Autier Philippe, Doi Giulia, Mullie Patrick, Vankrunkelsven Patrick, D'Ecclesiis Oriana, Gandini Sara
International Prevention Research Institute (iPRI), Bat. L'Américain, Dardilly, France.
Department of Experimental Oncology, European Institute of Oncology, IRCCS, Milano, Italy.
PLoS One. 2025 Jan 14;20(1):e0303316. doi: 10.1371/journal.pone.0303316. eCollection 2025.
Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients.
To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI.
A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al. 2021. Groups were formed including trials with total numbers of patients below or above the median size of all trials. The associations between VDS vs no VDS, and admission to ICU were evaluated using random-effects models from which summary odds ratios (SOR) and 95% confidence intervals (CI) were obtained. Meta-analyses were done for all trials and for each group of trials, which allowed testing a possible effect modification of trial size. Publication bias was assessed using the Louis-Furuya-Kanaruori (LFK) index (no bias if index between -1 and +1) and the trim and fill method.
Nine trials on VDS for preventing admission to ICU were identified, including 50 to 548 patients. The summary odds ratio (SOR) was 0.61 (95% CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (interaction p = 0.04). The LFK index was -3.79, and after trim and fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention included 25 to 16,000 patients. The SOR was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (interaction p = 0.0001). The LFK index was -3.11, and after trim and fill, the SOR was 0.96 (0.88-1.05).
Strong publication bias affected small randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.
2006年至2021年进行的随机试验表明，补充维生素D（VDS）能够预防重症新冠病毒病（COVID-19）和急性呼吸道感染（ARI）。然而，2022年发表的规模更大的随机试验并未证实VDS对COVID-19患者的健康益处。
通过系统评价和荟萃分析，研究针对COVID-19患者的VDS随机试验以及入住重症监护病房（ICU）的特征，以及VDS预防ARI的随机试验的特征。
通过系统检索获取针对COVID-19患者的VDS随机试验以及入住ICU的相关试验。关于VDS和ARI的数据来自乔利夫等人2021年的荟萃分析。形成了不同组，包括患者总数低于或高于所有试验中位数规模的试验。使用随机效应模型评估VDS与非VDS以及入住ICU之间的关联，从中获得汇总比值比（SOR）和95%置信区间（CI）。对所有试验以及每组试验进行荟萃分析，这使得能够检验试验规模可能产生的效应修饰。使用路易斯-古谷-金成指数（LFK指数，指数在-1至+1之间则无偏倚）和剪补法评估发表偏倚。
确定了9项关于VDS预防入住ICU的试验，包括50至548例患者。所有试验的汇总比值比（SOR）为0.61（95%CI：0.39 - 0.95），患者数为50至<106例的试验的SOR为0.34（0.13 - 0.93），患者数为106至548例的试验的SOR为0.88（0.62 - 1.24）（交互作用p = 0.04）。LFK指数为-3.79，剪补后SOR为0.80（0.40 - 1.61）。37项关于VDS预防ARI的试验的SOR包括25至1,6000例患者。所有试验的SOR为0.92（0.86 - 0.99），患者数为25至<248例的试验的SOR为0.69（0.57 - 0.83），患者数为248至16,000例的试验的SOR为0.98（0.94 - 1.03）（交互作用p = 0.0001）。LFK指数为-3.11，剪补后SOR为0.96（0.88 - 1.05）。
强烈的发表偏倚影响了关于VDS预防重症COVID-19和ARI的小型随机试验。系统评价应警惕通常会夸大健康益处的小型随机试验。
