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Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 23216

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Prof. Dr. Lucia Malaguarnera

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Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95124 Catania, Italy
Interests: immunology; degenerative diseases; nutrients
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Dr. Cristina Russo

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Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95124 Catania, Italy
Interests: physio-pathology; immunology; micronutrients
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Dr. Maria Stella Valle

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Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95124 Catania, Italy
Interests: physiopathology; respiratory diseases
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Special Issue Information

Dear Colleagues,

Since 2019, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been a global health concern. Several observational studies have suggested that Vitamin D status impacts susceptibility to SARS-CoV-2 infection and mortality. Nevertheless, some randomized controlled trials have reported contrasting results regarding the efficacy of vitamin D supplementation in the treatment of SARS-CoV-2.

The purpose of this Special Issue is to allow interested scientists to participate in a forum to further elucidate the effects of vitamin D in the supportive treatment of COVID-19. Authors are invited to submit original research or review articles describing the mechanisms used by vitamin D for modulating the immune response following a viral invasion, but also new investigations suggesting alternative strategies using vitamin D analogues or synergistic combinations.

Prof. Dr. Lucia Malaguarnera
Dr. Cristina Russo
Dr. Maria Stella Valle
Guest Editors

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Published Papers (7 papers)

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Research

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13 pages, 1422 KiB

Open AccessArticle

The Variability of Vitamin D Concentrations in Short Children with Short Stature from Central Poland—The Effects of Insolation, Supplementation, and COVID-19 Pandemic Isolation

by Joanna Smyczyńska, Natalia Pawelak, Maciej Hilczer, Anna Łupińska, Andrzej Lewiński and Renata Stawerska

Nutrients 2023, 15(16), 3629; https://doi.org/10.3390/nu15163629 - 18 Aug 2023

Viewed by 1247

Abstract

The aim of the study was to investigate the effects of seasonal variability of insolation, the implementation of new recommendations for vitamin D supplementation (2018), and the SARS-CoV-2 pandemic lockdown (2020) on 25(OH)D concentrations in children from central Poland. The retrospective analysis of variability of 25(OH)D concentrations during the last 8 years was performed in a group of 1440 children with short stature, aged 3.0–18.0 years. Significant differences in 25(OH)D concentrations were found between the periods from mid-2014 to mid-2018, from mid-2018 to mid-2020, and from mid-2020 to mid-2022 (medians: 22.9, 26.0, and 29.9 ng/mL, respectively). Time series models created on the grounds of data from 6 years of the pre-pandemic period and used for prediction for the pandemic period explained over 80% of the seasonal variability of 25(OH)D concentrations, with overprediction for the first year of the pandemic and underprediction for the second year. A significant increase in 25(OH)D concentrations was observed both after the introduction of new vitamin D supplementation guidelines and during the SARS-CoV-2 pandemic; however, the scale of vitamin D deficiency and insufficiency was still too high. Time series models are useful in analyzing the impact of health policy interventions and pandemic restrictions on the seasonal variability of vitamin D concentrations. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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11 pages, 485 KiB

Open AccessArticle

Significance of 1,25-Dihydroxyvitamin D₃ on Overall Mortality in Peritoneal Dialysis Patients with COVID-19

by Marko Baralić, Dragana Robajac, Ana Penezić, Voin Brković, Nikola Gligorijević, Ana Bontić, Jelena Pavlović, Jelena Nikolić, Goran Miljuš, Zorana Dobrijević, Miloš Šunderić, Lucia Pažitná, Jaroslav Katrlík, Olgica Nedić and Mirjana Laušević

Nutrients 2023, 15(9), 2050; https://doi.org/10.3390/nu15092050 - 24 Apr 2023

Cited by 1 | Viewed by 2759

Abstract

In previous publications, we pointed out the importance of mannosylation of fibrinogen for the development of cardiovascular complications and fucosylation as a predictor of peritoneal membrane dysfunction in patients on peritoneal dialysis (PD). After a follow-up period of 30 months from the onset of the COVID-19 pandemic, we evaluated the significance of 1,25-dihydroxyvitamin D₃ (calcitriol) therapy, primary disease, biochemical and hematologic analyzes, and previously performed glycan analysis by lectin-based microarray as predictors of mortality in this patient group. After univariate Cox regression analysis, diabetes mellitus (DM) and calcitriol therapy were found to be potential predictors of mortality. Additional multivariate Cox regression analysis confirmed that only DM was a predictor of mortality. Nevertheless, the use of calcitriol in therapy significantly reduced mortality in this patient group, as shown by the Kaplan–Meier survival curve. The presence of DM as a concomitant disease proved to be a strong predictor of fatal outcome in PD patients infected with SARS-CoV-2. This is the first study to indicate the importance and beneficial effect of calcitriol therapy on survival in PD patients with COVID-19 infection. In addition, this study points to the possibility that adverse thrombogenic events observed in PD patients during the pandemic may be caused by aberrant fibrinogen glycosylation. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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13 pages, 647 KiB

Open AccessArticle

The Effect of Weekly 50,000 IU Vitamin D₃ Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency

by Dana A. Bader, Anas Abed, Beisan A. Mohammad, Ahmad Aljaberi, Ahmad Sundookah, Maha Habash, Ahmad R. Alsayed, Mohammad Abusamak, Sami Al-Shakhshir and Mahmoud Abu-Samak

Nutrients 2023, 15(5), 1188; https://doi.org/10.3390/nu15051188 - 27 Feb 2023

Cited by 9 | Viewed by 3695

Abstract

This research aimed to evaluate the effects of high-dose cholecalciferol (VD₃) supplements (50,000 IU/week) on selected circulating cytokines associated with cytokine storms in adults with vitamin D deficiency. This clinical trial, based in Jordan, included 50 participants receiving vitamin D₃ supplements (50,000 IU/week) for 8 weeks; the exact number was assigned to the control group. Interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrotic factor-α (TNF-α), and leptin were measured in serum at baseline and 10 weeks (wash out: 2 weeks). Our results revealed that vitamin D₃ supplementation significantly increased the serum levels of 25OHD, IL-6, IL-10, IL-1β, and leptin compared with baseline. In contrast, the serum level of TNF-α insignificantly increased in the group receiving vitamin D₃ supplementation. Although the observations of this trial may refer to a potential negative effect of VD₃ supplementation during cytokine storms, further trials are required to clarify the potential benefits of VD₃ supplement during cytokine storms. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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19 pages, 3122 KiB

Open AccessArticle

The Efficacious Benefit of 25-Hydroxy Vitamin D to Prevent COVID-19: An In-Silico Study Targeting SARS-CoV-2 Spike Protein

by Tomy Muringayil Joseph, Akshay Maniyeri Suresh, Debarshi Kar Mahapatra, Józef Haponiuk and Sabu Thomas

Nutrients 2022, 14(23), 4964; https://doi.org/10.3390/nu14234964 - 23 Nov 2022

Cited by 1 | Viewed by 4680

Abstract

The environment has rapidly looked at proven specialist task forces in the aftermath of the COVID-19 pandemic to build public health policies and measures to mitigate the effects of emerging coronaviruses. According to the researchers, taking 10 μg of 25-hydroxy vitamin D daily is recommended to keep us safe. There have been several studies recently indicating that there is a reduced risk of contracting Coronavirus by 25-hydroxy vitamin D consumption, even though there is no scientific data to prove that one would not affect the COVID-19 viral infection by 25-hydroxy vitamin D consumption. In this regard, the present study investigates the important literature and the role of 25-hydroxy vitamin D to prevent COVID-19 infection by conducting an in-silico study with SARS-CoV-2 spike protein as a target. Lopinavir, a previously reported drug candidate, served as a reference standard for the study. MD simulations were carried out to improve predictions of receptor-ligand complexes which offer novelty and strength to the current study. MD simulation protocols were explored and subjected to 25-hydroxy vitamin D and a known drug, Lopinavir. Comparison of ligands at refined models to the crystal structure led to promising results. Appropriate timescale simulations have been used to understand the activation mechanism, the role of water networks for receptor function, and the ligand binding process. Furthermore, MD simulations in combination with free energy calculations have also been carried out for lead optimization, evaluation of ligand binding modes, and assessment of ligand selectivity. From the results, 25-hydroxy vitamin D was discovered to have the vital interaction and highest potency in LBE, lower RMSD, and lower inhibition intensity similar to the standard. The findings from the current study suggested that 25-hydroxy vitamin D would be more effective in treating COVID-19. Compared with Lopinavir, 25-hydroxy vitamin D had the most potent interaction with the putative binding sites of the SARS-CoV-2 spike protein of COVID-19. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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Review

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13 pages, 1527 KiB

Open AccessReview

The Effect of Vitamin D Supplementation on the Length of Hospitalisation, Intensive Care Unit Admission, and Mortality in COVID-19—A Systematic Review and Meta-Analysis

by Alexandru Constantin Sîrbu, Octavia Sabin, Ioana Corina Bocșan, Ștefan Cristian Vesa and Anca Dana Buzoianu

Nutrients 2023, 15(15), 3470; https://doi.org/10.3390/nu15153470 - 5 Aug 2023

Cited by 9 | Viewed by 2295

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has become a global health crisis and pushed researchers and physicians to discover possible treatments to improve the outcome of their patients. Vitamin D, known for its role in immune system function, has been hypothesized to play a role in COVID-19 treatment. A systematic review and meta-analysis were conducted to evaluate the efficacy of vitamin D supplementation in COVID-19, focusing on length of hospital stay (LOS), admission to the intensive care unit (ICU), and mortality. Thirteen randomized controlled trials (RCTs) were included, and the meta-analysis revealed that high-dose vitamin D supplementation showed potential benefits in reducing the length of hospital stay and ICU admission rates for patients with COVID-19. However, the overall effect on mortality did not reach statistical significance. While this systematic review suggests the potential benefits of high-dose vitamin D supplementation in reducing hospital stays and ICU admission in COVID-19 patients, caution is warranted due to the high heterogeneity and limitations of the included studies. Further large-scale randomized controlled trials with consistent study characteristics are needed to provide more robust evidence regarding the therapeutic benefits of vitamin D supplementation in COVID-19 outcomes. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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24 pages, 1987 KiB

Open AccessReview

Immunomodulatory Effects of Vitamin D in Respiratory Tract Infections and COVID-19 in Children

by Maria Nicolae, Cristina Maria Mihai, Tatiana Chisnoiu, Adriana Luminita Balasa, Corina Elena Frecus, Larisia Mihai, Vasile Valeriu Lupu, Irina Ion, Alexandru Cosmin Pantazi, Andreea Nelson Twakor, Antonio Andrusca, Claudia Simona Cambrea, Ioan Anton Arghir, Ancuta Lupu and Oana Cristina Arghir

Nutrients 2023, 15(15), 3430; https://doi.org/10.3390/nu15153430 - 2 Aug 2023

Cited by 9 | Viewed by 3251

Abstract

Acute respiratory tract infections (ARTIs) are one of the main reasons that the pediatric population goes to the doctor. The connection between ARTI and vitamin D (VD) is currently debated by the medical community, and so far, there has been little agreement with regard to the ideal level of 25(OH)D concentration that would provide protection for the respiratory tract, or the effectiveness of its administration in the treatment of respiratory infections. The purpose of this literature review was to bring attention to the immunomodulatory and antiviral function of vitamin D and its relation to the respiratory system by examining the main ARTIs, including SARS-CoV-2. The latter has affected the pediatric population in different ways, from asymptomatic patients to severe forms with multisystem inflammatory syndrome in children (MIS-C). Although there are not much clinical data on the SARS-CoV-2 disease in the pediatric population worldwide, we tried to find out whether there is a connection between the severity of this disease, other ARTIs, and vitamin D supplementation. We also aimed to find out if 25OHD deficiency had an adverse effect on the evolution of the disease and the recovery period in the case of younger patients affected by COVID-19. For this literature review, the PICO framework was selected as the methodological approach. Our results demonstrated many methods by which this vitamin may lower the risk of ARTI with regard to the COVID-19 infection. Despite these significant advancements, more research is needed to support the idea that 25(OH)D concentration can influence the evolution of respiratory tract infections in children. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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17 pages, 3653 KiB

Open AccessReview

Comparison of Vitamin D and Resveratrol Performances in COVID-19

by Cristina Russo, Maria Stella Valle, Luisa Malaguarnera, Ivana Roberta Romano and Lucia Malaguarnera

Nutrients 2023, 15(11), 2639; https://doi.org/10.3390/nu15112639 - 5 Jun 2023

Cited by 6 | Viewed by 4303

Abstract

Over the last few years, we have experienced the infection generated by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) often resulting in an exaggerated immune reaction and systemic inflammation. The preferred treatments against SARS-CoV-2 were those that mitigated immunological/inflammatory dysfunction. A variety of observational epidemiological studies have reported that vitamin D deficiency is often a crucial factor in many inflammatory diseases and autoimmune diseases, as well as the susceptibility to contract infectious diseases, including acute respiratory infections. Similarly, resveratrol regulates immunity, modifying the gene expression and the release of proinflammatory cytokines in the immune cells. Therefore, it plays an immunomodulatory role that can be beneficial in the prevention and development of non-communicable diseases associated with inflammation. Since both vitamin D and resveratrol also act as immunomodulators in inflammatory pathologies, many studies have paid particular attention to an integrated treatment of either vitamin D or resveratrol in the immune reaction against SARS-CoV-2 infections. This article offers a critical evaluation of published clinical trials that have examined the use of vitamin D or resveratrol as adjuncts in COVID-19 management. Furthermore, we aimed to compare the anti-inflammatory and antioxidant properties linked to the modulation of the immune system, along with antiviral properties of both vitamin D and resveratrol. Full article

(This article belongs to the Special Issue Vitamin D and COVID-19: New Mechanistic and Therapeutic Insights)

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