Jalaleddine, NourHachim, Mahmood YaseenSenok, AbiolaKandasamy, Richard KAl Heialy, Saba2023-03-302023-03-302022204-2022.65https://repository.mbru.ac.ae/handle/1/1111Abstract: Despite the growing number of the vaccinated population, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global health burden. Obesity, a metabolic syndrome affecting one-third of the population, has proven to be a major risk factor for COVID-19 severe complications. Several studies have identified metabolic signatures and disrupted metabolic pathways associated with COVID-19, however there are no reports evaluating the role of obesity in the COVID-19 metabolic regulation. In this study we highlight the involvement of obesity metabolically in affecting SARS-CoV-2 infection and the consequent health complications, mainly cardiovascular disease. We measured one hundred and forty-four (144) metabolites using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to identify metabolic changes in response to SARSCoV-2 infection, in lean and obese COVID-19 positive (n=82) and COVID-19 negative (n=24) patients. The identified metabolites are found to be mainly correlating with glucose, energy and steroid metabolisms. Further data analysis indicated twelve (12) significantly yet differentially abundant metabolites associated with viral infection and health complications, in COVID-19 obese patients. Two of the detected metabolites, n6- acetyl-l-lysine and p-cresol, are detected only among the COVID-19 cohort, exhibiting significantly higher levels in COVID-19 obese patients when compared to COVID-19 lean patients. These metabolites have important roles in viral entry and could explain the increased susceptibility of obese patients. On the same note, a set of six metabolites associated with antiviral and anti-inflammatory functions displayed significantly lower abundance in COVID-19 obese patients. In conclusion, this report highlights the plasma metabolome of COVID-19 obese patients as a metabolic feature and signature Frontiers in Immunology | www.frontiersin.org 1 May 2022 | Volume 13 | Article 827603 Edited by: Shailendra Saxena, King George’s Medical University, India Reviewed by: Shetty Ravi Dyavar, Adicet Bio, Inc,. United States Jatin P. Machhi, University of Nebraska Medical Center, United States *Correspondence: Saba Al Heialy Saba.Alheialy@mbru.ac.ae Nelson C. Soares nsoares@sharjah.ac.ae Specialty section: This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology Received: 21 January 2022 Accepted: 20 April 2022 Published: 19 May 2022 Citation: Jalaleddine N, Hachim M, Al-Hroub H, Saheb Sharif-Askari N, Senok A, Elmoselhi A, Mahboub B, Samuel Kurien NM, Kandasamy RK, Semreen MH, Halwani R, Soares NC and Al Heialy S (2022) N6-Acetyl-LLysine and p-Cresol as Key Metabolites in the Pathogenesis of COVID-19 in Obese Patients. Front. Immunol. 13:827603. doi: 10.3389/fimmu.2022.827603 ORIGINAL RESEARCH published: 19 May 2022 doi: 10.3389/fimmu.2022.827603 to help improve clinical outcomes. We propose n6-acetyl-l-lysine and p-cresol as potential metabolic markers which warrant further investigations to better understand their involvement in different metabolic pathways in COVID-19.enSARS-CoV-2COVID-19ObesityMetabolomicsUltra-high-performanceliquidchromatography-mass spectrometryArticle