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Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D - 27/05/22

Doi : 10.1016/j.biopha.2022.112965 
Montserrat Torres h, 1, , Guiomar Casado h, 1, Lorena Vigón h, 1, Sara Rodríguez-Mora h, i, Elena Mateos h, i, Fernando Ramos-Martín h, Daniel López-Wolf j, José Sanz-Moreno k, Pablo Ryan-Murua l, María Luisa Taboada-Martínez m, María Rosa López-Huertas h, i, , Miguel Cervero n, 1, Mayte Coiras h, i, 1,

on behalf of Multidisciplinary Group of Study of COVID-19 (MGS-COVID)1

  These authors contributed equally to this study.

Contributing members of the Multidisciplinary Group of Study of COVID-19 (in alphabetical order)

David Alonso-Menchén a, Sandra Arévalo Camacho b, Cristina Avila Calzada b, José Antonio Barbado Albaladejo b, Natalia Blanca López c, Irene Cañamares Orbis c, Gema Carrillo Blanco b, Almudena Cascajero Díaz d, María Teresa Chica Burguillo b, Ana Corrochano García b, Sara Corredera García b, Victor Díez Viñas c, Marta Gómez-Alvarez Domínguez b, Claudia Patricia Fernández Fernández b, Yanira Fernández Mondelo b, Eva Fonseca Aizpuri e, Concepción García Lacalle b, Javier García-Pérez d, f, Cristina Helguera Amezua e, Francisco José Hidalgo Correas b, Amparo Lucena Campillo b, Mariano Matarranz del Amo c, Oriol Martín Sagarra g, Emilio José Martínez Martín g, José Javier Martínez Simón g, María Novella-Mena a, Virginia Pardo Guimera c, María Luisa Pinillos Pardo b, Fr`ancisca Ramírez Fuentes b, Daniel Renuncio García b, María Angeles Rodríguez Dávila b, Almudena Roger Revilla b, Lourdes Sampablo Valverde b, José Sanz Moreno a, Rafael Torres Perea b, Jorge Valencia La Rosa c, María Velasco Arribas g, Ana Villanueva Fernández-Ardavín g
a Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain 
b Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain 
c Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain 
d AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain 
e Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain 
f Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain 
g Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain 

h Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain 
i Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain 
j Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain 
k Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain 
l Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain 
m Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain 
n Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain 

Corresponding author.Correspondence to: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220 Madrid, Spain.Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos IIICtra. Majadahonda-Pozuelo km2Madrid28220Spain

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Abstract

Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p < 0.0001). Although levels of inflammatory cytokines were not modified by treatment with 10,000 IU/day, there was an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells, with predominance of T central memory subpopulation. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was increased more than 4-fold in patients who received 10,000 IU/day. Moreover, levels of IFNγ were significantly higher in this group. Beneficial effect of supplementation with 10,000 IU/day was also observed in participants who developed ARDS and stayed at the hospital for 8.0 days, whereas those who received 2000 IU/day stayed for 29.2 days (p = 0.0381). Administration of high doses of vitamin D3 as adjuvant of the standard care treatment during hospitalization for COVID-19 may improve the inflammatory environment and cytotoxic response against pseudotyped SARS-CoV-2 infected cells, shortening the hospital stay and, possibly, improving the prognosis.

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Graphical Abstract




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Highlights

Treatment with 10,000 IU/day of cholecalciferol was safe during severe COVID-19.
Anti-inflammatory cytokine IL-10 was significantly increased in 10,000 IU/day group.
Individuals who received 10,000 IU/day of cholecalciferol showed increased CD4 count.
Individuals with ARDS in 10,000 IU/day group stayed at the hospital less time.
The 10,000 IU/day group showed increased antiviral cytotoxic activity.

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Keywords : COVID-19, SARS-CoV-2, Vitamin D supplementation, Immune cytotoxic response


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