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.

Keywords: Coronavirus disease 2019; high-dose Vitamin C; inflammation; severe acute respiratory syndrome coronavirus 2.

Figure 1

Flow diagram of patients. HDIVC: High-dose intravenous Vitamin C

Figure 2

Effect of treatment on SOFA score on days 0, 3, and 5. There was no significant change between treatment arms on days 0, 3, and 5. Differences between days show less increase on day 3 (+0.026 vs. +0.204) and more reduction on day 5 (−0.462 vs. −0.036). SOFA: Sequential Organ Failure Assessment

Figure 3

Changes in SF ratio, NEWS score, Ordinal Scale for Clinical Improvement, ferritin, CRP, and NLR during the treatment by Vitamin C or placebo. None of the variations in these parameters have reached statistical significance. SF ratio: SpO2/FiO2 ratio, NEWS score: National Early Warning Score, CRP: C-reactive protein, NLR: Neutrophil/lymphocyte ratio

Figure 4

The 28-day mortality from randomization (day 0) to day 28 among patients is based on types of treatment