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Can Vitamin C Prevent and Help to Treat COVID-19?

Many people assume that vitamin C can strengthen immunity to prevent being infected by coronavirus or COVID-19. Also, they believe that Vitamin C is useful to treat COVID-19. Based on previous studies, the benefits of giving vitamin C to patients with severe sepsis and Acute Respiratory Distress Syndrome (ARDS), so empirically there is a place of vitamin C for patients Coronavirus disease 2019 (COVID-19) with complications of sepsis or ARDS.

Can Vitamin C Prevent and Help to Treat COVID-19
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In severe cases, COVID-19 can be accompanied by acute respiratory distress syndrome (ARDS), sepsis and septic shock, multiorgan failure, including acute kidney injury (AKI), and cardiac injury. In COVID-19 patients, the total number of B cells, T cells, and natural killer cells (NK cells) decreased significantly. Currently, several potential therapies are used for the management of COVID-19 cases, one of which is vitamin C.

Safety of High-Doses of Vitamin C

A clinical trial assessed the safety of intravenous vitamin C use in patients with severe sepsis. The research subjects were divided into three groups:
1. a group that gets a placebo,
2. vitamin C at a dose of 50 mg/kg / 24 hours,
3. and vitamin C at a dose of 200 mg/kg / 24 hours.
The results of the study mentioned that there were no side effects that appeared in patients who received intravenous vitamin C and concluded that the administration of intravenous vitamin C was safe and tolerated by patients in this study.

Meanwhile, several case reports mention the occurrence of oxalate nephropathy in patients receiving vitamin C high doses. Oxalate nephropathy occurs due to the accumulation of calcium oxalate. This could be due to the high consumption of oxalate precursors, one of which is vitamin C. 

other risks to watch out for in using high-dose of vitamin C are:
  • hemolysis in patients with G6PD enzyme deficiency 
  • Iron overload in hemochromatosis patients.


The Roles of Vitamin C in COVID-19 

Among the various functions of vitamin C that are relevant to the critical condition in the case of COVID-19 are enhancing the immune system and as an antioxidant. Vitamin C can increase chemotaxis and neutrophil phagocytosis, thereby increasing microbial clearance. Also, vitamin C increases differentiation, proliferation, and modulation of the function of T cells, B cells, and natural killer cells. Vitamin C is also able to induce antibody production in humans.

Vitamin C deficiency can cause impaired immunity and increased susceptibility to infection. In COVID-19, the protective immune response is disrupted, the virus propagates and causes damage to the tissues. Damaged cells induce inflammation in the lungs, which is mostly mediated by pro-inflammatory macrophages and granulocytes.

In sepsis, oxidative stress occurs, and excessive pro-inflammatory mediators are formed, causing an increase in endothelial permeability resulting in microcirculation disorders. Vitamin C can limit endothelial damage caused by ROS (reactive oxygen species). High-dose of Vitamin C given intravenously can work pleiotropically as a prooxidant that helps increase alveolar fluid clearance and as an antioxidant that improves epithelial function.

Potential of Vitamin C in COVID-19 Therapy

Vitamin C has the potential to be used in COVID-19 therapy because it can enhance the immune system and function as an antioxidant. From several studies also found positive effects of vitamin C in critical conditions and sepsis, so it is expected to be useful in patients with COVID-19 with the same condition.

Marik et al. conducted an initial study regarding the use of vitamin C in sepsis. They used the before-after study design and concluded that the administration of vitamin C together with hydrocortisone and thiamine could prevent the progression of organ dysfunction and reduce mortality in patients with severe sepsis and septic shock.
However, that study had some limitations :
1. No disguises,
2. three interventions at once,
3. the sample size is relatively small so that it can limit the generalization of the results of the study.

Benefits of Vitamin C as Therapy for Sepsis and ARDS 

A systematic meta-analysis and study of the use of vitamin C in critically ill patients were carried out by Zhang and Jativa. The study summarized five randomized controlled trials (RCT) studies and one retrospective study with a total sample of 142 samples. The study found that the use of intravenous vitamin C was associated with a decrease in vasopressor requirements and reduced duration of mechanical ventilation. However, there was no difference in mortality between controls and the group given vitamin C. That study concluded that intravenous vitamin C had vasopressor sparing effects and reduced the need for mechanical ventilation in patients with a critical illness, without affecting mortality.

A meta-analysis by Hemila and Chalker involving 12 studies with a total of 1766 patients found that the administration of vitamin C could shorten the length of treatment in the ICU (Intensive Care Unit). A meta-analysis of 6 studies found that vitamin C can reduce the duration of the use of mechanical ventilation (Ventilator). 

Different results were obtained in a meta-analysis of 44 clinical trials also conducted by Putzu et al. This study found that the administration of vitamin C did not have a significant effect on the duration of hospitalization in the ICU or hospital.

Systematic review and meta-analysis by Lin et al. involved 4 RCTs and two retrospective studies. By the meta-analysis, they found that high doses of vitamin C (> 50 mg/kg weight/day) significantly reduced the mortality rate of patients with severe sepsis. However, the addition of high-dose vitamin C to severe sepsis therapy did not reduce the length of stay in the ICU. These results were supported by other results of a meta-analysis by Li, which concluded that there was a positive correlation between vitamin C administration in sepsis cases with better survival and the use of shorter vasopressor duration.

The Roles of Vitamin C in COVID-19

Until this article was written, there were no clinical trial results related to the use of vitamin C in COVID-19 cases. At present, The use of vitamin C is as an empirical therapy based on the experience of clinicians in China who provide intravenous vitamin C with doses ranging from 50 - 200 mg/kg weight according to the severity of the disease. In addition, the administration of vitamin C has shown to prevent transmission of acute respiratory infections in some special populations such as marathons, ski athletes, and members of the military, but not in the general population. From the study, it was found that regular supplementation with a minimum dose of 200 mg/day can reduce the duration of ARI by 8% in adults.

Currently, clinical trials regarding the use of intravenous vitamin C in COVID-19 cases are underway in China. In the clinical trial, the intravenous dose of vitamin C was 12 grams given twice daily for seven days and compared with the placebo. The clinical trial is expected to be completed by the end of September 2020 (ClinicalTrial.gov clinical trial number: NCT04264533).


Conclusion
Theoretically, there are various benefits of using vitamin C that is relevant to COVID-19 cases. Also, from several meta-analyses, several positive results were obtained from the use of vitamin C in cases of critical illness and sepsis. However, there are no clinical trial results or meta-analyzes regarding the use of vitamin C in COVID-19 cases. Currently, the use of vitamin C in COVID-19 is only empirical therapy based on the experience of clinicians in China. So must consider the risk-benefit ratio, especially concerning the risk of possible side effects before administrating Vitamin C.

author: Dr. Reni W


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