Biomedicine & Pharmacotherapy (Jun 2022)
Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D
- Montserrat Torres,
- Guiomar Casado,
- Lorena Vigón,
- Sara Rodríguez-Mora,
- Elena Mateos,
- Fernando Ramos-Martín,
- Daniel López-Wolf,
- José Sanz-Moreno,
- Pablo Ryan-Murua,
- María Luisa Taboada-Martínez,
- María Rosa López-Huertas,
- Miguel Cervero,
- Mayte Coiras,
- David Alonso-Menchén,
- Sandra Arévalo Camacho,
- Cristina Avila Calzada,
- José Antonio Barbado Albaladejo,
- Natalia Blanca López,
- Irene Cañamares Orbis,
- Gema Carrillo Blanco,
- Almudena Cascajero Díaz,
- María Teresa Chica Burguillo,
- Ana Corrochano García,
- Sara Corredera García,
- Victor Díez Viñas,
- Marta Gómez-Alvarez Domínguez,
- Claudia Patricia Fernández Fernández,
- Yanira Fernández Mondelo,
- Eva Fonseca Aizpuri,
- Concepción García Lacalle,
- Javier García-Pérez,
- Cristina Helguera Amezua,
- Francisco José Hidalgo Correas,
- Amparo Lucena Campillo,
- Mariano Matarranz del Amo,
- Oriol Martín Sagarra,
- Emilio José Martínez Martín,
- José Javier Martínez Simón,
- María Novella-Mena,
- Virginia Pardo Guimera,
- María Luisa Pinillos Pardo,
- Fr`ancisca Ramírez Fuentes,
- Daniel Renuncio García,
- María Angeles Rodríguez Dávila,
- Almudena Roger Revilla,
- Lourdes Sampablo Valverde,
- José Sanz Moreno,
- Rafael Torres Perea,
- Jorge Valencia La Rosa,
- María Velasco Arribas,
- Ana Villanueva Fernández-Ardavín
Affiliations
- Montserrat Torres
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Corresponding author.
- Guiomar Casado
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
- Lorena Vigón
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
- Sara Rodríguez-Mora
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain
- Elena Mateos
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain
- Fernando Ramos-Martín
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
- Daniel López-Wolf
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- José Sanz-Moreno
- Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain
- Pablo Ryan-Murua
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- María Luisa Taboada-Martínez
- Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain
- María Rosa López-Huertas
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain; Correspondence to: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220 Madrid, Spain.
- Miguel Cervero
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Mayte Coiras
- Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain; Correspondence to: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2, 28220 Madrid, Spain.
- David Alonso-Menchén
- Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain
- Sandra Arévalo Camacho
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Cristina Avila Calzada
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- José Antonio Barbado Albaladejo
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Natalia Blanca López
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- Irene Cañamares Orbis
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- Gema Carrillo Blanco
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Almudena Cascajero Díaz
- AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
- María Teresa Chica Burguillo
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Ana Corrochano García
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Sara Corredera García
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Victor Díez Viñas
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- Marta Gómez-Alvarez Domínguez
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Claudia Patricia Fernández Fernández
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Yanira Fernández Mondelo
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Eva Fonseca Aizpuri
- Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain
- Concepción García Lacalle
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Javier García-Pérez
- AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Center Network in Infectious Diseases (CIBERINFEC), Spain
- Cristina Helguera Amezua
- Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain
- Francisco José Hidalgo Correas
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Amparo Lucena Campillo
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Mariano Matarranz del Amo
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- Oriol Martín Sagarra
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- Emilio José Martínez Martín
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- José Javier Martínez Simón
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- María Novella-Mena
- Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain
- Virginia Pardo Guimera
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- María Luisa Pinillos Pardo
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Fr`ancisca Ramírez Fuentes
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Daniel Renuncio García
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- María Angeles Rodríguez Dávila
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Almudena Roger Revilla
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Lourdes Sampablo Valverde
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- José Sanz Moreno
- Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá Henares, Spain
- Rafael Torres Perea
- Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain
- Jorge Valencia La Rosa
- Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain
- María Velasco Arribas
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- Ana Villanueva Fernández-Ardavín
- Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
- Journal volume & issue
-
Vol. 150
p. 112965
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.