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1.
J Mol Med (Berl) ; 100(4): 555-568, 2022 04.
Article in English | MEDLINE | ID: covidwho-1653411

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic is overwhelming the healthcare systems. Identification of systemic reactions underlying COVID-19 will lead to new biomarkers and therapeutic targets for monitoring and early intervention in this viral infection. We performed targeted metabolomics covering up to 630 metabolites within several key metabolic pathways in plasma samples of 20 hospitalized COVID-19 patients and 37 matched controls. Plasma metabolic signatures specifically differentiated severe COVID-19 from control patients. The identified metabolic signatures indicated distinct alterations in both lipid and amino acid metabolisms in COVID-19 compared to control patient plasma. Systems biology-based analyses identified sphingolipid, tryptophan, tyrosine, glutamine, arginine, and arachidonic acid metabolism as mostly impacted pathways in COVID-19 patients. Notably, gamma-aminobutyric acid (GABA) was significantly reduced in COVID-19 patients and GABA plasma levels allowed for stratification of COVID-19 patients with high sensitivity and specificity. The data reveal large metabolic disturbances in COVID-19 patients and suggest use of GABA as potential biomarker and therapeutic target for the infection.


Subject(s)
COVID-19 , Biomarkers , Humans , Lipids , Metabolomics , Pandemics , Tryptophan
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296455

ABSTRACT

Obesity increases the risk for poor outcome in patients with coronavirus disease-19 (COVID-19). However, the role of adipose tissue for viral propagation and potential metabolic implications are not understood. We detected SARS-CoV-2 in adipose tissue of overweight but not lean male COVID-19 patients. SARS-CoV-2 replicates to high titres in cultured mature adipocytes, a process depending on lipid accumulation and mobilization. After intranasal inoculation, we observed high viral replication in fat depots of Golden Syrian hamsters, demonstrating dissemination from the respiratory tract and subsequent propagation in adipose tissue. Following induction of pro-inflammatory responses, expression of de novo lipogenesis enzymes was suppressed in adipose tissue. This specific down-regulation was reflected by lipidomic alterations in plasma of SARS-CoV-2 infected hamsters as well as in hospitalized COVID-19 patients. Overall, our study highlights that adipose tissue is an important site of SARS-CoV-2 replication, contributing to dysregulation of systemic lipid metabolism.<br><br>Funding: This study was supported by a rapid response grant from the Federal Ministry of Health (BMG;ZMV I 1-2520COR501 to GG), by DFG grants SCHE522/4-1 (LS) and SFB1328, project- ID:335447727 (JH). As part of the National Network University Medicine (NUM) funded by the Federal Ministry of Education and Research (BMBF, Germany), this work was funded within the research consortium DEFEAT PANDEMIcs, grant number 01KX2021 (FH, PL, KP, BO).<br><br>Declaration of Interests: The authors declare no competing interests.<br><br>Ethics Approval Statement: The Ethics Committee of the Hamburg Chamber of Physicians reviewed and approved the studies (PV7311, 2020-10353-BO-ff, WF-051/20, WF-053/20). For the preparation of primary human white adipocytes, biopsies of subcutaneous and visceral adipose tissues were taken during bariatric surgery at the Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf. All participants signed an informed consent and the study was approved by the Ethics Committee of the Hamburg Chamber of Physicians (PV4889).

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