Is adjunctive vitamin C beneficial to critically ill patients with COVID-19?

Use of adjunctive intravenous (IV) vitamin C for the management of critically ill patients with COVID-19 infection does not achieve the desired outcome of a reduction in the incidence of mortality, vasopressor requirements, Sequential Organ Failure Assessment (SOFA) scores, or ventilator settings, reports a study.

“In a preliminary observational cohort study from a single-centre community teaching hospital, we found that adjunctive IV vitamin C did not decrease the incidence of mortality in critically ill patients with COVID-19 infection,” the researchers said.

Intensive care unit (ICU) patients who received 1.5-grams IV vitamin C every 6 hours for up to 4 days for COVID-19 infection were included in this retrospective observational cohort study. Eight patients received IV vitamin C and were propensity-score matched to 24 patients.

In-hospital mortality was the primary outcome, while secondary ones included vasopressor requirements in norepinephrine equivalents, ICU length of stay, and change in SOFA score.

The rates of hospital mortality were higher among patients in the IV vitamin C group than among those in the control group (88 percent [n=7] vs 79 percent [n=19]; p=0.049). [J Pharm Pract 2023;doi:10.1177/08971900211015052]

No difference was observed in the daily vasopressor requirement in the treatment group or between the two cohorts. Length of stay in the ICU also did not differ between the treatment and control groups. On the other hand, mean SOFA scores post-treatment were higher among patients who received vitamin C than controls (12.4 vs 8.1; p<0.005).

An earlier retrospective before-and-after study first assessed the use of IV vitamin C in critically ill patients and found significant reduction in mortality, SOFA score, and vasopressor requirement when combined with hydrocortisone and thiamine. However, subsequent trials did not find any decrease in mortality rates. [Chest 2017;151:1229-1238; JAMA 2020;323:423-431; JAMA 2019;322:1261-1270]

“We adapted the treatment regimens utilized in these studies for our patients due to the lack of available literature supporting alternative regimens for COVID-19 infection,” the researchers said. “Additional studies are now underway investigating various dosing and duration regimens.” [BMJ Open 2020;10:e039519; https://clinicaltrials.gov/ct2/show/NCT04323514]

The present findings might have been mediated by time to initiation of IV vitamin C, according to the researchers. Profound inflammation and cytokine storm were both associated with severe acute respiratory distress syndrome (ARDS) and subsequent mortality seen in COVID-19. [Front Immunol 2020;11:1446; Front Immunol 2020;11:2132; J Infect 2020;80:607-613]

In addition, early treatment may be necessary to prevent and reduce the cytokine storm since the benefit of therapy such as corticosteroids in ARDS depends on time to initiation in the disease course, according to the researchers. [Biofactors 2009;35:5-13]

“Although the optimal timing is still unknown and requires further investigation, IV vitamin C was administered on average within 7 days of admission, which may have been too late in the patient’s disease course to make a significant impact,” they added.

“Additional studies are needed to establish the optimal dose, duration, and potential role of IV vitamin C,” the researchers said.