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高剂量维生素D对重症新型冠状病毒肺炎危重症患者的免疫调节作用——一项随机对照试验

The Immunomodulatory Activity of High Doses of Vitamin D in Critical Care Patients with Severe SARS-CoV-2 Pneumonia-A Randomized Controlled Trial.

作者信息

Gonçalves Ana Moura, Velho Sónia, Rodrigues Bárbara, Antunes Maria Lobo, Cardoso Miguel, Godinho-Santos Ana, Gonçalves João, Marinho António

机构信息

Intensive Care Medicine Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal.

Nutrition Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal.

出版信息

Nutrients. 2025 Jan 31;17(3):540. doi: 10.3390/nu17030540.

DOI:10.3390/nu17030540
PMID:39940396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11820001/
Abstract

Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. : A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes' VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [ = 0.002] and seventh [ < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes' VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. : Supplementation with higher doses of cholecalciferol may contribute to a significant increase in 25vitD levels but not in LL37 levels. Higher LL37 levels on admission may be related to a decrease in ICU, hospital, and 60-day mortality. VDR gene expression in monocytes is much higher in patients supplemented with higher doses of cholecalciferol.

摘要

维生素D受体[VDR]表达促进LL37表达,可能有助于宿主防御。研究假设是,25-羟维生素D[25vitD]水平升高可导致VDR表达增强和LL-37产生增加,从而有助于改善重症患者的预后。:开展了一项非盲随机对照试验。共纳入207例因严重SARS-CoV-2肺炎入住重症监护病房(ICU)的患者,他们在ICU及住院期间接受了不同剂量的胆钙化醇(500 MU、3 MU/天、不使用胆钙化醇)。在入院时及之后评估25vitD水平以及LL37和单核细胞的VDR基因表达。评估临床病情演变、ICU死亡率、医院死亡率和60天死亡率。中位年龄为57.7岁,大多数患者为白种人[87.4%]且为男性[70.5%]。在第3天[=0.002]和第7天[<0.001],各组间25vitD水平存在显著差异。补充500 MU胆钙化醇的患者单核细胞VDR基因表达显著增加,且在ICU中临床病情演变更佳,与病情演变因素显著相关。入院时较高的LL37水平与医院和ICU死亡率显著负相关,在调整合并症后与ICU、医院和60天死亡率的关联几乎显著。:补充较高剂量的胆钙化醇可能有助于显著提高25vitD水平,但对LL37水平无影响。入院时较高的LL37水平可能与ICU、医院和60天死亡率降低有关。补充较高剂量胆钙化醇的患者单核细胞中的VDR基因表达更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cec2/11820001/31e33bb8fb5a/nutrients-17-00540-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cec2/11820001/31e33bb8fb5a/nutrients-17-00540-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cec2/11820001/31e33bb8fb5a/nutrients-17-00540-g001.jpg

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本文引用的文献

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Nutrients. 2023 Oct 10;15(20):4309. doi: 10.3390/nu15204309.
2
Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.一项随机临床试验:单次高剂量维生素 D3 对中重度 COVID-19 患者住院时间的影响。
JAMA. 2021 Mar 16;325(11):1053-1060. doi: 10.1001/jama.2020.26848.
3
The unsettled science of nonrenal calcitriol production and its clinical relevance.非肾源性骨化三醇生成的未决科学及其临床相关性。
J Clin Invest. 2020 Sep 1;130(9):4519-4521. doi: 10.1172/JCI141334.
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Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37.维生素 D 缺乏和空气污染通过抑制抗病毒肽 LL37 加重 COVID-19。
Front Public Health. 2020 May 28;8:232. doi: 10.3389/fpubh.2020.00232. eCollection 2020.
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Vitamin D deficiency and supplementation in critical illness-the known knowns and known unknowns.维生素 D 缺乏与危重症患者的补充——已知的已知和已知的未知。
Crit Care. 2018 Oct 29;22(1):276. doi: 10.1186/s13054-018-2185-8.
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Vitamin D status contributes to the antimicrobial activity of macrophages against Mycobacterium leprae.维生素 D 状态有助于巨噬细胞对抗麻风分枝杆菌的抗菌活性。
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