Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Collection and Processing of Saliva Samples for Untargeted Metabolomics
2.3. Data Preprocessing and Quality Control
2.4. Statistical Analysis, Variable Selection, and Performance Assessment
2.5. Data Availability
3. Results
3.1. The Composition of Saliva Metabolites Clearly Distinguished the Clinical Groups
3.2. Amino Acid Metabolites Were Strongly Associated with Moderate COVID Cases and Bacterial Metabolites Were Srongly Associated with Severe Cases
3.3. Some Metabolites Distinguish Deceased from Severe-Hospitalized Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Group | Number of Cases | Description |
---|---|---|
Asymptomatic cases (ACs) | 30 | Asymptomatic cases, negative for SARS-CoV-2 infection |
Ambulatory patients (APs) | 102 | Ambulatory patients, PCR+ for SARS-CoV-2 |
Hospitalized patients (HPs) | 61 | Patients that required hospitalization because of severe symptoms, PCR+ for SARS-CoV-2 |
Total studied | 210 |
Microbial | Human | Environment | Drugs | |
---|---|---|---|---|
AC vs. AP | N-Methylisoleucine | N-Acetylserine | Val-Glu | S-Adenosyl-methionine |
Indole-3-carboxaldehyde | N-Methylserine | Ser-Pro-Arg | N,N Diethyl-2-aminoethanol | |
Muramic acid | gamma-aminobutyric acid | Serine | DMSO | |
Guanidine | Phenylalanine | Isradipine | ||
Inositol | Tyrosine | |||
L-Homocitrulline | Gluconolactone | Xanthine | ||
N-Acetylhistidine | 1,4-Cyclohexanedicarboxylic acid | Mannitol | ||
Met-Gln | Fluorene | Cefdinir | ||
Arachidonyl dopamine | Tryptophan | Benzphetamine | ||
Acetylenedicarboxylic acid | 2-Amino-4-tert-butylphenol | |||
Uridine diphosphate galactose | ||||
Glyceraldehyde | ||||
4-Pyridoxic acid | ||||
AC vs. HP | Pantothenic acid | N8-Acetylspermidine | Theobromine | Acetaminophen sulfate |
1-(2-Hydroxyethyl)-2,2,6,6-tetramethyl-4-piperidinol | 3-Methylcytidine | Theophylline | Ornidazole | |
Indole-3-carboxaldehyde | 1,7 Dimethyluric acid | Caffeine | Xanthine | |
N-Acetylneuraminic acid | Aconitic acid | Cefdinir | ||
N-Cinnamoylglycine | Dehydroisoandrosterone sulfate | Diethanolamine | ||
Oxypurinol | 1,4-Cyclohexanedicarboxylic acid | |||
N-Acetylhistidine | Ferulic acid | |||
Targinine | Catechol | |||
Uracil | ||||
5,6-Dihydrouracil | ||||
Uric acid | ||||
AP vs. HP | Muramic acid | N1-Acetylspermine | Ser-Pro-Arg | S-Adenosyl-methionine |
2-Amino-1-phenylethanol | 8-Oxo-2-deoxyadenosine | Met-Gln | DMSO | |
Allantoic acid | N-Methylisoleucine | Val-Glu | Cefdinir | |
3-Hydroxyanthranilic acid | Acetylenedicarboxylic acid | Phenylalanine | Benzphetamine | |
N8-Acetylspermidine | PyroGlu-Pro | Mannitol | ||
N-Methylserine | Tyrosine | Methotrexate | ||
Serine | Phenylacetaldehyde isomer | Isradipine | ||
Porphobilinogen | Gluconolactone | |||
3-Methylcytidine | Theobromine | |||
Diethyloxalpropionate | Theophylline | |||
N-Acetylserine | ||||
Uridine diphosphate galactose | Fluorene | |||
Cytidine 5′-diphosphocholine | 2-Amino-4-tert-butylphenol | |||
Pipecolic acid | ||||
Melamine | ||||
Valine |
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Larios-Serrato, V.; Vázquez-Manjarrez, N.; Resendis-Antonio, O.; Rios-Sarabia, N.; Meza, B.; Fiehn, O.; Torres, J. Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity. Metabolites 2025, 15, 192. https://doi.org/10.3390/metabo15030192
Larios-Serrato V, Vázquez-Manjarrez N, Resendis-Antonio O, Rios-Sarabia N, Meza B, Fiehn O, Torres J. Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity. Metabolites. 2025; 15(3):192. https://doi.org/10.3390/metabo15030192
Chicago/Turabian StyleLarios-Serrato, Violeta, Natalia Vázquez-Manjarrez, Osbaldo Resendis-Antonio, Nora Rios-Sarabia, Beatriz Meza, Oliver Fiehn, and Javier Torres. 2025. "Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity" Metabolites 15, no. 3: 192. https://doi.org/10.3390/metabo15030192
APA StyleLarios-Serrato, V., Vázquez-Manjarrez, N., Resendis-Antonio, O., Rios-Sarabia, N., Meza, B., Fiehn, O., & Torres, J. (2025). Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity. Metabolites, 15(3), 192. https://doi.org/10.3390/metabo15030192