Table 3.
Summary of findings from studies that included vitamin C supplementation in the COVID-19 treatment.
| References | Study design, setting, gender, age | Therapy, regimen | N, severity of COVID-19, and comorbidities | outcomes |
|---|---|---|---|---|
| Sulaiman et al. (42) | Cohort; ICU; Male (72%); 60.6 ± 14.8 years. | •Group 1 (N = 158): 1000 mg of VC enterally once daily with a median duration of administration of 11 days. •Group 2 (N = 581): no supplementation (ST). |
N = 296; Severe COVID-19; Comorbidity: DM (59%), hypertension (56%), dyslipidemia (29%). | •There was no association between the administration of VC and in-hospital mortality or the 30-day mortality. •Thrombosis/infraction rate: ↓ in the VC group compared to CG. |
| Xia et al. (44) | RCT; Hospital; Female (55%); 67 ± 1years. | •Group 1 (N = 85): 100 mg/kg diluted 50 mL of saline solution on day 1 plus 100 mg/kg of body weight VC diluted in 50mL of saline solution for next 5 days. •Group 2 (N = 151): no supplementation (ST). |
N = 236; severe COVID-19; Comorbidity: hypertension (15.0%), coronary heart disease (11.8%), DM (15.9%). | •CRP, IL-6, and tumor necrosis factor decreased in both groups, but the percentage of reduction in the VC group was better compared to CG. •VC group was independently associated with the percentage of reduction in levels of inflammatory markers. |
| Suna et al. (45) | Retrospective; Hospital; Male (63.1%); 62.2 ± 0.4 years. | •Group 1 (N = 153): 2 g/day intravenous VC. •Group 2 (N = 170): no supplementation (ST). |
N = 323; Severe COVID-19; Comorbidity: hypertension (42%), DM (29.8), CAD (16.7%), heart failure (5.2%), COPD (14.15%), asthma (6.8), malignancy (9%), renal failure (3.35%), interstitial lung (0.65%) and rheumatological (3.15%) disease. | •CRP, D-dimer, and ferritin in the VC group between baseline and post-treatment: No difference between the groups. •Length of hospital stay, re-admission rate, admission to intensive care, need for advanced oxygen support, need for advanced medical treatment, and mortality: No difference between the groups. •Adverse effects: None reported. |
| Xia et al. (47) | Cohort; Hospital; Male (46%); 69.5 ± 1.5years. | •Group 1 (N = 51): 100 mg/kg of intravenous VC (1 day) followed by 100 mg/kg (5 days) during hospitalization. •Group 2 (N = 62): no supplementation (ST). |
N = 113; Severe and critically COVID-19; Comorbidity: hypertension (45.3%), coronary heart disease (21.1%), DM (25.6%). | •VC group correlated (odds ratio 2.420, 95% CI 1.022–5.729) with the improvement of cardiac injury independent of mechanical ventilation and renal replacement therapy. •VC group improved myocardial damage among patients with SARS-CoV-2 infection in severe and critically ill conditions. •CRP, IL-6, IL-8, and tumor necrosis factor showed reduction at day 21 during hospitalization in the VC group compared to CG. |
| Kumari et al. (40) | RCT; Hospital; Male (56.9%); 52.5 ± 11.5 years. | •Group 1 (N = 75): 50 mg/kg/day of intravenous VC. •Group 2 (N = 75): no supplementation (ST). |
N=150; severe COVID-19; Comorbidity: NR. | •VC group became symptom-free earlier than CG. •↓days hospitalized in the VC group (vs CG). •Need for mechanical ventilation and mortality: No difference. |
| JamaliMoghadam Siahkali et al. (41) | RCT; Hospital; Male (50%); 59.3 ± 17.1 years. | •Group 1 (N = 30): 1500 mg of intravenous VC for 5 days. •Group 2 (N = 30): CG (lopinavir/ritonavir and HCQ). |
N = 60; Severe COVID-19; Comorbidity: hypertension (41.6%), DM (38.3), ischemic heart disease (18.3%), thyroid disease (8.3%), COPD (10%). | •↓mean body temperature and ↑SpO2 in the VC group on the 3rd day of hospitalization. •The length of hospitalization in the VC group was longer than the CG. •ICU stay, mortality rate, and intubation: No difference. •Fever and myalgia were less frequent in the VC group. |
| Zhang et al. (39) | RCT; ICU; Male (66.1%); 66.7 ± 12.7years. | •Group 1 (N = 27): 24 g of intravenous VC per day for 7 days. •Group 2 (N = 29): placebo (bacteriostatic water infusion). |
N = 56; Severe COVID-19 Comorbidity: DM (30.4%), hypertension (44.6%), coronary heart disease (21.4%), chronic lung disease (5.4%), chronic renal failure (1.8%), malignant tumor (5.4%), nervous system diseases (20.4%). | •No difference in days of absence (in 28 days) of mechanical ventilation between both groups. •VC group exhibited a trend (p=0.06) of reduction in 28-day mortality in more severe patients (SOFA score ≥3).•SOFA score: ↓ in the VC group, ↑ in the placebo group. •IL-6: ↓ in the VC group and ↑ in the placebo group. •Infectious indicators: No difference. |
| Thomas et al. (37) | RCT; Ambulatory; Female (61.7%); 45.2± 14.6years. | •Group 1 (N = 48): 8000 mg of VC (10 days). •Group 2 (N = 58): 50 mg of zinc gluconate (10 days). •Group 3 (N = 58): a combination of both therapies in groups 1 and 2 (10 days). •Group 4 (N = 50): no supplementation (ST). |
N = 214; Moderate and Severe COVID-19; Comorbidity: DM (13.6%), hypertension (32.7%), dyslipidemia (26.2%), asthma (15.4%), anxiety (18.2%) depression (15.4%). | •Days required to reach 50% reduction in symptoms: No difference among the groups. •No distinction in the number of days to reach no presence of cough, fever, shortness of breath, or fatigue among the groups. |
| Zhao et al. (43) | Retrospective BACMCS; Hospital; Male (61.8%); 36 years. | •Group 1 (N = 55): 100 mg/kg/day for 7 days from admission for one month. •Group 2 (N = 55): no supplementation (ST). |
N = 110; Moderate COVID-19; Comorbidity: hypertension (6.4%), DM (6.4%). | •VC group: less incidence of the final diagnosis of severe or critical COVID-19. •On Day 7, there were fewer patients with SIRS in the VC group compared to CG. However, the duration of SIRS was significantly shorter in the VC group compared to CG. •On Day 7, CRP levels: ↓ in VC group compared to CG. •VC group: improved effect on the CD4+ T lymphocyte deficiency on admission. •There were no obvious effects of the VC therapy of CD4+ T cell counts, CD8+ T cell counts, and lymphocytes counts on days 3 and 7 for the entire study population. •D-dimer levels: ↓VC group compared to CG. •APTT in the VC group (seconds) was significantly shorter than in the CG. |
| Gao et al. (46) | Cohort; Hospital; Male (46.1%); 61 years. | •Group 1 (N = 46): 6 g of intravenous VC (1° day), plus 6 g of VC per day (4 days). •Group 2 (N = 30): no supplementation (ST). |
N = 76; Moderate and severe COVID-19; Comorbidity: DM (19.7%), hypertension (28.9%), coronary heart disease (6.6%), underlying lung disease (7.9%), chronic liver disease (5.3%), chronic kidney disease (2.6%). | •Risk of mortality: ↓VC group compared to CG. •In the VC group, clinical improvement was better for patients younger than 60 years old. Moreover, the VC treatment was better for patients who received low-flow oxygen, and those with CRP <1 mg/L than their counterparts. •CRP, procalcitonin, and IL-8 levels: ↓ in the VC group compared to CG. •Thrombocytopenia and increased total bilirubin events were common in both groups. However, the incidence was lower in the VC group compared to CG. •Six patients showed serious adverse events (respiratory failure or ARDS, shock, and sepsis): one in the VC group and five in the CG. Moreover, respiratory failure or ARDS were more common in the CG. |
COVID-19, coronavirus disease 2019; CG, control group; NR, not reported; CAD, Coronary artery disease; DM, diabetes mellitus; mg: milligram; kg, kilogram; mL, milliliter; g, gram; HCQ, hydroxychloroquine; VC, vitamin C; SpO2, peripheral capillary oxygen saturation; IL, interleukin; ICU, intensive care unit; SOFA, sequential organ failure assessment; ST, standard therapy; SIRS, systemic inflammatory response syndrome; CRP, C-reactive protein; APTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; LSEQ: COPD, chronic obstructive pulmonary disease; Leeds sleep evaluation questionnaire; WBC, white blood cell; CI, confidence interval; ↑, increase; ↓, decrease.