Table 3.

Retrospective cohort studies investigating the effect of intravenous vitamin C (IVC) in patients with COVID-19.

Population Mean Age Location	Intervention Duration	Findings (IVC vs. Control)	Reference
76 patients with moderate to severe COVID-19 Age = 61 (52–71) years Xi’an, Shaanxi, China	IVC 1 6 g/12 h on first day, 6 g/day for following 4 days + standard therapy (n = 30) or standard therapy (n = 46) for 5 days	Improved oxygen support status (64% vs. 36%) Reduced risk of 28-day mortality (HR 2 = 0.14, 95% CI, 0.03–0.72, p = 0.037) Reduced CRP 3, PCT 4 and IL-8 5 concentrations	[32]
110 patients with moderate COVID-19 pneumonia Age = 36 (31–47) years Shanghai, China	IVC 100 mg/kg/day + standard therapy or standard therapy (55 per group) for 7 days	Fewer patients progressing to severe type (4 vs. 12; RR 6 0.28 [0.08, 0.93], p = 0.03) Reduction in duration (p < 0.001) and incidence of SIRS 7 (p = 0.008) Lower CRP concentrations (p = 0.005) Lower activated partial thromboplastintime (p = 0.02) Higher CD4+ (helper) T cells (p = 0.0004)	[35]
232 patients with COVID-19-pneumonia Age = 60 ± 14 years Ankara, Turkey	IVC 2 g/day + standard therapy (n = 153) or standard therapy (n = 170)	Shorter length of hospital stay (7 vs. 8 d, p = 0.05) No difference in re-admission rate (p = 0.94), admission to ICU 8, need for advanced oxygen support (p = 0.49), and mortality (p = 0.52) Need for advanced medical treatment (p < 0.001)	[36]
34 critically ill patients with COVID-19 Age = 65 ± 12 years New York, USA	IVC 1.5 g/6 h + standard therapy (n = 8) or standard therapy (n = 24) for 4 days	Higher rate of hospital mortality (19 [79%] vs. 7 [88%], p = 0.049) and SOFA scores (12 ± 3 vs. 8 ± 4, p < 0.005) No difference in daily vasopressor requirement or ICU length of stay	[37]
236 patients with severe COVID-19 Age = 66 (57–73) years Wuhan, China	IVC 100 mg/kg/6 h on day 1 then 100 mg/kg/12 h for the next 5 days + standard therapy (n = 85) or standard therapy (n = 151)	Reduction in inflammatory markers (CRP, p = 0.032; IL-6, p = 0.005; TNF-α 9, p = 0.015)	[33]
113 patients with severe COVID-19 and cardiac injury Age = 68 (59–77) years Wuhan, China	IVC 100 mg/kg/6 h on day 1 then 100 mg/kg/12 h for the next 5 days + standard therapy (n = 51) or standard therapy (n = 62)	IVC was associated with ameliorated cardiac injury (OR 2.42 [1.02, 5.73], p = 0.04) Reduced levels of inflammatory markers (CRP, IL-6, IL-8, TNF-α) at 21 days of hospitalisation	[34]

¹ IVC: intravenous vitamin C, ² HR: hazard ratio, ³ CRP: C-reactive protein, ⁴ PCT: procalcitonin, ⁵ IL: interleukin, ⁶ RR: relative risk, ⁷ SIRS: systemic inflammatory response syndrome, ⁸ ICU: Intensive care unit, ⁹ TNF: tumor necrosis factor.