The Role of Vitamin C in the Prevention and Treatment of COVID-19: A Literature Review

The study explores whether vitamin C, a micronutrient integral to immune function, can serve as a viable preventive or therapeutic modality against COVID-19. Context includes the global impact of SARS-CoV-2, the inflammatory nature of severe disease (including cytokine storm), and the search for cost-effective adjuncts to existing treatments. The hypothesis is that vitamin C’s roles in immune cell function, antioxidant defense, and tissue repair may translate into prophylactic and therapeutic benefits in COVID-19.

The review summarizes decades of research on vitamin C’s immunological roles, its antioxidant properties, and effects on tissue repair/wound healing. It collates pre-COVID-19 evidence for vitamin C in preventing or attenuating respiratory infections (e.g., common cold, URTI), and COVID-19-era studies assessing prophylaxis and treatment efficacy, including mixed findings across randomized trials, cohort studies, and case reports. Evidence suggests benefit in vitamin C-deficient individuals and in certain complications like sepsis, while demonstrating limited or inconsistent benefits for ARDS and pneumonia outcomes and for preventing COVID-19 in non-deficient populations.

Literature was identified via PubMed using terms including COVID-19, coronavirus, Vitamin, Vitamin C, nutrition, pneumonia, and sepsis. Randomized controlled trials and clinical trials cited are primarily from 2020–2021. Background sources are mostly from the last 20 years, with some older. Articles were screened for relevance and included to support discussion and conclusions in this narrative review.

- Immune function: Leukocytes concentrate vitamin C up to ~100-fold over plasma; supplementation increased neutrophil chemotaxis by ~20%. Vitamin C supports neutrophil chemotaxis, phagocytosis, T cell maturation/proliferation/viability, and B-cell immunoglobulin production (increases in IgA, IgG, IgM reported). Cytokine modulation observed with high-dose vitamin C (decreases in IL-1α, IL-2, IL-8, TNF-α) and with vitamins C+E (increases in IL-1β, TNF-α) suggesting regulatory effects. - Antioxidant effects: Vitamin C directly scavenges ROS and regenerates antioxidants (vitamin E, glutathione). Supplementation reduced oxidative stress by 60–90% in one study; 500 mg/day increased glutathione by ~516% in COPD patients. - Tissue repair: Essential cofactor for collagen hydroxylation; deficiency leads to impaired wound healing (scurvy). Trials show improved healing (e.g., 500 mg/day oral vitamin C accelerated chronic foot ulcer healing; improved soft tissue recovery after dental procedures; topical vitamin C increased dermal collagen I/III mRNA and related enzymes). - Prophylaxis (non-COVID respiratory infections): Daily ~200 mg reduced cold duration (~8% adults; ~13.5% children); benefits stronger under high physical stress; combination with probiotics reduced RTI incidence in preschoolers by ~33%; high-dose at symptom onset reduced severity/duration in some studies; results heterogeneous and sometimes sex-specific. - COVID-19 prophylaxis: Likely helpful to correct deficiency, particularly in elderly (who have lower serum vitamin C and higher COVID-19 mortality). For non-deficient individuals, evidence for preventing infection is lacking; in an open-label RCT, oral vitamin C was inferior to hydroxychloroquine or povidone-iodine throat spray for prophylaxis. - COVID-19 treatment: Mixed results. Small case series/observational reports suggest biomarker improvements (e.g., reduced D-dimer/ferritin with 1 g q8h; improved oxygenation and lower IL-6 with 12 g q12h IV) and a case report of rapid recovery after 11 g/day IV. An RCT (n=100) with 500 mg/day oral vitamin C for two weeks showed higher mean survival duration (8 vs 4 days) and a linear relationship between days of therapy and survival (B=1.66). Other trials found no significant improvements in ventilator-free days, ICU stay, oxygenation, or mortality with 6 g/day IV or in matched cohorts; one cohort suggested reduced thrombotic events without mortality benefit. - COVID-19 complications: ARDS—limited evidence of benefit; many ICU patients with ARDS had low vitamin C levels (82% below 0.4 mg/dL) but high-dose infusion did not clearly reduce vascular inflammation/damage. Pneumonia—continuous infusion (~60 mg/kg/day for 4 days) reduced need for mechanical ventilation and vasopressors but not mortality. Sepsis—vitamin C rapidly depleted; high-dose IV may lower SOFA scores and vascular injury, and in combination with hydrocortisone and thiamine reduced SOFA scores and prevented organ failure in some studies; overall mortality effects mixed across trials.

Vitamin C’s established roles in immune regulation, antioxidant defense, and tissue repair justify interest as a low-cost adjunct in respiratory infections. Prophylactically, maintaining recommended intakes is prudent, with supplementation particularly relevant in deficient or elderly individuals. For COVID-19 specifically, prophylactic benefit in non-deficient individuals is unproven. Therapeutically, current clinical evidence is inconsistent: some studies show improvements in select biomarkers, oxygenation, antibody titers, or survival duration, but consistent benefits on critical outcomes (mortality, ICU stay, ventilator-free days) are not demonstrated. For COVID-19 complications, vitamin C may aid in sepsis management given mechanistic plausibility and some favorable data, whereas evidence for ARDS and pneumonia remains inconclusive. Overall, findings partially support the hypothesis that vitamin C could aid immunity and reduce oxidative/inflammatory burden but do not yet establish it as a standalone COVID-19 therapy.

Clinical research to date does not definitively support vitamin C as an effective standalone prophylactic or treatment for COVID-19. Given its essential role in leukocyte function and antioxidant activity, maintaining adequate daily intake via diet or supplements is recommended to support immune function. High-dose vitamin C may be considered as an adjunct in moderate-to-severe disease alongside established therapies (e.g., corticosteroids, antibodies, antivirals), and in managing sepsis, but further well-designed trials are needed to clarify efficacy for COVID-19 prevention, treatment, and specific complications.

- Limited number of COVID-19 clinical trials and generally small sample sizes. - Heterogeneity in dosing regimens (oral vs IV, dose ranges, duration) and co-treatments complicates comparisons. - Mixed study designs (open-label, observational, retrospective) introduce bias and limit causal inference. - Inconsistent outcome measures across studies; few trials powered for mortality or ICU endpoints. - Lack of definitive evidence for prophylaxis in non-deficient individuals.