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

SILVA MG; INSERRA F; MARIANI J; ANTONIETTI L; NUÑEZ M; TAJER C; FERDER L; INSERRA P; ROSS F; SÁNCHEZ CUNTO M; BERTELLI M; CELA E; GONZALEZ MAGLIO D; GIRONACCI MM; MANUCHA W

Exploration of Medicine

Open Exploration Publishing Inc

Año: 2023

Background: Angiotensin-converting enzyme 2 (ACE2) metabolizes angiotensin II (Ang II) intoAng-(1-7), which exerts protective effects, and also acts as a receptor for SARS-CoV-2, which maycause the severe acute respiratory syndrome. ACE2 is sequestered by the virus, thus an imbalancein the renin-angiotensin system (RAS) axes is generated. Since vitamin D (vitD) favors theprotective axis of the RAS, we hypothesized that COVID-19 patients treated with high doses ofvitD would have their RAS reduced. Aims: To evaluate Ang II and Ang-(1-7) levels and thecytokine profile in patients hospitalized with mild COVID-19 and treated with high doses of vitD.Methods: A cohort of patients from the CARED study (ClinicalTrials.gov NCT04411446) wasevaluated. From the 218 adult patients recruited, 16 participated in the sub-study and wererandomized to a single oral dose of 500,000 IU vitamin D3 (n=10) or placebo (n=6). Plasmatic AngII and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10and TNF-α by ELISA before and after treatment. Parallel, serum 25-OH vitamin D concentrations(vitamin D status) was measured by a chemiluminescence immunoassay. Results: A trend towardsan increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treatedCOVID-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 withILs profile. COVID-19 patients showed an increase in the protective component of the RAS whichwas not improved by vitD treatment. Conclusions: VitD did not improve RAS disbalance inCOVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD mayshow a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, wewould like to highlight the limitations of this preliminary study, namely the small number ofpatients and the use of a large single bolus dose of vitD rather than lower daily doses for extendedperiods with prolonged follow-up times. All these factors need special consideration in the designsof new vitD supplementation trials