Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary referral hospital

Cereda, Emanuele; Bogliolo, Laura; Klersy, Catherine; Lobascio, Federica; Masi, Sara De; Crotti, Silvia; Stefano, Ludovico De; Bruno, Raffaele; Corsico, Angelo Guido; Sabatino, Antonio Di; Perlini, Stefano; Montecucco, Carlomaurizio; Caccialanza, Riccardo; Belliato, Mirko; Ludovisi, Serena; Mariani, Francesca; Ferrari, Alessandra; Musella, Valeria; Muggia, Chiara; Croce, Gabriele; Barteselli, Chiara; Mambella, Jacopo; Terlizzi, Francesco Di

doi:10.1016/j.clnu.2020.10.055

Cited by 80 publications

(97 citation statements)

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“…Among 15 studies that assessed the relation between mortality and VDD, 13 studies were included in the analysis. Pooled analysis of 4 adjusted studies that used the Cox survival method ( 13 , 51 , 56 , 60 ) (HR: 2.35; 95% CI: 1.22, 4.52; I 2 : 84%; Figure 4 A ) and 5 studies ( 44 , 47 , 53 , 55 , 62 ) with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I 2 : 47.8%; Figure 4B ) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression ( 54 , 59 , 65 ), no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I 2 : 76.6%). Two studies were not included in the analysis since 1 study had an RCT design ( 36 ) and another one used different statistical methods ( 64 ).…”

Section: Resultsmentioning

confidence: 97%

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

Kazemi

Mohammadi

Aghababaee

et al. 2021

Advances in Nutrition

107

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This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I2: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I2: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I2 = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I2 = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I2: 47.9%), and adjusted studies that used the Cox survival method (HR: 2.35; 95% CI: 1.22, 4.52; I2: 84%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I2: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.

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Section: Resultsmentioning

confidence: 97%

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

Kazemi

Mohammadi

Aghababaee

et al. 2021

Advances in Nutrition

107

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“…Table A describes the characteristics of the 31 included observational studies ordered by outcome severity [ [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] ]. These studies reported on mortality from COVID-19 ( n = 20), ICU admission ( n = 5), length of ICU stay ( n = 1), invasive ventilation ( n = 7), non-invasive ventilation ( n = 4), hospitalization ( n = 3), length of hospital stay (n = 5), disease severity ( n = 12), pneumonia (n = 1), multi-organ damage (n = 1), acute kidney injury (n = 1), ARDS (n = 5), SARS-CoV-2 positivity (n = 4), and 25(OH)D levels ( n = 7).…”

Section: Resultsmentioning

confidence: 99%

The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis

et al. 2021

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Background Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes. Methods We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses. Results We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level < 20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95%CI [−9.5, −2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/d, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/d, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes. Conclusion While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

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“…A clinically relevant issue is to understand whether hypovitaminosis D may influence the outcome of COVID-19 [12]. Some studies provided evidence that subjects exposed to vitamin D deficiency may develop a more severe COVID-19 [13][14][15][16], whereas other studies failed to find such an association [17][18][19]. Moreover, the effects of vitamin D supplementation on clinical outcome of COVID-19 is still a matter of uncertainty [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Variability in clinical end-points may explain the heterogeneity of results of these studies evaluating the impact of hypovitaminosis D and its treatment on COVID-19 outcome. Moreover, the potential effects of low calcium [23][24][25] and high parathyroid hormone (PTH) [17,25] may influence the impact of hypovitaminosis D on the outcome of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

Mazziotti

Lavezzi

Brunetti

et al. 2021

J Endocrinol Invest

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Purpose Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. Methods Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. Results In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). Conclusion This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

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Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary referral hospital

Cited by 80 publications

References 10 publications

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

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