Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia.

Dear Editor,

We read with great interest the study by Kavurgacı et al., which was published online-ahead-of-print in Medicina Clinica. In this retrospective study, 323 patients hospitalized with severe COVID-19 pneumonia were divided into two groups and the clinical features of patients who received high-dose vitamin C (VitC) were compared with those who did not. There was no difference in terms of length of hospital stay, re-admission rate, admission rate to the intensive care unit (ICU), and the need for advanced oxygen therapy between the groups that received and did not receive VitC, whereas the need for advanced medical treatment was higher in the group receiving VitC with no difference in terms of mortality. This is an important issue but there are some practical questions to be answered for a proper clinical extrapolation.

Firstly, when the baseline characteristics of the groups that received and did not receive VitC were investigated, there seems no difference in terms of gender and comorbidities. In this study where clinical data was very insufficient, among the inflammatory parameters that was examined in the study, C-reactive protein levels were similar between two groups, whereas ferritin level was higher in the group given VitC (median 415.5 vs 271 ng/mL; p  = 0.029). There was no difference between the groups in terms of SpO2 (87.3 ± 8.7% vs 87.9 ± 8.3%; p  = 0.07), which was the only clinical data presented in the study. The information obtained from the study regarding the severity of the COVID-19 patients is limited. Considering that this study was retrospective, it is understood that the administration of VitC was done randomly. As emphasized in the introduction part of the study, no scoring was used for cytokine storm in COVID-19 patients. Therefore, VitC delivery criteria should be defined more clearly. In addition, the group which did not receive VitC was older (64.3 ± 14.5 vs 60.2 ± 13.7; p  = 0.009). The group receiving VitC had an increase in ferritin levels after treatment (415.5 vs 530.6 ng/ml; p  = 0.006). This results are in contrast to the possible expected positive results of VitC in COVID-19.

Secondly; the need for advanced medical treatment was higher in the group that received VitC (24.2% vs 8.8%; p  < 0.001). The studies conducted with the use of VitC in COVID-19 patients with severe pneumonia and hypoxic respiratory failure resulted in positive results with the VitC level varying between 6 g/day and 20 g/day. In the study of Kavurgacı et al., the level of 2 g/day given for 3 days seems to be at the supplement level and should be considered as below the treatment dose.

COVID-19 can cause acute respiratory distress syndrome (ARDS), secondary infections, and sepsis. An intravenous treatment with high-dose VitC has shown beneficial effects on sepsis and septic shock. An intravenous infusion of VitC (50 mg/kg body weight) every 6 h for 96 h significantly decreased mortality and increased the number of ICU-free days in patients with sepsis and ARDS, compared to the control group. Although it was stated that all of the patients in Kavurgacı’s et al.’s study had severe acute respiratory syndrome, there was no data regarding the PaO2/FIO2 ratios of the patients, and the type of oxygen respiratory support treatments applied. It was reported that mortality rates were similar between groups that received and did not receive VitC (11.1% vs 14.1%; p  = 0.52). However, in this study, no data regarding the APACHE-II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment Score) scores of the patients were presented. In addition, in Kavurgacı’s et al. study only 7% of the patients were followed up in the ICU which may have affected the mortality assessment. In our recent study, we included the patients who were intubated in the ICU with the diagnosis of COVID-19 associated ARDS and who have ICU follow-up for at least 48 h. We accepted as high-dose VitC being equal to or above 200/mg/kg/day for at least 4 days. It was observed that high-dose VitC reduced mortality and prolonged life expectancy in this severe patient group. In the daily SOFA follow-up, daily improvement in the score was detected in our VitC group.

Further prospective clinical trials need to confirm appropriate usage of VitC in COVID-19 patients with severe acute respiratory syndrome.

Conflict of interest

The authors declared no conflict of interest.