Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

The relevance of magnesium homeostasis in COVID-19.

PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.

Magnesium in Infectious Diseases in Older People.

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.