Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients

Richard Vollenberg; Phil-Robin Tepasse; Manfred Fobker; Anna Hüsing-Kabar

doi:10.3390/nu14102007

Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients

Nutrients. 2022 May 10;14(10):2007. doi: 10.3390/nu14102007.

Authors

Richard Vollenberg¹, Phil-Robin Tepasse¹, Manfred Fobker², Anna Hüsing-Kabar¹

Affiliations

¹ Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
² Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, Germany.

Abstract

The SARS-CoV-2 virus is the causative agent of the COVID-19 pandemic. The disease causes respiratory failure in some individuals accompanied by marked hyperinflammation. Vitamin A (syn. retinol) can exist in the body in the storage form as retinyl ester, or in the transcriptionally active form as retinoic acid. The main function of retinol binding protein 4 (RBP4), synthesized in the liver, is to transport hydrophobic vitamin A to various tissues. Vitamin A has an important role in the innate and acquired immune system. In particular, it is involved in the repair of lung tissue after infections. In viral respiratory diseases such as influenza pneumonia, vitamin A supplementation has been shown to reduce mortality in animal models. In critically ill COVID-19 patients, a significant decrease in plasma vitamin A levels and an association with increased mortality have been observed. However, there is no evidence on RBP4 in relation to COVID-19. This prospective, multicenter, observational, cross-sectional study examined RBP4 (enzyme-linked immunosorbent assay) and vitamin A plasma levels (high-performance liquid chromatography) in COVID-19 patients, including 59 hospitalized patients. Of these, 19 developed critical illness (ARDS/ECMO), 20 developed severe illness (oxygenation disorder), and 20 developed moderate illness (no oxygenation disorder). Twenty age-matched convalescent patients following SARS-CoV-2 infection, were used as a control group. Reduced RBP4 plasma levels significantly correlated with impaired liver function and elevated inflammatory markers (CRP, lymphocytopenia). RBP4 levels were decreased in hospitalized patients with critical illness compared to nonpatients (p < 0.01). In comparison, significantly lower vitamin A levels were detected in hospitalized patients regardless of disease severity. Overall, we conclude that RBP4 plasma levels are significantly reduced in critically ill COVID-19 patients during acute inflammation, and vitamin A levels are significantly reduced in patients with moderate/severe/critical illness during the acute phase of illness.

Keywords: ARDS; COVID-19; SARS-CoV-2; inflammation; pandemic; pneumonia; retinoic acid; retinol; retinol binding protein 4; vitamin A.

Publication types

Multicenter Study
Observational Study

MeSH terms

COVID-19* / blood
Critical Illness
Cross-Sectional Studies
Humans
Prospective Studies
Retinol-Binding Proteins, Plasma* / analysis
Vitamin A* / blood

Substances

RBP4 protein, human
Retinol-Binding Proteins, Plasma
Vitamin A

Grants and funding

Founding by Innovative Medizinische Forschung (IMF), Medizinische Fakultät, Westfälische Wilhelms-Universität Münster, Germany (Funding Number: TE212102).