Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study

Abstract

Ascorbic acid represents an appealing option for clinicians to utilize in the context of the global COVID-19 pandemic due to its proposed clinical efficacy, relative safety, and low cost. The aim of this study was to evaluate the efficacy and safety of using ascorbic acid in supplemental doses as adjunctive therapy for patients critically ill with COVID-19. This was a two-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 diagnosis between March 1st and December 31st, 2020, were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the clinical outcomes of low-dose ascorbic acid as adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systematic use of corticosteroids, and study centers. A number of 739 patients were included in this study, among whom 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality or the 30-day mortality [OR (95% CI) 0.77 (0.47, 1.23), p value = 0.27 and OR (95% CI) 0.73 (0.43, 1.20), p value = 0.21, respectively]. Using ascorbic acid was associated with a lower incidence of thrombosis compared with the non-ascorbic-acid group [6.1% vs. 13% respectively; OR (95% CI) 0.42 (0.184, 0.937), p value = 0.03]. Low dose of ascorbic acid as an adjunctive therapy in COVID-19 critically ill patients was not associated with mortality benefits, but it was associated with a lower incidence of thrombosis. Further studies are required to confirm these findings.

Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

“…The latter could be addressed by performing a meta-analysis. Baseline severity is presented as Sequential Organ Failure Assessment Score (SOFA) (23,28) as Acute Physiology And Chronic Health Evaluation (APACHE II) (29) or other (25,32). *Data from the entire cohort of patients (not only critically ill) are presented.…”

“…However, we attempted to address this limitation by performing a sensitivity analysis of the 5 randomized controlled trials. Lastly, the included studies (23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in the meta-analysis did not consistently report on adverse events potentially related to administration of vitamin C, such as oxalate nephropathy, hypernatremia and glucometer error. Nevertheless, relevant evidence before the pandemic indicated that high-dose vitamin C may be relatively safe (36).…”

“…2). In the sensitivity analysis of studies with low risk of bias (23,25,(28)(29)(30)32), mortality was 25.1% in the vitamin C group and 32.2% in the control group (RR 1.13, 95% CI 0.59-2.16; p = 0.72; six studies; 1,344 patients; 410 deaths; Supplementary Figure 1); while, in the sensitivity analysis of randomized controlled trials (25,27,29,31,32), the relevant numbers were 10.5 and 17.2%, respectively (RR 0.66, 95% CI 0.39-1.14; p = 0.14; five studies; 346 patients; 48 deaths; Supplementary Figure 2).…”

Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients

“…Although a few observational research and preliminary clinical studies on vitamin C in patients with COVID-19 corroborate their findings by noting a reduction in hyper inflammation (43,44,47), improvement in the oxygen support status (39,41,46,47), lower incidence of thrombosis (42), and also the reduced disease aggravation in the early stage of COVID-19 pneumonia (43), the mortality rate is still controversial among the studies. Some authors found a reduction in mortality (46) whereas other studies with vitamin C did not observe a difference in mortality when compared to patients in the control group (40,42,45). Controversial research with vitamin C also demonstrated failure to ameliorate the mechanical ventilation of patients with COVID-19 (39,40) and did not find a substantial decrease in the duration of symptoms (37).…”

“…Among 108 coronavirus-associated melatonin articles extracted and assessed for eligibility, three studies with a melatonin approach were included (33)(34)(35). Moreover, among the 399 coronavirus-associated zinc studies extracted and evaluated for eligibility, three studies entered the inclusion criteria (36)(37)(38), whereas among 344 coronavirus-associated vitamin C (or ascorbic acid) papers initially extracted and analyzed for eligibility, a total of 10 papers were also included as RCTs or observational research (37,(39)(40)(41)(42)(43)(44)(45)(46)(47).…”