A protocol for systematic review and meta-analysis
Lifang Huang, MB,aLang Wang, MB,aJianghong Tan, MB,bHong Liu, MB,a and Yanhui Ni, MBc
Published online 2021 May 14
Patients infected with a virus usually lack vitamin C. High-dose vitamin C has an antiviral effect, and has been used by several researchers to treat COVID-19 by intravenous infusion, achieving good results. However, the efficacy and safety of vitamin C in the treatment of patients with COVID-19 remain unclear. Thus, the aim of the present study was to investigate the efficacy of high-dose vitamin C infusion in the treatment of patients with COVID-19.
The outbreak of the novel coronavirus (COVID-19) began in December 2019, and remains a prevalent threat around the world. COVID-19 is highly infectious and has high mortality, especially in patients with underlying health issues (such as diabetes). At present, there is no specific drug for the treatment of COVID-19, and many potential therapeutic drugs have been included in the scope of clinical trials. Several institutions have focused on verifying the therapeutic effect of vitamin C on COVID-19.[2,3]
Also known as L-ascorbic acid, vitamin C is a kind of water-soluble vitamin that exists in blood and cells in the form of reduced ascorbic acid. Clinically, vitamin C is mainly used for the treatment of scurvy, and also for the adjuvant treatment of various acute and chronic infectious diseases. Vitamin C is an essential vitamin for human immune system, which can enhance the body's immunity to viruses in a number of ways. High concentration of vitamin C can enhance the antiviral ability, especially in the form of dehydroascorbic acid, which can inhibit influenza A virus.[4,5] As revealed by prior research, vitamin C has a strong antiviral effect only in large doses, and serum vitamin C levels are low in most critically ill patients with COVID-19.[7,8] Hence, the use of high-dose vitamin C in the treatment of patients with COVID-19 is certainly feasible.
Despite the feasibility, there is a scarcity of high-quality evidence to support the efficacy and safety of high-dose vitamin C in patients with COVID-19. For this reason, in the present study, the efficacy of vitamin C therapy was systematically evaluated, so as to provide evidence-based guidance for clinical application.
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Vitamin C has been extensively applied in the treatment of viral infections, with studies revealing that patients with pneumonia and sepsis have low levels of vitamin C and elevated oxidative stress. Owing to the direct inhibitory effect thereof on pathogens, there is sufficient evidence to suggest that vitamin C is effective in the treatment of pneumonia and infection. Further, vitamin C has been shown to reduce the severity and duration of pneumonia, while meta-analysis of 12 trials in 1766 patients calculated that vitamin C reduced ICU stay by an average of 8%. Another meta-analysis found that vitamin C reduced the duration of mechanical ventilation in ICU patients. Novel coronavirus pneumonia is a new respiratory disease caused by COVID-19, and is severely infectious. Thus, vitamin C novel coronavirus pneumonia can also be applied to the treatment of patients.
In viral infections, vitamin C can attenuate pro-inflammatory response, enhance epithelial barrier function, increase alveolar fluid clearance rate, and prevent sepsis related coagulation abnormalities. The implementation of high-dose vitamin C treatment can significantly reduce the demand for high-dose corticosteroids, antibiotics, and antiviral drugs, as these drugs may have the effects of immunosuppression, adrenal suppression and toxicity, complicating the course of the disease. Combined with traditional Chinese medicine, Yali used a large dose of vitamin C (20 g/60 kg per day) to treat COVID-19. As a result of Yali treatment, the symptoms of fatigue, cough, dry throat, and shortness of breath were significantly improved, and no adverse events occurred. Zhang used a large dose of vitamin C (24 g/day) at the rate of 12 mL/h to treat patients with COVID-19, with the results revealing that the PaO2/FiO2 of patients increased steadily, and the 28 day mortality of patients decreased significantly. Therefore, high-dose vitamin C infusion may be a significantly effective therapeutic agent in COVID-19 treatment.
Since there is currently a scarcity of related research, whether high-dose vitamin C can improve the prognosis of patients with COVID-19 is yet to be ascertained, and is a high-priority concern for medical scholars. The present study is the first systematic review and meta-analysis of the efficacy of high-dose vitamin C in patients with COVID-19. Notably, the lack of adequate randomized controlled trials could be regarded as a limitation of the present meta-analysis.