Mitochondrial dysfunction, lipids metabolism, and amino acid biosynthesis are key pathways for COVID-19 recovery

Alba Sánchez; Graciano García-Pardo; Fréderic Gómez-Bertomeu; Miguel López-Dupla; Elisabet Foguet-Romero; Maria José Buzón; Benito Almirante; Montserrat Olona; Sonia Fernández-Veledo; Francesc Vidal; Silvia Chafino; Anna Rull; Joaquim Peraire; COVIDOMICS Study Group

doi:10.1016/j.isci.2023.107948

Mitochondrial dysfunction, lipids metabolism, and amino acid biosynthesis are key pathways for COVID-19 recovery

iScience. 2023 Sep 19;26(10):107948. doi: 10.1016/j.isci.2023.107948. eCollection 2023 Oct 20.

Authors

Alba Sánchez^{1

2}, Graciano García-Pardo^{1

2

3

4}, Fréderic Gómez-Bertomeu^{1

2

3

4}, Miguel López-Dupla^{1

2

3

4}, Elisabet Foguet-Romero⁵, Maria José Buzón^{6

7}, Benito Almirante^{3

6}, Montserrat Olona^{1

2

3

4}, Sonia Fernández-Veledo^{1

2

4

8}, Francesc Vidal^{1

2

3

4}, Silvia Chafino^{1

2

3}, Anna Rull^{1

2

3

4}, Joaquim Peraire^{1

2

3

4}; COVIDOMICS Study Group

Affiliations

¹ Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
² Hospital Universitari de Tarragona Joan XXIII (HJ23), Tarragona, Spain.
³ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
⁴ Universitat Rovira i Virgili (URV), Tarragona, Spain.
⁵ Eurecat, Centre Tecnologic de Catalunya, Centre for Omic Sciences (Joint Unit Eurecat - Universitat Rovira i Virgili), Unique Scientific and Technical Infrastructure (ICTS), Reus, Spain.
⁶ Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁷ Infectious Diseases Department, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, (VHIR) Task Force COVID-19, Barcelona, Spain.
⁸ Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

The metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.

Keywords: Biological sciences; Human metabolism.