Longitudinal <sup>1</sup>H NMR-Based Metabolomics in Saliva Unveils Signatures of Transition from Acute to Post-Acute Phase of SARS-CoV-2 Infection
Luiza Tomé Mendes,
Marcos C. Gama-Almeida,
Desirée Lopes Reis,
Ana Carolina Pires e Silva,
Rômulo Leão Silva Neris,
Rafael Mello Galliez,
Terezinha Marta Pereira Pinto Castiñeiras,
on behalf of the UFRJ COVID-19 Working Group,
Christian Ludwig,
Ana Paula Valente,
Gilson Costa dos Santos Junior,
Tatiana El-Bacha,
Iranaia Assunção-Miranda
Affiliations
Luiza Tomé Mendes
LaRIV-Laboratory of Cellular Response to Viral Infections, Instituto de Microbiologia Paulo de Góes, Departamento de Virologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Marcos C. Gama-Almeida
LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Desirée Lopes Reis
LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Ana Carolina Pires e Silva
LaRIV-Laboratory of Cellular Response to Viral Infections, Instituto de Microbiologia Paulo de Góes, Departamento de Virologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Rômulo Leão Silva Neris
LaRIV-Laboratory of Cellular Response to Viral Infections, Instituto de Microbiologia Paulo de Góes, Departamento de Virologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Rafael Mello Galliez
Núcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-599, Brazil
Terezinha Marta Pereira Pinto Castiñeiras
Núcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-599, Brazil
on behalf of the UFRJ COVID-19 Working Group
Christian Ludwig
Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK
Ana Paula Valente
National Center for Nuclear Magnetic Resonance—Jiri Jonas, Institute of Medical Biochemistry, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Gilson Costa dos Santos Junior
LabMet-Laboratory of Metabolomics, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Tatiana El-Bacha
LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Iranaia Assunção-Miranda
LaRIV-Laboratory of Cellular Response to Viral Infections, Instituto de Microbiologia Paulo de Góes, Departamento de Virologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a 1H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH3)3 choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.
