Evidence mapPaperPMID 39808630Full record

SynthesisPloS one2025

Vitamin D, acute respiratory infections, and Covid-19: The curse of small-size randomised trials. A critical review with meta-analysis of randomised trials.

Philippe Autier, Giulia Doi, Patrick Mullie, Patrick Vankrunkelsven, Oriana D'Ecclesiis, Sara Gandini

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Philippe AutierInternational Prevention Research Institute (iPRI), Bat. L'Américain, Dardilly, France.ORCID https://orcid.org/0000-0003-1538-5321
Giulia DoiDepartment of Experimental Oncology, European Institute of Oncology, IRCCS, Milano, Italy.
Patrick MullieAcademic Centre for General Practice, Department of Public Health and Primary Care, Catholic University Leuven, Leuven, Belgium.
Patrick VankrunkelsvenAcademic Centre for General Practice, Department of Public Health and Primary Care, Catholic University Leuven, Leuven, Belgium.ORCID https://orcid.org/0000-0003-1047-9732
Oriana D'EcclesiisDepartment of Experimental Oncology, European Institute of Oncology, IRCCS, Milano, Italy.
Sara GandiniDepartment of Experimental Oncology, European Institute of Oncology, IRCCS, Milano, Italy.ORCID https://orcid.org/0000-0002-1348-4548

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRandomised 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.

objectiveTo 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.

methodA 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.

resultsNine 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).

conclusionStrong 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.

Indexed as

COVID-19Respiratory Tract InfectionsVitamin DDietary SupplementsHumansIntensive Care UnitsRandomized Controlled Trials as TopicSARS-CoV-2VitaminsVitamin DVitamins

Identifiers

PMID39808630
PMCPMC11731873

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.