维生素 D、维生素 D 结合蛋白、游离维生素 D 与住院患者 COVID-19 死亡率的关系。
Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients.
机构信息
Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
出版信息
Am J Clin Nutr. 2022 May 1;115(5):1367-1377. doi: 10.1093/ajcn/nqac027.
BACKGROUND
Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed.
OBJECTIVES
We aimed to examine the relationship between vitamin D status and mortality from COVID-19.
METHODS
In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression.
RESULTS
There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality.
CONCLUSIONS
Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).
背景
维生素 D 缺乏与更严重的 2019 年冠状病毒病（COVID-19）结局有关，但循环 25-羟维生素 D [25(OH)D] 主要与维生素 D 结合蛋白（DBP）或白蛋白结合，两者在疾病发生时往往都会下降，使得 25(OH)D 状态难以解释。因此，已经提出了测量非结合（“游离”）和白蛋白结合（“生物可用”）25(OH)D 的方法。
目的
我们旨在研究维生素 D 状态与 COVID-19 死亡率之间的关系。
方法
本观察性研究在英国利物浦进行，对有多余血清可用于 25(OH)D 分析的住院 COVID-19 患者进行了研究。从病历中提取了临床数据，包括年龄、种族和合并症。测量了血清 25(OH)D、DBP 和白蛋白浓度。计算了游离和生物可用的 25(OH)D。通过 logistic 回归分析总、游离和生物可用的 25(OH)D 与 28 天死亡率之间的关系。
结果
共纳入 472 例 COVID-19 患者，其中 112 例（23.7%）在 28 天内死亡。非幸存者的年龄（平均年龄，73 岁；范围，34-98 岁）大于幸存者（平均年龄，65 岁；范围，19-95 岁；P=0.003），且更可能为男性（67%；P=0.02）。非幸存者（71/112；63.4%）和幸存者（204/360；56.7%；P=0.15）之间严重缺乏症[25(OH)D <25 nmol/L]的频率相似，但经过年龄、性别和合并症的调整后，死亡率的比值比在严重缺乏症[25(OH)D <25 nmol/L：OR，2.37；95%CI，1.17-4.78]或高 25(OH)D（≥100 nmol/L；OR，4.65；95%CI，1.51-14.34）中升高与 25(OH)D 值为 50-74 nmol/L（参考）相比。调整 25(OH)D、年龄、性别和合并症后，血清 DBP 水平与死亡率无关。游离和生物可用的 25(OH)D 值均与死亡率无关。
结论
血清 25(OH)D 水平（<50 nmol/L）定义的维生素 D 缺乏症与 COVID-19 死亡率的增加无关，但极低（<25 nmol/L）和极高（>100 nmol/L）水平可能与死亡率相关。游离和生物可用的 25(OH)D 值均与死亡率无关。研究方案已获得伦敦-萨里研究伦理委员会的批准（20/HRA/2282）。
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