Potential Benefit of High-Dose Intravenous Vitamin C for Coronavirus Disease 2019 Pneumonia
The coronavirus disease 2019 (COVID-19) pandemic, declared by the World Health Organization, has posed significant challenges to global healthcare systems. While most COVID-19 patients experience mild to moderate symptoms, approximately 15% progress to severe pneumonia, and about 5% develop acute respiratory distress syndrome (ARDS), often requiring mechanical ventilation (MV) or even extracorporeal membrane oxygenation. The mortality rate among COVID-19 patients who require MV is alarmingly high, reaching up to 66%. Consequently, effective treatment strategies must focus on two critical aspects: preventing disease progression in mild and moderate cases and providing rescue therapy for severe and critical patients.
High-dose intravenous vitamin C (HDIVC) has been employed in the treatment of critical illnesses for nearly a decade. Previous in vivo research demonstrated that HDIVC protects against hemorrhagic shock-related multiple organ failure (MOF) by inhibiting inflammatory cytokines and oxidative indicators through the activation of the Sirtuin1 pathway. Building on this foundation, HDIVC has been applied in the treatment of COVID-19 pneumonia since February 2, 2020, at the Shanghai Public Health Clinical Center. A protocol for HDIVC was subsequently developed by the Shanghai COVID-19 Clinical Treatment Expert Group, tailored to the severity of the disease, which is classified as mild, moderate, severe, and critical.
The HDIVC protocol varies based on disease severity. Mild cases do not require HDIVC treatment. For moderate, severe, and critical cases, the protocol includes two main components: routine HDIVC administration at admission and continued for seven consecutive days, which may help prevent disease progression, and rescue therapy, which is crucial for saving lives when disease aggravation occurs. Retrospective case series studies have shown that HDIVC improves inflammatory response, immune function, and organ function. Additionally, the number of moderate COVID-19 patients progressing to severe disease was reduced following HDIVC protocol application.
The rationale for using HDIVC in COVID-19 treatment is based on several key mechanisms. First, HDIVC rapidly scavenges reactive oxygen species (ROS) and mitigates ROS-related inflammatory responses, endothelial dysfunction, coagulopathy, ARDS, and MOF. In COVID-19 patients, hypoxemia induces massive ROS production in mitochondria, leading to cytokine and chemokine release through pathways such as nuclear factor kappa B (NF-kB) signaling. This “cytokine storm” damages vascular endothelial cells, causing pulmonary interstitial edema, a hallmark of ARDS. ROS also trigger platelet aggregation and activate the coagulation system, leading to coagulopathy, which is common in COVID-19 and characterized by elevated D-dimer and fibrin degradation product levels, as well as prolonged activated partial thromboplastin time. HDIVC, by eliminating ROS directly and indirectly, has been shown to benefit severe sepsis patients, with one large randomized clinical trial reporting reduced 28-day all-cause mortality in septic patients with ARDS treated with HDIVC.
Second, HDIVC may improve lymphopenia, which is correlated with ARDS development and disease severity. Severe acute respiratory coronavirus 2 (SARS-CoV-2) induces lymphopenia by inhibiting hematopoietic cell growth, promoting T lymphocyte apoptosis, and triggering autoimmune antibody production and cytokine release. Vitamin C is essential for T-lymphocyte development, maturation, and proliferation. Although studies on HDIVC’s effect on lymphocytes in sepsis are limited, HDIVC has been associated with increased CD4+ T lymphocyte counts in COVID-19 patients.
Third, HDIVC helps maintain circulatory function stability. Vitamin C is a crucial co-factor for synthesizing endogenous hormones, including catecholamines, corticosteroids, and vasopressin. Clinical studies have shown that HDIVC reduces the need for vasopressors and lowers 28-day mortality in septic shock patients. For COVID-19 patients with septic shock, HDIVC, particularly when administered as a high bolus dose over a short period, may aid in the recovery of circulatory failure.
Fourth, HDIVC rapidly attenuates COVID-19-related scurvy. Severe COVID-19 patients often have undetectable vitamin C levels, a condition correlated with MOF in critically ill patients. Intravenous vitamin C quickly increases serum vitamin C levels from scurvy levels (10–20 mmol/L) to normal levels, providing rapid supplementation compared to oral intake.
Finally, HDIVC is considered safe, with no confirmed evidence of adverse effects such as oxalate nephropathy or urine stone formation in critically ill patients. No potential adverse events were observed in the studies reviewed.
In conclusion, HDIVC is an efficient and safe treatment for COVID-19 patients. It may be applied to prevent disease progression in moderate cases and as rescue therapy for severe and critical cases. However, high-quality randomized clinical trials are necessary to further validate these findings.
doi.org/10.1097/CM9.0000000000001746
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