Experimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk and its associated outcomes. Mendelian randomization (MR) studies provide valuable insight into the causal relationship between an exposure and disease outcomes.

The aim was to conduct a systematic review and meta-analysis of causal inference studies that apply MR approaches to assess the role of these micronutrients, particularly VD, in COVID-19 risk, infection severity, and related inflammatory markers.

Searches (up to July 2023) were conducted in 4 databases.

The quality of the studies was evaluated based on the MR-STROBE guidelines. Random-effects meta-analyses were conducted where possible.

There were 28 studies (2 overlapped) including 12 on micronutrients (8 on VD) and COVID-19, 4 on micronutrients (all on VD) and inflammation, and 12 on inflammatory markers and COVID-19. Some of these studies reported significant causal associations between VD or other micronutrients (vitamin C, vitamin B6, iron, zinc, copper, selenium, and magnesium) and COVID-19 outcomes. Associations in terms of causality were also nonsignificant with regard to inflammation-related markers, except for VD levels below 25 nmol/L and C-reactive protein (CRP). Some studies reported causal associations between cytokines, angiotensin-converting enzyme 2 (ACE2), and other inflammatory markers and COVID-19. Pooled MR estimates showed that VD was not significantly associated with COVID-19 outcomes, whereas ACE2 increased COVID-19 risk (MR odds ratio = 1.10; 95% CI: 1.01-1.19) but did not affect hospitalization or severity of the disease. The methodological quality of the studies was high in 13 studies, despite the majority (n = 24) utilizing 2-sample MR and evaluated pleiotropy.

MR studies exhibited diversity in their approaches but do not support a causal link between VD/micronutrients and COVID-19 outcomes. Whether inflammation mediates the VD-COVID-19 relationship remains uncertain, and highlights the need to address this aspect in future MR studies exploring micronutrient associations with COVID-19 outcomes.

PROSPERO registration no. CRD42022328224.

The SARS-CoV-2 vaccine is an important keystone in fighting against the virus. The vaccination alone could not prevent all SARS-CoV-2 viral infections or even its spread, especially after the emergence of newly mutant strains. The immune response to the SARS-CoV-2 vaccines varies greatly from one person to another. Age, along with adequate micronutrients, especially vitamin D, are major factors influencing immunity. We aimed to analyze SARS-CoV-2 vaccine neutralization potency and the total IgG antibodies along with 25-hydroxy-cholecalciferol concentrations in a cohort of healthy Egyptian vaccinated adults. 196 individuals were included; 145 females and 51 males, with an age range between 22 and 59 years old, from the first time of vaccination and over 16 weeks long. Three blood samples were taken from each individual at three time points; before the 1st dose of vaccination, before the 2nd dose of vaccination, and after 8 weeks of complete vaccination. The samples were analyzed using a chemiluminescent immunoassay to measure vitamin D level and titer of neutralizing and IgG antibodies. A lower level of neutralizing antibodies was detected in deficient and insufficient vitamin D-vaccinated individuals. However, a sufficient titer was detected in individuals with normal vitamin D. Vitamin D deficiency is associated with a suppressed immune response against SARS-CoV-2 despite vaccination. Thus, we made inquiries about using vitamin D as an adjuvant to SARS-CoV-2 vaccination, and its relation with the production of anti-SARS-CoV-2 antibodies.

COVID-19 remains globally pandemic, and although several meta-analyses have explored the association between vitamin D and COVID-19 relative to clinical outcomes, a unified view has not yet emerged.

To summarize the evidence for associations between vitamin D levels and COVID-19-related clinical outcomes and to assess the strength and validity of these associations.

PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews databases were searched from January 1, 2020, to June 15, 2024.

Two reviewers independently extracted data and assessed study quality.

Low vitamin D levels increased the risk of infection by 1.26- to 2.18-fold, the risk of severe illness by 1.50- to 5.57-fold, the risk of intensive care unit (ICU) admission by more than 2-fold, and the risk of death by 1.22- to 4.15-fold. In addition, patients with vitamin D deficiency had an average increase in length of hospital stay of 0.54 days compared with patients with high vitamin D levels. Overall, vitamin D supplementation may reduce severity (eg, ICU admissions, need for mechanical ventilation) and shorter length of hospital stay but has a nonsignificant effect on infection and mortality rates. In addition, there were significant differences in vitamin D levels between individuals testing positive for COVID-19 and those testing negative (mean difference [MD] = -3.22 ng mL-1; 95% CI, -5.18 to -1.25), those with severe cases and those with mild cases (MD = -4.60 ng mL-1; 95% CI, -5.49 to -3.71), and nonsurvivors and survivors of COVID-19 infection (MD = -6.59 ng mL-1; 95% CI: -8.94 to -4.24).

Low vitamin D levels are associated with higher infection rates, more severe disease, and higher mortality rates among individuals with COVID-19, whereas vitamin D supplementation may reduce patients' disease severity. The beneficial effects on infection rates and mortality remain to be further explored, however, in higher-quality, randomized controlled studies. Nonetheless, caution is warranted because the methodological quality of most meta-analyses and the level of evidence for most outcomes are very low.

PROSPERO registration No. CRD42022385036.

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly impacted global health, with pneumonia emerging as a major complication in severe cases. The pathogenesis of COVID-19 is marked by the overproduction of reactive oxygen species (ROS) and an excessive inflammatory response, resulting in oxidative stress and significant tissue damage, particularly in the respiratory system. Antioxidants have garnered considerable attention for their potential role in managing COVID-19 pneumonia by mitigating oxidative stress and modulating immune responses. This review provides a comprehensive overview of the literature on the use of antioxidants in hospitalized patients with mild-to-moderate COVID-19. Studies exploring antioxidants, including vitamins, trace elements, nitric oxide (NO), ozone (O3), glutathione (GSH), L-carnitine, melatonin, bromelain, N-acetylcysteine (NAC), and numerous polyphenols, have yielded promising outcomes. Through their ROS-scavenging properties, these molecules support endothelial function, reduce the thrombosis risk, and may help mitigate the effects of the cytokine storm, a key contributor to COVID-19 morbidity and mortality. Clinical evidence suggests that antioxidant supplementation may improve patient outcomes by decreasing inflammation, supporting immune cell function, and potentially shortening recovery times. Furthermore, these molecules may mitigate the symptoms of COVID-19 by exerting direct antiviral effects that inhibit the infection process and genomic replication of SARS-CoV-2 in host cells. Moreover, antioxidants may work synergistically with standard antiviral treatments to reduce viral-induced oxidative damage. By integrating findings from the literature with real-world data from our clinical experience, we gain a more profound understanding of the role of antioxidants in managing COVID-19 pneumonia. Further research combining comprehensive literature reviews with real-world data analysis is crucial to validate the efficacy of antioxidants and establish evidence-based guidelines for their use in clinical practice.

The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA).

The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.-9-154 C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed.

The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models.

This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.

Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients.

Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase.

Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated.

Adult patients suffering from COVID-19 were studied.

Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients.

Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.

The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19).

This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform.

Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883).

Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.

Evidence supporting the extra-skeletal role of vitamin D in modulating immune responses is centred on the effects of its final metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, also known as calcitriol), which is regarded as a true steroid hormone. 1,25(OH)2D3, the active form of vitamin D, can modulate the innate immune system in response to invading pathogens, downregulate inflammatory responses and support the adaptive arm of the immune system. Serum concentrations of its inactive precursor 25-hydroxyvitamin D3 (25(OH)D3, also known as calcidiol) fluctuate seasonally (being lowest in winter) and correlate negatively with the activation of the immune system as well as with the incidence and severity of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Thus, a low serum concentration of 25(OH)D3 is considered to be a risk factor for autoimmune rheumatic diseases and vitamin D3 supplementation seems to improve the prognosis; moreover, long-term vitamin D3 supplementation seems to reduce their incidence (i.e. rheumatoid arthritis). In the setting of COVID-19, 1,25(OH)2D3 seems to downregulate the early viral phase (SARS-CoV-2 infection), by enhancing innate antiviral effector mechanisms, as well as the later cytokine-mediated hyperinflammatory phase. This Review provides an update of the latest scientific and clinical evidence concerning vitamin D and immune response in autoimmune rheumatic diseases and COVID-19, which justify the need for monitoring of serum 25(OH)D3 concentrations and for appropriate supplementation following clinical trial-based approaches.

Vitamin D was investigated as a prognostic biomarker in COVID-19, in relation to both disease susceptibility and outcomes in infected individuals. Patients admitted to the hospital with a confirmed COVID-19 diagnosis were included if they had a vitamin D measurement prior to hospitalization. Using age- and sex-matched controls, vitamin D levels were investigated for an association with COVID-19 related hospitalizations. Further, vitamin D levels were investigated for an association with 30-day mortality in hospitalized COVID-19 patients. Additionally, three meta-analyses were conducted, investigating the association of vitamin D with the following outcomes: Having a positive SARS-CoV-2 test, hospitalization with COVID-19, and mortality in COVID-19 patients. A total of 685 hospitalized COVID-19 patients were included in the single-center study. Compared to controls, they had higher vitamin D levels. Unadjusted analysis of these 685 cases found higher vitamin D levels associated with increased 30-day mortality. This association disappeared after adjusting for age. In the fully adjusted model, no association between vitamin D and 30-day mortality was found. The meta-analyses found significant associations between lower vitamin D and having a positive SARS-CoV-2 test, and mortality among hospital-admitted COVID-19 patients. The relationship between lower vitamin D and COVID-19 related hospital admissions trended towards being positive but was not statistically significant. Many factors seem to influence the associations between vitamin D and COVID-19 related outcomes. Consequently, we do not believe that vitamin D in and of itself is likely to be a clinically useful and widely applicable predictor for the susceptibility and severity of COVID-19 infections.

Observational studies have shown that vitamin D supplementation reduces the risk of COVID-19 infection, yet little is known about the shared genomic architectures between them. Leveraging large-scale genome-wide association study (GWAS) summary statistics, we investigated the genetic correlation and causal relationship between genetically determined vitamin D and COVID-19 using linkage disequilibrium score regression and Mendelian randomization (MR) analyses, and conducted a cross-trait GWAS meta-analysis to identify the overlapping susceptibility loci of them. We observed a significant genetic correlation between genetically predicted vitamin D and COVID-19 (r_g  = -0.143, p = 0.011), and the risk of COVID-19 infection would decrease by 6% for every 0.76 nmol L^-1 increase of serum 25 hydroxyvitamin D (25OHD) concentrations in generalized MR (OR = 0.94, 95% CI: 0.89-0.99, p = 0.019). We identified rs4971066 (EFNA1) as a risk locus for the joint phenotype of vitamin D and COVID-19. In conclusion, genetically determined vitamin D is associated with COVID-19. Increased levels of serum 25OHD concentration may benefit the prevention and treatment of COVID-19.

Nutrients and diets have an important impact on our immune system and infection risk and a huge number of papers have been published dealing with various aspects of nutrition in relation to SARS-CoV-2 infection risk or COVID-19 severity. This narrative review aims to give an update on this association and tries to summarize some of the most important findings after three years of pandemic. The analysis of major studies and systematic reviews leads to the conclusion that a healthy plant-based diet reduces the risks for SARS-CoV-2 infection and especially COVID-19 severity. Regarding micronutrients, vitamin D is to the fore, but also zinc, vitamin C and, to some extent, selenium may play a role in COVID-19. Furthermore, omega-3-fatty acids with their anti-inflammatory effects also deserve attention. Therefore, a major aim of societal nutritional efforts in future should be to foster a high quality plant-based diet, which not only exerts beneficial effects on the immune system but also reduces the risk for non-communicable diseases such as type 2 diabetes or obesity which are also primary risk factors for worse COVID-19 outcomes. Another aim should be to focus on a good supply of critical immune-effective nutrients, such as vitamin D and zinc.

The pandemic caused by the SARS-CoV-2 virus has triggered great interest in the search for the pathophysiological mechanisms of COVID-19 and its associated hyperinflammatory state. The presence of prognostic factors such as diabetes, cardiovascular disease, hypertension, obesity, and age influence the expression of the disease's clinical severity. Other elements, such as 25-hydroxyvitamin D (25(OH)D3) concentrations, are currently being studied. Various studies, mostly observational, have sought to demonstrate whether there is truly a relationship between 25(OH)D3 levels and the acquisition and/or severity of the disease. The objective of this study was to carry out a review of the current data that associate vitamin D status with the acquisition, evolution, and/or severity of infection by the SARS-CoV-2 virus and to assess whether prevention through vitamin D supplementation can prevent infection and/or improve the evolution once acquired. Vitamin D system has an immunomodulatory function and plays a significant role in various bacterial and viral infections. The immune function of vitamin D is explained in part by the presence of its receptor (VDR) and its activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) in immune cells. The vitamin D, VDR, and Retinoid X Receptor complex allows the transcription of genes with antimicrobial activities, such as cathelicidins and defensins. COVID-19 characteristically presents a marked hyperimmune state, with the release of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. Thus, there are biological factors linking vitamin D to the cytokine storm, which can herald some of the most severe consequences of COVID-19, such as acute respiratory distress syndrome. Hypovitaminosis D is widespread worldwide, so the prevention of COVID-19 through vitamin D supplementation is being considered as a possible therapeutic strategy easy to implement. However, more-quality studies and well-designed randomized clinical trials are needed to address this relevant question.

Coronavirus disease 2019 (COVID-19) became a global pandemic that may be associated with significant associated risk factors.

The aim of this study was to evaluate the factors predisposing risk to death in COVID-19 patients.

This is a retrospective study that presents the demographic, clinical presentation, and laboratory findings on our patients to determine risk factors contributing to their COVID-19 outcome.

We used logistic regression (odds ratios) to examine associations between clinical findings and risk of death in COVID-19 patients. All analyses were done using STATA 15.

A total of 206 COVID-19 patients were investigated, 28 of them died, and 178 survived. Expired patients were older (74.04 ± 14.45 vs. 55.56 ± 18.41 in those who survived) and mainly of male gender (75% vs. 42% in those who survived). The following factors were strong predictors of death: hypertension (OR: 5.48, 95% CI: 2.10-13.59, P < 0.001), cardiac disease (OR: 5.08, 95% CI: 1.88-13.74, P = 0.001), and hospital admission (OR: 39.75, 95% CI: 5.28-299.12, P < 0.001). In addition, blood group B was more frequent in expired patients (OR: 2.27, 95% CI: 0.78-5.95, P = 0.065).

Our work adds to the current knowledge about the factors predisposing to death in COVID-19 patient. In our cohort, expired patients were of older age and male gender plus they were more likely to have hypertension, cardiac disease, and hospital severe disease. These factors might be used to evaluate risk of death in patients recently diagnosed of COVID-19.

Purpose: Airway epithelial barrier leak and the involvement of proinflammatory cytokines play a key role in a variety of diseases. This study evaluates barrier compromise by the inflammatory mediator Tumor Necrosis Factor-α (TNF-α) in the human airway epithelial Calu-3 model. Methods: We examined the effects of TNF-α on barrier function in Calu-3 cell layers using Transepithelial Electrical Resistance (TER) and transepithelial diffusion of radiolabeled probe molecules. Western immunoblot analyses of tight junctional (TJ) proteins in detergent soluble fractions were performed. Results: TNF-α dramatically reduced TER and increased paracellular permeability of both 14C-D-mannitol and the larger 5 kDa probe, 14C-inulin. A time course of the effects shows two separate actions on barrier function. An initial compromise of barrier function occurs 2-4 hours after TNF-α exposure, followed by complete recovery of barrier function by 24 hrs. Beginning 48 hrs. post-exposure, a second more sustained barrier compromise ensues, in which leakiness persists through 144 hrs. There were no changes in TJ proteins observed at 3 hrs. post exposure, but significant increases in claudins-2, -3, -4, and -5, as well as a decrease in occludin were seen at 72 hrs. post TNF-α exposure. Both the 2-4 hr. and the 72 hr. TNF-α induced leaks are shown to be mediated by the ERK signaling pathway. Conclusion: TNF-α induced a multiphasic transepithelial leak in Calu-3 cell layers that was shown to be ERK mediated, as well as involve changes in the TJ complex. The micronutrients, retinoic acid and calcitriol, were effective at reducing this barrier compromise caused by TNF-α. The significance of these results for airway disease and for COVID-19 specifically are discussed.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an infectious disease with rapid onset and high case fatality rate. The study was to explore the clinical value by examining the serum level of 25-hydroxyvitamin D (25 (OH) D) in SFTS patients.

One hundred and five patients and 156 healthy controls were included. Univariate and multivariate regression analyses were performed to identify independent risk factors for disease progression. Subject operating characteristics (ROC) curves were drawn, and the corresponding area under the curve (AUC) was calculated to assess the sensitivity and specificity of the diagnostic disease.

The 25 (OH) D level of disease group was lower than that of healthy control group (22.12 (18.43, 25.86) ng/mL vs 27.36 (23.20, 32.71) ng/mL; P<0.05). The 25 (OH) D level of severe disease group was lower than that of mild disease group (20.55(16.30, 24.44) ng/mL vs 24.94(20.89, 31.91) ng/mL; P<0.05). And there was no significant difference of 25 (OH) D level between the survival group and death group in severe disease group. Multivariate Logistic regression analysis showed that the 25 (OH) D level under 19.665 ng/mL was an independent risk factor for the development of SFTS (OR = 0.901, P=0.040). Furthermore, age more than 68.5 years old and lactate dehydrogenase (LDH) more than 1023.5U/L were independent risk factors for death in severe patients with SFTS.

Patients with SFTS have reduced 25 (OH) D level, and 25 (OH) D is a risk factor for disease severity in patients with SFTS. Vitamin D supplementation may be an effective measure to reduce the risk of infection and improve the prognosis.

COVID-19 infection has a spectrum of variable clinical severity between populations because of their characteristic demographic features, co-morbidities, and immune system reactions. This pandemic tested the healthcare system's preparedness, which depends on predictors of severity and factors related to the duration of hospital stays. Therefore, we carried out a single-center, retrospective cohort study in a tertiary academic hospital to investigate these clinical features and predictors of severe disease and study the different factors that affect hospital stay. We utilized medical records from March 2020 to July 2021, which included 443 confirmed (positive RT-PCR) cases. The data were explained using descriptive statistics and analyzed via multivariate models. Among the patients, 65.4% were female and 34.5% were male, with a mean age of 45.7 years (SD ± 17.2). We presented seven age groups with ranges of 10 years and noticed that patients aged 30-39 years old comprised 23.02% of the records, while patients aged 70 and above comprised 10%. Nearly 47% were diagnosed as having mild, 25% as moderate, 18% as asymptomatic, and 11% as having a severe case of COVID-19 disease. Diabetes was the most common co-morbidity factor in 27.6% of patients, followed by hypertension (26.4%). Our population's predictors of severity included pneumonia, identified on a chest X-ray, and co-morbid conditions such as cardiovascular disease, stroke, ICU stay, and mechanical ventilation. The median length of hospital stay was six days. It was significantly longer in patients with a severe disease and who were administered systemic intravenous steroids. An empirical assessment of various clinical parameters could assist in effectively measuring the disease progression and follow-up with patients.

Interest in the immunomodulatory function of vitamin D has grown since the COVID-19 pandemic started. Our study investigated the possible association between vitamin D deficiency and COVID-19 severity, intensive care needs, and mortality in patients hospitalized with COVID-19. A prospective cohort study was performed on 2342 COVID-19 hospitalized patients between April 2020 and May 2022 in a Romanian tertiary hospital for infectious diseases. A multivariate generalized linear model for binary data was fit with dependent variables: severe/critical form of COVID-19, intensive care need, and fatal outcome as a function of vitamin D deficiency, controlling for age, comorbidities, and vaccination status. More than half of the patients (50.9%) were classified with vitamin D deficiency based on a serum concentration of less than 20 ng/mL. There was a negative association between vitamin D and age. Vitamin D-deficient patients presented with more cardiovascular, neurological, and pulmonary diseases, as well as diabetes, and cancer. In multivariate logistic regression models, vitamin D-deficient patients had higher odds of severe/critical forms of COVID-19 [OR = 1.23 (95% CI 1.03-1.47), p = 0.023] and higher odds of death [OR = 1.49 (95% CI 1.06-2.08), p = 0.02]. Vitamin D deficiency was associated with disease severity and death outcome in hospitalized COVID-19 patients.

The present study aimed to determine the impact of vitamin D supplementation (VDs) on recovery delay among COVID-19 patients.

We performed a randomized controlled clinical trial at the national COVID-19 containment center in Monastir (Tunisia), from May to August 2020. Simple randomization was done in a 1:1 allocation ratio. We included patients aged more than 18 years who had confirmed reverse transcription-polymerase chain reaction (RT-PCR) and who remained positive on the 14th day. The intervention group received VDs (200,000 IU/1 ml of cholecalciferol); the control group received a placebo treatment (physiological saline (1 ml)). We measured the recovery delay and the cycle threshold (Ct) values in RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The log-rank test and hazard ratios (HR) were calculated.

A total of 117 patients were enrolled. The mean age was 42.7 years (SD 14). Males represented 55.6%. The median duration of viral RNA conversion was 37 days (95% confidence interval (CI): 29-45.50) in the intervention group and 28 days (95% CI: 23-39) in the placebo group (p=0.010). HR was 1.58 (95% CI: 1.09-2.29, p=0.015). Ct values revealed a stable trend over time in both groups.

VDs was not associated with a shortened recovery delay when given to patients for whom the RT-PCR remained positive on the 14th day.

This study was approved by the Human Subjects Protection Tunisia center (TN2020-NAT-INS-40) on April 28, 2020, and by ClinicalTrial.gov on May 12, 2021 with approval number ClinicalTrials.gov ID: NCT04883203 .

Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a risk factor for the development of many thyroid disorders, including autoimmune thyroid diseases and thyroid cancer. However, the interaction between vitamin D and thyroid function is still not fully understood. This review discusses studies involving human subjects that (1) compared vitamin D status (primarily determined by serum calcidiol (25-hydroxyvitamin D [25(OH)D]) levels) with thyroid function assessed by thyroid stimulating hormone (TSH), thyroid hormones, and anti-thyroid antibody levels; and (2) evaluated the effect of vitamin D supplementation on thyroid function. Due to the many inconsistencies in the results between the studies, it is still difficult to draw a definite conclusion on how vitamin D status affects thyroid function. Studies in healthy participants observed either a negative correlation or no association between TSH and 25(OH)D levels, while the results for thyroid hormones showed high variability. Many studies have observed a negative association between anti-thyroid antibodies and 25(OH)D levels, but equally many studies have failed to observe such an association. Regarding the studies that examined the effect of vitamin D supplementation on thyroid function, almost all observed a decrease in anti-thyroid antibody levels after vitamin D supplementation. Factors that could contribute to the high variability between the studies are the use of different assays for the measurement of serum 25(OH)D levels and the confounding effects of sex, age, body-mass index, dietary habits, smoking, and the time of year when the samples were collected. In conclusion, additional studies with larger numbers of participants are needed to fully understand the effect of vitamin D on thyroid function.

The aim of this research was to develop innovative cheeses fortified with vitamin D3 (VD3). Formulation studies and analyses of textural properties and chemicals were carried out for these developments. Two traditional Italian varieties of cheese (giuncata and burrata) were studied. For giuncata, the fortification of milk for cheese production provided a VD₃ retention level of 43.9 ± 0.6% in the food matrix. For burrata, the VD₃ ingredient was incorporated into the creamy inner part after mixing, maintaining the textural quality of the product (adhesiveness 4.3 ± 0.4 J × 10^-3; firmness 0.7 ± 0.0 N; and cohesiveness 0.8 ± 0.2). The optimized enrichment designs allowed to obtain homogenous contents of VD₃ during the production of giuncata (0.48 ± 0.01 µg/g) and burrata cheeses (0.32 ± 0.02 µg/g). Moreover, analyses revealed the high stability of VD₃ during the storage of the two fortified cheese types (2 weeks, 4 °C). These fortification designs could be implemented at an industrial scale to obtain new cheese types enriched in VD₃ and thus contribute to the reduction in VD deficiency prevalence.

Minority ethnic groups are at increased risk of COVID-19 related mortality or morbidity yet continue to have a disproportionally lower uptake of the vaccine. The importance of adherence to prevention and control measures to keep vulnerable populations and their families safe therefore remains crucial. This research sought to examine the knowledge, perceived risk, and attitudes toward COVID-19 among an ethnically diverse community.

A cross-sectional self-administered questionnaire was implemented to survey ethnic minority participants purposefully recruited from Luton, an ethnically diverse town in the southeast of England. The questionnaire was structured to assess participants knowledge, perceived risk, attitudes toward protective measures as well as the sources of information about COVID-19. The questionnaire was administered online via Qualtrics with the link shared through social media platforms such as Facebook, Twitter, and WhatsApp. Questionnaires were also printed into brochures and disseminated via community researchers and community links to individuals alongside religious, community and outreach organisations. Data were analysed using appropriate statistical techniques, with the significance threshold for all analyses assumed at p = 0.05.

1,058 participants (634; 60% females) with a median age of 38 (IQR, 22) completed the survey. National TV and social networks were the most frequently accessed sources of COVID-19 related information; however, healthcare professionals, whilst not widely accessed, were viewed as the most trusted. Knowledge of transmission routes and perceived susceptibility were significant predictors of attitudes toward health-protective practises.

Improving the local information provision, including using tailored communication strategies that draw on trusted sources, including healthcare professionals, could facilitate understanding of risk and promote adherence to health-protective actions.

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin-angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil-lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.

The coronavirus disease 2019 (COVID19) pandemic continues to represent a substantial public health concern. It can rapidly progress to severe disease, with poor prognosis and a high mortality risk. An early diagnosis and specific prognostic tools can help healthcare providers to start interventions promptly, understand the likely prognosis and to identify and treat timely individuals likely to develop severe disease with enhanced mortality risk. Here we focused on an impressive set of systematic reviews and meta-analyses that were performed since the start of the COVID19 pandemic and summarized their results related to the levels of hematologic, inflammatory, immunologic biomarkers as well as markers of cardiac, respiratory, hepatic, gastrointestinal and renal systems and their association with the disease progression, severity and mortality. The evidence outlines the significance of specific biomarkers, including inflammatory and immunological parameters (C-reactive protein, procalcitonin, interleukin-6), hematological (lymphocytes count, neutrophil-to-lymphocyte ratio, D-dimer, ferritin, red blood cell distribution width), cardiac (troponin, CK-MB, myoglobin), liver (AST, ALT, total bilirubin, albumin) and lung injury (Krebs von den Lungen-6) that can be used as prognostic biomarkers to aid the identification of high-risk patients and the prediction of serious outcomes, including mortality, in COVID19. Thus, these parameters should be used as essential tools for an early risk stratification and adequate intervention in improving disease outcomes in COVID19 patients.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected millions of individuals with various implications. Consistent with the crucial role of the microbiome in determining health and disease in humans, various studies have investigated the gut and respiratory microbiome effect on the COVID-19. Microbiota dysbiosis might support the entry, replication, and establishment of SARS-CoV-2 infection by modulating various mechanisms. One of the main mechanisms that the modulation of respiratory microbiota composition during the COVID-19 infection affects the magnitude of the disease is changes in innate and acquired immune responses, including inflammatory markers and cytokines and B- and T-cells. The diversity of respiratory microbiota in COVID-19 patients is controversial; some studies reported low microbial diversity, while others found high diversity, suggesting the role of respiratory microbiota in this disease. Modulating microbiota diversity and profile by supplementations and nutrients can be applied prophylactic and therapeutic in combating COVID-19. Here, we discussed the lung microbiome dysbiosis during various lung diseases and its interaction with immune cells, focusing on COVID-19.

Introduction: Low serum vitamin D has been shown to be a risk factor for Coronavirus 2019 (COVID-19). The aim of this study was to assess the effects of high dose vitamin D supplementation on hs-CRP, ESR and clinical outcomes, including duration of hospitalization, quality of life and New York Heart Association (NYHA) Functional Classification, in adults with COVID-19. Methods: This double-blind, randomized control trial will be conducted on patients with RT-PCR and/or chest CT scan diagnosis of COVID-19 admitted in Imam Reza Hospital, Mashhad, Iran. Participants will be randomized into control and intervention groups based on randomization sampling. The intervention group will receive soft gel containing 50,000 IU vitamin D on the first day followed by 10,000 IU/day through a supplement drop daily for 29 days. The control group will receive 1000 IU vitamin D daily through supplement drop and a placebo soft gel. All participants will undergo laboratory assessment including inflammatory markers, serum 25)OH)D, complete blood count (CBC), liver and renal profile, lipid profile and erythrocyte sedimentation rate (ESR) at baseline and at day 30. The mortality rate will be recorded in both groups. Results: Data will be presented using descriptive statistics. Comparison of changes in study parameters over the study period will be performed using analysis of covariance adjusting for possible confounders. Conclusions: The findings of this will provide evidence on the effects of high dose vitamin D supplementation on inflammatory markers in hospitalized COVID-19 patients.

(1) Background: The efficacy of tocilizumab in COVID-19 has been doubted. The study aimed to investigate factors affecting disease stability and response to tocilizumab among severe COVID-19 patients. (2) Methods: This was a cohort study of 70 severe COVID-19 patients at NMC Royal Hospital, UAE, from April to June 2020. (3) Results: Elderly patients and those with cardiovascular comorbidities had a higher risk of unstable COVID-19 (p = 0.025). Regarding tocilizumab therapy timing, compared to the critical group receiving tocilizumab, the unstable severe patients receiving tocilizumab had a significantly higher rate of improvement (86%). In contrast, the late critical subgroup showed a significantly increased mortality rate (52.9%). The risk for secondary infection and adverse events following tocilizumab was higher in the late critical group than in the unstable severe and early critical groups (p = 0.024 and p = 0.006, respectively). Therapeutic doses of anticoagulation and high-dose vitamin D were correlated with better outcomes than the prophylactic dose and the treatment dose of vitamin D (p < 0.001 and p = 0.07, respectively). (4) Conclusions: elderly patients and those with cardiovascular disease developed unstable COVID-19. Tocilizumab is a potentially effective choice against severe and critical COVID-19. Early tocilizumab administration combined with therapeutic dose anticoagulation and high vitamin D doses could improve the patients’ outcomes.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Recent research has demonstrated that critically ill patients with coronavirus disease 2019 (COVID-19) show significant immune system dysregulation. Due to that, some nutrients that influence immunomodulation have been suggested as a form of treatment against the infection. This review collected the information on the impact of vitamins on the prognosis of COVID-19, with the intention of facilitating treatment and prevention of the disease risk status in patients. The collected information was obtained using the PubMed electronic database by searching for articles that relate COVID-19 and the mechanisms/effects of the nutrients: Proteins, glucose, lipids, vitamin B12, vitamin D, calcium, iron, copper, zinc, and magnesium, including prospective, retrospective, and support articles. The findings reveal an optimal response related mainly to omega-3, eicosapentaenoic acid, docosahexaenoic acid, calcium, and iron that might represent benefits in the treatment of critically ill patients. However, nutrient supplementation should be done with caution due to the limited availability of randomized controlled studies.

Vitamin D play a substantial role in immune function, but little is known about its prevention in coronavirus disease 2019 (COVID-19). A detail bibliometric analysis of the published scientific literature indexed in Web of Science on vitamin D as a therapeutic option for the COVID-19 patients' treatment is lacking. Thus, the current study was conducted to determine the key bibliometric indices and plot the global research on vitamin D and COVID-19.

The Web of Science Core Collection database was utilized to retrieve publications on vitamin D and COVID-19. A Boolean search strategy was applied and the obtained data were exported to Microsoft Excel to generate relevant graphs. Furthermore, VOSviewer software version 1.6.17 for Windows was used to generate co-authorship countries, bibliographic coupling sources and co-occurrence keyword network visualization mapping. In addition, RStudio and Bibliometric online tool were used to generate WordCloud and thematic map, and intercountries relation map, respectively.

A total of 818 publications on vitamin D and COVID-19 were included in the final analysis. These publications were cited 10,713 times, with an H-index of 50. The number of publications and citations score from 2020 to November 2021 increased from 317 (2423 citations) to 501 (8290 citations). Delanghe JR and Speeckaert MM were the most prolific authors with 13 publications each. The most productive journal was Nutrients (n = 63). The most studied research area is nutrition dietetics. The most widely used author keywords were COVID-19 (n = 444), Vitamin D (n = 312), and SARS-CoV-2 (n = 190). The National Institute of Health and US Department of Health and Human Services were the leading funding agencies. Harvard University was the most active institution with 25 publications. The United States of America was the highly contributing and influential country in terms of publications (n = 203) and total link strength (n = 185).

It was concluded that an increasing trend in the number of publications on vitamin D and COVID-19 has been observed. Significantly, the majority of the research has been conducted in developed countries. Most importantly, over the time, the direction of research has been changed and the recent trend topics are vitamin D deficiency, risk and infection, and vitamin D supplementation based on KeyWords Plus. The use of vitamin D supplement is one of the promising therapeutic options for COVID-19 treatment. Therefore, the current study not only highlight the global research trends but also provide standard bibliographic information for future studies.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

Extensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection.

We searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated.

Significantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; p=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; p<0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; p=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally non-significant, associations with COVID-19 infection.

Low serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.

Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency.

Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined.

Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype.

25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

The immune system protects human health from the effects of pathogenic organisms; however, its activity is affected when individuals become infected. These activities require a series of molecules, substrates, and energy sources that are derived from diets. The consumed nutrients from diets help to enhance the immunity of infected individuals as it relates to COVID-19 patients. This study aims to review and highlight requirement and role of macro- and micronutrients of COVID-19 patients in enhancing their immune systems. Series of studies were found to have demonstrated the enhancing potentials of macronutrients (carbohydrates, proteins, and fats) and micronutrients (vitamins, copper, zinc, iron, calcium, magnesium, and selenium) in supporting the immune system's fight against respiratory infections. Each of these nutrients performs a vital role as an antiviral defense in COVID-19 patients. Appropriate consumption or intake of dietary sources that yield these nutrients will help provide the daily requirement to support the immune system in its fight against pathogenic viruses such as COVID-19.