Serum magnesium in patients with severe acute respiratory syndrome coronavirus 2 from Wuhan, China.

The aim of the study was to evaluate the significance of hypomagnesemia in patients with coronavirus disease 2019 (COVID-19) and clarify its possible pathogenesis. A retrospective cohort study was conducted by reviewing 83 patients hospitalized in Guanggu district, Wuhan Third Hospital, China. Clinical histories, laboratory findings and outcome data were collected. Eighteen patients had hypomagnesemia during hospitalization. Fourteen patients were in the critical group and six died. In the critical group, serum magnesium (0.72 ± 0.15 mmol/L) was much lower than that in the moderate and severe groups. At the same time, we also found that several indicators are correlated with the level of magnesium. The level of magnesium was positively associated with the lymphocyte count (r = 0.203, P = 0.004) and platelet count (r = 0.217, P = 0.002) but negatively related to the levels of CRP (r = -0.277, P = 0.000), LDH (r = -0.185, P = 0.011) and α-hydroxybutyrate dehydrogenase (r = -0.198, P = 0.008) in the critical group. Hypomagnesemia might increase symptoms and may be associated with mortality in COVID-19 by affecting enzyme activity and activating the inflammatory response. Thus, magnesium might play a key role in the pathogenesis of COVID-19.

Serum magnesium levels in hospitalized patients with SARS-CoV-2.

Early studies have reported various electrolyte abnormalities at admission in patients with severe COVID-19. 104 out of 193 patients admitted to our institution presented with hypermagnesemia at presentation. It is believed this may be important in the evaluation of severe SARS-CoV-2 infections. This study evaluated the outcomes of hypermagnesemia in patients with COVID-19. A retrospective chart review of patients admitted to the hospital with confirmed SARS-CoV-2 infection was conducted. A review of the medical literature regarding hypermagnesemia, magnesium levels in critical care illness and electrolyte abnormalities in patients with COVID-19 was performed. Differences in demographic and clinical characteristics of patients with hypermagnesemia and normomagnesemia were evaluated using descriptive statistics. Other known variables of disease severity were analyzed. 104 patients (54%) were identified with hypermagnesemia (≥2.5 mg/dL). 48 of those patients were admitted to the intensive care unit (46%, p<0.001). 34 patients required ventilator support (32%, p<0.0001). With age-adjusted logistic regression analysis hypermagnesemia was associated with mortality (p=0.007). This study demonstrates that hypermagnesemia is a significant marker of disease severity and adverse outcome in SARS-CoV-2 infections. We recommend serum magnesium be added to the panel of tests routinely ordered in evaluation of severe SARS-CoV-2 infections.

Renal function, serum magnesium levels and mortality in COVID-19 patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR <60 mL/min per 1.73 m2). T2D patients had lower eGFR and serum magnesium levels when compared to non-diabetics (59.7 ± 32.8 vs. 78.4 ± 33.8 mL/min per 1.73 m2, P = 0.008 and 1.9 ± 0.3 vs. 2.1 ± 0.3 mEq/L, P = 0.012). Survival was worse in T2D patients with eGFR levels less than 60 mL/min per 1.73 m2 as estimated by Kaplan-Meier analyses (log-rank test <0.0001). The Cox model for T2D patients showed that eGFR (HR 0.970, 95% CI 0.949 to 0.991, P = 0.005) and magnesium (HR 8.025, 95% CI 1.226 to 52.512, P = 0.030) were associated with significantly increased risk of death. Reduced eGFR and magnesium levels were associated with increased mortality in our population. These results suggest that early assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce morbidity and mortality among Latin American COVID-19 patients with T2D.

Trace elements and the carotid plaque: the GOOD (Mg, Zn, Se), the UGLY (Fe, Cu), and the BAD (P, Ca)?

Multiple epidemiological studies have suggested that industrialization and progressive urbanization should be considered one of the main factors responsible for the rising of atherosclerosis in the developing world. In this scenario, the role of trace metals in the insurgence and progression of atherosclerosis has not been clarified yet. In this paper, the specific role of selected trace elements (magnesium, zinc, selenium, iron, copper, phosphorus, and calcium) is described by focusing on the atherosclerotic prevention and pathogenesis plaque. For each element, the following data are reported: daily intake, serum levels, intra/extracellular distribution, major roles in physiology, main effects of high and low levels, specific roles in atherosclerosis, possible interactions with other trace elements, and possible influences on plaque development. For each trace element, the correlations between its levels and clinical severity and outcome of COVID-19 are discussed. Moreover, the role of matrix metalloproteinases, a family of zinc-dependent endopeptidases, as a new medical therapeutical approach to atherosclerosis is discussed. Data suggest that trace element status may influence both atherosclerosis insurgence and plaque evolution toward a stable or an unstable status. However, significant variability in the action of these traces is evident: some - including magnesium, zinc, and selenium - may have a protective role, whereas others, including iron and copper, probably have a multi-faceted and more complex role in the pathogenesis of the atherosclerotic plaque. Finally, calcium and phosphorus are implicated in the calcification of atherosclerotic plaques and in the progression of the plaque toward rupture and severe clinical complications. In particular, the role of calcium is debated. Focusing on the COVID-19 pandemia, optimized magnesium and zinc levels are indicated as important protective tools against a severe clinical course of the disease, often related to the ability of SARS-CoV-2 to cause a systemic inflammatory response, able to transform a stable plaque into an unstable one, with severe clinical complications.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Dysmagnesemia in Covid-19 cohort patients: prevalence and associated factors.

Hypomagnesemia and hypermagnesemia could have serious implications and possibly lead to progress from a mild form to a severe outcome of Covid-19. Susceptibility of subjects with low magnesium status to develop and enhance this infection is possible. There is little data on the magnesium status of patients with Covid-19 with different degrees of severity. This study was conducted to evaluate prevalence of dysmagnesemia in a prospective Covid-19 cohort study according to the severity of the clinical manifestations and to identify factors associated. Serum magnesium was measured in 300 of 549 patients admitted to the hospital due to severe Covid-19. According to the WHO guidelines, patients were classified as moderate, severe, or critical. 48% patients had a magnesemia below 0.75 mmol/L (defined as magnesium deficiency) including 13% with a marked hypomagnesemia (<0.65 mmol/L). 9.6% had values equal to or higher than 0.95 mmol/L. Serum magnesium concentrations were significantly lower in female than in male (0.73 ± 0.12 vs 0.80 ± 0.13 mmol/L), whereas the sex ratio M/F was higher in severe and critical form (p<0.001). In a bivariate analysis, the risk of magnesium deficiency was significantly and negatively associated with infection severity (p<0.001), sex ratio (M/F, p<0.001), oxygenotherapy (p<0.001), stay in critical care unit (p=0.028), and positively with nephropathy (p=0.026). Logistic regression analysis revealed that the strongest predictors of magnesium deficiency were female sex (OR=2.67, p<0.001) and nephropathy (OR=2.12, p=0.032) and after exclusion of sex ratio, the severity of infection (OR=0.46, p=0.04 and OR=0.39 p=0.01), for critical and moderate forms, respectively. This transversal study reveals a high prevalence of hypomagnesemia in hospitalized patients for Covid-19, while high-level serum magnesium concentration was more prevalent in critical form.

Sudden Cardiac Death in Haemodialysis Patients under Hydroxychloroquine Treatment for COVID-19: A Report of Two Cases.

Hydroxychloroquine (HQ) has been used for the treatment of novel coronavirus disease (COVID-19) even though there is no clear evidence for its effectiveness yet. In contrary, HQ has major side effects like QTc prolongation and subsequent development of ventricular arrhythmias. Such side effects may possess additional risks on end-stage renal disease (ESRD) patients who have higher cardiovascular risks than general population. We herein present 2 cases of sudden cardiac death in 2 ESRD patients with COVID-19 for whom a treatment regimen including HQ was preferred. Both patients were clinically stable at the time of arrest. Death could not be attributed to worsening of the COVID-19 since the patients' clinical picture and laboratory values were improving. The cardiac events coincided with the end of routine haemodialysis sessions of both patients. Electrocardiography controls upon admission and on the 24 and 48 h of treatment showed normal QTc intervals. Potential risks contributing to sudden cardiac death during HQ treatment of ESRD patients are discussed.

Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition?

Background: In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients.Methods: A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19.Results: Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its "calcium-channel blocking" effects that lead to downstream suppression of nuclear factor-Kß, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others.Conclusion: As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.

Clinical guidance for navigating the QTc-prolonging and arrhythmogenic potential of pharmacotherapy during the COVID-19 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), has rapidly spread since December 2019 to become the focus of healthcare systems worldwide. Its highly contagious nature and significant mortality has led to its prioritization as a public health issue. The race to prevent and treat this disease has led to "off-label" prescribing of medications such as hydroxychloroquine, azithromycin, and Kaletra (lopinavir/ritonavir). Currently, there is no robust clinical evidence for the use of these drugs in the treatment of COVID-19, with most, if not all of these medications associated with the potential for QT interval prolongation, torsades de pointes, and resultant drug-induced sudden cardiac death. The aim of this document is to help healthcare providers mitigate the potential deleterious effects of drug-induced QTc prolongation.

The COVID-19 pandemic: is there a role for magnesium? Hypotheses and perspectives.

More and more studies are accumulating about COVID-19. Some aspects of the pathogenesis of the disease recall events occurring in Mg deficiency, such as a drop of T cells, increased plasma concentration of inflammatory cytokines, and endothelial dysfunction. We hypothesize that a low Mg status, which is rather common, might foment the transition from mild to critical clinical manifestations of the disease. Epidemiological, clinical, and fundamental research is needed to clarify the potential role of Mg deficiency in COVID-19.