TY - JOUR
T1 - Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19
AU - Gama-Almeida, Marcos C.
AU - Pinto, Gabriela D. A.
AU - Teixeira, Lívia
AU - Hottz, Eugenio D.
AU - Ivens, Paula
AU - Ribeiro, Hygor
AU - Garrett, Rafael
AU - Torres, Alexandre G.
AU - Carneiro, Talita I. A.
AU - Barbalho, Bianca de O.
AU - Ludwig, Christian
AU - Struchiner, Claudio J.
AU - Assunção-Miranda, Iranaia
AU - Valente, Ana Paula C.
AU - Bozza, Fernando A.
AU - Bozza, Patrícia T.
AU - dos Santos, Gilson C.
AU - El-Bacha, Tatiana
PY - 2023/7/24
Y1 - 2023/7/24
N2 - Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients’ sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
AB - Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients’ sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
KW - SARS-CoV-2
KW - virus-host interactions
KW - metabolic alterations
KW - metabolomics
KW - fatal COVID-19
KW - 1H-NMR
KW - high-resolution mass spectrometry
KW - sex differences
U2 - 10.3390/metabo13070879
DO - 10.3390/metabo13070879
M3 - Article
SN - 2218-1989
VL - 13
JO - Metabolites
JF - Metabolites
IS - 7
M1 - 879
ER -