Abstract: nutrients Article Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis Phil-Robin Tepasse 1, *,† , Richard Vollenberg 1,† , Manfred Fobker 2 , Iyad Kabar 1 , Hartmut Schmidt 1 , Jörn Arne Meier 1 , Tobias Nowacki 1 and Anna Hüsing-Kabar 1 1 2 * †



 Citation: Tepasse, P.-R.; Vollenberg, R.; Fobker, M.; Kabar, I.; Schmidt, H.; Meier, J.A.; Nowacki, T.; Hüsing-Kabar, A. Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis. Nutrients 2021, 13, 2173. https://doi.org/10.3390/nu13072173 Academic Editors: Dimitrios T. Karayiannis and Zafeiria Mastora Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, 48149 Muenster, Germany; richard.vollenberg@ukmuenster.de (R.V.); iyad.kabar@ukmuenster.de (I.K.); hepar@ukmuenster.de (H.S.); joernarne.meier@ukmuenster.de (J.A.M.); tobias.nowacki@ukmuenster.de (T.N.); Anna.Huesing-Kabar@ukmuenster.de (A.H.-K.) Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, Germany; manfred.fobker@ukmuenster.de Correspondence: phil-robin.tepasse@ukmuenster.de; Tel.: +49-251-834-4882 These authors contributed equally to this work. Abstract: COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01–30.26]; p = 0.048) and mortality (OR 5.21 [1.06–25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality. Received: 27 May 2021 Accepted: 20 June 2021 Published: 24 June 2021 Keywords: COVID-19; vitamin A; retinol; retinoic acid; ARDS; pneumonia; pandemic; SARS-CoV2; inflammation Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license..