ABSTRACT
Aim: To study the efficacy of intravenous vitamin C in management of moderate and severe COVID-19. Objective: To determine the efficacy of intravenous vitamin C in reducing in-hospital mortality in moderate and severe cases of COVID-19. Design: Parallel, double-blinded randomized controlled trial with placebo. Ethical clearance was obtained from the institutional ethics committee, AIIMS Patna. The trial was registered with the Clinical Trials Registry - India (registration number- CTRI/2020/11/029230.). Setting: A tertiary care centre in Bihar, India. Participants: All patients above the age of 18 years both males and females, admitted in ICU with a diagnosis of moderate and severe COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period (01/10/2020-31/12/2020) not having any of the exclusion criteria. Intervention: The patients in the intervention arm were given 1 gram (2 ampoules of 2 ml each containing 500 mg of vitamin C mixed in 100 ml normal saline) intravenous vitamin C 8 hourly for four days. The patients in the placebo arm received similar looking ampoules (2 ampoules of 2 ml sterile water for injection mixed in 100 ml normal saline) intravenously 8 hourly for four days. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with adjustments as per treating team's judgement. Outcome Measures: Primary outcome was reduction in in-hospital mortality. Secondary outcomes were improvement in qSOFA score, pO2/fiO2 ratio, fall in inflammatory markers, need for mechanical ventilation and vasopressors. Results: Regarding primary outcome, 10 (33.3%) patients died in intervention group compared to 13 (43.3%) in placebo. Worth noting from baseline characteristics is that 86.7% in intervention arm were of severe category compared to 66.7% severe category patients in placebo group. Though number of severe cases were more in intervention arm there has been comparatively less mortality in this group. Regarding secondary outcomes, amongst 30 patients in vitamin C group, 11 (36.7%) required invasive mechanical ventilation compared to 14 (46.7%) out of 30 in placebo group but the difference was not statistically significant. Although there were a greater number of moderate cases in placebo group, invasive ventilation requirement (and NIV requirement) was more in this group, thus it could be considered that vitamin C might have a role in reducing the severity of disease. The need for vasopressor therapy was higher in intervention arm 33.3% compared to 26.7% in placebo but not significant statistically. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. Conclusion: In the current study, by the observations and results of the double-blind placebo controlled randomised trial, we concluded that as the primary outcome of the study, there was reduction in In-hospital mortality and need for mechanical ventilation in the vitamin C intervention group compared to placebo, although these results did not reach statistical significance due to small sample size and use of moderate dose of IV vitamin C. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. In summary, high dose of intravenous vitamin C may reduce inflammatory reaction, improve oxygen support status, and reduce mortality in COVID-19 patients, without adverse events. High dose intravenous vitamin C may be a promising therapy for patients of moderate to severe COVID-19.
ABSTRACT
BACKGROUND: Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously (IVC) has been extensively investigated in cancer treatment with a known safety profile and has been proposed to play a role in managing COVID-19. IVC was used to treat COVID-19 patients in hospitals in China, USA, and Europe with reported benefits. We report here unexpected beneficial results from the use of IVC in two severely ill oncology patients with documented COVID-19 lung disease. CASE REPORT: two oncology patients were diagnosed with SARS-CoV-2 infection. Prior to receiving IVC, lung infiltrates and systemic inflammation in both patients were progressing despite multiple anti-viral, antibiotic, and anti-inflammatory treatments with intensive supportive care. Both patients subsequently received 12 g of IVC delivered intravenously over 30 min, given 2 times daily for 7 days. Serial SARS-CoV-2 nucleic acid tests showed that the viral load was negative only after the 7-day IVC treatment. In both patients after receiving IVC infusions, imaging by chest CT or X-ray showed improving lung infiltrates. There were reductions in systematic inflammation by high-sensitivity C-reactive protein (hsCRP), and Interleukin-6 (IL-6) testing. No adverse events were observed related to IVC treatment. CONCLUSION: the use of high-dose IVC demonstrated unexpected clinical benefits in treating COVID-19 in two cancer patients presenting with complicated severe comorbidities where an unfavorable prognosis was anticipated.
ABSTRACT
Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. Vitamin C (ascorbic acid, AA) is an essential nutrient with many biological roles that have been proven to play an important part in immune function; it serves as an antioxidant, an anti-viral, and exerts anti-thrombotic effects among many other physiological benefits. Research has proven that AA at pharmacological doses can be beneficial to patients with acute respiratory distress syndrome (ARDS) and other respiratory illnesses, including sepsis. In addition, High-Dose Intravenous Vitamin C (HDIVC) has proven to be effective in patients with different viral diseases, such as influenza, chikungunya, Zika, and dengue. Moreover, HDIVC has been demonstrated to be very safe. Regarding COVID-19, vitamin C can suppress the cytokine storm, reduce thrombotic complications, and diminish alveolar and vascular damage, among other benefits. Due to these reasons, the use of HDIVC should be seriously considered in complicated COVID-19 patients. In this article, we will emphasize vitamin C's multiple roles in the most prominent pathophysiological processes presented by the COVID-19 disease.
ABSTRACT
Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death. Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA). Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels. Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed. Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient). Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study's patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.
ABSTRACT
Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients.
ABSTRACT
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.
ABSTRACT
Background and objective The anti-inflammatory properties of vitamin C (VC) and the promising results it has shown in the treatment for common cold have prompted clinicians to use it as adjuvant therapy in the treatment of COVID-19. The purpose of this study was to find out the role of VC as adjunctive therapy in coronavirus disease 2019 (COVID-19). Methodology This study was conducted from March to July 2020 in the COVID-19 unit of a tertiary care hospital in Karachi. In this randomized controlled trial (RCT), one group received the intervention [50 mg/kg/day of intravenous (IV) VC] along with the standard therapy, and the other group received standard therapy only. Data such as age, gender, vitals, and biochemical values as well as outcomes including the number of days required for treatment, hospital stay, need for ventilation, and mortality were compared between the two groups and recorded using a self-structured questionnaire. Results COVID-19 patients who received IV VC became symptom-free earlier (7.1 ± 1.8 vs. 9.6 ± 2.1 days, p-value: <0.0001) and spent fewer days in the hospital (8.1 ± 1.8 vs. 10.7 ± 2.2 days, p-value: <0.0001) compared to those who received standard therapy only. However, there was no significant difference in the need for mechanical ventilation (p-value: 0.406) and mortality (p-value: 0.31) between the two groups. Conclusion VC can significantly improve clinical symptoms in patients affected with COVID-19; however, it had no impact on mortality and the need for mechanical ventilation. More large-scale studies are required to further assess the role of VC in the treatment of COVID-19.
ABSTRACT
BRIEF OVERVIEW: Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections (ARI) by reducing fever and chills, relieving chest pain and assist in reducing symptoms of common cold-induced asthma. Intravenous (IV) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital. COVID-19 has similar signs and symptoms of ARI. Further studies involving patients with COVID-19, either through administration of oral vitamin C in mild cases or IV vitamin C in critical cases, would be advantageous to examine if it is safe and efficacious. VERDICT: Oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. For individuals admitted to hospital with community-acquired pneumonia, vitamin C may improve respiratory function in more severe cases. No major adverse events nor interactions were reported by either method of administration. However, there is an absence of high quality, contemporary clinical research examining this topic. Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI, including COVID-19.