Table 3.

Magnesium in Neurological and Psychiatric Complications of COVID-19.

Neurological or Psychiatric Complication of COVID-19	Possible Link with Mg
Memory and cognition [147,148]	Mg plays a role in mechanisms of memory and cognition, and Mg deficit is involved in significant reduction in memory [149,150,159]
	Increasing brain Mg in rats is positively correlated with increased working, long-term, and short-term memory [151]
	Mg has been shown to be involved in prevention of memory loss or recovery of memory via increased neuroplasticity [151,156] upregulation of cAMP [23] modulation of transcription factors (c-Fos, NF-κB) [23,154] increased BDNF action [23] reduced oxidative stress in the brain [23] increased levels of reduced glutathione [23] reduced proinflammatory cytokine synthesis and release [23,155,161] reversed upregulation of TNF-α/NF-κB signaling in the hippocampus [154]
Impaired c-Fos activation [152]	Impaired activation of c-Fos is necessary for memory formation [152]
	Low Mg impairs c-Fos activity [153]
	Mg administration normalizes c-Fos expression [153]
Neuroplasticity and synaptic interconnection mediate memory [156]	Mg improves synaptic plasticity [151]
	Mg plus environmental enrichment synergistically improved recognition/spatial memory by reducing synaptic loss and restoring the NMDAR signaling pathway in AD mice [159]
	Chronically reducing Ca2+ flux enhancement synaptic plasticity [151]
CREB-mediated transcription involved in long-and short-term memory [152]	Mg upregulated CREB-mediated transcription [158]
Loss of taste and smell [138,143,170]	TAS2R7 taste receptor is activated by Mg [167]
	Patients with COVID-19 and low Mg status showed change and/or loss of taste and/or smell [168,170]
Loss of appetite [85,130,172]	Mg deficiency causes loss of appetite [171]
Ataxia [138]	Mg depletion is associated with decreased cerebellar functions, including ataxia [24,173,174,175,176,177]
	Mg administration contributed to improvement in cerebellar clinical symptoms [173,174,175]
	There are no clinical trials of Mg therapy for patients with patients with COVID-19 presenting with ataxia, but we consider Mg administration should be considered and studied
Impaired consciousness [132,138]	Impaired consciousness occurs in about 14% of patients with patients with COVID-19 [132,138]
	Both hypo- and hyper-magnesemia sometimes cause severe disturbances of consciousness [179,180]
Mental fatigue and inattention [181,182]	These clinical manifestations were reversible with Mg administration [183]
Demyelination, cranial nerve palsy, and axonal neuropathies [184]	In patients with MS, Mg has protective action at the level of myelin [193,194,195,196]. MS demyelination is associated with low plasma as well as low cerebral spinal fluid Mg [197]; these low blood Mg levels are associated with decreased concentrations of other metallic elements [198]
	Data on Mg and metal trace elements in patients with patients with COVID-19 are few, but we consider that partial protective mechanism of Mg in MS is the same mechanism by which Mg can reduce demyelination in COVID-19 complications
Convulsions or generalized seizures [138,143,188]	Hypomagnesemia is associated with the production of convulsions, lower convulsive threshold, and increases in brain glutamate concentrations [25,183]
Headache [130,138,143,199]	Headache complication of COVID-19 related to direct viral invasion as well as cytokine release syndrome [130,199] and hypoxia [130], both of which are associated with low Mg status [115,126]
Dizziness [137,138,143]	Mg administration improves symptoms and alleviates dizziness [203,204]

Abbreviations: AD, Alzheimer’s disease; BDNF, brain-derived neurotrophic factor; CREB, cAMP response element-binding protein; Mg, magnesium; MS, multiple sclerosis; NF-κB, nuclear factor-κB; NMDAR, N-methyl-d-aspartate receptor; TNF, tumor necrosis factor.