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0 0.5 1 1.5 2+ Hospitalization -44% Improvement Relative Risk Recovery time 12% primary Zinc  COVIDAtoZ  EARLY TREATMENT  RCT Is early treatment with zinc beneficial for COVID-19? RCT 108 patients in the USA (April 2020 - February 2021) Faster recovery with zinc (not stat. sig., p=0.38) Thomas et al., JAMA Network Open, February 2021 Favors zinc Favors control

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial

Thomas et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369, COVIDAtoZ, NCT04342728
Feb 2021  
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Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. Study performed in the USA where zinc deficiency is relatively uncommon. The zinc dosage is relatively low, 50mg zinc gluconate (7mg elemental zinc), one tenth of that shown to reduce the duration of colds in other studies
This study includes vitamin C and zinc.
risk of hospitalization, 43.7% higher, RR 1.44, p = 0.72, treatment 5 of 58 (8.6%), control 3 of 50 (6.0%).
recovery time, 11.9% lower, relative time 0.88, p = 0.38, treatment mean 5.9 (±4.9) n=58, control mean 6.7 (±4.4) n=50, mean time to a 50% reduction in symptoms, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Thomas et al., 12 Feb 2021, Randomized Controlled Trial, USA, peer-reviewed, 11 authors, study period 8 April, 2020 - 11 February, 2021, trial NCT04342728 (history) (COVIDAtoZ).
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Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection
MD, MBA Suma Thomas, MD, MS Divyang Patel, BSN, RN Barbara Bittel, MPH Kathy Wolski, MS Qiuqing Wang, MD, MS Anirudh Kumar, Zachary J Il’giovine, MD, MS Reena Mehra, MD Carla Mcwilliams, MD Steve E Nissen, MD, MBA Milind Y Desai
JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369
IMPORTANCE There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. OBJECTIVE To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and
ARTICLE INFORMATION Additional Contributions: Serpil Erzurum, MD, James Young, MD, Daniel Culver, MD, Joan Booth, RN, Nancy Obuchowski, MPH, and John Petrich, RPh (Cleveland Clinic), were members of the operational and safety monitoring board. They were not compensated for their time. We would like to thank Samantha Xu, BS (Cleveland Clinic), for help with logistics of study set-up and coordination. She was compensated for her time.
Carr, Vitamin C administration in the critically ill: a summary of recent meta-analyses, Crit Care, doi:10.1186/s13054-019-2538-y
Eby, Davis, Halcomb, Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study, Antimicrob Agents Chemother, doi:10.1128/AAC.25.1.20
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Velthuis, Van Den Worm, Sims, Baric, Snijder et al., Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture, PLoS Pathog, doi:10.1371/journal.ppat.1001176
Wang, Il'giovine, Mehra, Nissen, Desai, None
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, JAMA, doi:
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