Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients

Abstract

Background: No specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.Results: Only fifty-six critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P=0.01). Patients with SOFA scores ≥3 in the HDIVC group exhibited a trend of reduction in 28-day mortality (P=0.06) in univariate survival analysis. IL-6 in the HDIVC) group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P=0.04) on day 7. Conclusion: This pilot trial showed that HDIVC might show a potential signal of benefit for critically ill patients with COVID-19, improving oxygenation even though it failed to improve IMVFD28. Clinicaltrial.gov identifer and date: NCT04264533. Registered February 14 2020.

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial

“…It is worthy to note that some studies have used higher doses of vitamin C in their patients [39,40]. The highest dose was used in the work of Zhang et al who have used 24 g daily in the form of 12 g of vitamin C/50 ml every 12 h for 7 days at a rate of 12 ml/h.…”

Inhibition of ACE2 Expression by Ascorbic Acid Alone and its Combinations with Other Natural Compounds

“…8 Recently there were publications reporting clinical benefits of intravenous ascorbate supplementation in critically ill patients with COVID-19. 9,10 However, the mechanisms involved are poorly understood.…”

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

“…Besides, the same authors reported in a meta-analysis of 12 clinical trials that vitamin C reduces the length of the intensive care unit stay by 7.8% and the duration of mechanical aided ventilation [ 41 , 42 , 43 ]. Emerging evidence, carried out on a small clinical trial with 54 critical COVID-19 patients, demonstrated that high dose vitamin C infusion decreased the IL-6 level, concluding that this therapeutical regimen may provide a protective clinical effect without any adverse events in critical COVID-19 patients [ 44 ]. Other outcomes were considered in the same clinical trial, including organ failure score, intensive care unit length, and mortality.…”

“…Other outcomes were considered in the same clinical trial, including organ failure score, intensive care unit length, and mortality. According to the authors, a significant decrease in intensive care unit stay and hospital mortality was observed in the vitamin C treated patients [ 44 ]. Overall, vitamin C seemed to possess relevant pharmacological properties against severe respiratory infections, including COVID-19 [ 45 , 46 ].…”