• 
• 

Three Part Question

Is [high intravenous dose of vitamin C] [adjunctive treatment] for [coronavirus disease 2019 (COVID-19) critically ill patients]?

Clinical Scenario

A 59-year-old male is admitted to our ICU because of fever, low level of consciousness, decreased SPO2,he has a past medical history of diabetes mellitus. Chest radiography (CXR) was performed, which reported patchy air space opacity in the right upper lobe suspicious for pneumonia . Lung HRCT revealed bilateral ground-glass opacities (GGOs). LAB data shows leukocytosis and elevated CRP and ESR levels

Search Strategy

Pubmed and Medline December 2019/ august 2020
Cochrane library database reviews
Further searches were carried out on google scholar

[exp vitamin C OR exp Ascorbic acid] AND [exp high-dose OR exp intravenous] AND [ exp covid-19 OR exp coronavirus] .ti,ab
limit to humans and English language.

Search Outcome

24 papers were found of which 4 papers were more relevant to the discussion .

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Fang Liu, Yuan Zhu, Jing Zhang, Yiming Li, Zhiyong Peng 2020 china	308 adults diagnosed with COVID-19 and transferred into the intensive care unit hospitalized in the icu of Zhongnan Hospital of Wuhan University and the ICU of Leishenshan Hospital of Wuhan . The intervention lasted for 7 days. For the treatment group, 12 g VC will be diluted in sterile water to a total volume of 50 mL and will be infused within 4 hours by an infusion pump. This treatment will be repeated every 12 hours.	multicenter, prospective randomized, placebo-controlled trial	clarifying the effect of high-dose vitamin C for the treatment of severe COVID-19	The primary outcome is ventilation-free days within 28 observational days, some secondary outcomes were noticed like: Changes in SOFA scores. Changes in plasma biomarkers of inflammation, Changes in pulmonary infection estimated by chest radiography/CT imaging and lung ultrasound and changes in pulmonary function measured by Murray lung injury scores.	As the duration and distribution of infected cases were unpredictable geographically and temporally, the number of recruited patients at each center was also unpredictable, in spite of competitive enrolment, also complete blinding was not feasible due to the lack of available resources, such as placebos in the same package as VC
Hafiz Muhammad Waqas Khan, Niraj Parikh, Shady Maher Megala, and George Silviu Predeteanu 2020 USA	A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia	Case report	evaluated the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients	The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. there was an early recovery and shortened length of mechanical ventilation and ICU stay was observed.	As it was a case report, it is hard to generalize the results.
Raul Hiedra , Kevin Bryan Lo , Mohammad Elbashabsheh , Fahad Gul , Robert Matthew Wright , Jeri Alba 2020 USA	17 patients who were Sequentially identified and confirmed to be Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive via single-test nasopharyngeal swab PCR who were requiring 30% or more fraction of inspired oxygen (FiO2) and who received IV vitamin C as part of the COVID-19 treatment. Vitamin C was administered at a dose of 1 g every 8 h for 3 days	Sequential study	reviewed the feasibility of using vitamin C in the setting of COVID-19 in a series of patients	The inpatient mortality rate in this series was 12% with 17.6% rates of intubation and mechanical ventilation. We noted a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration.	Small number of cases as well as they were unable to take into consideration the use of other medications that may influence relevant outcomes
Daryoush Hamidi Alamdari et al 2020 iran	five out of 25 ICU COVID-19 patients were recruited in clinical trial and treatment with MCN(MB, VITAMIN C and N-acetyl Cysteine)	Retrospective clinical trial	Evaluation of the therapeutic effect of administered MCN	Four out of the five patients responded well to the treatment	the trial enrolled as combination therapy and it is not possible to determine the exact effect of vitamin c individually

Comment(s)

Available data are unable to support mortality benefit from high dose vitamin c infusion. Although it is revealed by several reports that vitamin C can suppress cytokine storms in covid-19 patients and subsequently improves pulmonary function, VC is currently not mentioned in the treatment guidelines for COVID-19. High dose of vitamin C has been proven in critical care medicine, however the efficacy of its administration in order to reduce ICU stay remains debatable and requires further clinical trials.

Clinical Bottom Line

There is no existing evidence that directly points out the efficacy of intravenous vitamin C as an adjunctive treatment in preventing mortality or shortening disease course among adults positive for COVID-19

References

1. Fang Liu, Yuan Zhu, Jing Zhang, Yiming Li, Zhiyong Peng Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial
2. Hafiz Muhammad Waqas Khan, Niraj Parikh, Shady Maher Megala, and George Silviu Predeteanu Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C
3. Raul Hiedra , Kevin Bryan Lo , Mohammad Elbashabsheh , Fahad Gul , Robert Matthew Wright , Jeri Albano , Zurab Azmaiparashvili , Gabriel Patarroyo Aponte , 2020, Philadelphia , USA The use of IV vitamin C for patients with COVID-19: a case series
4. Daryoush Hamidi Alamdari et al Application of methylene blue -vitamin C –N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial