Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patientshttps://www.mdpi.com/2072-6643/14/10/2007
Vollenberg et al.
, Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19..
, Nutrients, doi:10.3390/nu14102007
Prospective study of 59 hospitalized COVID-19 patients and 20 matched convalescent control patients in Germany, showing significantly lower vitamin A levels in COVID-19 patients.
Vollenberg et al., 10 May 2022, prospective, Germany, peer-reviewed, 4 authors.
firstname.lastname@example.org (corresponding author), email@example.com, firstname.lastname@example.org, email@example.com.
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
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/
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;
firstname.lastname@example.org (P.-R.T.); email@example.com (A.H.-K.)
Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, Germany;
Correspondence: firstname.lastname@example.org; 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
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