Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial
Dagan Coppock,
Pierre-Christian Violet,
Gustavo Vasquez,
Katherine Belden,
Michael Foster,
Bret Mullin,
Devon Magee,
Isabelle Mikell,
Lokesh Shah,
Victoria Powers,
Brian Curcio,
Daniel Monti,
Mark Levine
Affiliations
Dagan Coppock
Division of Infectious Diseases, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Chestnut Street, Philadelphia, PA 19107, USA
Pierre-Christian Violet
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Gustavo Vasquez
Division of Infectious Diseases, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Chestnut Street, Philadelphia, PA 19107, USA
Katherine Belden
Division of Infectious Diseases, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Chestnut Street, Philadelphia, PA 19107, USA
Michael Foster
Jefferson Clinical Research Institute, Thomas Jefferson University, 833 Chestnut Street, Philadelphia, PA 19107, USA
Bret Mullin
Jefferson Clinical Research Institute, Thomas Jefferson University, 833 Chestnut Street, Philadelphia, PA 19107, USA
Devon Magee
Jefferson Clinical Research Institute, Thomas Jefferson University, 833 Chestnut Street, Philadelphia, PA 19107, USA
Isabelle Mikell
Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA
Lokesh Shah
Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA
Victoria Powers
Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA
Brian Curcio
Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Chestnut Street, Philadelphia, PA 19107, USA
Daniel Monti
Department of Integrative Medicine and Nutritional Sciences, Sidney Kimmel Medical College, Thomas Jefferson University, 925 Chestnut Street, Philadelphia, PA 19107, USA
Mark Levine
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.
