Vitamin C Supplementation for the Treatment of COVID-19: A Systematic Review and Meta-Analysis

Abstract

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), millions of people have died, and the medical system has faced significant difficulties. Our purpose was to perform a meta-analysis to estimate the effect of vitamin C on in-hospital mortality and the ICU or hospital length of stay for patients diagnosed with COVID-19. We conducted a systematic review with meta-analysis in the following databases: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials. We included studies that evaluated the effect of vitamin C supplementation, compared with standard treatment in COVID-19 patients who are ≥18 y of age. Nineteen trials were included in the meta-analysis. In-hospital mortality with and without vitamin C supplementation was 24.1% vs. 33.9% (OR = 0.59; 95%CI: 0.37 to 0.95; p = 0.03), respectively. Sub-analysis showed that, in randomized clinical trials, in-hospital mortality varied and amounted to 23.9% vs. 35.8% (OR = 0.44; 95%CI: 0.25 to 0.76; p = 0.003), respectively. In the non-randomized trials, in-hospital mortality was 24.2% vs. 33.5% (OR = 0.72; 95%CI: 0.38 to 1.39; p = 0.33), respectively. The ICU length of stay was longer in patients treated with vitamin C vs. standard therapy, 11.1 (7.3) vs. 8.3 (4.7) days (MD = 1.91; 95%CI: 0.89 to 2.93; p < 0.001), respectively. Acute kidney injury in patients treated with and without vitamin C varied and amounted to 27.8% vs. 45.0% (OR = 0.56; 95%CI: 0.40 to 0.78; p < 0.001), respectively. There were no differences in the frequency of other adverse events among patients’ treatment with and without vitamin C (all p > 0.05). The use of vitamin C reduces hospital mortality. The length of stay in the ICU is longer among patients treated with vitamin C. In terms of patient safety, vitamin C has an acceptable profile. Low doses of vitamin C are effective and safe. Despite some evidence of the usefulness of vitamin C in modifying the course of COVID-19, it is too early to modify guidelines and recommendations. Further studies, in particular randomized clinical trials, are necessary.

Keywords: Ascorbic Acid; COVID-19; Corona Virus Disease 2019; SARS-CoV-2; hospital mortality; length of stay; meta-analysis; vitamin C.

Figure 1

Vitamin C activities—summary.

Figure 2

PRISMA flow diagram of the study selection process.

Figure 3

Forest plot of in-hospital mortality among COVID-19 patients with and without vitamin C supplementation. The center of each square represents the odds ratios for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results [32,33,34,35,36,37,39,40,41,42,43,44,45,46,47,48,50].

Figure 4

Forest plot of Intensive Care Unit length of stay among COVID-19 patients with and without vitamin C supplementation. The center of each square represents the mean differences for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results [32,35,39,41,43,48].

Figure 5

Forest plot of hospital length of stay among COVID-19 patients with and without vitamin C supplementation. The center of each square represents the mean differences for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results [32,38,39,40,43,45,46,48].