SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19

Abstract

The use of vitamin D to reduce the severity of COVID-19 complications is receiving considerable attention, backed by encouraging data. Its purported mode of action is as an immune modulator. Vitamin D, however, also affects metabolism of phosphate and Mg, which may well play a critical role in SARS-CoV-2 pathogenesis. SARS-CoV-2 may induce a cytokine storm that drains ATP whose regeneration requires phosphate and Mg. These minerals, however, are often deficient in conditions that predispose people to severe COVID-19, including older age (especially males), diabetes, obesity, and usage of diuretics. Symptoms observed in severe COVID-19 also fit well with those seen in classical hypophosphatemia and hypomagnesemia, such as thrombocytopenia, coagulopathy, dysfunction of liver and kidneys, neurologic disturbances, immunodeficiency, failure of heart and lungs, delayed weaning from a respirator, cardiac arrhythmia, seizures, and finally multi-organ failure. Deficiencies of phosphate and Mg can be amplified by kidney problems commonly observed in COVID-19 patients resulting in their wastage into urine. Available data show that phosphate and Mg are deficient in COVID-19 with phosphate showing a remarkable correlation with its severity. In one experiment, COVID-19 patients were supplemented with a cocktail of vitamin D3, Mg, and vitamin B12, with very encouraging results. We thus argue that COVID-19 patients should be monitored and treated for phosphate and Mg deficiencies, ideally already in the early phases of infection. Supplementation of phosphate and Mg combined with vitamin D could also be implemented as a preventative strategy in populations at risk.

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients

“…We found interestingly that the pathways related to viral and antiviral activities identified in the plasma of severe patient were both enhanced in the blood cells of COVID-19 patients, indicating the viral replication was active in blood cells and the immune system of blood cells were intensively involved in the viral defense. Meanwhile, the genes identified in plasma DNA consistently downregulated in lung cells with SARS-CoV-2 infection were predominantly enriched in the ATP synthesis pathways, suggesting the decreased ATP and energy reserves due to the lung injury during SARS-COV-2 infection, which has been evidenced to be closely related to the severe COVID-19 symptoms (Patel and Sriram, 2009;van Kempen and Deixler, 2020). These findings were further clearly observed in another sample set.…”

“…In the meantime, we found that the genes downregulated in both plasma and lung cells were mostly located in the mRNA and RNA metabolic pathways, as well as the adenosine triphosphate (ATP) synthesis during cellular respiration (Figure 5C), which reflected the severe injury of lung tissue during the SARS-CoV-2 infection. Importantly, it has been reported that people with low ATP and low energy reserves were more likely to develop severe COVID-19 symptoms (Patel and Sriram, 2009;van Kempen and Deixler, 2020), such as a cytokine storm and ARD since the depletion of intracellular ATP may cause cell death by necrosis and membrane instability, leading to the release of ATP into extracellular space (Le et al, 2019), which would over-activate the immune system (Iyer et al, 2009) and result in these severe consequences (Trautmann, 2009;Nomura et al, 2015;Kouhpayeh et al, 2020). Whereas, the pathways enriching the upregulated genes in lung cells were mainly involved in RNA splicing, segmentation, regulation of nucleocytoplasmic transport, somite development, and regulation of RNA export from nucleus (Figure 5D).…”

Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases

“…Additionally, magnesium is important in the activation of vitamin D. Therefore, taking into account that magnesium and vitamin D are essentials for adequate immune function, a deficiency in either could contribute to cytokine storm in COVID-19 infection. Consequently, the supplementation with magnesium would be an attractive strategy for the prevention and treatment of COVID-19, especially in populations at risk [ 199 , 200 ].…”

On the prospects for the use of thiamine, pyridoxine, and cyanocobalamin in the complex therapy and rehabilitation of patients with COVID-19

“…В клиническом исследовании показано, что уровни фолатов в сыворотке крови, зависящие от В 12 , ассоциированы с тяжестью стеатогепатита (n = 200) [29]. Установлена взаимосвязь между уровнем витамина B 12 в сыворотке крови и выраженностью неалкогольной жировой болезни печени [30], а также положительные эффекты смеси витаминов D 3 , В 12 и магния на функцию почек [31].…”