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COVID-19 is characterized by lung infection with potential progressive organ failure. The systemic consequences of both disease on the systemic blood metabolome are not fully understood. The aim of this study was to compare the blood metabolome of both diseases and we hypothesize that plasma metabolomics may help to identify the systemic effects of these diseases. Therefore, we profiled the plasma metabolome of 43 cases of COVID-19 pneumonia, 23 cases of non-COVID-19 pneumonia, and 26 controls using a non-targeted approach. Metabolic alterations differentiating the three groups were detected, with specific metabolic changes distinguishing the two types of pneumonia groups. A comparison of venous and arterial blood plasma samples from the same subjects revealed the distinct metabolic effects of pulmonary pneumonia. In addition, a machine learning signature of four metabolites was predictive of the disease outcome of COVID-19 subjects with an area under the curve (AUC) of 86 \u00b1 10%. Overall, the results of this study uncover systemic metabolic changes that could be linked to the etiology of COVID-19 pneumonia and non-COVID-19 pneumonia.<\/jats:p>","DOI":"10.3390\/metabo12111058","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:53:07Z","timestamp":1667447587000},"page":"1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Plasma Metabolome Alterations Discriminate between COVID-19 and Non-COVID-19 Pneumonia"],"prefix":"10.3390","volume":"12","author":[{"given":"Tushar H.","family":"More","sequence":"first","affiliation":[{"name":"Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universit\u00e4t Braunschweig, 38106 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahareh","family":"Mozafari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8243-3285","authenticated-orcid":false,"given":"Andre","family":"M\u00e4rtens","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universit\u00e4t Braunschweig, 38106 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-0912","authenticated-orcid":false,"given":"Philipp M.","family":"Lepper","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Danziger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5175-7159","authenticated-orcid":false,"given":"Thomas","family":"Volk","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Hoersch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-0777","authenticated-orcid":false,"given":"Marcin","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Gastroenterology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Guenther","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Hiller","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universit\u00e4t Braunschweig, 38106 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Bals","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany"},{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University Campus, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.7861\/clinmed.2019-coron","article-title":"What We Know so Far: COVID-19 Current Clinical Knowledge and Research","volume":"20","author":"Lake","year":"2020","journal-title":"Clin. 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