Nutrimuscle Forum : Mobile & Tablette

Vitamine D et virus?

Actualités sport, fitness & musculation, vidéos des pros, études scientifiques. Discutez avec la communauté Nutrimuscle et partagez votre expérience...

Modérateurs: Nutrimuscle-Conseils, Nutrimuscle-Diététique

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 4 Jan 2022 14:38

Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial
Karin Ried Cureus. 2021 Nov 25;13(11):e19902.

Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide.

In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death.

Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA).

Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels.

Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed.

Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient).

Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study's patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 4 Jan 2022 15:11

The effect of vitamin D supplementation on mortality and Intensive Care Unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression
Nikolaos Tentolouris Diabetes Metab Res Rev. 2021 Dec 29;e3517.

Aims: The aim of this systematic review and meta-analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID-19 patients.

Methods: A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID-19 was conducted on March, 26th , 2021. Comprehensive Meta-Analysis software was used for the quantitative assessment of data and random-effects model was applied. To investigate the association between the dose of vitamin D and the outcomes of interest, meta-regression analysis was performed.

Results: 2,078 patients from 9 studies with data on mortality were included (583 received vitamin D supplementation, while 1,495 did not). 61 (10.46%) individuals in the treated group died, compared to 386 (25.81%) in the non-treated group [odds ratio (OR): 0.597; 95% CI: 0.318-1.121; p=0.109]. 860 patients from 6 studies with data on ICU admission were included (369 received vitamin D supplementation, while 491 did not). 45 (12.19%) individuals in the treated group were admitted to ICU, compared to 129 (26.27%) in the non-treated group (OR: 0.326; 95%CI: 0.149-0.712; p=0.005). No significant linear relationship between vitamin D dose and log OR of mortality or log OR of ICU admission was observed.

Conclusion: This meta-analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID-19 patients. Further research is urgently needed to understand the benefit of vitamin D in Covid-19.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Diététique » 4 Jan 2022 16:53

Traduction de l'étude :wink:

L'effet de la supplémentation en vitamine D sur la mortalité et l'admission en unité de soins intensifs des patients COVID-19. Une revue systématique, une méta-analyse et une méta-régression
Nikolaos Tentolouris Diabetes Metab Res Rev. 2021 29 décembre;e3517.

Objectifs : L'objectif de cette revue systématique et méta-analyse était d'étudier l'effet de la supplémentation en vitamine D sur la mortalité et l'admission en unité de soins intensifs (USI) des patients COVID-19.

Méthodes : Une recherche systématique de PubMed, Google Scholar, Embase, Web of Science et medRxiv avec des termes relatifs à la supplémentation en vitamine D et COVID-19 a été menée le 26 mars 2021. Un logiciel complet de méta-analyse a été utilisé pour l'évaluation quantitative de un modèle de données et d'effets aléatoires a été appliqué. Pour étudier l'association entre la dose de vitamine D et les résultats d'intérêt, une analyse de méta-régression a été réalisée.

Résultats : 2 078 patients issus de 9 études avec des données sur la mortalité ont été inclus (583 ont reçu une supplémentation en vitamine D, tandis que 1 495 n'en ont pas reçu). 61 (10,46 %) individus du groupe traité sont décédés, contre 386 (25,81 %) dans le groupe non traité [rapport de cotes (OR) : 0,597 ; IC à 95 % : 0,318-1,121 ; p=0,109]. 860 patients de 6 études avec des données sur l'admission en soins intensifs ont été inclus (369 ont reçu une supplémentation en vitamine D, tandis que 491 n'en ont pas). 45 (12,19 %) personnes du groupe traité ont été admises en soins intensifs, contre 129 (26,27 %) dans le groupe non traité (OR : 0,326 ; IC 95 % : 0,149-0,712 ; p = 0,005). Aucune relation linéaire significative entre la dose de vitamine D et le log OR de mortalité ou le log OR d'admission en USI n'a été observée.

Conclusion : Cette méta-analyse indique un rôle bénéfique de la supplémentation en vitamine D sur l'admission en soins intensifs, mais pas sur la mortalité, des patients COVID-19. Des recherches supplémentaires sont nécessaires de toute urgence pour comprendre les bienfaits de la vitamine D dans le Covid-19.
Avatar de l’utilisateur
Nutrimuscle-Diététique
 
Messages: 12380
Inscription: 4 Mar 2013 09:39
Localisation: Athus

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 5 Jan 2022 14:58

Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all?
John P. Bilezikian Reviews in Endocrine and Metabolic Disorders volume 22, pages1201–1218 (2021)

The 4th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended.

Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes.

Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.

Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 5 Jan 2022 15:02

Infections

Immune cells have all the machinery for the production and action of active vitamin D. They synthesize the VDR and also have the ability to produce the enzyme 1-alpha hydroxylase (CYP27B1), responsible for converting 25(OH)D to the active metabolite. Thus, for this autocrine action on the immune system, appropriate serum levels of 25(OH)D are important [3]. Active vitamin D regulates the innate immune system, improving the ability of cells to kill pathogenic microorganisms [3]. Serum levels of 25(OH)D are inversely associated with infection risk. In children, pneumonia is more frequent among those with vitamin D deficiency (25-OH D <20 ng/mL) [129]. In adults, when 25(OH)D ranged between 30 and 50 ng/mL, the risk of hospital-acquired infections was reduced [130]. A protective effect of vitamin D supplementation on acute respiratory infections (ARI) was demonstrated in a double-blind RCT in children from Mongolia with very low 25(OH)D baseline levels (RR: 0.41 [95% CI: 0.20– 0.82] [131]. On the other hand, no benefits of vitamin D supplementation were observed in children with mean baseline levels <35 ng/mL [132].

A metanalysis of RTCs concluded that daily or weekly vitamin D supplementation significantly reduces the risk of acute respiratory infections by 19%. Among those with baseline levels <10 ng/mL, daily or weekly doses of vitamin D were associated with a 70% reduction in risk. Even among those with baseline concentrations >10 ng/mL, a significant 25% reduction was observed [133]. A recent update of this metanalysis included 73,398 participants in RTCs (aged 0 to 95 years) and confirmed the protective effect of vitamin D supplementation with 400 to 1,000 IU daily on acute respiratory infection, independent of baseline levels [134]. Bolus doses, however, were not protective [133, 134].

COVID-19

A link between the COVID-19 and Vitamin D was hypothesized early in the pandemic [135] due to the aforementioned immunomodulatory actions of vitamin D [4]. Since those early days, several studies, mostly observational, cross-sectional, or retrospective, have attempted to elucidate this potentially very relevant relationship. Vitamin D deficiency or even insufficiency, defined as 25(OH) D below 20 ng/mL and 30 ng/mL respectively were associated with an increased risk of SARS-CoV-2 infection with mean vitamin D values lower in subjects who tested positive [136]. Not all published studies are in agreement with these data because others did not find any significant relationship between vitamin D status and predisposition to SARS-CoV-2 infection risk [137].

Vitamin D deficiency was also reported to correlate with the severity of COVID-19, particularly in the elderly. Besides the frequent finding of hypovitaminosis D in patients with comorbidities such as diabetes mellitus and obesity [105], which are known to increase the severity of COVID-19 [138, 139], it was found that subjects with severe disease were more likely to have vitamin D deficiency and obesity or hyperglycemia [41] as compared to patients with less severe forms of the disease. Nevertheless, even mild vitamin D insufficiency consistently predicts hospitalization and mortality [140]. Moreover, very low vitamin D levels appear to be associated with greater risk for admission to an intensive care unit (ICU) [141] and consequent mortality (50%) [142, 143].

Only few interventional placebo-controlled prospective randomized studies have been published so far, with contrasting results [143, 144]. Hospitalized COVID-19 patients treated with calcifediol (532 ug on day one plus 266 ug on days 3, 7, 15, and 30) had lower risk (OR 0.13) of ICU admission and mortality (OR 0.21) [145]. However, in another study, a single dose of 200,000 IU vitamin D3 in COVID-19 hospitalized patients did not reduce mortality or time of hospitalization [146]. Future studies are needed to confirm these observations, taking into account possible confounding factors.

In COVID-19 patients, vitamin D deficiency has been observed also to be associated, with an impaired PTH response, with hypocalcemia [147,148,149,150,151]. COVID-19 related hypocalcemia has been recently identified by several studies, reviews and meta-analyses as a potentially useful biomarker for disease severity and outcome in patients with SARS-CoV-2 infection [152,153,154]. Therefore, vitamin D supplementation might have a therapeutic role in these patients [6]. Another unresolved issue is related to the role of maintaining adequate 25 OH Vitamin D levels [20] in the post-COVID-19 recovery or persistent phase [155, 156].

Although not universally accepted guidelines on vitamin D treatment in the prevention of COVID-19 are available [143], it seems reasonable to recommend a goal of 25-OH Vitamin D levels >30 ng/mL. This would include those who are at particularly high risk such as older men with co-morbidities such as diabetes and obesity [105, 157].
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 6 Jan 2022 13:12

Role of the T cell vitamin D receptor in severe COVID-19
Jay K. Kolls Nature Immunology volume 23, pages5–6 (2022)

New research provides evidence of an impaired vitamin D gene signature in CD4+ T cells in patients with severe COVID-19. Mechanistically, it is shown that vitamin D alters the epigenetic landscape of CD4+ T cells, as well as inducing key transcription factors such as STAT3, BACH2 and JUN that reduce levels of IFN-γ and increase IL-10. These changes generate pro-resolving TH1 cells that may be beneficial in resolving or preventing severe COVID-19.

As of November 2021, SARS-CoV-2, the cause of the COVID-19 pandemic, has infected more than 250 million people worldwide. Infections can be asymptomatic or lead to severe acute respiratory distress syndrome (ARDS), which can be fatal. Host factors that attribute to this spectrum of illness include male sex, obesity, diabetes, hypertension and microbiome status, as well as nutritional status1,2. It is well documented that severe COVID can arise due to an insufficient immune response, such as that which may occur in immunocompromised individuals3. Severe COVID-19 also occurs in non-immunosuppressed individuals and when the immune response is too vigorous, resulting in a cytokine storm4. In this issue of Nature Immunology, Chauss and colleagues5 provide new data showing that severe COVID-19 in some individuals may result from a failure to resolve an exuberant type I immune response, and specifically implicate vitamin D receptor (VDR) signaling in this process.

Dexamethasone—a potent anti-inflammatory steroid—improves outcomes in COVID-19-associated ARDS, but has no effect or can even worsen ARDS caused by other triggers. To approach this conundrum, the authors mined single-cell RNA sequencing (RNA-seq) data from the lungs of patients with COVID-19 for comparison with control samples. They found upregulation of STAT1, TBX21, IL18R1 and IFNG, genes that regulate type 1 T helper (TH1) cells in patients with COVID-19. Further analysis showed upregulation of the complement pathway in TH1 cells, confirming a prior observation in lung CD4+ T cells6. CD46, the receptor for complement 3b, which has been previously show to regulate the production of IFN-γ and interleukin-10 (IL-10) by CD4+ T cells7, was also upregulated in the TH1 cells of patients with COVID-19. However, in individuals with severe COVID-19, IL10 expression was undetectable in TH1 cells, suggesting that IL-10 expression—and possibly CD46 signaling—was perturbed. Co-activation of the T cell receptor and CD46 leads to expression of IL-10 in TH1 cells.

Twenty-four transcription factors were enriched in these cells, including VDR, a member of the nuclear hormone family of transcription factors. Vitamin D has been shown to negatively regulate T cell populations such as TH17 cells8 and TH2 cells9, but the effects on TH1 cells were unexpected. Moreover, the authors5 found that the T cells also expressed CYP27B1, which encodes the 1α-hydroxylase enzyme that converts 25-hydroxy vitamin D (25(OH)D) to its active di-hydroxylated form. The importance of CD46 in regulating both VDR and CYP27B1 was confirmed by studying T cells from CD46-deficient patients.

Next, the authors showed in vitro that active di-hydroxylated vitamin D could repress IFN-γ production and induce IL-10 production in human CD4+ T cells (Fig. 1). As evidence of functional CYP27B1 expression in this ex vivo system, the authors demonstrated that inactive 25(OH)D3 could recapitulate the active vitamin D findings. Vitamin D induced known genes such as those encoding the immunoregulatory molecule CTLA4 and the enzyme CYP24A1—the latter being a biomarker of vitamin D activity10—and repressed both type 1 genes and type 17 genes, consistent with prior work with TH17 cells8. The authors did not observe the emergence of a regulatory T cell population (either type 1 regulatory (Tr1) or T regulatory (Treg) cells) in this system, but observed potent induction of STAT3 by vitamin D as well as the STAT3 activator IL-6. Blockade of the IL-6 receptor (IL-6R) or antagonism of vitamin D induced STAT3 activation and reduced IL-10 production in CD4+ TH1 cells.

Vitamin D treatment also resulted in epigenetic alterations in CD4+ T cells, including increased open chromatin (identified by H3K27ac CUT&RUN assays) in areas that were enriched for superenhancers associated with STAT3, BACH2 and IL10. JUN, VDR, STAT3 and BACH2 binding were increased in vitamin-D-treated cells across many regions of chromatin, as assayed by CUT&RUN or CUT&TAG, demonstrating that there was a profound effect of vitamin D on CD4+ T cells. Using chromatin immunoprecipitation–polymerase chain reaction (ChIP–PCR), the authors demonstrated that VDR itself binds to the STAT3 promotor, as well as the positive control CYP27A1. Using BACH2 haplo-insufficient human cells and cells from Bach2–/– mice showed that BACH2 was critical for IL6R induction by vitamin D, as well as BACH2 binding to the Il10 locus.

Returning to COVID-19, the authors noted that steroids such as dexamethasone can increase VDR expression11 and suggested that some of the effects of dexamethasone may be through this pathway. They found evidence that vitamin-D-repressed genes were enriched in patients wtih COVID-19 compared to healthy controls, with an association to TH1 genes. The authors did not find any differences in vitamin-D-enhanced genes between COVID-19 and healthy controls, suggesting that the data were more specific for the repressed dataset. It is unclear whether or not CYP24A1 was differentially regulated.

Could vitamin D be used to treat severe COVID-19? Except for some support in open-label trials, there is only limited evidence of a therapeutic benefit of vitamin D in COVID-19. One small randomized controlled trial with 25(OH)D in subjects with COVID-19 with serum 25(OH)D levels of <30 ng ml–1, showed that supplementation with oral 25(OH)D3 was associated with preserved lymphocyte counts in blood and an increased neutrophil-to-lymphocyte ratio12. There was a trend to a reduced number of days of intensive care utilization in the vitamin D arm, but this was not statistically significant. On the basis of their current results, Chauss et al.5 advocate for larger trials and perhaps higher doses of the vitamin D for treatment of COVID-19.

Clinical trials of vitamin D are difficult because most interventions use pro-hormones that need to be activated. The studies of Chauss et al.5 identify novel, but extremely complex, pathways regulated by VDR in CD4+ T cells. They also provide important tools that may enable the profound effects of vitamin D to be exploited for clinical benefit in severe COVID-19. Although healthy CD4+ T cells express CYP24B, we do not know how functional this enzyme is in the context of disease. Once active vitamin D is converted to its active form, it can bind cytoplasmic VDR, translocate to the nucleus and regulate gene expression. But this latter effect is likely to be quite different in naive CD4+ T cells versus effector cells or in tissue-resident memory cells. Thus, timing of vitamin D intervention may be critical. We currently do not know whether the exaggerated type 1 response is some individuals is an over-exuberant response or a response that was insufficient early on, leading to a too-little-too-late exuberant response.

Dosing with vitamin D would also be a challenge as the level needed to treat bone disease (>30 ng ml–1) may be insufficient for immune-modulatory effects. An important caveat is that serum levels of 25(OH)D may not reflect tissue levels of active vitamin D10. The dataset in this paper identifies genes and epigenetic markers that may serve as important biological readouts informing T-cell-intrinsic vitamin D status.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 6 Jan 2022 13:15

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial
Endocr. Pract VOLUME 27, ISSUE 12, P1242-1251, DECEMBER 01, 2021 Zhila Maghbooli,

Objective
The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D3 (25(OH)D3) in improving vitamin D status in vitamin D–deficient/vitamin D–insufficient patients infected with the SARS-CoV-2 (COVID-19) virus.
Methods
This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review].
Results
A total 106 hospitalized patients who had a circulating 25(OH)D3 concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D3 had a sufficient circulating 25(OH)D3 concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D3 concentration during the 2-month follow-up.
We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D3 group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D3 was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality.
Conclusion
Our analysis indicated that oral 25(OH)D3 was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D3 may be needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in patients with COVID-19.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 6 Jan 2022 13:48

Image
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 6 Jan 2022 13:50

Vitamin D shuts down T cell-mediated inflammation
Kirsty Minton Nature Reviews Immunology volume 22, page1 (2022)

The importance of maintaining a balance between inflammatory responses necessary for pathogen clearance and their timely resolution to prevent tissue damage is clearly exemplified by patients with severe COVID-19, who develop life-threatening hyper-inflammation characterized by high levels of complement activation. Complement itself has been shown to drive both the differentiation of interferon-γ (IFNγ)-producing T helper 1 (TH1) cells as well as the eventual shutdown of their pro-inflammatory features through IL-10 expression. This study by Chauss et al. links the complement-mediated retraction of TH1 cell responses to vitamin D receptor (VDR) signalling, which provides a possible mechanistic explanation for the epidemiological associations between vitamin D deficiency and adverse outcomes in COVID-19 and potentially other infectious diseases.

Single-cell RNA sequencing of CD4+ T cells from the blood and bronchoalveolar lavage fluid (BALF) of eight patients with COVID-19 showed that they have a prominent pro-inflammatory TH1 cell signature, enriched for IFNγ and complement pathway genes, but with lower levels of expression of IL10 than CD4+ T cells from healthy controls. To better understand the pro-inflammatory nature of these COVID-19-associated TH1 cells, the authors looked in more detail at the previously described effects of complement on contraction of TH1 cell responses. Transcriptomic analysis of CD4+ T cells activated with anti-CD3 and anti-CD46 (the receptor for complement component C3b) showed upregulation of both VDR and CYP27B1, which encodes the enzyme catalysing the final activation step of vitamin D. This suggests that complement stimulates T cells to both activate and respond to vitamin D. T cells from CD46-deficient individuals or T cells treated with an inhibitor that blocks intracellular generation of C3b did not upregulate VDR or CYP27B1. In response to inactive vitamin D, T cells stimulated with anti-CD3 and anti-CD46 repressed IFNγ expression and upregulated IL-10 expression, suggesting that complement-induced VDR signalling promotes shutdown of TH1 cell responses.

Further transcriptomic and proteomic analysis showed that vitamin D promotes the production of IL-10 by inducing expression of IL-6, IL-6 receptor (IL-6R) and the transcription factor STAT3, leading to STAT3 phosphorylation and activation downstream of IL-6R. Vitamin D also induced genome-wide changes in histone acetylation and recruitment of transcription factors, including at STAT3, IL10 and BACH2 loci. A significant proportion of vitamin D-driven transcription was shown to be BACH2 dependent, including IL6R transcription. Indeed, vitamin D-treated CD4+ T cells from a BACH2 haploinsufficient individual did not upregulate the expected vitamin D-dependent gene set, and the IL-6–STAT3–IL-10 signalling axis was disrupted.

Given the observed association of COVID-19 severity with vitamin D deficiency, the authors looked at the expression of vitamin D-regulated genes in the BALF CD4+ T cells of patients with COVID-19. On a per-cell basis, they observed a reciprocal relationship between the expression of TH1 cell-associated genes and vitamin D-modulated genes. The results suggest that in patients with severe COVID-19, who have a strongly pro-inflammatory TH1 cell phenotype, the transcriptional response to vitamin D is impaired, leading to a failure to switch to IL-10 production and inflammatory resolution. This could be a result of vitamin D insufficiency or some other dysregulation of complement-induced autoregulatory VDR signalling; in either case, clinical trials may help shed light on whether there is clinical benefit to using vitamin D as an adjunct therapy for COVID-19. Furthermore, IL-6 is generally thought to be a pro-inflammatory cytokine involved in cytokine storm responses, but the results also suggest that vitamin D as adjunct therapy for COVID-19 might divert IL-6 to pro-resolution functions and thus provide an alternative to blocking IL-6R signalling. The researchers did not test vitamin D as an adjunct treatment for COVID-19 and caution the results should not be taken as a clinical recommendation.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 6 Jan 2022 13:59

25-Hydroxyvitamin D level is associated with mortality in patients with critical COVID-19: a prospective observational study in Mexico City
Israel Parra-Ortega Nutr Res Pract. 2021 Dec;15(Suppl 1):S32-S40.

Background/objectives: Considering the high number of deaths from coronavirus disease 2019 (COVID-19) in Latin American countries, together with multiple factors that increase the prevalence of vitamin D deficiency, we aimed to determine 25-hydroxyvitamin D (25[OH]D) levels and its association with mortality in patients with critical COVID-19.

Subjects/methods: This was a prospective observational study including adult patients with critical COVID-19. Data, including clinical characteristics and 25(OH)D levels measured at the time of intensive care unit admission, were collected. All patients were followed until hospital discharge or in-hospital death. The patients were divided into those surviving and deceased patient groups, and univariate and multivariate logistic regression analyses were performed to determine independent predictors of in hospital mortality.

Results: The entire cohort comprised 94 patients with critical COVID-19 (males, 59.6%; median age, 61.5 years). The median 25(OH)D level was 12.7 ng/mL, and 15 (16%) and 79 (84%) patients had vitamin D insufficiency and vitamin D deficiency, respectively. The median serum 25(OH)D level was significantly lower in deceased patients compared with surviving (12.1 vs. 18.7 ng/mL, P < 0.001). Vitamin D deficiency was present in 100% of the deceased patients. Multivariate logistic regression analysis revealed that age, body mass index, other risk factors, and 25(OH)D level were independent predictors of mortality.

Conclusions: Vitamin D deficiency was present in 84% of critical COVID-19 patients. Serum 25(OH)D was independently associated with mortality in critical patients with COVID-19.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Diététique » 6 Jan 2022 14:30

Traduction de l'étude :wink:

Le niveau de 25-hydroxyvitamine D est associé à la mortalité chez les patients atteints de COVID-19 critique : une étude observationnelle prospective à Mexico
Israël Parra-Ortega Nutr Res Pract. 2021 ; 15 (Suppl 1) : S32-S40.

Contexte/objectifs : Compte tenu du nombre élevé de décès dus à la maladie à coronavirus 2019 (COVID-19) dans les pays d'Amérique latine, ainsi que de multiples facteurs qui augmentent la prévalence de la carence en vitamine D, nous avons cherché à déterminer la 25-hydroxyvitamine D (25[OH] D) les niveaux et son association avec la mortalité chez les patients atteints de COVID-19 critique.

Sujets/méthodes : Il s'agissait d'une étude observationnelle prospective incluant des patients adultes atteints de COVID-19 critique. Les données, y compris les caractéristiques cliniques et les niveaux de 25(OH)D mesurés au moment de l'admission en unité de soins intensifs, ont été recueillies. Tous les patients ont été suivis jusqu'à leur sortie de l'hôpital ou leur décès à l'hôpital. Les patients ont été divisés en groupes de patients survivants et décédés, et des analyses de régression logistique univariées et multivariées ont été effectuées pour déterminer des prédicteurs indépendants de la mortalité hospitalière.

Résultats : L'ensemble de la cohorte comprenait 94 patients atteints de COVID-19 critique (hommes, 59,6 % ; âge médian, 61,5 ans). Le niveau médian de 25(OH)D était de 12,7 ng/mL, et 15 (16 %) et 79 (84 %) patients avaient respectivement une insuffisance et une carence en vitamine D. Le taux sérique médian de 25(OH)D était significativement plus faible chez les patients décédés par rapport aux survivants (12,1 vs 18,7 ng/mL, P < 0,001). Une carence en vitamine D était présente chez 100% des patients décédés. Une analyse de régression logistique multivariée a révélé que l'âge, l'indice de masse corporelle, d'autres facteurs de risque et le niveau de 25(OH)D étaient des prédicteurs indépendants de la mortalité.

Conclusions : Une carence en vitamine D était présente chez 84 % des patients critiques atteints de COVID-19. Le sérum 25(OH)D était indépendamment associé à la mortalité chez les patients critiques atteints de COVID-19.
Avatar de l’utilisateur
Nutrimuscle-Diététique
 
Messages: 12380
Inscription: 4 Mar 2013 09:39
Localisation: Athus

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 12 Jan 2022 14:41

Single Treatment of Vitamin D3 Ameliorates LPS-Induced Acute Lung Injury through Changing Lung Rodentibacter abundance
Ai Jin,Yan Zhao Mol Nutr Food Res 11 December 2021

Acute lung injury (ALI) is characterized by severe inflammation. Vitamin D3 is discussed to reduce inflammation in ALI, but the mechanism is not well understood. This study assesses the effect of different calcitriol administration strategies on inflammation and the lung microbiota composition in ALI. In a mouse model, the alveolus and airway pathology are assessed by immunohistology. mRNA expression is determined by Real-Time Quantitative PCR and protein expressions is detected by Western-blotting. The composition of microbiota is performed by 16s DNA high-throughput sequencing.

Short-term vitamin D3 supplementation prevents lipopolysaccharide-induced ALI by preventing pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). In contrast, long-term treatment over 3 days, 6 days, or 10 days had no such effect. Short-term vitamin D3, but not long-term pretreatment significantly reduces the phosphorylation of signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3, but upregulates the phosphorylation of inhibitor of nuclear factor-κ-gene binding. Furthermore, an increased relative abundance of Rodentibacter genus in LPS-challenged mice bronchoalveolar lavage fluid is observed, which is sensitive to short-term vitamin D3 treatment, effectively alleviating the Rodentibacter abundance. Correlation analysis shows that the load of Rodentibacter positively correlated with the IL-1β, IL-6, and TNF-α gene expression.

The data support that a single administration of vitamin D3 may work as an adjuvant therapy for acute lung inflammation.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Diététique » 12 Jan 2022 17:19

Traduction de l'étude :wink:

Le traitement unique de la vitamine D3 améliore les lésions pulmonaires aiguës induites par le LPS en modifiant l'abondance pulmonaire de Rodentibacter
Ai Jin, Yan Zhao Mol Nutr Food Res 11 décembre 2021

Les lésions pulmonaires aiguës (ALI) se caractérisent par une inflammation sévère. La vitamine D3 est discutée pour réduire l'inflammation dans l'ALI
, mais le mécanisme n'est pas bien compris. Cette étude évalue l'effet de différentes stratégies d'administration de calcitriol sur l'inflammation et la composition du microbiote pulmonaire dans l'ALI. Dans un modèle murin, la pathologie des alvéoles et des voies respiratoires est évaluée par immunohistologie. L'expression de l'ARNm est déterminée par PCR quantitative en temps réel et les expressions protéiques sont détectées par Western-blot. La composition du microbiote est réalisée par séquençage d'ADN à haut débit 16s.

La supplémentation à court terme en vitamine D3 prévient l'ALI induite par les lipopolysaccharides en empêchant les cytokines pro-inflammatoires
, notamment l'interleukine-1β (IL-1β), l'interleukine-6 ​​(IL-6) et le facteur de nécrose tumorale α (TNF-α). En revanche, un traitement à long terme sur 3 jours, 6 jours ou 10 jours n'a pas eu un tel effet. La vitamine D3 à court terme, mais pas le prétraitement à long terme, réduit de manière significative la phosphorylation du transducteur de signal et de l'activateur de la transcription 3 et du suppresseur de la signalisation des cytokines 3, mais régule positivement la phosphorylation de l'inhibiteur de la liaison du facteur nucléaire au gène κ. En outre, une augmentation de l'abondance relative du genre Rodentibacter dans le liquide de lavage bronchoalvéolaire des souris atteintes de LPS est observée, qui est sensible au traitement à court terme à la vitamine D3, réduisant efficacement l'abondance de Rodentibacter. L'analyse de corrélation montre que la charge de Rodentibacter est positivement corrélée avec l'expression des gènes IL-1β, IL-6 et TNF-α.

Les données soutiennent qu'une seule administration de vitamine D3 peut fonctionner comme traitement adjuvant de l'inflammation pulmonaire aiguë.
Avatar de l’utilisateur
Nutrimuscle-Diététique
 
Messages: 12380
Inscription: 4 Mar 2013 09:39
Localisation: Athus

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Conseils » 15 Jan 2022 16:04

Clinical Significance of Micronutrient Supplements in Patients with Coronavirus Disease 2019: A Comprehensive Systematic Review and Meta-Analysis
Azizullah Beran, Clin Nutr January 12, 2022DOI:https://doi.org/10.1016/j.clnesp.2021.12.033


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.
Avatar de l’utilisateur
Nutrimuscle-Conseils
Forum Admin
 
Messages: 54010
Inscription: 11 Sep 2008 19:11

Re: Vitamine D et virus?

Messagepar Nutrimuscle-Diététique » 16 Jan 2022 15:53

Traduction de l'étude :wink:

Importance clinique des suppléments de micronutriments chez les patients atteints de la maladie à coronavirus 2019 : une revue systématique complète et une méta-analyse
Azizullah Beran, Clin Nutr 12 janvier 2022DOI : https://doi.org/10.1016/j.clnesp.2021.12.033


Contexte et objectifs
Des suppléments de micronutriments tels que la vitamine D, la vitamine C et le zinc ont été utilisés dans la gestion des maladies virales. Cependant, la signification clinique de ces micronutriments individuels chez les patients atteints de la maladie à coronavirus 2019 (COVID-19) reste incertaine. Nous avons effectué cette méta-analyse pour fournir une évaluation quantitative de l'importance clinique de ces micronutriments individuels dans le COVID-19.
Méthodes
Nous avons effectué une recherche documentaire complète à l'aide des bases de données MEDLINE, Embase et Cochrane jusqu'au 5 décembre 2021. Tous les micronutriments individuels rapportés par ≥ 3 études et comparés à la norme de soins (SOC) ont été inclus. Le critère de jugement principal était la mortalité. Les critères de jugement secondaires étaient le taux d'intubation et la durée d'hospitalisation (LOS). Les risques relatifs (RR) et la différence moyenne (DM) regroupés avec les intervalles de confiance (IC) à 95 % correspondants ont été calculés à l'aide du modèle à effets aléatoires.
Résultats
Nous avons identifié 26 études (10 essais contrôlés randomisés et 16 études observationnelles) impliquant 5633 patients COVID-19 qui ont comparé trois suppléments individuels de micronutriments (vitamine C, vitamine D et zinc) avec le SOC. Neuf études ont évalué la vitamine C chez 1488 patients (605 en vitamine C et 883 en SOC). La supplémentation en vitamine C n'a eu aucun effet significatif sur la mortalité (RR 1,00, IC à 95 % 0,62-1,62, P = 1,00), le taux d'intubation (RR 1,77, IC à 95 % 0,56-5,56, P = 0,33) ou la DS (DM 0,64 ; 95 % IC -1,70, 2,99 ; P = 0,59). Quatorze études ont évalué l'impact de la vitamine D sur la mortalité chez 3497 patients (927 en vitamine D et 2570 en SOC). La vitamine D n'a pas réduit la mortalité (RR 0,75, IC à 95 % 0,49-1,17, P = 0,21) mais a réduit le taux d'intubation (RR 0,55, IC à 95 % 0,32-0,97, P = 0,04) et la DS (DM -1,26 ; IC à 95 % -2,27, -0,25 ; P = 0,01). L'analyse des sous-groupes a montré que la supplémentation en vitamine D n'était pas associée à un bénéfice de mortalité chez les patients recevant de la vitamine D avant ou après le diagnostic de COVID-19. Cinq études, incluant 738 patients, ont comparé l'apport en zinc au SOC (447 en zinc et 291 en SOC). La supplémentation en zinc n'était pas associée à une réduction significative de la mortalité (RR 0,79, IC à 95 % 0,60-1,03, P = 0,08).
conclusion
Les suppléments individuels en micronutriments, y compris la vitamine C, la vitamine D et le zinc, n'étaient pas associés à un avantage en termes de mortalité dans le COVID-19. La vitamine D peut être associée à un taux d'intubation plus faible et à une durée de séjour plus courte, mais la vitamine C n'a pas réduit le taux d'intubation ou la durée de séjour. Des recherches supplémentaires sont nécessaires pour valider nos conclusions.
Avatar de l’utilisateur
Nutrimuscle-Diététique
 
Messages: 12380
Inscription: 4 Mar 2013 09:39
Localisation: Athus

PrécédenteSuivante

Retourner vers Actualités, vidéos, études scientifiques

Qui est en ligne

Utilisateurs parcourant ce forum: Aucun utilisateur enregistré et 29 invités