JMIR Publications

ABSTRACT

Background:

Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature.

Objective:

To describe a protocol for a living systematic review, evaluating the effectiveness and safety of parenteral vitamin C in adults with severe infections, including in those with COVID-19.

Methods:

We searched Ovid MEDLINE, EMBASE, CINAHL, CDC COVID-19 Database, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to 30 March 2021, for randomized clinical trials (RCTs) evaluating parenteral vitamin C vs. no parenteral vitamin C in adults with hospitalized severe infection. Eligible studies will include at least one arm involving any dose of parenteral vitamin C alone, or in combination with other co-interventions, and at least one arm not involving parenteral vitamin C. Primary outcomes of interest will include in-hospital, 30-day and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation using a modified risk of bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modelling for meta-analyses, with study weights generated using the inverse variance method. We will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Meta-analyses will be updated iteratively as new trial evidence is available.

Results:

Of 1,386 citations identified as of 30 March 2021, 17 eligible RCTs have been identified as of September 2021; we are in the process of updating the search strategy and associated data analyses.

Conclusions:

The results will be of importance to critical care physicians and hospitalists managing severe infection in daily practice, and may directly inform international clinical guidance. The World Health Organization has identified parenteral vitamin C as a candidate treatment for COVID-19; our systematic review will incorporate most recent trial evidence. Ongoing trials may change our confidence in the estimate of effects, necessitating iterative updates as a living review.