Abstract: Internal and Emergency Medicine https://doi.org/10.1007/s11739-022-02954-6 EM - ORIGINAL High‑dose intravenous vitamin C decreases rates of mechanical ventilation and cardiac arrest in severe COVID‑19 Andrea L. Hess1 · Alexandra Halalau1,2 · Jonathan J. Dokter1 · Tania S. Paydawy3 · Patrick Karabon4 · Aveh Bastani1,5 · Rebecca E. Baker3 · Abdalla Kara Balla2 · Stephen A. Galens1,6 Received: 30 March 2021 / Accepted: 22 February 2022 © The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI) 2022 Abstract Intravenous vitamin C (IV-VitC) has been suggested as a treatment for severe sepsis and acute respiratory distress syndrome; however, there are limited studies evaluating its use in severe COVID-19. Efficacy and safety of high-dose IV-VitC (HDIVC) in patients with severe COVID-19 were evaluated. This observational cohort was conducted at a single-center, 530 bed, community teaching hospital and took place from March 2020 through July 2020. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes in patients with severe COVID-19 treated with and without HDIVC. Patients were enrolled if they were older than 18 years of age and were hospitalized secondary to severe COVID-19 infection, indicated by an oxygenation index < 300. Primary study outcomes included mortality, mechanical ventilation, intensive care unit (ICU) admission, and cardiac arrest. From a total of 100 patients enrolled, 25 patients were in the HDIVC group and 75 patients in the control group. The average time to death was significantly longer for HDIVC patients (P = 0.0139), with an average of 22.9 days versus 13.7 days for control patients. Patients who received HDIVC also had significantly lower rates of mechanical ventilation (52.93% vs. 73.14%; ­ORIPTW = 0.27; P = 0.0499) and cardiac arrest (2.46% vs. 9.06%; ­ORIPTW = 0.23; P = 0.0439). HDIVC may be an effective treatment in decreasing the rates of mechanical ventilation and cardiac arrest in hospitalized patients with severe COVID-19. A longer hospital stay and prolonged time to death may suggest that HDIVC may protect against clinical deterioration in severe COVID-19. Keywords Ascorbic acid · Vitamin C · Treatment · Intensive care · SARS-CoV-2