# The Distinct Regulation of the Vitamin D and Aryl Hydrocarbon Receptors in COVID-19

## TL;DR

This study shows that vitamin D and aryl hydrocarbon receptor pathways are regulated differently in mild versus severe COVID-19 cases, suggesting potential benefits of vitamin D treatment.

## Contribution

The study reveals distinct regulation of VDR and AhR pathways in mild and severe COVID-19, proposing a novel therapeutic approach combining antivirals and vitamin D.

## Key findings

- VDR-specific mRNA was significantly upregulated in mild COVID-19 patients compared to controls.
- Critically ill patients showed impaired VDR upregulation and downregulation compared to survivors.
- 25(OH)-vitamin D3 levels were not significantly different between critically ill survivors and non-survivors.

## Abstract

(1) Background: SARS-CoV-2 affects several immune pathways, including the vitamin D (VDR) and the aryl hydrocarbon receptor pathways (AhR). The aim of the study was the evaluation of the VDR and AhR pathways in the blood of COVID-19 patients with regard to the severity of disease. (2) Methods: Observational, single-center, case–control design. A total of 240 samples were selected for exploration. Patients who tested negative for SARS-CoV-2 but suffered from other respiratory infections (ORIs) served as a control group. (3) Results: VDR-specific mRNA in the blood of patients with mild symptoms (131.2 ± 198.6) was significantly upregulated relative to the VDR expression of the ORI group (23.24 ± 42.60; p < 0.0001); however, VDR expression of critically ill patients showed an impaired upregulation (54.73 ± 68.34; p < 0.001). CYP27B1 expression was not significantly regulated during SARS-CoV-2 infection. There was a downregulation of VDR and CYP27B1 compared to survivors. There was no significant difference in 25(OH)-vitamin D3 levels between critically ill patients with regard to survival (24.3 ± 9.4 vs. 27.1 ± 11.3; p = 0.433). (4) Conclusion: The VDR and AhR pathways are distinctively regulated in patients suffering from COVID-19 depending on the severity of disease. A combination treatment of antiviral drugs and vitamin D substitution should be evaluated for potentially improved prognosis in COVID-19.