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Copyright ©The Author(s) 2022.
World J Virol. Sep 25, 2022; 11(5): 300-309
Published online Sep 25, 2022. doi: 10.5501/wjv.v11.i5.300
Table 1 Different studies evaluating the role of high dose intravenous Vitamin C in COVID-19
S. No.
Title
Year of publication
Country of origin
Study design
Sample size in the control arm
Sample size in the intervention arm
Intervention summary
Results in brief
1Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia[14]2022TurkeyRetrospective study170 patients153 patients2 g/d IVNo difference in mortality
2High-dose intravenous vitamin C decreases rates of mechanical ventilation and cardiac arrest in severe COVID-19[33]2022USARetrospective cohort study75 patients25 patients3 gm 6 hrly for 7 d IVHDIVC group had a prolonged hospital stay, prolonged ICU stay, and prolonged time to deathCRP levels were lower in the HDIVC group while other inflammatory markers (d-dimer and ferritin) were similar in both groups.HDIVC patients had significantly lower rates of IMV and cardiac arrest
3Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial[43]2021IranRCT1110IV vitamin C (2 g, q6hr), oral; melatonin (6 mg, 6 hourly), and oral zinc sulfate (50 mg, 6 hourly) for 10 dNo differences in PaO2/FiO2, CRP, ESR or LDH levels and ICU LOS
4Pilot trial of high-dose vitamin C in critically ill COVID-19 patients[12]2021ChinaMulti center RCT29 in control27 treatment group12 g of vitamin C/50 ml every 12 h for 7 d at a rate of 12 mL/h IVNo difference in IMV free days at D28; no difference in 28-d mortality. Steady rise in the PaO2/FiO2 in vitamin C group
5No significant benefit of moderate-dose vitamin C on severe COVID-19 cases[34]2021ChinaRetrospective cohort study327702-4 gm/dNo significant difference in clinical improvement or mortality rate
6Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study[35]2021ChinaRetrospective case series12 patients71 to 350 mg/kg/d for 3 d IVReduction in CRPImproved PaO2/FiO2 and SOFA score
7High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study[36]2021ChinaRetrospective before-after study55 patients55 patients100 mg/kg/d IV for 7 dSignificant reduction in progression to severe disease.Reduced levels of CRP, D-dimer and APTT
8Safety and effectiveness of high-dose vitamin C in patients with COVID-19: A randomized open-label clinical trial[44]2021IranRandomised open-label study30 patients30 patients6 g/d IVReduced temperature and improved SaO2 in HDIVC group. No difference in ICU or hospital mortalityLonger hospital LOS in HDIVC group
9Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection[37]2021USARetrospective cohort study24 patients8 patients1.5 grams IV vitamin C every 6 h for up to 4 dHDIVC group had higher rates of hospital mortality and mean SOFA scores post-treatment. No difference in daily vasopressor requirement or ICU LOS
10High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019[38]2021ChinaRetrospective cohort study15185100 mg/kg every 6 h for day 1 followed by 100 mg/kg evry 12 h for the next 5 dSignificantly reduced inflammatory markers (hs-CRP, IL-6, TNF-alpha)
11The efficiency and safety of high-dose vitamin C in patients with COVID-19: A retrospective cohort study[39]2021ChinaRetrospective cohort study30466 g twice a day on day 1 followed by 6 gm once a day for 4 d IVReduced 28 d mortality. No change in oxygen support
12High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: A retrospective cohort study[40]2021ChinaRetrospective cohort study6251100 mg/kg every 6 h for day 1 followed by 100 mg/kg evry 12 h for the next 5 dHDIVC can ameliorate cardiac injury through alleviating hyperinflammation
13The Role of Vitamin C as Adjuvant Therapy in COVID-19[13]2020PakistanRCT75 patients75 patients50 mg/kg/day of intravenous (IV)Earlier resolution of symptoms and reduced hospital LOS. No significant difference in the need for IMV and mortality
14Activities of serum ferritin and treatment outcomes among COVID-19 patients treated with vitamin c and dexamethasone:An uncontrolled single-center observational study[41]2020IndiaProspective, observational study50 patientsNAMortality 6%
15The use of IV vitamin C for patients with COVID-19: A case series[11]2020USACase series17 patients1 g every 8 h for 3 d IVSignificant decrease in inflammatory markers. Mortality 12%
16Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial[42]2020IranPhase I clinical trial25 ICU COVID-19 patients. 5 received MCN as last resort25 healthy individualsMethylene blue (1 mg/kg) along with vitamin C (1500 mg/kg) and N-acetyl Cysteine (1500 mg/kg) orally or intravenouslyReduced methhemoglobin levels, survival of 4/5 patients
Table 2 Meta-analyses evaluating the role of Vitamin C in COVID-19
S. No.
Title
Year of publication
Country of origin
Included studies
Included sample size
Results in brief
1Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis[45]2022China7 studies (3 RCTs, 4 observational studies)807 patientsIV vitamin C treatment did not affect disease severity or mortality
2The effectiveness of high-dose intravenous vitamin C for patients withcoronavirus disease 2019: A systematic review and meta-analysis[46]2022Korea5 studies (3 RCTs, 2 retrospective trials)374 patients (186 HDIVC and 184 control group)No difference in hospital LOS or mortality
3Vitamin C and COVID-19 treatment: A systematic review and metaanalysis of randomized controlled trials[47]2021India6 RCTs572 patientsVitamin C treatment didn’t reducemortality, ICU LOS, hospital LOS or need for invasive mechanical ventilation
Table 3 Adverse effects reported with vitamin C
Item
Description
GeneralInterference with laboratory tests, phlebitis, nausea, vomiting
Neuro-muscularLethargy, fatigue, muscle cramps, headache, altered mental status
MetabolicHyperglycemia, hypernatremia
HaematologicalHaemolysis, disseminated intravascular coagulation, methemoglobinemia
RenalOxalosis, renal stones, acute kidney injury