High-dose intravenous Vitamin C in early stages of severe acute respiratory syndrome coronavirus 2 infection: A double-blind, randomized, controlled clinical trial

Abstract

Objective: Based on previous studies in the sepsis population, Vitamin C could prevent injuries when administered in high doses and before the damage is established. This study aimed to evaluate the protective potentials of high-dose Vitamin C in the progression of coronavirus disease 2019 (COVID-19). Methods: A double-blind, placebo-controlled clinical trial was conducted. Patients with moderate-to-severe disease severity based on the World Health Organization definition were enrolled and received 12 g/d Vitamin C (high-dose intravenous Vitamin C [HDIVC]) or placebo for 4 days. Sequential Organ Failure Assessment (SOFA) score as a primary outcome, National Early Warning Score, Ordinal Scale of Clinical Improvement, and cytokine storm biomarkers were recorded on days 0, 3, and 5. Survival was also assessed on day 28 after enrollment. Findings: Seventy-four patients (37 patients in each group) were enrolled from April 5, 2020, to November 19, 2020, and all patients completed follow-up. A lower increase in SOFA score during the first 3 days of treatment (+0.026 vs. +0.204) and a higher decrease in this parameter in the last 2 days (−0.462 vs. −0.036) were observed in the treatment group. However, these differences did not reach a significance level ( P = 0.57 and 0.12, respectively). Other indices of clinical and biological improvement, length of hospitalization, and intensive care unit admission days were the same between the two groups. Treatment did not affect the 28-day mortality. Conclusion: Among patients with moderate-to-severe disease of COVID-19, the use of HDIVC plus standard care resulted in no significant difference in SOFA score or 28-day mortality compared to the standard care alone.

The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

“…Most of the randomized trials investigating the mortality outcomes with the use of vitamin C in patients with COVID-19 had some concerns of bias. In addition, other than the trial reported by Majidi et al (2021), none of the individual trials (Beigmohammadi et al 2021;Cao et al 2020;JamaliMoghadamSiahkali et al 2021;Kumar et al 2022;Kumari et al 2020;Labbani-Motlagh et al 2022;Leal-Martínez et al 2022;Tehrani et al 2022;Thomas et al 2021;Zhang et al 2021) reported significant mortality reduction with the administration of vitamin C in patients with COVID-19. In addition, variation in the dosing regimen of vitamin C used across the included trials precludes recommendation of the most appropriate method(s) for the administration of vitamin C in patients with COVID-19 to reduce their risk of mortality.…”

“…Eight studies were excluded either due to observational study design or reported no mortality events. In total, we included eleven randomized controlled trials (Beigmohammadi et al 2021 ; Cao et al 2020 ; JamaliMoghadamSiahkali et al 2021 ; Kumar et al 2022 ; Kumari et al 2020 ; Labbani-Motlagh et al 2022 ; Leal-Martínez et al 2022 ; Majidi et al 2021 ; Tehrani et al 2022 ; Thomas et al 2021 ; Zhang et al 2021 ) in our systematic review and meta-analysis, with 445 patients randomized to receive vitamin C and 494 patients randomized to receive comparative interventions.…”

“…The regimen of vitamin C in the intervention group differed across the included trials. Most of the included trials (n = 6) (Beigmohammadi et al 2021 ; JamaliMoghadamSiahkali et al 2021 ; Kumar et al 2022 ; Labbani-Motlagh et al 2022 ; Tehrani et al 2022 ; Zhang et al 2021 ) administered vitamin C intravenously at a fixed non–weight-based dose ranging from 2 to 24 g daily for a duration of 4 to 7 days. One trial (Kumari et al 2020 ) administered vitamin C intravenously at a weight-based dose of 50 mg/kg daily.…”

“…We adjudicated five trials (Kumar et al 2022 ; Labbani-Motlagh et al 2022 ; Leal-Martínez et al 2022 ; Majidi et al 2021 ; Thomas et al 2021 ) as having a low risk of bias in all domains and, thus an overall low risk of bias. We rated the remaining trials as having overall some concerns of bias (some concerns of bias in at least one domain): the four trials reported by Zhang et al ( 2021 ), by JamaliMoghadamSiahkali et al ( 2021 ), by Tehrani et al ( 2022 ), and by Beigmohammadi et al ( 2021 ) respectively, had some concerns of bias in the domain of ‘deviations from intervention’ due to open-label/single-blind trial design; the trial reported by Kumari et al ( 2020 ) had some concerns of bias in the domain of ‘randomization’ due to inadequate information on allocation concealment as well as in the domain of ‘deviations from intervention’ due to single-blind trial design; the trial reported by Cao et al ( 2020 ) had some concerns of bias and in the domain of ‘deviations from intervention’ due to single-blind trial design as well as in the domain of ‘selection of the reported results’ since it was unclear whether the trial was analyzed as pre-specified.…”

“…The meta-analysis of eleven trials (Beigmohammadi et al 2021 ; Cao et al 2020 ; JamaliMoghadamSiahkali et al 2021 ; Kumar et al 2022 ; Kumari et al 2020 ; Labbani-Motlagh et al 2022 ; Leal-Martínez et al 2022 ; Majidi et al 2021 ; Tehrani et al 2022 ; Thomas et al 2021 ; Zhang et al 2021 ) using a random-effects model reported reduction in the risk of all-cause mortality with the administration of vitamin C in patients with COVID-19 compared to non-administration of vitamin C; the pooled odds ratio is with significant evidence to indicate mortality benefits, at the current sample size (Fig. 1 ; pooled odds ratio = 0.53; 95% confidence interval 0.30 to 0.92; I 2 = 22%).…”