No significant benefit of moderate-dose vitamin C on severe COVID-19 cases

Abstract

There is no specific drug for coronavirus disease 2019 (COVID-19). We aimed to investigate the possible clinical efficacy of moderate-dose vitamin C infusion among inpatients with severe COVID-19. Data of 397 adult patients with severe COVID-19 admitted to a designated clinical center of Wuhan Union Hospital (China) between February 13 and February 29, 2020, were collected. Besides standard therapies, patients were treated with vitamin C (2–4 g/day) or not. The primary outcome was all-cause death. Secondary outcome was clinical improvement of 2 points on a 6-point ordinal scale. About 70 participants were treated with intravenous vitamin C, and 327 did not receive it. No significant association was found between vitamin C use and death on inverse probability treatment weighting (IPTW) analysis (weighted hazard ratio [HR], 2.69; 95% confidence interval [CI], 0.91–7.89). Clinical improvement occurred in 74.3% (52/70) of patients in the vitamin C group and 95.1% (311/327) in the no vitamin C group. No significant difference was observed between the two groups on IPTW analysis (weighted HR, 0.76; 95% CI, 0.55–1.07). Our findings revealed that in patients with severe COVID-19, treatment with moderate dose of intravenous vitamin C had no significant benefit on reducing the risk of death and obtaining clinical improvement.

Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

“…However, we attempted to address this limitation by performing a sensitivity analysis of the 5 randomized controlled trials. Lastly, the included studies (23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in the meta-analysis did not consistently report on adverse events potentially related to administration of vitamin C, such as oxalate nephropathy, hypernatremia and glucometer error. Nevertheless, relevant evidence before the pandemic indicated that high-dose vitamin C may be relatively safe (36).…”

“…2). In the sensitivity analysis of studies with low risk of bias (23,25,(28)(29)(30)32), mortality was 25.1% in the vitamin C group and 32.2% in the control group (RR 1.13, 95% CI 0.59-2.16; p = 0.72; six studies; 1,344 patients; 410 deaths; Supplementary Figure 1); while, in the sensitivity analysis of randomized controlled trials (25,27,29,31,32), the relevant numbers were 10.5 and 17.2%, respectively (RR 0.66, 95% CI 0.39-1.14; p = 0.14; five studies; 346 patients; 48 deaths; Supplementary Figure 2).…”

“…Table3summarizes characteristics of the included studies. Six of them were retrospective observational studies(23,24,26,28,30) and five were randomized controlled trials(25,27,29,31,32). Supplementary Table1summarizes risk of bias assessment of the included studies.…”

“…Supplementary Table1summarizes risk of bias assessment of the included studies. Six(23,25,(28)(29)(30)32) of them were considered to have low risk of bias.All 11(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) studies provided data on all-cause mortality. Statistical heterogeneity was important (I 2 = 74%).…”

“…Mortality was not lower in the vitamin C than control group (25.8 vs. 34.7%; RR 0.85, 95% CI 0.57-1.26; p = 0.42; 11 studies; 1,807 patients; 561 deaths; Figure2). In the sensitivity analysis of studies with low risk of bias(23,25,(28)(29)(30)32), mortality was 25.1% in the vitamin C group and 32.2% in the control group (RR 1.13, 95% CI 0.59-2.16; p = 0.72; six studies; 1,344 patients; 410 deaths; Supplementary Figure1); while, in the sensitivity analysis of randomized controlled trials(25,27,29,31,32), the relevant numbers were 10.5 and 17.2%, respectively (RR 0.66, 95% CI 0.39-1.14; p = 0.14; five studies; 346 patients; 48 deaths; Supplementary Figure2).Regarding secondary outcomes of the meta-analysis, ICU length of stay was longer in the vitamin C than control group (MD 1.56 days, 95% CI 0.63-2.49 days; p = 0.001; four studies; 887 patients; Supplementary Figure3). There was no difference between the vitamin C group and control group in terms of duration of mechanical ventilation (MD 0.40 days, 95% CI −1.81-2.60 days, p = 0.73; 2 studies; 852 patients; Supplementary Figure4) or need for renal replacement therapy (21.6 vs. 34.0%; RR 1.27, 95% CI 0.68-2.39; p = 0.45; two studies; 169 patients; 53 events; Supplementary Figure5).…”