PMID- 35020796 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20230302 IS - 1938-3207 (Electronic) IS - 0002-9165 (Print) IS - 0002-9165 (Linking) VI - 115 IP - 3 DP - 2022 Mar 4 TI - Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19. PG - 790-798 LID - 10.1093/ajcn/nqab426 [doi] AB - BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in Sao Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1beta, IL-6, IL-10, TNF-alpha, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1beta (MIP-1beta), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean +/- SD age of 55.5 +/- 14.3 y and BMI of 32.2 +/- 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition. FAU - Fernandes, Alan L AU - Fernandes AL AUID- ORCID: 0000-0002-6786-3922 AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Murai, Igor H AU - Murai IH AUID- ORCID: 0000-0002-0077-5004 AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Reis, Bruna Z AU - Reis BZ AUID- ORCID: 0000-0001-8726-8699 AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Sales, Lucas P AU - Sales LP AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Santos, Mayara D AU - Santos MD AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Pinto, Ana J AU - Pinto AJ AD - Applied Physiology & Nutrition Research Group, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Goessler, Karla F AU - Goessler KF AD - Applied Physiology & Nutrition Research Group, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Duran, Camila S C AU - Duran CSC AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Silva, Carla B R AU - Silva CBR AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Franco, Andre S AU - Franco AS AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Macedo, Marina B AU - Macedo MB AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Dalmolin, Henrique H H AU - Dalmolin HHH AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Baggio, Janaina AU - Baggio J AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Balbi, Guilherme G M AU - Balbi GGM AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Antonangelo, Leila AU - Antonangelo L AD - Clinical Pathology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo,, Sao Paulo, Brazil. FAU - Caparbo, Valeria F AU - Caparbo VF AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Gualano, Bruno AU - Gualano B AUID- ORCID: 0000-0001-7100-8681 AD - Applied Physiology & Nutrition Research Group, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. AD - Food Research Center, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Pereira, Rosa M R AU - Pereira RMR AUID- ORCID: 0000-0002-3723-5028 AD - Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. LA - eng SI - ClinicalTrials.gov/NCT04449718 GR - 2020/11102-2/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/ GR - 305556/2017-7/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Nutr JT - The American journal of clinical nutrition JID - 0376027 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vitamins) RN - 1C6V77QF41 (Cholecalciferol) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adult MH - Aged MH - Brazil MH - COVID-19/immunology MH - Chemokines/*drug effects MH - Cholecalciferol/*administration & dosage MH - Cytokines/*drug effects MH - Double-Blind Method MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/*drug effects MH - Humans MH - Intercellular Signaling Peptides and Proteins/blood MH - Male MH - Middle Aged MH - SARS-CoV-2/immunology MH - Vascular Endothelial Growth Factor A/*drug effects MH - Vitamins/*administration & dosage MH - *COVID-19 Drug Treatment PMC - PMC8807215 OTO - NOTNLM OT - SARS-CoV-2 OT - acute-phase reactants OT - immune response OT - inflammation OT - vitamin D EDAT- 2022/01/13 06:00 MHDA- 2022/03/12 06:00 PMCR- 2023/01/21 CRDT- 2022/01/12 17:29 PHST- 2021/08/06 00:00 [received] PHST- 2021/12/27 00:00 [accepted] PHST- 2022/01/13 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2022/01/12 17:29 [entrez] PHST- 2023/01/21 00:00 [pmc-release] AID - S0002-9165(22)00196-4 [pii] AID - 10.1093/ajcn/nqab426 [doi] PST - ppublish SO - Am J Clin Nutr. 2022 Mar 4;115(3):790-798. doi: 10.1093/ajcn/nqab426.