Abstract: nutrients Article Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients Richard Vollenberg 1, * , Phil-Robin Tepasse 1 , Manfred Fobker 2 and Anna Hüsing-Kabar 1 1 2 * Citation: Vollenberg, R.; Tepasse, P.-R.; Fobker, M.; Hüsing-Kabar, A. Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients. Nutrients 2022, 14, 2007. https://doi.org/10.3390/ nu14102007 Academic Editors: Andrea P. Rossi and Marwan El Ghoch Received: 12 April 2022 Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; phil-robin.tepasse@ukmuenster.de (P.-R.T.); anna.huesing-kabar@ukmuenster.de (A.H.-K.) Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, Germany; manfred.fobker@ukmuenster.de Correspondence: richard.vollenberg@ukmuenster.de; Tel.: +49-25-1834-9198 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, crosssectional 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. Accepted: 8 May 2022 Published: 10 May 2022 Publisher’s Note: MDPI stays neutral Keywords: COVID-19; retinol binding protein 4; vitamin A; retinol; retinoic acid; ARDS; pneumonia; pandemic; SARS-CoV-2; inflammation with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an..