The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study.

BACKGROUND: The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019. METHODS: We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30). RESULTS: The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy. CONCLUSION: High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.

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

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Pilot trial of high-dose vitamin C in critically ill COVID-19 patients.

BACKGROUND: Few specific medications have 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 h for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way within 48 h of arrival to ICU. The primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28). Secondary outcomes were 28-day mortality, organ failure (Sequential Organ Failure Assessment (SOFA) score), and inflammation progression (interleukin-6). RESULTS: Only 56 critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups (26.0 [9.0-28.0] in HDIVC vs 22.0 [8.50-28.0] in control, p = 0.57). HDIVC failed to reduce 28-day mortality (P = 0.27). 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), which was not observed in the control group. IL-6 in the HDIVC group was lower than that in the control 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 failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.

Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.

BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.

Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19. METHODS AND ANALYSIS: The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04264533.