Abstract: | Revised: 22 July 2022 | Accepted: 31 July 2022 Received: 15 September 2021 DOI: 10.1002/fsn3.3034 REVIEW ARTICLE Antioxidants and clinical outcomes of patients with coronavirus disease 2019: A systematic review of observational and interventional studies Sahar Foshati1 Reza Amani1 | Fatemeh Mirjalili1 | Mahsa Rezazadegan1 | Farnoosh Fakoorziba2 | 1 Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 2 Marquise Hospitality, Compass Group, Mississauga, Ontario, Canada Correspondence Reza Amani, Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Email: r_amani@nutr.mui.ac.ir; rezaamani@ hotmail.com Funding information Isfahan University of Medical Sciences, Grant/Award Number: 299234 Abstract Coronavirus disease 2019 (COVID-­19) is a newly emerging viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-­CoV-­2). Oxidative stress appears to be a prominent contributor to the pathogenicity of SARS-­CoV-­2. Therefore, we carried out a systematic review of human observational and interventional studies to investigate the role of some antioxidants such as vitamins A, E, D, and C, selenium, zinc, and α-­lipoic acid in the main clinical outcomes of subjects with COVID-­19. Google Scholar, Cochrane Library, Web of Science, Scopus, and Medline were searched using Medical Subject Headings (MeSH) and non-­MeSH terms without restrictions. Finally, 36 studies for vitamins C and D, selenium, and zinc were included in this systematic review; however, no eligible studies were found for vitamins A and E as well as α-­lipoic acid. The results showed the promising role of vitamin C in inflammation, Horowitz index, and mortality; vitamin D in disease manifestations and severity, inflammatory markers, lung involvement, ventilation requirement, hospitalization, intensive care unit (ICU) admission, and mortality; selenium in cure rate and mortality; and zinc in ventilation requirement, hospitalization, ICU admission, biomarkers of inflammation and bacterial infection, and disease complications. In conclusion, it seems that antioxidants, especially vitamins C and D, selenium, and zinc, can improve multiple COVID-­19 clinical outcomes. Nevertheless, more studies are necessary to affirm these results. KEYWORDS antioxidants, ascorbic acid, COVID-­19, oxidative stress, SARS-­CoV-­2, selenium, vitamin D, zinc 1 | I NTRO D U C TI O N results in mild to moderate influenza-­like symptoms, including fever, dry cough, and fatigue but can also lead to serious out- Coronavirus disease 2019 (COVID-­19) is a viral infection caused comes, such as hypoxemia, dyspnea, chest pain, and death. In early by a highly contagious pathogen named severe acute respira- 2020, COVID-­19 infection speedily spread throughout the world tory syndrome coronavirus 2 (SARS-­C oV-­2). This disease usually and was announced as a global pandemic by the World Health This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC. Food Sci Nutr. 2022;00:1–14.  wileyonlinelibrary.com/journal/fsn3 | 1 2 | FOSHATI et..