Metabolic Signatures of Pulmonary Embolism in COVID-19: Insights from Longitudinal Intensive Care Unit Profiles

Background Pulmonary embolism is a severe complication of COVID-19 infection, associated with a hypercoagulable state and heightened risk of blood clots. As SARS-CoV-2 has become endemic, understanding pulmonary embolism’s metabolic effects in COVID-19 patients is warranted. This study investigated the longitudinal metabolic profiles of 66 Intensive Care Unit-admitted COVID-19 patients at Erasmus Medical Center to identify metabolites and mechanisms associated with pulmonary embolism.

A total of 1209 metabolic species were measured, including amines and lipids. Metabolic changes were analysed across four timeframes: i) general analysis of pulmonary embolism, ii) 72 hours prior to pulmonary embolism, iii) 48 hours prior and the day of pulmonary embolism, and iv) the day of and 48 hours post-pulmonary embolism.

The general analysis revealed significant upregulation of amines, triglycerides, phosphatidylethanolamines, ether-linked phosphatidylethanolamines, and eicosanoids in patients who developed a pulmonary embolism. Phosphatidylethanolamines containing the 20:3 fatty acid side chain were notably elevated. Minimal metabolic dysregulation was observed 72 hours before pulmonary embolism, with subtle increases in lysophosphatidylcholines and lysophosphatidylethanolamines. In contrast, there was a strong metabolic response during and post-pulmonary embolism, phosphatidylethanolamines (47%), ether-linked phosphatidylethanolamines(96%) and sphingosines(40%).

These findings underscore the critical role of lipid metabolism in pulmonary embolism, particularly triglycerides and specific lipid species. The limited metabolic perturbations before pulmonary embolism suggest early prediction challenges, emphasising the need for further research into temporal metabolic changes and their clinical applications. Competing Interest Statement The authors have declared no competing interest. ABBREVIATIONS - -O - alkyl substituent - -P - alkenyl substituent - 11,12-DiHETrE - 11,12-dihydroxy-5Z,8Z,14Z-eicosatrienoic acid - 13-HODE - Coriolic acid - 14,15-DiHETE - (+/-)-14,15-dihydroxy-5Z,8Z,11Z,17Z-eicosatetraenoic acid - 15-HETE - 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid - 15-HETRrE - 15S-hydroxy-8Z,11Z,13E-eicosatrienoic acid - 9,10-DiHoME - 9,10-dihydroxy-12Z-octadecenoic acid - 9-HOTrE - 9S-hydroxy-10E,12Z,15Z-octadecatrienoic acid - CE - Cholesterol esters - Cer - Ceramides - COVID-19 - Coronavirus Disease 2019 - DCER - Dihydroceramides - DG - Diacyclglycerols - EDTA - ethylenediaminetetraacetic acid - FA - Free fatty acids - GluCer - Glucoceramides - LacCer - Lactosylceramides - LC-MS - Liquid Chromatography–Mass Spectrometry - LPA - Lysophosphatidic acids - LPC - Lysophosphatidylcholines - LPE - Lysophosphatidylethanolamines - LPG - Lysophosphatidylglycerols - LPI - Lysophosphatidylinositols - LPS - Lysophosphatidylserines - PC - Phosphatidylcholines - PE - Phosphatidylethanolamines - PG - Phosphatidylglycerols - PI - Phosphatidylinositols - PS - Phosphatidylserines - SARS-CoV-2 - Severe Acute Respiratory Syndrome Coronavirus 2 - serotinin/Trp - serotonin to tryptophan ratio - SM - Sphingomyelins - SP - Sphingosine - TG - Triglycerides - Trp/LNAA - Tryptophan to Large Neutral Amino Acids ratio