Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Data Collection
Determination of Trace Element Levels
2.3. Statistical Analysis
3. Results
3.1. Trace Element Levels According to Disease Severity
3.2. Baseline Characteristics of ICU COVID-19 Patients
3.3. Association between Plasma Levels of Trace Elements and Outcomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Guan, W.; Ni, Z.; Hu, Y.; Liang, W.H.; Ou, C.Q.; He, J.X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C.; et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720. [Google Scholar] [CrossRef]
- Karimi, A.; Shobeiri, P.; Kulasinghe, A.; Rezaei, N. Novel Systemic Inflammation Markers to Predict COVID-19 Prognosis. Front. Immunol. 2021, 12, 741061. [Google Scholar] [CrossRef] [PubMed]
- Moore, J.B.; June, C.H. Cytokine release syndrome in severe COVID-19. Science 2020, 368, 473–474. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- RECOVERY Collaborative Group; Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; et al. Dexamethasone in Hospitalized Patients with Covid-19. N. Engl. J. Med. 2021, 384, 693–704. [Google Scholar]
- RECOVERY Collaborative Group; Abani, O.; Abbas, A.; Abbas, F.; Abbas, M.; Abbasi, S.; Abbass, H.; Abbott, A.; Abdallah, N.; Abdelaziz, A.; et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021, 397, 1637–1645. [Google Scholar] [CrossRef]
- Grasselli, G.; Greco, M.; Zanella, A.; Albano, G.; Antonelli, M.; Bellani, G.; Bonanomi, E.; Cabrini, L.; Carlesso, E.; Castelli, G.; et al. Risk Factors Associated with Mortality among Patients with COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern. Med. 2020, 180, 1345–1355. [Google Scholar] [CrossRef]
- Demircan, K.; Chillon, T.S.; Bracken, T.; Bulgarelli, I.; Campi, I.; Du Laing, G.; Fafi-Kremer, S.; Fugazzola, L.; Garcia, A.A.; Heller, R.; et al. Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe. Front. Immunol. 2022, 13, 1022673. [Google Scholar] [CrossRef]
- Voelkle, M.; Gregoriano, C.; Neyer, P.; Koch, D.; Kutz, A.; Bernasconi, L.; Conen, A.; Mueller, B.; Schuetz, P. Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study. Nutrients 2022, 14, 1862. [Google Scholar] [CrossRef]
- Yasui, Y.; Yasui, H.; Suzuki, K.; Saitou, T.; Yamamoto, Y.; Ishizaka, T.; Nishida, K.; Yoshihara, S.; Gohma, I.O.Y. Analysis of the predictive factors for a critical illness of COVID-19 during treatment—Relationship between serum zinc level and critical illness of COVID-19. Int. J. Infect. Dis. 2020, 100, 230–236. [Google Scholar] [CrossRef]
- Eden, T.; McAuliffe, S.; Crocombe, D.; Neville, J.; Ray, S. Nutritional parameters and outcomes in patients admitted to intensive care with COVID-19: A retrospective single-centre service evaluation. BMJ Nutr. Prev. Health 2021, 4, 416–424. [Google Scholar] [CrossRef]
- Wessels, I.; Rolles, B.; Rink, L. The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis. Front. Immunol. 2020, 11, 1712. [Google Scholar] [CrossRef] [PubMed]
- Berger, M.M.; Shenkin, A.; Schweinlin, A.; Amrein, K.; Augsburger, M.; Biesalski, H.-K.; Bischoff, S.C.; Casaer, M.P.; Gundogan, K.; Lepp, H.-L.; et al. ESPEN micronutrient guideline. Clin. Nutr. 2022, 41, 1357–1424. [Google Scholar] [CrossRef] [PubMed]
- Velthuis, A.J.W.; van den Worml, S.H.E.; Sims, A.C.; Baric, R.S.; Snijder, E.J.; van Hemert, M.J. Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010, 6, e1001176. [Google Scholar] [CrossRef]
- Zhang, L.; Liu, Y. Potential interventions for novel coronavirus in China: A systematic review. J. Med. Virol. 2020, 92, 479–490. [Google Scholar] [CrossRef] [Green Version]
- Gordon, Y.J.; Asher, Y.; Becker, Y. Irreversible inhibition of herpes simplex virus replication in BSC 1 cells by zinc ions. Antimicrob. Agents Chemother. 1975, 8, 377–380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ścibior, A.; Wnuk, E. Elements and COVID-19: A Comprehensive Overview of Studies on Their Blood/Urinary Levels and Supplementation with an Update on Clinical Trials. Biology 2022, 11, 215. [Google Scholar] [CrossRef] [PubMed]
- Basak, A.; Doruk, E.; Engin, A. Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients? Environ. Toxicol. Pharmacol. 2022, 95, 103937. [Google Scholar]
- Guiomar, P.; Brasiel, D.A. The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis. Clin. Nutr. ESPEN 2020, 38, 65–66. [Google Scholar]
- Fooladi, S.; Matin, S.; Mahmoodpoor, A. Copper as a potential adjunct therapy for critically ill COVID-19 patients. Clin. Nutr. ESPEN 2020, 40, 90–91. [Google Scholar] [CrossRef]
- Primmaz, S.; Le Terrier, C.; Suh, N.; Ventura, F.; Boroli, F.; Bendjelid, K.; Cereghetti, S.; Giraud, R.; Heidegger, C.; Pugin, D.; et al. Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients. Crit Care Explor. 2020, 8, 0173. [Google Scholar] [CrossRef]
- Stringhini, S.; Wisniak, A.; Piumatti, G.; Azman, A.S.; Lauer, S.A.; Baysson, H.; De Ridder, D.; Petrovic, D.; Schrempft, S.; Marcus, K.; et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): A population-based study. Lancet 2020, 19–21. [Google Scholar] [CrossRef]
- Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.M.; et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016, 66, 299–305. [Google Scholar] [CrossRef] [PubMed]
- Jafari, P.; Thomas, A.; Haselbach, D.; Watfa, W.; Pantet, O.; Michetti, M.; Raffoul, W.; Applegate, L.A.; Augsburger, M.; Berger, M.M. Trace element intakes should be revisited in burn nutrition protocols: A cohort study. Clin. Nutr. 2018, 37, 958–964. [Google Scholar] [CrossRef] [PubMed]
- Shenkin, A.; Berger, M.M. Micronutrients: A low blood concentration is not equivalent to deficiency. Clin. Nutr. 2022, 41, 2562–2564. [Google Scholar] [CrossRef] [PubMed]
- Fromonot, J.; Gette, M.; Ben Lassoued, A.; Guéant, J.L.; Guéant-Rodriguez, R.M.; Guieu, R. Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19. Clin. Nutr. 2022, 41, 3115–3119. [Google Scholar] [CrossRef] [PubMed]
- Du Laing, G.; Petrovic, M.; Lachat, C.; De Boevre, M.; Klingenberg, G.J.; Sun, Q.; De Saeger, S.; De Clercq, J.; Ide, L.; Vandekerckhove, L.; et al. Course and survival of covid-19 patients with comorbidities in relation to the trace element status at hospital admission. Nutrients 2021, 13, 3304. [Google Scholar] [CrossRef] [PubMed]
- Fakhrolmobasheri, M.; Mazaheri-Tehrani, S.; Kieliszek, M.; Zeinalian, M.; Abbasi, M.; Karimi, F.; Mozafari, A.M. COVID-19 and Selenium Deficiency: A Systematic Review. Biol. Trace Elem. Res. 2021, 200, 3945–3956. [Google Scholar] [CrossRef]
- Lee, Y.H.; Bang, E.S.; Lee, J.H.; Lee, J.D.; Kang, D.R.; Hong, J.; Lee, J.M. Serum Concentrations of Trace Elements Zinc, Copper, Selenium, and Manganese in Critically Ill Patients. Biol. Trace Elem. Res. 2019, 188, 316–325. [Google Scholar] [CrossRef] [Green Version]
- Delgado-roche, L.; Mesta, F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch. Med. Res. 2020, 51, 384–387. [Google Scholar] [CrossRef]
- Arrieta, F.; Martinez-Vaello, V.; Bengoa, N.; Jiménez-Mendiguchia, L.; Rosillo, M.; de Pablo, A.; Voguel, C.; Martinez-Barros, H.; Pintor, R.; Belanger-Quintana, A.; et al. Serum zinc and copper in people with COVID-19 and zinc supplementation in parenteral nutrition. Nutrition 2021, 91–92, 111467. [Google Scholar] [CrossRef]
- Khatiwada, S.; Subedi, A. A Mechanistic Link Between Selenium and Coronavirus Disease 2019 (COVID-19). Curr. Nutr. Rep. 2021, 10, 125–136. [Google Scholar] [CrossRef] [PubMed]
- Moghaddam, A.; Heller, R.A.; Sun, Q.; Seelig, J.; Cherkezov, A.; Seibert, L.; Hackler, J.; Seemann, P.; Diegmann, J.; Pilz, M.; et al. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients 2020, 12, 2098. [Google Scholar] [CrossRef]
- Bayraktar, N.; Bayraktar, M.; Ozturk, A.; Ibrahim, B. Evaluation of the Relationship Between Aquaporin-1, Hepcidin, Zinc, Copper, and İron Levels and Oxidative Stress in the Serum of Critically Ill Patients with COVID-19. Biol. Trace Elem. Res. 2022, 200, 5013–5021. [Google Scholar] [CrossRef] [PubMed]
- Heller, R.A.; Sun, Q.; Hackler, J.; Seelig, J.; Seibert, L.; Cherkezov, A.; Minich, W.B.; Seemann, P.; Diegmann, J.; Pilz, M.; et al. Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker. Redox. Biol. 2021, 38, 101764. [Google Scholar] [CrossRef] [PubMed]
- Berger, M.M.; Talwar, D.; Shenkin, A. Pitfalls in the interpretation of blood tests used to assess and monitor micronutrient nutrition status. Nutr. Clin. Pract. 2023, 38, 56–69. [Google Scholar] [CrossRef]
- Beran, A.; Mhanna, M.; Srour, O.; Ayesh, H.; Stewart, J.M.; Hjouj, M.; Khokher, W.; Mhanna, A.S.; Ghazaleh, D.; Khader, Y.; et al. Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis. Clin. Nutr. ESPEN 2022, 48, 167–177. [Google Scholar] [CrossRef]
- Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233. [Google Scholar] [CrossRef]
- Balboni, E.; Zagnoli, F.; Filippini, T.; Fairweather-tait, S.J.; Vinceti, M. Zinc and selenium supplementation in COVID-19 prevention and treatment: A systematic review of the experimental studies. J. Trace Elem. Med. Biol. 2022, 71, 126956. [Google Scholar] [CrossRef]
- Ben Abdallah, S.; Mhalla, Y.; Trabelsi, I.; Sekma, A.; Youssef, R.; Bel Haj Ali, K.; Ben Soltane, H.; Yacoubi, H.; Msolli, M.A.; Stambouli, N.; et al. Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial. Clin. Infect Dis. 2023, 76, 185–191. [Google Scholar] [CrossRef]
- Al Sulaiman, K.; Aljuhani, O.; Al Shaya, A.I.; Kharbosh, A.; Kensara, R.; Al Guwairy, A.; Alharbi, A.; Algarni, R.; Al Harbi, S.; Vishwakarma, R.; et al. Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: A two center propensity-score matched study. Crit. Care 2021, 25, 1–8. [Google Scholar] [CrossRef]
- Manzanares, W.; Dhaliwal, R.; Jiang, X.; Murch, L.; Heyland, D.K. Antioxidant micronutrients in the critically ill: A systematic review and meta-analysis. Crit. Care 2012, 16, R66. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allingstrup, M.A.A. Selenium supplementation for critically ill adults. Cochrane. Database. Syst. Rev. 2015, 34, 206–207. [Google Scholar] [CrossRef] [PubMed]
n = 118 | |
---|---|
Male gender, n (%) | 91 (77.1%) |
Age, median (IQR) | 65 (57–73) |
BMI, median (IQR) | 28.1 (25.6–31.9) |
Smoking status, n (%) | 17 (14.4%) |
Any comorbidity *, n (%) | 94 (79.7%) |
SAPS II on ICU admission, median (IQR) | 52 (41–64) |
CRP (mg/L) on ICU admission, median (IQR) | 158 (102–208) |
Leucocytes (g/L) on ICU admission, median (IQR) | 7.9 (5.8–10.4) |
Copper on ICU admission in µmol/L, median (IQR) | 18.3 (16.2–20.5) |
Zinc on ICU admission in µmol/L, median (IQR) | 8.2 (6.9–9.7) |
Selenium on ICU admission in µmol/L, median (IQR) | 0.8 (0.7–1) |
PaO2/FiO2 (kPa) on ICU admission, median (IQR) | 18.6 (13.6–23.4) |
Prone positioning, n (%) | 89 (75.4%) |
Number of Prone positioning session, median (IQR) | 3 (2–4) |
ECMO during ICU stay, n (%) | 10 (8.5%) |
Septic shock during ICU stay, n (%) | 24 (20.3%) |
Thrombosis event during ICU stay, n (%) | 17 (14.4%) |
Days under mechanical ventilation, median (IQR) | 13 (9–17) |
Length of stay in the ICU (days), median (IQR) | 16 (11–22) |
Length of stay in the hospital (days), median (IQR) | 28 (19–40) |
Mortality at day 28, n (%) | 18 (15.3%) |
Normal Zinc n = 59 | Lower Zinc n = 59 | p | Normal Copper n = 59 | Lower Copper n = 59 | p | Normal Selenium n = 59 | Lower Selenium n = 59 | p | |
---|---|---|---|---|---|---|---|---|---|
Days under MV, median (IQR) | 13 (8–17) | 13 (10–19) | 0.3 | 11 (8–15) | 15 (11–21) | <0.01 | 12 (9–15) | 13 (8–24) | 0.09 |
Septic shock, n (%) | 8 (13.6%) | 16 (27.1%) | 0.07 | 9 (15.3%) | 15 (25.4%) | 0.3 | 9 (15.3%) | 15 (25.4%) | 0.3 |
Mortality J28, n (%) | 5 (8.5%) | 13 (22%) | 0.07 | 8 (13.6%) | 10 (17%) | 0.8 | 5 (8.5%) | 13 (22%) | 0.07 |
Lower versus Normal Zinc, OR (CI 95%) | p | Lower versus Normal Copper, OR (CI 95%) | p | Lower versus Normal Selenium, OR (CI 95%) | p | |
Septic shock * | 2.6 (0.97–7) | 0.06 | 1.8 (0.7–4.6) | 0.2 | 1.9 (0.7–4.9) | 0.2 |
Mortality * | 1.9 (0.6–6.5) | 0.3 | 2.3 (0.7–7.4) | 0.2 | 2.6 (0.8–8.5) | 0.1 |
Lower versus normal Zinc, β coefficient (CI 95%) | Lower versus normal Copper, β coefficient (CI 95%) | Lower versus normal Selenium, β coefficient (CI 95%) | p | |||
Days under MV * | 2.3 (−0.9–5.5) | 0.2 | 3.5 (0.4–6.6) | 0.03 | 3.3 (0.2–6.3) | 0.04 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wozniak, H.; Le Terrier, C.; Primmaz, S.; Suh, N.; Lenglet, S.; Thomas, A.; Vuilleumier, N.; Pagano, S.; de Watteville, A.; Stringhini, S.; et al. Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients. Nutrients 2023, 15, 3308. https://doi.org/10.3390/nu15153308
Wozniak H, Le Terrier C, Primmaz S, Suh N, Lenglet S, Thomas A, Vuilleumier N, Pagano S, de Watteville A, Stringhini S, et al. Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients. Nutrients. 2023; 15(15):3308. https://doi.org/10.3390/nu15153308
Chicago/Turabian StyleWozniak, Hannah, Christophe Le Terrier, Steve Primmaz, Noémie Suh, Sébastien Lenglet, Aurélien Thomas, Nicolas Vuilleumier, Sabrina Pagano, Aude de Watteville, Silvia Stringhini, and et al. 2023. "Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients" Nutrients 15, no. 15: 3308. https://doi.org/10.3390/nu15153308