The relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted to hospital with COVID-19.

BACKGROUND: Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19. METHODS: Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020-6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann-Whitney U or Kruskal Wallis tests. RESULTS: 281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029). CONCLUSION: Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.

Total plasma magnesium, zinc, copper and selenium concentrations in obese patients before and after bariatric surgery.

Obesity enhances the risk of type-2 diabetes, cardiovascular disease and inflammatory conditions and often leads to metal dyshomeostasis, which contributes to the negative health aspects associated with the disease. In severe cases, bariatric surgery can be recommended to achieve sustained weight loss and improvement in health. Here, magnesium, zinc, copper and selenium concentrations were examined in 24 obese patients (7 males; 17 females) before and 9 months after undergoing Roux-en-Y gastric bypass surgery. All patients lost weight over this period, with the mean BMI reducing from 51.2±7.1 kg/m2 to 37.2±5.5 kg/m2. Moreover, whole-blood glycated haemoglobin (HbA1c), as a marker of average glycaemia, was also measured and a correlative analysis of this parameter with metal concentrations performed. Significant alterations in the plasma concentrations of magnesium, zinc (both increased by 13.2% and 25.2% respectively) and copper (decreased by 7.9%) were observed over this period (plasma selenium concentration was unchanged), with BMI values correlating with plasma magnesium (p = 0.004) and zinc (p = 0.022) concentrations. At 9 months post-surgery, an increase in mean zinc/copper ratio was observed (0.86±0.29 compared to 0.63±0.14 pre-surgery). Comparison of whole-blood HbA1c concentrations pre- and post-surgery revealed a reduction from 6.50±1.28% pre-surgery to 5.51±0.49% post-surgery. Differences in plasma HbA1c and magnesium at either pre- and post-surgery correlated significantly, as did HbA1c and magnesium levels when pre- and post-surgery values were analysed together. Collectively, this work reveals that bariatric surgery, in conjunction with lifestyle/dietary changes, lead to improvements in the nutritional status of magnesium, zinc and copper. Furthermore, the observed improvements in magnesium and zinc were associated with weight loss and in the case of magnesium, to better glycaemic control.

Development of age-dependent micronutrient centile charts and their utility in children with chronic gastrointestinal conditions at risk of deficiencies: A proof-of-concept study.

BACKGROUND & AIMS: Interpretation of blood micronutrient levels requires age-appropriate reference intervals. This study developed age-dependent micronutrient centiles for healthy children (HC) and explored their utility in sick children. METHODS: 244 blood samples were collected from normal HC who underwent tests for acute illness. Age-dependent, centile charts were fitted for zinc, copper, magnesium and selenium in plasma and erythrocytes (RBC), and for vitamins B1, B2 and B6 in RBC. For 34 children with Crohn's disease (CrD) and 55 with coeliac disease (CoeD), Z-scores for the levels of these micronutrients were computed, using the new charts. Associations were explored between plasma and RBC micronutrient Z-scores, and in CrD with CRP and serum albumin. RESULTS: In HC, plasma zinc and selenium increased and plasma copper, magnesium and RBC vitamins B1, B2 and B6 decreased with age. In HC and in CrD, plasma and RBC Z-scores for copper, selenium and magnesium (all p < 0.001) were positively correlated, but not for zinc. In CrD, albumin was related with plasma zinc (rho = 0.62; p < 0.001) and selenium Z-scores (rho = 0.65; p < 0.001) and plasma copper Z-score with CRP (rho = 0.45; p = 0.02). A higher proportion of CrD children had low levels for B2 (21% vs 0%; p = 0.01) and B6 (18% vs 0%; p = 0.02) using the new centile charts than the local laboratory references. CONCLUSION: Age-dependent micronutrient centile charts enable tracking of micronutrient status, Z-score calculation and may prevent misdiagnosis and inappropriate treatment of deficiencies. In systemic inflammatory conditions, RBC measurements of certain micronutrients may be more reliable to use than measurements in plasma.

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet.

INTRODUCTION: In coeliac disease (CD) micronutrient deficiencies may occur due to malabsorption in active disease and diminished intake during treatment with a gluten-free diet (GFD). This study assessed the micronutrient status in children with CD at diagnosis and follow-up. METHODS: Fifteen micronutrients were analysed in 106 blood samples from newly diagnosed CD and from patients on a GFD for <6 months, 6-12 months and with longstanding disease (>12 months). Predictors of micronutrient status included: demographics, disease duration, anthropometry, gastrointestinal symptoms, raised tissue transglutaminase antibodies (TGA), multivitamin use and faecal gluten immunogenic peptide (GIP). Micronutrient levels were compared against laboratory reference values. RESULTS: At CD diagnosis (n = 25), low levels in ≥10% of patients were observed for: vitamins E (88%), B1 (71%), D (24%), K (21%), A (20%) and B6 (12%), ferritin (79%), and zinc (33%). One year post-diagnosis, repletion of vitamins E, K, B6 and B1 was observed (<10% patients). In contrast, deficiencies for vitamins D, A and zinc did not change significantly post-diagnosis. Copper, selenium and magnesium did not differ significantly between diagnosis and follow-up. All samples for B2, folate, vitamin C (except for one sample) and B12 were normal. A raised TGA at follow-up was associated with low vitamins A and B1 (raised vs normal TGA; vitamin A: 40% vs 17%, p = 0.044, vitamin B1: 37% vs 13%, p = 0.028). Low vitamin A (p = 0.009) and vitamin D (p = 0.001) were more common in samples collected during winter. There were no associations between micronutrient status with GIP, body mass index, height, socioeconomic status, or gastrointestinal symptom. Multivitamin use was less common in patients with low vitamin D. CONCLUSIONS: Several micronutrient deficiencies in CD respond to a GFD but others need to be monitored long-term and supplemented where indicated.

Three-year follow up of using combination therapy with fresh-frozen plasma and iron chelation in a patient with acaeruloplasminemia.

Acaeruloplasminemia is a rare autosomal recessive condition caused by inactivating mutations of the CP gene encoding caeruloplasmin (ferroxidase). Caeruloplasmin is a copper-containing plasma ferroxidase enzyme with a key role in facilitating cellular iron efflux. We describe a case of a patient with acaeruloplasminemia, confirmed by genetic analysis, treated with combination therapy of monthly fresh-frozen plasma (FFP) or Octaplas and iron chelation over a 3-year period. This 19-year-old male was diagnosed at the age of 14 after developing issues with social interaction at school prompting investigation. Prior to this, he had been well with a normal childhood. He was found to have an iron deficient picture with a paradoxically high ferritin, with low serum copper and undetectable caeruloplasmin. Genetic testing identified a homozygous splicing mutation, c.(1713 + delG);(c.1713 + delG), in intron 9 of the caeruloplasmin gene. Ferriscan showed a high liver iron concentration of 5.3 mg/g dry tissue (0.17-1.8). Brain and cardiac T2-weighted magnetic resonance (MR) imaging did not detect iron deposition of the brain or heart respectively. Treatment with monthly Octaplas infusion was commenced alongside deferasirox (540 mg o.d.) in an attempt to increase caeruloplasmin levels and reduce iron overload, respectively. After 3 years of treatment, there was biochemical improvement with a reduction in ferritin from 1084 (12-250) to 457 µg/L, ALT from 87 (<50) to 34 U/L together with improvement in his microcytic anaemia. No significant adverse events occurred. This case report adds further evidence of treatment efficacy and safety of combined FFP and iron chelation therapy in acaeruloplasminemia.

The relationship between plasma albumin, alkaline phosphatase and pyridoxal phosphate concentrations in plasma and red cells: Implications for assessing vitamin B6 status.

BACKGROUND: Plasma concentrations of most vitamins decrease as part of the systemic inflammatory response (SIR). Thus low plasma values do not necessarily indicate deficiency. Vitamin B6 status is usually assessed by measurement of pyridoxal phosphate (PLP) in plasma, although vitamin concentrations in blood cells tend to be better markers of cellular stores. In health, plasma PLP appears to be determined primarily by intake, its binding to albumin, and its hydrolysis by alkaline phosphatase (ALP). OBJECTIVE: To examine, using in vitro studies, the effect of albumin concentration and ALP activity on PLP concentration in plasma and red blood cells of healthy subjects (HS) and critically ill patients (CI). DESIGN: Heparin and EDTA (ALP inhibited) whole blood samples from HS (n = 8) and CI (n = 26) were incubated with PLP. Concentration of PLP in plasma and red cells was measured. Albumin and ALP levels were determined in plasma. RESULTS: In PLP incubated heparin samples, there was a strong direct relationship between albumin in the concentration range 10-44 g/L and increase in plasma PLP concentration (rs = 0.93, P < 0.001) and an inverse relationship with increase in red cell PLP concentration (rs = -0.90, P < 0.001). In contrast, ALP activity was inversely associated with increase in plasma PLP concentration (rs = -0.42; P = 0.013) and directly associated with red cell PLP concentration (rs = 0.49; P = 0.003). CONCLUSIONS: Plasma albumin concentration and to a lesser extent ALP activity influences PLP concentration in plasma and red cells. In conditions associated with low albumin (e.g. SIR) or altered ALP activity, red cell PLP measurements are more likely to be reliable than plasma measurements in differentiating true from apparent vitamin B6 deficiency and to guide vitamin B6 supplementation.