Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity
George Mpekoulis,
Katerina I. Kalliampakou,
Raphaela S. Milona,
Despoina Lagou,
Anastasios Ioannidis,
Edison Jahaj,
Christos T. Chasapis,
Dionysis Kefallinos,
Ioannis Karakasiliotis,
Anastasia Kotanidou,
Stylianos Chatzipanagiotou,
Dido Vassilacopoulou,
Alice G. Vassiliou,
Emmanouil Angelakis,
Niki Vassilaki
Affiliations
George Mpekoulis
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
Katerina I. Kalliampakou
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
Raphaela S. Milona
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
Despoina Lagou
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
Anastasios Ioannidis
Department of Nursing, University of Peloponnese, 23100 Sparti, Greece
Edison Jahaj
GP Livanos and M Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services, National and Kapodistrian University of Athens Medical School, Evangelismos Hospital, 10676 Athens, Greece
Christos T. Chasapis
Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
Dionysis Kefallinos
School of Electrical Engineering and Computer Science, National Technical University of Athens, 9 Iroon Polytechniou Street, Zografou, 15773 Athens, Greece
Ioannis Karakasiliotis
Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
Anastasia Kotanidou
GP Livanos and M Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services, National and Kapodistrian University of Athens Medical School, Evangelismos Hospital, 10676 Athens, Greece
Stylianos Chatzipanagiotou
Department of Medical Biopathology, Medical School, University of Athens, Eginition Hospital, 11528 Athens, Greece
Dido Vassilacopoulou
Section of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15772 Athens, Greece
Alice G. Vassiliou
GP Livanos and M Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services, National and Kapodistrian University of Athens Medical School, Evangelismos Hospital, 10676 Athens, Greece
Emmanouil Angelakis
Department of Diagnostics, Hellenic Pasteur Institute, Athens 11521, Greece
Niki Vassilaki
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection (ACE2, dACE2, EPO), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.
