Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial

Abstract

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.

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

“…The full text of thirty-seven potentially eligible articles was assessed. Nineteen studies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ] finally met relevant standards and the screening process is shown in Figure 2 .…”

“…The characteristics of the 19 retrieved trials were reported in Table 1 . Ten studies were designed as randomized controlled trials [ 33 , 34 , 38 , 40 , 46 , 47 , 48 ]. Fourteen trials concerned intravenous vitamin C supplementation [ 32 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 48 , 49 , 50 ].…”

“…Ten studies were designed as randomized controlled trials [ 33 , 34 , 38 , 40 , 46 , 47 , 48 ]. Fourteen trials concerned intravenous vitamin C supplementation [ 32 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 48 , 49 , 50 ]. Of the 19 trials, six were performed in Iran [ 33 , 35 , 38 , 43 , 46 ], four in the USA [ 34 , 39 , 41 , 47 ], four in China [ 36 , 48 , 49 , 50 ], two in Turkey [ 44 , 45 ] and one in each of the following countries: Saudi Arabia [ 32 ], Pakistan [ 40 ] and Greece [ 37 ].…”

“…In turn, in-hospital mortality in the group of studies in which vitamin C was used without co-supplementation with other molecules [ 28 , 29 , 30 , 31 , 32 , 34 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] was 20.7% and 37.4%, respectively, for patients treated without vitamin C (OR = 0.50; 95%CI: 0.39 to 0.66; p < 0.001). In turn, in the group of studies where vitamin C has been supplemented with other molecules [ 33 , 35 , 38 , 47 ], pooled analysis of in-hospital mortality was 27.4% vs. 21.2% (OR = 1.39; 95%CI: 0.25 to 7.77; p = 0.71), respectively.…”

“…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 ].…”