Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19

Karonova, Tatiana; Kuznetsova, R. N.; Golovatyuk, Ksenia A.; Aquino, Arthur D.; Kalinina, Olga; Andreeva, Alena; Zaikova, Ekaterina; Lebedev, Denis L; Головкин, А. С.; Shlyakhto, Е. V.

doi:10.3390/ph15030305

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…A study conducted in the United States showed that patients with a positive SARS-CoV-2 test and a 25(OH)D concentration of 15 ng/mL compared to 40 ng/mL had a 20% greater risk of hospitalization (p = 0.009) and an increased risk of mortality by 53% (p = 0.001) [19]. The same results were obtained in a study of 311 hospitalized COVID-19 patients: low serum 25(OH)D concentrations were found in patients with poorer clinical outcomes compared to those with a moderate and mild clinical course (p = 0.001) [10].…”

Section: Discussionsupporting

confidence: 67%

“…Recently published systematic reviews and meta-analyses have demonstrated that vitamin D insufficiency and deficiency are highly prevalent in patients with moderate and severe COVID-19 [1,17]. At present, there are sufficient data to demonstrate that a low serum 25(OH)D concentration increases the disease severity and risk of death in patients with COVID-19 [10,18]. A study conducted in the United States showed that patients with a positive SARS-CoV-2 test and a 25(OH)D concentration of 15 ng/mL compared to 40 ng/mL had a 20% greater risk of hospitalization (p = 0.009) and an increased risk of mortality by 53% (p = 0.001) [19].…”

Section: Discussionmentioning

confidence: 99%

“…The severity of COVID-19 is determined by the hyperactive immune response and cytokine storm, accompanied by dysregulated innate and adaptive immune responses [15,32]. Previous studies showed that COVID-19 patients deficient in vitamin D demonstrated higher levels of acute phase reactants compared to those with a normal serum 25(OH)D concentration [10,21]. Rastogi et al showed a significant decrease in fibrinogen levels after cholecalciferol supplementation at a dose of 60,000 IU daily, with a therapeutic target of 25(OH)D > 50 ng/mL [22].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that most hospitalized patients with COVID-19 had vitamin D deficiency, which was associated with a 3.79-fold increase in the risk of a severe course of COVID-19 and a 4.07-fold increase in the risk of a fatal outcome. The threshold of a serum 25(OH)D level of 11.4 ng/mL was associated with mortality, as well as with stimulation of type 2 T-helper cells and downregulation of T-helper 17 cell polarization [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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“…Other studies have also found that a decreased CD4/CD8 ratio is associated with low 25(OH)D levels [ 81 ] and that the administration of 5000–10,000 IU of vitamin D3 is attributable to an increase in the CD4/CD8 ratio, reflecting immune regulation [ 76 , 82 ]. Serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of adaptive immunity in patients with COVID-19 [ 83 ]. In this sense, the trial conducted by Torres and colleagues showed that the administration of a high dose of vitamin D equal to 10,000 IU/day leads to an increase in anti-inflammatory cytokines, such as IL10, and higher levels of CD4+ T cells, which may contribute to decreasing the inflammatory state in severe forms of COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis

et al. 2023

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Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. Methods: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. Results: We identified 78 bibliographic citations. After the reviewers’ screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34–0.72) and 0.28 (0.20–0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.

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High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials

Zhong,

Zhao,

Zhao

et al. 2023

Food Science & Nutrition

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The efficacy of administering high doses of vitamin D to patients diagnosed with COVID‐19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high‐dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID‐19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta‐analysis included 5 RCTs with a total of 834 patients. High‐dose vitamin D supplementation did not show any significant benefits for mortality (I2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685–1.742, p = .711) or intensive care unit (ICU) admission (I2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454–1.102, p = .126) in COVID‐19 patients compared to the control group. However, it was found to be safe and well‐tolerated (I2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930–1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448–13.312, p = .303) or compared to the placebo (I2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711–3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high‐dose vitamin D supplementation in improving clinical outcomes among individuals with COVID‐19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.

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Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19

Cited by 15 publications

References 47 publications

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis

High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials

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