MECHANISTIC APPROACHING STUDY IN COVID-19 PATIENTS TREATED WITH HIGH DOSES OF VITAMIN D

MAURO G. SILVA; FELIPE INSERRA; JAVIER MARIANI; LAURA ANTONIETTI; MYRIAM NUÑEZ; CARLOS DANIEL TAJER; LEÓN FERDER; PABLO I. F. INSERRA; FERNANDO ROSS; MILAGROS SÁNCHEZ CUNTO; MAGALÍ BERTELLI; GABRIELA DE LARRAÑAGA; ELIANA CELA; DANIEL GONZÁLEZ MAGLIO; MARIELA GIRONACCI; WALTER MANUCHA

Exploration of Medicine

Open Exploration

Año: 2023 vol. 4 p. 246 - 253

Background: Angiotensin-converting enzyme 2 (ACE2) metabolizes angiotensin II (Ang II) into Ang-(1-7), which exerts protective effects, and also acts as a receptor for SARS-CoV-2, which causes -by mean cytokine storm- a severe acute respiratory syndrome. ACE2 is sequestered by the virus, losing its catalytic effect and causing an imbalance in the renin-angiotensin system (RAS) axes. Of interest, vitamin D interacts with the RAS/ACE/ACE-2 axis and is therefore postulated as a possible treatment for COVID-19 disease attenuation. Aims: To evaluate levels of Ang II and Ang-(1-7), as well as the cytokine profile in patients hospitalized for mild COVID-19 and treated with high doses of vitamin D. Methods: We worked with a cohort of patients from the CARED study (ClinicalTrials.gov NCT04411446). We recruited 218 adult patients and accessed pathophysiology sub-study 16, who were randomized to a single oral dose of 500,000 IU vitamin D3 (n=10) or placebo (n=6). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8 and 10 and TNF-α by ELISA before and after treatment. Results: Plasma levels of Ang-(1-7) increased while those of Ang II decreased in both the placebo and vitamin D3 groups. The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in both groups. Excluding very old patients and those with morbid obesity we found that, in the vitamin D3 treated patients, there was a trend to a decline inflammatory ILs and an increase in protective markers, such as serum levels of Ang-(1-7), Ang-(1-7)/Ang II ratio.Conclusions: Acute treatment with high doses of vitamin D3 did not significantly modify the levels of cytokines or Ang II and Ang-(1-7)