Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults

This study sought to assess the association between specific dietary mineral intakes with COVID-19 infection in the older adult population. Taken together, dietary magnesium, iron, and potassium intake were significantly lower in COVID-19-positive compared to COVID-19-negative patients. Dietary intake of iron was significantly associated with the risk of COVID-19 infection. Patients hospitalized due to COVID-19 had a significantly lower intake of zinc. Dietary zinc intake was also significantly associated with the risk of hospitalization due to COVID-19 infection. In the dynamical system models, it was observed that dietary intakes of calcium, zinc, and iron below the specified cut-offs, as well as iodine intake above the cut-off, were associated with an elevated risk of COVID-19 incidence.

Based on our findings, there was a significant association between iron intake and COVID-19 incidence. Specifically, each unit increase in iron intake was linked to a 6% decrease in the risk of COVID-19 incidence. About 6.5% of human enzymes depend on iron, and virus replication is dependent on host cellular processes. The cellular iron status could affect viral pathogenesis and host response to viral infection [17, 18]. Besides, iron concentration is associated with macrophage function and cytokine production, influencing inflammatory responses to COVID-19 infection [19]. Iron deficiency also enhances impaired lung function and hypoxia, common traits of severe COVID-19 disease [20]. A recent meta-analysis showed that serum iron levels and hemoglobin indices are inversely associated with COVID-19 infection severity and mortality [21].

Our results indicate a significant association between dietary zinc intake and the risk of hospitalization due to COVID-19 infection. Specifically, each unit increase in zinc consumption was associated with approximately a 30% reduction in the risk of hospitalization. Zinc is an essential trace element for the immune system's growth and function [22]. Zinc deficiency due to inadequate intake or malabsorption results in immune system imbalance and increases the risk of inflammatory and infectious diseases [23]. An observational cohort study in 2021 demonstrated that lower serum zinc levels at admission are associated with more viral expansion, more unfavorable clinical presentation, longer time to become stable, and higher mortality [24]. Another prospective observational study also indicated that COVID-19 patients had significantly lower serum zinc levels, and zinc deficiency was associated with a higher rate of complications, prolonged hospitalization, and increased mortality [25].

Based on the results of the dynamical system, the risk of COVID-19 infection in the group with daily consumption of calcium < 1138.13 mg per day was 5.2 times greater than in those who consume more. According to previous studies, hypocalcemia was reported to be an independent risk factor for poor COVID-19 outcomes, together with C-reactive protein and interleukin 6. Hypocalcemia was also correlated with a more severe inflammatory response, hematologic complications, and mortality in COVID-19 patients [26,27,28,29]. Although previous studies showed that hypocalcemia is negatively associated with COVID-19, it should be considered that lower dietary intake of calcium is very difficult to cause hypocalcemia. An ecological study on 158 countries across the world demonstrated that the infection rate of COVID-19 increased by raising calcium consumption. It was justified that this may be due to the effect of higher calcium intakes on other chronic diseases like myocardial infarction [30].

Although there was no significant difference in dietary intake of iodine between COVID-19-positive and negative patients, the results of the dynamical system showed that the risk of COVID-19 infection in the group with daily consumption of iodine > 52.19 μg/day was associated with a greater risk of COVID-19 disease by three-fold. Iodine, a trace element required for thyroid function, is needed in small quantities to maintain health. According to previous studies, iodine has some roles in strengthening the immune system function and removing pathogens [31]. According to the Food and Nutrition Board of the Institute of Medicine, the recommended iodine intake is 150 µg/d. To achieve the iodine intake standards, the salt iodization program in Iran started in 1996; the main dietary source of iodine in our population is iodinated salt. In fact, in our population, iodine intake is correlated with salt intake. This harmful correlation may justify the adverse effect of iodine consumption on COVID-19 infection in our dynamical system analysis.

Numerous studies have examined changes in dietary intake during the COVID-19 pandemic. However, to our knowledge, there are only a few studies that have assessed the impact of dietary intakes on the risk of COVID-19 and its associated hospitalization. One of the strengths of this study was evaluating the association of past dietary intakes with the incidence of COVID-19 during its pandemic. Although COVID-19 is subsiding, our results may be helpful to prevent infectious disease crises in our population. We also applied advanced data analysis methods to determine the risk of COVID-19 disease in accordance with dietary intakes of minerals. Besides its strengths, some limitations should also be considered. First, to determine COVID-19 patients we only relied on PCR results from all clinical sites in Mashhad. Patients without a PCR positive result were considered as COVID-19 negative. It should be noted that this may prone the study to classification bias. Because some patients affected by Corona virus did not have a PCR test. Besides, we have not considered the frequency of COVID-19 infection and the time of disease occurrence in each person during the pandemic period. Individuals with dietary intake missing were excluded which may influence the generalizability of our results. It should also be considered that we did not define the system, therefore we did not mention the components, delays, or calibration methods. In this study, we only focused on the association of mineral intake with COVID-19 incidence and hospitalization. It should be noted that other factors, including chronic diseases, medications, taking supplements or dietary changes during the time may influence the association between mineral intake and risk of COVID-19 which have not been considered in this study.

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