Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D

Author:

Silva Mauro G.1,Inserra Felipe2,Mariani Javier3,Antonietti Laura3,Nuñez Myriam4,Tajer Carlos3,Ferder León2,Inserra Pablo I. F.5,Ross Fernando6,Cunto Milagro Sánchez7,Bertelli Magalí7,de Larrañaga Gabriela7,Cela Eliana M.8,Maglio Daniel H. González8,Gironacci Mariela M.1,Manucha Walter9

Affiliation:

1. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina

2. Department of Biosciences, Universidad Maimónides, Ciudad Autónoma de Buenos Aires, Buenos Aires 1405, Argentina

3. Hospital de Alta Complejidad en Red El Cruce-Néstor Kirchner, Florencio Varela, Buenos Aires 1888, Argentina

4. Cátedra de Matemáticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina

5. Centro de Estudios Biomédicos, Básicos, Aplicados y Desarrollo (CEBBAD), Universidad Maimónides, CONICET, Buenos Aires 1405, Argentina

6. Medical Clinic Section, Clínica Santa Isabel, Ciudad Autónoma de Buenos Aires, Buenos Aires 1406GZJ, Argentina

7. Medical Clinic Section, Hospital de Infecciosas Francisco Javier Muñiz, Ciudad Autónoma de Buenos Aires, Buenos Aires 1282AEN, Argentina

8. Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina; Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Buenos Aires 1113, Argentina

9. Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET-Universidad Nacional de Cuyo, Mendoza 5500, Argentina; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina

Abstract

Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment. Conclusions: VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).

Publisher

Open Exploration Publishing

Subject

General Medicine

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