major Trauma, Shock
Brodin, Hackler, Misra, Wendt, Sun et al., Selenoprotein P as Biomarker of Selenium Status in Clinical Trials with Therapeutic Dosages of Selenite, Nutrients,
doi:10.3390/nu12041067Buicu, Cernea, Benedek, Buicu, Benedek, Systemic Inflammation and COVID-19 Mortality in Patients with Major Noncommunicable Diseases: Chronic Coronary Syndromes, Diabetes and Obesity, J. Clin. Med,
doi:10.3390/jcm10081545Cabral, Kuxhaus, Eichelmann, Kopp, Alker et al., Trace element profile and incidence of type 2 diabetes, cardiovascular disease and colorectal cancer: Results from the EPIC-Potsdam cohort study, Eur. J. Nutr,
doi:10.1007/s00394-021-02494-3Calder, Bosco, Bourdet-Sicard, Capuron, Delzenne et al., Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition, Ageing Res. Rev,
doi:10.1016/j.arr.2017.09.001Dettorre, Patel, Gennari, Pentheroudakis, Romano et al., The systemic pro-inflammatory response: Targeting the dangerous liaison between COVID-19 and cancer, ESMO Open,
doi:10.1016/j.esmoop.2021.100123Forceville, Vitoux, Gauzit, Combes, Lahilaire et al., Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients, Crit. Care Med,
doi:10.1097/00003246-199809000-00021Gasmi, Tippairote, Mujawdiya, Peana, Menzel et al., Micronutrients as immunomodulatory tools for COVID-19 management, Clin. Immunol,
doi:10.1016/j.clim.2020.108545Gorji, Khaleghi Ghadiri, Potential roles of micronutrient deficiency and immune system dysfunction in the coronavirus disease 2019 (COVID-19) pandemic, Nutrition,
doi:10.1016/j.nut.2020.111047Guillin, Vindry, Ohlmann, Chavatte, Selenium, Selenoproteins and Viral Infection, Nutrients
Haase, Schomburg, You'd Better Zinc-Trace Element Homeostasis in Infection and Inflammation, Nutrients
Heller, Sun, Hackler, Seelig, Seibert et al., Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker, Redox Biol
Huang, Rose, Hoffmann, The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities, Antioxid. Redox Signal,
doi:10.1089/ars.2011.4145Hughes, Fedirko, Jenab, Schomburg, Meplan et al., Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort, Int. J. Cancer,
doi:10.1002/ijc.29071Jothimani, Kailasam, Danielraj, Nallathambi, Ramachandran et al., COVID-19: Poor outcomes in patients with zinc deficiency, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.09.014Kipp, Strohm, Brigelius-Flohe, Schomburg, Bechthold et al., Revised reference values for selenium intake, J. Trace Elem. Med. Biol,
doi:10.1016/j.jtemb.2015.07.005Lossow, Kopp, Schwarz, Finke, Winkelbeiner et al., Aging affects sex-and organ-specific trace element profiles in mice, Aging,
doi:10.18632/aging.103572Maehira, Luyo, Miyagi, Oshiro, Yamane et al., Alterations of serum selenium concentrations in the acute phase of pathological conditions, Clin. Chim. Acta,
doi:10.1016/S0009-8981(01)00744-6Majeed, Nagabhushanam, Gowda, Mundkur, An exploratory study of selenium status in healthy individuals and in patients with COVID-19 in a south Indian population: The case for adequate selenium status, Nutrition,
doi:10.1016/j.nut.2020.111053Moghaddam, Heller, Sun, Seelig, Cherkezov et al., Selenium Deficiency Is Associated with Mortality Risk from COVID-19, Nutrients,
doi:10.3390/nu12072098Monsen, Dietary reference intakes for the antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids, J. Am. Diet. Assoc,
doi:10.1016/S0002-8223(00)00189-9Ng, Tipih, Makoah, Vermeulen, Goedhals et al., Comorbidities in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis, mBio,
doi:10.1128/mBio.03647-20Renko, Hofmann, Stoedter, Hollenbach, Behrends et al., Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice, FASEB J,
doi:10.1096/fj.08-119370Salonen, Alfthan, Huttunen, Pikkarainen, Puska, Association between Cardiovascular Death and Myocardial-Infarction and Serum Selenium in a Matched-Pair Longitudinal-Study, Lancet,
doi:10.1016/S0140-6736(82)91028-5Samad, Sodunke, Abubakar, Jahan, Sharma et al., The Implications of Zinc Therapy in Combating the COVID-19 Global Pandemic, J. Inflamm. Res,
doi:10.2147/JIR.S295377Santos, Sinha, Obesity and aging: Molecular mechanisms and therapeutic approaches, Ageing Res. Rev
Schomburg, The other view: The trace element selenium as a micronutrient in thyroid disease, diabetes, and beyond, Hormones,
doi:10.1007/s42000-019-00150-4Sherlock, Sjostrom, Sian, Delaney, Tipple et al., Hepatic-Specific Decrease in the Expression of Selenoenzymes and Factors Essential for Selenium Processing After Endotoxemia, Front. Immunol,
doi:10.3389/fimmu.2020.595282Sies, Jones, Reactive oxygen species (ROS) as pleiotropic physiological signalling agents, Nat. Rev. Mol. Cell Biol,
doi:10.1038/s41580-020-0230-3Steinbrenner, Al-Quraishy, Dkhil, Wunderlich, Sies, Dietary selenium in adjuvant therapy of viral and bacterial infections, Adv. Nutr,
doi:10.3945/an.114.007575Steinman, Lum, Ho, Kaminski, Steinman, Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics, Proc. Natl. Acad. Sci,
doi:10.1073/pnas.2012358117Stoedter, Renko, Hog, Schomburg, Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice, Biochem. J,
doi:10.1042/BJ20091868Subedi, Tchen, Gaire, Hu, Hu, Adjunctive Nutraceutical Therapies for COVID-19, Int. J. Mol. Sci,
doi:10.3390/ijms22041963Thomson, Assessment of requirements for selenium and adequacy of selenium status: A review, Eur. J. Clin. Nutr,
doi:10.1038/sj.ejcn.1601800Vogel-Gonzalez, Tallo-Parra, Herrera-Fernandez, Perez-Vilaro, Chilton et al., Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection, Nutrients,
doi:10.3390/nu13020562Wiehe, Cremer, Wisniewska, Becker, Rijntjes et al., Selenium status in neonates with connatal infection, Br. J. Nutr,
doi:10.1017/S0007114516002208Yang, Zheng, Gou, Pu, Chen et al., Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: A systematic review and meta-analysis, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.03.017Zhang, Taylor, Bennett, Saad, Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, Am. J. Clin. Nutr,
doi:10.1093/ajcn/nqaa095
