Relation of Serum Copper Status to Survival in COVID-19

Abstract

The trace element copper (Cu) is part of our nutrition and essentially needed for several cuproenzymes that control redox status and support the immune system. In blood, the ferroxidase ceruloplasmin (CP) accounts for the majority of circulating Cu and serves as transport protein. Both Cu and CP behave as positive, whereas serum selenium (Se) and its transporter selenoprotein P (SELENOP) behave as negative acute phase reactants. In view that coronavirus disease (COVID-19) causes systemic inflammation, we hypothesized that biomarkers of Cu and Se status are regulated inversely, in relation to disease severity and mortality risk. Serum samples from COVID-19 patients were analysed for Cu by total reflection X-ray fluorescence and CP was quantified by a validated sandwich ELISA. The two Cu biomarkers correlated positively in serum from patients with COVID-19 (R = 0.42, p < 0.001). Surviving patients showed higher mean serum Cu and CP concentrations in comparison to non-survivors ([mean+/-SEM], Cu; 1475.9+/-22.7 vs. 1317.9+/-43.9 µg/L; p < 0.001, CP; 547.2.5 +/- 19.5 vs. 438.8+/-32.9 mg/L, p = 0.086). In contrast to expectations, total serum Cu and Se concentrations displayed a positive linear correlation in the patient samples analysed (R = 0.23, p = 0.003). Serum CP and SELENOP levels were not interrelated. Applying receiver operating characteristics (ROC) curve analysis, the combination of Cu and SELENOP with age outperformed other combinations of parameters for predicting risk of death, yielding an AUC of 95.0%. We conclude that the alterations in serum biomarkers of Cu and Se status in COVID-19 are not compatible with a simple acute phase response, and that serum Cu and SELENOP levels contribute to a good prediction of survival. Adjuvant supplementation in patients with diagnostically proven deficits in Cu or Se may positively influence disease course, as both increase in survivors and are of crucial importance for the immune response and antioxidative defence systems.

Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients

“…However, in our study, the difference in serum copper levels in relation to severely ill patients is very small when compared to mild and moderate groups. Contrary to our results, a study in Germany did not find any relative change in serum copper levels during the hospital stay [ 38 ]. The recent study also found a weak and non-significant positive correlation with both PCT and hsCRP which is in agreement with the results of the study done by Fooladi et al [ 37 ].…”

COVID-19 and Selenium Deficiency: a Systematic Review

“…Analysis of a cross-sectional study [20] in Germany of 35 COVID-19 patients (171 serum samples) showed that circulating selenium and SELENOP concentrations increased in the discharge group (n = 29) during hospitalization and unlike deaths (n = 6), and generally the amount of selenium and SELENOP in serum was higher in discharged patients compared to deaths. These authors also investigated the circulating level of selenium and SELENOP in 35 patients (173 serum samples, discharges = 28, deaths = 7) in another study, and the results go along with each other [27]. Another study [22] conducted by the same research team on 33 COVID-19 patients suggested remarkably lower levels of serum selenium, SELENOP, and glutathione peroxidase-3 in deaths comparing to discharges.…”

Potential metal-related strategies for prevention and treatment of COVID-19

“…People with metal deficiency are susceptible to COVID-19 [ 16 , 18 , 19 , 23 , 72 ], which may be due to being out of balance in immune regulation. Supplementing metal nutrients in the early stages of infection can help support optimal immune function and be used as a preventive strategy for high-risk groups [ 73 ].…”

“…Some metal elements, such as selenium, iron, and copper, are known to interrupt the infectious interaction between the virus and the host, preventing the virus from entering the host and/or alleviating the symptoms [ 15 – 18 ]. Trace metal elements such as zinc, selenium, and magnesium are known to play an important role in regulating the human immune system, and their deficiencies are related to the severity of the symptoms in COVID-19 patients [ 19 – 25 ].…”