Abstract: Beigmohammadi et al. Trials (2021) 22:802 https://doi.org/10.1186/s13063-021-05795-4 RESEARCH Open Access The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: a randomized clinical trial Mohammad Taghi Beigmohammadi1, Sama Bitarafan2,3* , Azin Hoseindokht1, Alireza Abdollahi4,5, Laya Amoozadeh1 and Danesh Soltani2 Abstract Background and objective: Because of the effect of vitamins on modulating the immune system function, we have evaluated the effect of supplementation with vitamins A, B, C, D, and E in ICU-admitted patients with COVID19. Methods: This study was a randomized and single-blinded clinical trial in which 60 subjects were randomly assigned to two groups. The intervention group (n=30) received vitamins, and the control group did not receive any vitamin or placebo. The intervention was included 25,000 IU daily of vitamins A, 600,000 IU once during the study of D, 300 IU twice daily of E, 500 mg four times daily of C, and one amp daily of B complex for 7 days. At baseline and after the 7-day intervention, the serum levels of inflammatory markers, vitamins, and the SOFA score were assessed. In addition, the mortality rate and duration of hospitalization were evaluated after the intervention (IRCT registration number: IRCT20200319046819N1/registration date: 2020-04-04, https://www.irct.ir/trial/46838). Results: Significant changes were detected in serum levels of vitamins (p < 0.001 for all vitamins), ESR (p < 0.001), CRP (p = 0.001), IL6 (p = 0.003), TNF-a (p = 0.001), and SOFA score (p < 0.001) after intervention compared with the control group. The effect of vitamins on the mortality rate was not statistically significant (p=0.112). The prolonged hospitalization rate to more than 7 days was significantly lower in the intervention group than the control group (p=0.001). Regarding the effect size, there was a significant and inverse association between receiving the intervention and prolonged hospitalization (OR = 0.135, 95% CI 0.038–0.481; p=0.002); however, after adjusting for confounders, it was not significant (OR=0.402, 95% CI 0.086–1.883; p=0.247). * Correspondence: Bitarafans@gmail.com 2 Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 3 FHMS Clinic, Burnaby Hospital, Neurology Department, University of British Columbia, Vancouver, Canada Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver..