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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

Torres et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.112965

Apr 2022

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

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RCT comparing 41 patients treated with 10,000IU/day cholecalciferol and 44 treated with 2,000IU/day in Spain, showing significantly shorter hospitalization for ARDS patients with the higher dose. There was also an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was over 4-fold higher in patients receiving the higher dose.

Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 39% [26‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.

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risk of death, 7.3% higher, RR 1.07, p = 1.00, treatment 1 of 41 (2.4%), control 1 of 44 (2.3%).

risk of ICU admission, 57.1% lower, RR 0.43, p = 0.44, treatment 2 of 41 (4.9%), control 5 of 44 (11.4%), NNT 15.

risk of ARDS, 28.5% lower, RR 0.72, p = 0.74, treatment 4 of 41 (9.8%), control 6 of 44 (13.6%), NNT 26.

hospitalization time, 31.2% lower, relative time 0.69, treatment 41, control 44.

hospitalization time, 72.6% lower, relative time 0.27, p = 0.04, ARDS patients.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Torres et al., 14 Apr 2022, Single Blind Randomized Controlled Trial, Spain, peer-reviewed, median age 65.0, 51 authors, study period June 2020 - March 2021, average treatment delay 7.0 days, dosage 10,000IU days 1-14.

This Paper Vitamin D All

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, María 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

Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.112965

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin DImmunomodulatory effect of vitamin D supplementation in patients with COVID-19, Biomedicine & Pharmacotherapy,

Drug Cholecalciferol (vitamin D) used in the study was donated by Italfarmaco Group (Cholecalciferol 25,000IU/2,5ml oral solution). Italfarmaco Group had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or the preparation, review, or approval of the manuscript. Conflicts of interest The authors declare no conflict of interest. Author Contributions MCer and MCo conceptualized the project. MT, GC and MCo wrote the manuscript. MT, GC and LV performed the study of cytotoxicity. MT, GC and SRM performed the analysis of cell populations by flow cytometry with technical assistance from EM. J o u r n a l P r e -p r o o f MRLH and GC performed the analysis of cytokines in plasma. FR and EM processed and stored all blood samples. DLW, MNM, PRM, MLTM and MCer identified, selected, and recruited the patients, and also collected the blood samples. MT, MCer and MRLH collected and analyzed the clinical data. All co-authors read and approved the final version of the manuscript. Author Contributions MCer and MCo conceptualized the project. MT, GC and MCo wrote the manuscript. MT, GC and LV performed the study of cytotoxicity. MT, GC and SRM performed the analysis of cell populations by flow cytometry with technical assistance from EM. MRLH and GC performed the analysis of cytokines in plasma.  Anti-inflammatory cytokine IL-10 was significantly increased in 10,000 IU/day group.  Individuals who received 10,000..

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