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BackgroundIndividuals with long-COVID exhibit a higher frequency of hypomagnesemia, vitamin D deficiency, and depression. Objective. To evaluate the efficacy and safety of oral supplementation with magnesium chloride plus vitamin D in alleviating depressive symptoms related to long-COVID.MethodsA total of 60 subjects, aged 52.8±12.6 years, with a diagnosis of hypomagnesemia, vitamin D deficiency, and mild-to-moderate depression (MMD) related to long-COVID, were enrolled in an open-label randomized, controlled clinical trial. Participants were randomly allocated into an intervention group (n=30) that received magnesium chloride (1300 mg) plus vitamin D (4000 IU), or a control group (n=30) that received vitamin D (4000 IU), for four months. Using the Beck Depression Inventory (BDI), diagnosis of MMD was established based on a score of ≥11ResultsMild adverse events that did not require withdrawal from intervention were documented in six (20.0%) and three (10%) individuals of the intervention and control group, respectively. By comparing baseline vs. final measurements, the BDI score was significantly reduced in individuals in the intervention (28.8±3.7 to 9.2±7.5, ppp=0.006.ConclusionOur results show that, among patients with hypomagnesemia and vitamin D deficiency, combined oral supplementation with magnesium plus vitamin D is effective and safe in alleviating MMD related to long-COVID.