key: cord-0011937-zxvzswpy authors: Kim, Sun Bean; Yeom, Joon Sup title: Reply: Vitamin C as a Possible Therapy for COVID-19 date: 2020-05-27 journal: Infect Chemother DOI: 10.3947/ic.2020.52.2.224 sha: f6d25813730cc067ac96e4fb846c858beb43fa27 doc_id: 11937 cord_uid: zxvzswpy nan We appreciate the comment from Hemilä et al [1] . Previous studies based on in-vitro experiments have identified that high dosage intravenous Vit-C with copper and/or iron is virucidal [2] . However, despite these studies, the in-vivo virucidal activity of Vit-C has not been confirmed in detail. Previously, your meta-analyses of clinical trial data showed that regular Vit-C intake shortened the duration of the common cold by 8% [3] . However, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2) whose genome sequence differs from other human coronaviruses causing the common cold [4] . Moreover, two recent clinical trials have demonstrated no significant difference in the development of sepsis, or severe acute respiratory failure, between Vit-C and non-Vit-C groups. In the CITRIS-ALI trial, no significant difference was found between the Vit-C (50 mg/kg every 6 hours for 96 hours) and placebo groups in the primary outcomes measured. These included modified Sequential Organ Failure Assessment score, C-reactive protein levels, and thrombomodulin levels at 168 hours. However, secondary outcome measures did differ between the groups with 28-day all-cause mortality significantly lower and intensive care unit-free days significantly shorter in the placebo groups than in the Vit-C groups [5] . The Vitamin C, hydrocortisone and thiamine in patients with septic shock (VITAMINS) trial also reported that among patients with septic shock, a combination of intravenous Vit-C, hydrocortisone, and thiamine did not significantly improve the primary outcome measure (duration of time alive and free of vasopressor administration over 7 days) compared with that after the intravenous hydrocortisone treatment alone [6] . Although Vit-C generally exhibits low toxicity, taking >2 g of Vit-C per day may cause adverse gastrointestinal events including abdominal pain, diarrhea, and/or nausea. Although Vit-C is a water-soluble vitamin, with excess excreted in the urine, it can contribute to the formation of renal stones [7] . Additionally, glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic condition that results in inadequate G6PD levels, can cause hemolytic anemia following intravenous Vit-C treatment [8] . Currently, multiple clinical trials investigating the effect of Vit-C on severe COVID-19 are on going [9] . However, this therapy can only be considered, and therefore incorporated into treatment guidelines, based on sufficient confirmatory research results. For now, we will have to wait. Vitamin C as a possible therapy for COVID-19 The significance of the evidence about ascorbic acid and the common cold Vitamin C for preventing and treating the common cold Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: The CITRIS-ALI randomized clinical trial Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the vitamins randomized clinical trial The controversial place of vitamin C in cancer treatment Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency gov is a database of privately and publicly funded clinical studies conducted around the world