Protocol for a living systematic review of the Effectiveness and Safety of Vitamin D for COVID-19
Creators: name: Reyes, María Ximena Rojas
name: De Val, María Soledad Isern
name: Blasco, Juan Antonio
name: Rosario, María Piedad
name: Sabalete, Trinidad
name: López, Luz Angela Torres
name: Rispau, Ariadna Auladell
Publisher: name: OSF Registries
Year: 2024
Subjects: subject: Public Health
subject: Medicine and Health Sciences
subject: health decision-making
subject: healthtechnology
subject: living evidence

description: ABSTRACT 

Objective 
To gather all available evidence on the benefits and harms of the use of vitamin D for the prevention of severe COVID-19 and/or treatment in patients with mild, moderate, or severe illness for COVID-19. 

Methods
Design
This is a Living Evidence synthesis, that will start with a baseline synthesis report of the effects of the use of Vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol) and their metabolites on all-cause mortality, COVID-19-related hospitalisation, intensive care unit admission, quality of life, adverse events related to the Vitamin D intake, length of hospital stay, and long COVID 19 rates . Based on its conclusions, we will set up the living evidence approach and the evidence monitoring will begin.

Evidence identification
The Epistemonikos “Living OVerview of Evidence (L.OVE)” platform will be used for evidence identification, screening, and selection. The Epistemonikos team maintaining the L·OVE platform will devise the literature search to identify systematic reviews, randomized control trials, and non-randomized studies. An automated living search will be performed in all data bases following the Epistemonikos procedure. The results of the literature searches will be automatically incorporated into the L·OVE platform where automated classifiers will exclude references with a low probability of being relevant. We will continuously monitor the evidence by performing daily searches and monthly screening of the retrieved references. Additionally, each three months we will manually search for ongoing studies in the International Clinical Trials Registry Platform trial registries.

Study selection and data extraction
For the baseline report, we will include systematic reviews, randomized and non-randomized studies evaluating the effect of Vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), and their metabolites ercalcidiol, calcifediol, calcitriol, and ercalcitriol, in individuals with a risk of SARS-CoV-2 infection or patients with mild, moderate, or severe illness for COVID-19 . Studies comparing high-dose interventions (&gt;4,000 I/day) versus placebo or no intervention will be included. Main outcomes defined as critical or important for decision-making include all-cause mortality, COVID-19 related hospitalisation, intensive care unit (ICU) admission, quality of life and adverse events, and the secondary outcomes, length of hospital stay, long COVID 19 rates. 
Two reviewers will independently screen each study for eligibility, extract data, and assess its methodological quality using appropriate tools. We will perform meta-analyses of the study’s results when pertinent. We will assess the certainty of the evidence for each outcome by applying the GRADE approach. These findings will be used to refine the parameters for setting up the living evidence approach. 

Living evidence approach
We will continuously monitor the evidence until the criteria to suspend monitoring are reached . If a new study is identified as eligible during monitoring, the risk of bias assessment and data extraction will be performed prior to update the evidence synthesis of the outcomes reported by the new included study. The decision to immediately incorporate or postpone the incorporation of new studies will follow a systematic and reproducible process, as well as the process to update of the decisions that this synthesis informs. The question will withdraw from the living mode according to predefined specific criteria.

Results
As part of the baseline synthesis, the estimates for all outcomes evaluated will be presented in GRADE summary of finding tables. Regular updates will be reported and key messages on changes will be added to the evidence synthesis conclusions. We will resubmit new complete updates every time the conclusions change or whenever there are substantial updates for the main outcomes of interest. 

Keywords: “Vitamin D”, “COVID-19”, “Systematic Review”