Micronutrients, genetics and COVID-19.

PURPOSE OF REVIEW: Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. RECENT FINDINGS: In patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor ( VDR ) gene, most notably rs2228570 (FokI) "f" allele and rs7975232 (ApaI) "aa" genotype as poor prognostic markers. SUMMARY: Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.

Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2: A narrative review.

BACKGROUND: COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. METHODS: We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. RESULTS: Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. CONCLUSION: There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.

Molecular mechanisms and therapeutic effects of different vitamins and minerals in COVID-19 patients.

COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.

The Roles and Pathogenesis Mechanisms of a Number of Micronutrients in the Prevention and/or Treatment of Chronic Hepatitis, COVID-19 and Type-2 Diabetes Mellitus.

A trace element is a chemical element with a concentration (or other measures of an amount) that is very low. The essential TEs, such as copper (Cu), selenium (Se), zinc (Zn), iron (Fe) and the electrolyte magnesium (Mg) are among the most commonly studied micronutrients. Each element has been shown to play a distinctive role in human health, and TEs, such as iron (Fe), zinc (Zn) and copper (Cu), are among the essential elements required for the organisms' well-being as they play crucial roles in several metabolic pathways where they act as enzyme co-factors, anti-inflammatory and antioxidant agents. Epidemics of infectious diseases are becoming more frequent and spread at a faster pace around the world, which has resulted in major impacts on the economy and health systems. Different trace elements have been reported to have substantial roles in the pathogenesis of viral infections. Micronutrients have been proposed in various studies as determinants of liver disorders, COVID-19 and T2DM risks. This review article sheds light on the roles and mechanisms of micronutrients in the pathogenesis and prevention of chronic hepatitis B, C and E, as well as Coronavirus-19 infection and type-2 diabetes mellitus. An update on the status of the aforementioned micronutrients in pre-clinical and clinical settings is also briefly summarized.

Clinical nutrition approach in medical management of COVID-19 hospitalized patients: A narrative review.

BACKGROUND: Malnutrition in COVID-19 hospitalized patients is associated with a high-risk condition to increase disease severity and prolonging the recovery period. Therefore, nutritional therapy, including supplements plays a critical role to reduce disease-related complications and the length of hospital stay. AIM: To review the latest evidence on nutritional management options in COVID-19 hospitalized patients, as well as possibly prescribed supplements. Methods: This review was conducted by considering the latest recommendations, using the guidelines of the American Society of Enteral and Parenteral (ASPEN) and the European Society of Enteral and Parenteral (ESPEN), and searching Web of Science, PubMed/Medline, ISI, and Medline databases. The relevant articles were found using a mix of related mesh terms and keywords. We attempted to cover all elements of COVID-19 hospitalized patients' dietary management. Results: Energy demand in COVID-19 patients is a vital issue. Indirect Calorimetry (IC) is the recommended method to measure resting energy expenditure. However, in the absence of IC, predictive equations may be used. The ratio of administered diet for the macronutrients could be based on the phase and severity of Covid-19 disease. Moreover, there are recommendations for taking micronutrient supplements with known effects on improving the immune system or reducing inflammation. Conclusions: Nutritional treatment of COVID-19 patients in hospitals seems to be an important element of their medical care. Enteral nutrition would be the recommended feeding method for early nutrition support. However, data in the COVID-19 nutritional domain relating to micronutrient supplementation are still fragmentary and disputed, and further study is required.

The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson's Disease.

Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.

Multiple Micronutrient Supplementation: As a Supportive Therapy in the Treatment of COVID-19.

During the infection and treatment of the SARS-CoV-2 viral infection, age and comorbidities play a major role in the successful management of COVID-19. The nutritional status changes which occur in the body vary with the age and underlying conditions and has a vital role in the functioning of the immune system and cellular membrane integrity, thus minimizing the vulnerability to the infection. Considering the data already published by eminent researchers, a few micronutrients have shown outstanding results as supportive therapies in the treatment of viral infections. Micronutrient like zinc improves the membrane barrier integrity, has anti-inflammatory activity, and is involved in antibody production. Vitamin A supports the phagocytic activity of macrophages, while vitamin C reduces the worsening of respiratory tract infections by restoring the dysfunctional epithelial barrier of the lungs. Vitamin D, vitamin E, selenium, and omega-3 fatty acid metabolites play a major role in immunomodulation and in the inhibition of proinflammatory cytokine production. Magnesium is involved in the synthesis of antibodies, while copper, vitamin B12, and folate have significant effects on immune cells. A few researchers suggest that iron supplementation has reduced the risk of acquiring respiratory tract infections in children. As the age of the patient increases, the need for micronutrients increases, thus leading to an imbalanced nutritional status which in turn increases the risk and fatality of the infections. The use of micronutrients in modulating the inflammatory, immune responses, and the epithelial barrier integrity is explored during the treatment of viral infections for faster recovery.

COVID-19 and micronutrient deficiency symptoms - is there some overlap?

BACKGROUND & AIMS: COVID-19 is highly inflammatory and when it affects the elderly who have multiple comorbidities, the risk of malnutrition is high. The aim of this review is to highlight the evidence for COVID-19 and risk for malnutrition (macro- and micro-nutrient deficiency) sharing two case reports. METHODS: We report two cases of patients with COVID-19. The first case includes a 75-year-old male with increasing confusion, delirium and malnutrition once he had clinically resolved from his COVID-19 diagnosis. The patient had a number of comorbidities and was treated with diuretics before and after his hospital admission. He was treated with intravenous thiamine and enteral nutrition. The second case includes a 77-year-old male with diabetes who presented with suspected vitamin C deficiency likely due to chronic aspirin use nearly two weeks prior to being diagnosed with pneumonia and COVID-19. The patient recovered from his COVID-19 diagnosis but continued to decline nutritionally and was readmitted sixty days later with failure to thrive. RESULTS: The first case had significant improvements in his appetite and neurological conditions following thiamine infusion and enteral nutrition and was discharged to home after a 19-day hospital stay. The second case presented with a vitamin C deficiency before testing positive for COVID-19. Although he did recover from COVID-19 he struggled to meet nutritional needs post-COVID and passed away 60 days after his COVID-19 diagnosis with pneumonia and failure to thrive. CONCLUSION: Elderly patients with chronic diseases who use nutrient depleting medications are particularly high risk for micronutrient deficiency when they also experience the inflammatory insult of COVID-19. Patients who continue to have poor nutrition intake even after they appear to be clinically resolved from the virus should be closely monitored.

Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

BACKGROUND AND AIMS: Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. METHODS: We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P = 0.08). CONCLUSIONS: Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.

Natural Supplements for COVID19-Background, Rationale, and Clinical Trials.

Worldwide, the turmoil of the SARS-CoV-2 (COVID-19) pandemic has generated a burst of research efforts in search of effective prevention and treatment modalities. Current recommendations on natural supplements arise from mostly anecdotal evidence in other viral infections and expert opinion, and many clinical trials are ongoing. Here the authors review the evidence and rationale for the use of natural supplements for prevention and treatment of COVID-19, including those with potential benefit and those with potential harms. Specifically, the authors review probiotics, dietary patterns, micronutrients, antioxidants, polyphenols, melatonin, and cannabinoids. Authors critically evaluated and summarized the biomedical literature published in peer-reviewed journals, preprint servers, and current guidelines recommended by expert scientific governing bodies. Ongoing and future trials registered on clinicaltrials.gov were also recorded, appraised, and considered in conjunction with the literature findings. In light of the controversial issues surrounding the manufacturing and marketing of natural supplements and limited scientific evidence available, the authors assessed the available data and present this review to equip clinicians with the necessary information regarding the evidence for and potential harms of usage to promote open discussions with patients who are considering dietary supplements to prevent and treat COVID-19.

Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.

Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS.

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1ß (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.

[The role of micronutrients in the comprehensive rehabilitation of patients with the novel coronavirus infection COVID-19].

Post-COVID disorders syndrome (PCDS) is an umbrella term for a complex of persistent symptoms that a patient can develop after suffering from COVID-19. The aim of the research was to systematize data on the role of micronutrients in the treatment of PCDS. Material and methods. The authors carried out a systematic analysis of foreign (ncbi. nlm.nih.gov) and Russian (elibrary.ru) scientific publications. Results. The most common symptoms that can persist for a long time after a coronavirus infection can be divided into 4 groups: 1) hypoxic syndrome (respiratory and oxygen deficiency); 2) asthenic syndrome; 3) syndrome of neuropsychiatric disorders; 4) gastrointestinal symptoms. Adequate dietary intake of vitamins and mineral substances is critical for the proper functioning of the immune system and maintenance of the organism functional reserves. The optimal consumption of vitamins D, C and E, zinc and ω-3 fatty acids with ration can be useful for preventing infection, supporting immunity during COVID-19 disease and in the complex of rehabilitation of patients with PCDS. Conclusion. Intake of dietary supplements containing complex of micronutrients can be recommended as a rational adjuvant therapy during the rehabilitation period after COVID-19. However, further research is essential to determine the effective dosage of vitamins and other micronutrients to reduce the manifestations of PCDS.

Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action.

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).

OBJECTIVES: The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS: This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS: Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS: A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19.

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.

The Role of Micronutrients in Support of the Immune Response against Viral Infections.

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).