Table 1.
Characteristics and findings of the concluded observational and interventional studies investigating the effect of vitamin C in patients with a SARS-CoV-2 infection.
| First Author, Year and Country | Population | Study Design | Exposure/Intervention with Dosage | Outcomes | Key Findings |
|---|---|---|---|---|---|
| Capone S. et al., USA, 2020 [30] | 102 patients (median age 63 years) affected by SARS-CoV-2 and managed by intensive care team |
Observational, retrospective | Supplementation of vitamin C (plus zinc). Posology not specified |
Overall survival | 72% received supplementation with vitamin C and zinc. No association between vitamin C and overall survival was observed |
| Krishnana S. et al., USA, 2020 [31] | 152 patients (median age 68 years) affected by SARS-CoV-2, requiring mechanical ventilation |
Observational, retrospective | Supplementation of vitamin C. Posology not specified | Overall survival | 52% received supplementation with vitamin C. Survival was higher in patients managed with vitamin C (65%, vs. 43%, p = 0.007) |
| Li J. et al., China, 2020 [32] | 596 patients (mean age 56 years) affected by SARS-CoV-2, evaluated at the Hospital | Observational, retrospective | Supplementation of vitamin C. Posology not specified | Prognosis of patients with and without cardiovascular diseases | 16% received vitamin C. Patients with cardiovascular diseases received vitamin C more frequently (23% vs. 12%, p < 0.001) than patients without. No data on prognosis related to the supplementation of vitamin C were available |
| Liu XH et al., China, 2020 [33] | 58 patients (median age 29 years) admitted to the hospital with a SARS-CoV-2 infection | Observational, retrospective | Supplementation of vitamin C. Posology not specified | Clinical characteristics | 69% received vitamin C. No data about the association between vitamin C and clinical outcomes were available |
| Alamdari DH et al., Iran, 2020 [34] | 5 patients (mean age 63 years) admitted to ICU for respiratory distress due to SARS-CoV-2 infection | Phase-I clinical trial | Administration of vitamin C (1500 mg/kg) both oral and intravenous | Respiratory symptoms and safety | Four patients showed improvement both in respiratory symptoms and oxygen saturation after vitamin C administration. The patients were discharged in 10 (4–23) days. One patient discontinued the therapy due to limitations of the drug preparation and expired on the second day of admission |
| JamaliMoghadamSiahkali S. et al., Pakistan, 2020 [35] | A total of 60 patients with a severe SARS-CoV-2 infection: 30 patients (mean age 58 years) received lopinavir/rito- navir and hydroxychloroquine plus vitamin C and 30 (mean age 61 years) only lopinavir/rito- navir and hydroxychloroquine | Randomized open-label clinical trial | Administration of intravenous vitamin C (1.5 g every six hours, total 6 g daily) | The main outcomes were: decrease in mortality, length of hospitalization, and number of patients admitted to ICU. Secondary outcomes were: increase in SpO2 and improvements in vital signs and overall wellbeing | Patients managed with and without vitamin C did not differ for any of the outcomes, except for body temperature (36.8 ± 0.5 vs. 37.2 ± 0.7, respectively, p = 0.001) and SpO2 (90.5 [88.0–92.0] vs. 88.0 [80.0–91.0], respectively p = 0.014) on third day of hospitalization. On the contrary, length of hospitalization was higher in patients managed with vitamin C (8.5 days vs. 6.5 days, p = 0.028) |
| Zang J. et al., China, 2021 [36] | 56 patients (mean age 67 years) with a SARS-CoV-2 infection admitted to intensive care | Randomized, controlled, clinical trial |
Administration of intravenous vitamin C (12 g every 12 h, total 24 g daily) for 7 days | The main outcome was invasive mechanical ventilation-free days in 28 days. Secondary outcomes were 28-day mortality, organ failure severity, and interleukin-6 levels | Patients managed with and without vitamin C showed no difference in terms of invasive mechanical ventilation-free days in 28 days and 28-day mortality. A rise in the PaO2/FiO2 (229 vs. 151 mmHg, 95% CI 33 to 122) and lower levels of IL-6 on day 7 (19.42 vs. 158.00, 95% CI −301.72 to −29.79), lower ICU mortality (Hazard Ratio = 0.22, 95% CI 0.1–0.9) in patients with severe multiorgan score failure were observed in patients managed with vitamin C. |
| Kumari P. et al., Pakistan, 2020 [37] | A total of 150 patients admitted for a SARS-CoV-2 infection: 75 (mean age 52 years) were managed with vitamin C and 75 (mean age 53 years) without | Randomized controlled trial | Administration of intravenous vitamin C (50 mg/kg/day). Length of the intervention not specified | The endpoints were: number of days before symptoms disappearance, length of hospital stay, need for ventilation and mortality | Patients managed with vitamin C were symptom-free earlier (7.1 ± 1.8 vs. 9.6 ± 2.1 days, p < 0.0001)) and had a shorter duration of hospitalization (8.1 ± 1.8 vs. 10.7 ± 2.2 days, <0.0001) compared to patients managed without vitamin C. No difference was observed in the need for mechanical ventilation and mortality |
| Thomas S. et al., USA, 2021 [38] | A total of 214 outpatients with a SARS-CoV-2 infection: 48 (mean age 46 years) were managed with vitamin C, 50 (mean age 42 years) with the standard care, 58 (mean age 44 years) with zinc and 58 (mean age 49 years) with vitamin C and zinc | Randomized factorial open-label trial | Administration of: (1) vitamin C (8000 mg in 2–3 times per day), (2) 50 mg of zinc gluconate, (3) both vitamin C and zinc | The main outcome was the number of days to obtain a 50% reduction in symptoms. Secondary outcomes were: days required to resolve symptoms, cumulative severity score symptoms at day 5, hospitalizations, adjunctive prescribed medications, mortality and safety | The study was ended for lack of benefits after the interim analysis |