Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence

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.

Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

“…The latter review, albeit detailed, lacked a metaanalytic approach (34). Taken together, our and previous (33,34) contributions may provide the readers with the whole picture of the potential role of vitamin C in patients with COVID-19.…”

“…On the other hand, the authors of another recent relevant pragmatic review of the literature concluded that "intravenous vitamin C intervention may improve oxygenation parameters and reduce inflammatory markers" (34). The latter review, albeit detailed, lacked a metaanalytic approach (34). Taken together, our and previous (33,34) contributions may provide the readers with the whole picture of the potential role of vitamin C in patients with COVID-19.…”

“…In contrast, our endeavor may be more comprehensive (by taking into consideration both randomized controlled trials and observational studies) and focused (by taking into consideration only critically ill patients). On the other hand, the authors of another recent relevant pragmatic review of the literature concluded that "intravenous vitamin C intervention may improve oxygenation parameters and reduce inflammatory markers" (34). The latter review, albeit detailed, lacked a metaanalytic approach (34).…”

Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction: Relationship to Body Weight

“…In the New Zealand context, Māori and Pasifika peoples are at increased risk for all of these risk factors [ 50 ], as well as for morbidity and mortality from severe COVID-19 [ 51 , 52 ]. It is interesting to note that these risk factors also contribute to hypovitaminosis C [ 28 ], as does COVID-19 itself [ 53 ]. Due to vitamin C’s well-known immune supportive roles [ 54 ], future research restoring adequate vitamin C status in people with hypovitaminosis C and infection risk factors, and exploring its effects on infection susceptibility and severity appear warranted.…”

Multi-Level Immune Support by Vitamins C and D during the SARS-CoV-2 Pandemic

“…Severe COVID-19 is characterised by the complications of pneumonia, acute respiratory distress syndrome (ARDS) and sepsis, typically requiring hospitalisation and intensive care for respiratory support [ 36 ]. Patients with pneumonia, ARDS and sepsis generally have severely depleted vitamin C levels [ 9 ]; comparable findings have been reported with COVID-19 patients [ 37 ]. Vitamin C supplementation of hospitalised patients with pneumonia has indicated decreased respiratory symptoms in the most severely ill and a dose-dependent decrease in the duration of hospital stay [ 29 ].…”