Evolution of Status of Trace Elements and Metallothioneins in Patients with COVID-19: Relationship with Clinical, Biochemical, and Inflammatory Parameters

The inflammatory reaction and pathogenesis of COVID-19 may be modulated by circulating trace elements (Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn)) and Metallothioneins (MTs). Thus, the present study aimed to investigate their relationship with clinical, biochemical, and inflammatory parameters in patients with COVID-19 at the early Intensive Care Unit (ICU) phase. Critically ill patients (n = 86) were monitored from the first day of ICU admission until the third day of stay. Serum samples were used to assess mineral levels via Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and MT levels via differential pulse voltammetry. Levels of Cu and MTs were significantly decreased after 3 days (p < 0.05), increasing the prevalence of Cu-deficient values from 50% to 65.3% (p = 0.015). Fe and Zn were shown to have a predictive value for mortality and severity. The present study suggests trace element deficiency may be a risk factor during early ICU treatment of COVID-19, as it is related to different biochemical and clinical parameters, indicating a possible beneficial effect of restoring proper levels of these micronutrients.European Regional Development Fund (ERDF) “a way of making Europe”Consejería de Transformación Económica, Industria, Conocimiento y Universidades de la Junta de Andalucía (REF. A-CTS-708-UGR20)Project FIS PI10/1993 from the Spanish Carlos III Health Institute(REF. FPU18/03702)(REF. FPU18/03655)Spanish Ministry of Educatio

Effect of zinc supplementation on circulating concentrations of homocysteine, vitamin B12, and folate in a postmenopausal population

Introduction: The decrease in estrogen levels associated with menopause increases the risk of deficiencies of key micronutrients such as zinc and of disturbances in methylation cycle-related markers. The present study assesses the effect of 8-week Zn supplementation upon circulating concentrations of Hcy, B12, and Fol levels in a population of postmenopausal women. Methods: Fifty-one postmenopausal women aged between 44 and 76 years took part in the study. Two randomized groups (placebo and zinc [50 mg/day]) were treated during 8 weeks. Nutrient intake was assessed based on the 72-hour recall method. Zinc was analyzed by flame atomic absorption spectrophotometry. Clinicalnutritional parameters were determined by enzyme immunoassay techniques. Results: Folate levels increased significantly (p < 0.05) in the zinc group on comparing the baseline versus followup values. Homocysteine decreased in the inter-group analysis (p < 0.05) after the intervention. Furthermore, higher folate (r = - 0.632; p = 0.005) and vitamin B12 (r = - 0.512; p = 0.030) levels were correlated to low homocysteine levels in the zinc group after the intervention, although the zinc intervention had the same effect on B12 levels in both groups. Conclusion: Zinc supplementation enhanced circulating folate and homocysteine by improving the folate values in the zinc-supplemented group and decreasing homocysteine levels inter-groups. Further studies involving larger samples and optimizing the doses and intervention period are needed to reinforce our main findings.Thanks are due to all the postmenopausal women who participated in the present study. We also thank the English revision and edition provided by a scientific translator. Funding for open access charge: Universidad de Huelva, Spain / CBUA

Relationship between Body Composition and Biochemical Parameters with Antioxidant Status in a Healthy Cohort of Postmenopausal Women

An adequate prooxidant-antioxidant balance-which may be influenced by body composition and biochemical status-is essential to maintain human health, especially in circumstances under which the antioxidant defense decreases, such as menopause. The present study aimed to examine the relationship between body composition and biochemical parameters with antioxidant status in a healthy cohort of postmenopausal women. This cross-sectional study was carried out in a cohort of 78 postmenopausal women aged 44-76 years. The body composition profile was assessed through bioelectrical impedance. The determination of the total antioxidant capacity and superoxide dismutase activity was conducted by the colorimetric method, and glutathione peroxidase activity was determined by the enzymatic immunological method. The vitamin D levels were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The mineral status was assessed through flame atomic absorption spectrophotometry. The rest of the biochemical parameters were assessed through an immunoassay. The total antioxidant capacity and antioxidant gap were negatively influenced by body composition (all p <= 0.049) and positively related to protein metabolism parameters (all p <= 0.048), whereas circulating levels of different micronutrients (all p <= 0.048) and enzymes (all p <= 0.047) appeared to play an important role in the glutathione peroxidase and superoxide dismutase activities. In conclusion, the menopause-related antioxidant status changes may be influenced by key body composition and biochemical profiles. To confirm this statement, further trials aiming to evaluate the body composition and biochemical intervention-induced changes upon antioxidant defense are needed.Spanish Ministry of Education and Professional Formation FPU18/03655 FPU18/0370

Vitamin D Status in Critically Ill Patients with SIRS and Its Relationship with Circulating Zn and Related Parameters during ICU Stay

Critically ill patients are exposed to different stressors which may generate Systemic Inflammatory Response Syndrome (SIRS). This situation hinders the assessment of micronutrients status, such as vitamin D or Zinc (Zn), potentially affecting patients’ treatment and recovery. The aim of the present study was to assess the evolution of circulating 25–Hydroxyvitamin D (25–OH–D) levels after seven days of Intensive Care Unit (ICU) stay and the influence on changes in plasma and erythrocyte Zn levels, as well as other parameters related to phosphorus–calcium metabolism. A prospective analytical study was conducted on 65 critically ill patients (42% women) aged 31–77 years with SIRS. Total 25–OH–D levels were measured in plasma samples by liquid chromatographytandem mass spectrometry, and Zn content was analyzed by flame atomic absorption spectrometry. Both 25–OH–D and 25–OH–D3 levels were directly associated with erythrocyte Zn concentration at follow-up (p = 0.046 and p = 0.011, respectively). A relationship between erythrocyte and plasma Zn was also found at this follow-up point. No such clear associations were found when considering 25– OH–D2. Different disturbances in levels of phosphorus–calcium metabolism parameters were found, suggesting a relationship between the changes of 25–OH–D3 levels and parathormone (p = 0.019) and phosphorus (p = 0.005). The findings of the present study suggest an interaction between vitamin D and Zn, in which the correct status of these micronutrients could be a potentially modifiable factor and a beneficial approach in the recovery of critically ill patients.FIS projects of the Carlos III Health Institute PI10/1993Spanish Government A-CTS-708-UGR20 FPU18/03702 FPU18/0365

Association between Body Fatness and Vitamin D3 Status in a Postmenopausal Population

We especially thank all the postmenopausal women who participated in our study and Bienza translators who provided English editing.Vitamin D is a micronutrient that plays a key role in phosphocalcic metabolism. The postmenopausal population presents a risk of deficiency in this vitamin due to hormonal alterations which, in the case of obesity, would be exacerbated. The objective was to assess the status of vitamin D in a postmenopausal population and determine the relationship of 25-hydroxivitamin D [25(OH)D] and its metabolites with anthropometric parameters. The study included 78 healthy postmenopausal women aged from 44 to 76. The nutrient intake assessment was carried out using the 24 h reminder (R24h). 25(OH)D was analyzed using ultra-high-performance liquid chromatography (UHPLC). A total of 80% and 68% of the women studied did not reach sufficient values of 25(OH)D and 25-hydroxivitamin D3 [25(OH)D3], respectively, which was inversely correlated with Body Mass Index (BMI) (r = −0.25, p = 0.04), hip perimeter (r = −0.26 and r = −0.24, all p < 0.05), arm circumference (r = −0.29, p = 0.01) and fat mass (r = −0.28 and r = −0.26, all p < 0.05). 25(OH)D3 is the metabolite that contributed most to this association. In conclusion, 25(OH)D3 levels are related to anthropometric parameters in the postmenopausal women in this study, confirming insufficient status in the majority of the population. Approach strategies are necessary to correct and avoid this risk in order to ensure future quality of life.This research was funded by FIS Carlos III (REF. PI10/1993)

Erythrocyte Zn concentration and antioxidant response after supplementation with Zn in a postmenopausal population. A double-blind randomized trial

Background & aims: Menopausal hormonal changes increase the risk of deficiencies of minerals such as zinc (Zn), which could further worsen the decreased antioxidant defense of postmenopausal women. This study assesses the effect of 8 weeks of Zn supplementation upon the antioxidant status and clinical nutritional parameters of a postmenopausal population. Methods: Fifty-one postmenopausal women were divided into two groups: placebo (PbG) and zinc supplementation (ZnG). Mineral status was determined by Flame Atomic Absorption Spectrophotometry (FAAS). Total Antioxidant Capacity (TAC) and Superoxide Dismutase (SOD) were analyzed by kinetic colorimetric methods. Glutathione Peroxidase (GPx) was assessed by an enzymatic immunological method. Results: Poor Zn status was initially observed in erythrocyte samples. Total antioxidant capacity showed a significant correlation (r = 0.730; p < 0.05) to erythrocyte Zn after the intervention (ZnG: r = 0.96; p < 0.001). Moreover, erythrocyte Zn concentration in ZnG was positively correlated to GPx activity after the intervention (r = 0.61; p < 0.01). Conclusions: The postmenopausal women initially presented Zn deficiency, and the status of this mineral improved after the intervention. Zinc supplementation may be an effective approach for correcting the observed deficiencies, enhancing antioxidant defense in this risk population.We wish to thank all the women volunteers taking part in this study. We also acknowledge the expertise translator who provided English editing. Funding for open access charge: Universidad de Huelva/CBUA

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

Aim: The aim of this study was to evaluate oxidative stress from glutathione depletion in critically ill patients with a septic shock through the abnormal presence of pyroglutamic acid (PyroGlu) in the urine (indirectly) and through its serum level (directly). Methods: This was a prospective analytical study of 28 critically ill patients with a septic shock who were monitored from admission (initial) to 3 days of stay (final) in the intensive care unit (ICU). Data collected included PyroGlu and glutamic acid (Glu) using liquid chromatography/mass spectrometry, and glutathione peroxidase (GPX) activity with a colorimetric assay. The differences in Glu, PyroGlu, and GPX activity between the septic shock group and healthy control group serving as reference values were evaluated using the Mann–Whitney test. The correlations between Glu, PyroGlu, and GPX activity and clinical outcomes were determined using Spearman’s correlation coefficient. Results: In patients with septic shock, serum and urine PyroGlu levels were higher, erythrocyte GPX activity/gr Hb was lower, and urine Glu levels were lower compared to healthy control reference values, for both initial and final values. Initial serum Glu levels were also lower. Serum PyroGlu levels had a correlation with both initial and final serum Glu levels; levels also correlated in the urine. Initial serum Glu correlated with the days of mechanical ventilation (P = 0.016) and the days of ICU stay (P = 0.05). Urine Glu/mg creatinine correlated with APACHE II (P = 0. 030). This positive correlation observed for serum Glu was not observed for PyroGlu. Conclusions: The current study found that septic patients have higher levels of PyroGlu, lower levels of Glu, and lower erythrocyte GPX activity, suggesting that these biomarkers could be used as an indicator of glutathione depletion. In addition, Glu is related to severity parameters. This study can guide future studies on the importance of monitoring the levels of pyroglutamic acidosis in critical patients with septic shock in order to preserve the oxidative status and its evolution during the stay in the ICU.Financial support for the study was provided by Project FIS PI10/1993 from the Spanish Carlos III Health Institute and FEDER European Funds

Influence of Nutritional Parameters on the Evolution, Severity and Prognosis of Critically Ill Patients with COVID-19

This study evaluated the clinical and nutritional status, the evolution over three days, and the relationship between nutritional, inflammatory, and clinical parameters of critically ill patients with COVID-19. A longitudinal study was conducted in the Intensive Care Unit of the Virgen de las Nieves University Hospital in Granada (Spain). The study population comprised patients with a positive polymerase chain reaction test for COVID-19 presenting critical clinical involvement. Clinical outcomes were collected, and inflammatory and nutritional parameters (albumin, prealbumin, transferrin, transferrin saturation index, cholesterol, triglycerides and Controlling Nutritional Status (CONUT) score) were determined. A total of 202 critical patients with COVID-19 were selected, presenting highly altered clinical-nutritional parameters. The evolution experienced by the patients on the third day of admission was a decrease in albumin (p < 0.001) and an increase in prealbumin (p < 0.001), transferrin (p < 0.002), transferrin saturation index (p < 0.018), and cholesterol (p < 0.001). Low levels of albumin, prealbumin (on the third day) and high CONUT score (on the third day) showed an association with higher mortality. Nutritional variables were inversely correlated with clinical and inflammatory parameters. Critically ill patients with COVID-19 have poor nutritional status related to a poor prognosis of disease severity and mortality.Spanish Carlos III Health InstituteEuropean Regional Development Fund (ERDF) Andalucia FIS PI10/1993Spanish Government REF. A-CTS-708-UGR20 REF. FPU18/03702 REF. FPU18/0365

Bad Prognosis in Critical Ill Patients with COVID‐19 during Short‐Term ICU Stay Regarding Vitamin D Levels

Background and aims: Vitamin D inadequacy may be involved in the mechanisms of SARS‐CoV‐2 infection and in potential risk factors for disease propagation or control of coronavirus disease 2019 (COVID‐19). This study assessed a short‐term evolution of vitamin D status and its influence upon different clinical parameters in critically ill patients with COVID‐19. Methods: A prospective analytical study in which 37 critically ill volunteers between 41 and 71 years of age with COVID‐19 were evaluated at baseline and three days of intensive care unit (ICU) stay. 25‐OH‐D3 and 25‐OH‐D2 were analyzed by liquid chromatography–tandem mass spectrometry and total 25‐ OH‐D levels were calculated as the sum of both. Results: All patients presented low 25‐OH‐D levels at baseline, decreasing total 25‐OH‐D (p = 0.011) mainly through 25‐OH‐D2 (p = 0.006) levels during ICU stay. 25‐OH‐D2 levels decreased a mean of 41.6% ± 89.6% versus 7.0% ± 23.4% for the 25‐OH‐ D3 form during the ICU stay. Patients who did not need invasive mechanical ventilation presented higher levels of 25‐OH‐D2 at baseline and follow‐up. Lower 25‐OH‐D and 25‐OH‐D3 levels were associated with higher D‐dimer at baseline (p = 0.003; p = 0.001) and at follow up (p = 0.029), higher procalcitonin levels (p = 0.002; p = 0.018) at follow up, and lower percentage lymphocyte counts (p = 0.044; p = 0.040) during ICU stay. Conclusions: Deficient vitamin D status in critical patients was established at the admission and further worsened after three days of stay. Lower vitamin D levels were related to key altered clinical and biochemical parameters on patients with SARS‐CoV‐2 infec‐ tion. Given the different response of the 25‐OH‐D3 and 25‐OH‐D2 forms, it would be useful to mon‐ itor them on the evolution of the critically ill patient.FIS Projects from Carlos III Health Institute [REF. PI10/1993]Spanish Ministry of Educatio

Acidemia piroglutámica, glutatión y estrés oxidativo como predictores en la evolución del paciente crítico con shock séptico

En los pacientes con shock séptico aparece un elevado estrés oxidativo que se produce tanto por exceso en la producción de radicales libres como por el déficit en las defensas antioxidantes. Uno de los sistemas antioxidantes defensivos endógenos más importante y más abundante es la glutatión peroxidasa, enzima que requiere de glutatión reducido para su acción, quedando regenerada para poder eliminar radicales libres. En estos pacientes coincide el aumento de radicales libres con el descenso de glutatión reducido por consumo. El correcto funcionamiento de la ruta gamma-glutamil es clave para la síntesis correcta del glutatión y, para que éste se encuentre en condiciones óptimas para regenerar la enzima glutatión peroxidasa. En este estudio pretendemos medir la prevalencia de pacientes que presentan elevados niveles de ácido piroglutámico como consecuencia de un elevado estrés oxidativo. Esta molécula se encuentra acumulada como consecuencia de la depleción de glutatión y bloqueo de la ruta gamma-glutamil provocado por el consumo de ATP. Nuestro propósito es esclarecer el comportamiento de las moléculas involucradas en esta ruta en pacientes críticos para poder proponer y utilizar tratamientos que repongan directa o indirectamente el glutatión y que la eliminación de radicales libres no perjudique en gran medida a estos pacientes. El tratamiento de reposición con acetil-cisteína puede ser una posibilidad terapéutica. Resultados. Entre nuestros resultados encontramos que los pacientes críticos con shock séptico presentaron altos niveles de ácido piroglutámico, y bajos niveles de ácido glutámico y glutatión peroxidasa, lo que demuestra que se produce un bloqueo en el ciclo gamma-glutamil, no llegando a sintetizarse el glutatión, y no regenerándose la glutatión peroxidasa, por lo que no se eliminan los radicales libres, y el estado clínico de los pacientes críticos puede agravarse. También se relacionaron algunos de estos componentes del ciclo gamma-glutamil con marcadores clínicos y bioquímicos del estudio en estos pacientes. Conclusiones. La alta presencia de ácido piroglutámico en pacientes con shock séptico sería un indicador de alto estrés oxidativo debido a la deficiencia de glutatión, lo que permite prevenir y corregir esta situación desde el inicio y durante su estancia en la Unidad de Cuidados Intensivos, mejorando su respuesta al tratamiento y evolución.Tesis Univ. Granada