Molecular fingerprint by omics-based approaches in saliva from patients affected by SARS-CoV-2 infection.

Clinical expression of coronavirus disease 2019 (COVID-19) infectionis widely variable including fatal cases and patients with mild symptoms and a rapid resolution. We studied saliva from 63 hospitalized COVID-19 patients and from 30 healthy controls by integrating large-scale proteomics, peptidomics and targeted metabolomics to assess the biochemical alterations following the infection and to obtain a set of putative biomarkers useful for noninvasive diagnosis. We used an untargeted approach by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomics and peptidomics analysis and targeted LC-multiple reaction monitoring/MS for the analysis of amino acids. The levels of 77 proteins were significantly different in COVID-19 patients. Among these, seven proteins were found only in saliva from patients with COVID-19, four were up-regulated and three were down-regulated at least five-folds in saliva from COVID-19 patients in comparison to controls. The analysis of proteins revealed a complex balance between pro-inflammatory and anti-inflammatory proteins and a reduced amount of several proteins with immune activity that possibly favours the spreading of the virus. Such reduction could be related to the enhanced activity of endopeptidases induced by the infection that in turn caused an altered balance of free peptides. In fact, on a total of 28 peptides, 22 (80%) were differently expressed in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and control subjects. The multivariate analysis of such peptides permits to obtain a diagnostic algorithm that discriminate the two populations with a high diagnostic efficiency. Among amino acids, only threonine resulted significantly different between COVID-19 patients and controls, while alanine levels were significantly different between COVID-19 patients with different severity. In conclusion, the present study defined a set of molecules to be detected with a quick and easy method based on mass spectrometry tandem useful to reveal biochemical alterations involved in the pathogenesis of such a complex disease. Data are available via ProteomeXchange with identifier PXD045612.

Pinto G ，Gelzo M ，Cernera G ，Esposito M ，Illiano A ，Serpico S ，Pinchera B ，Gentile I ，Castaldo G ，Amoresano A ... -  《-》

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19.

Costanzo M ，Caterino M ，Fedele R ，Cevenini A ，Pontillo M ，Barra L ，Ruoppolo M ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

A rapid and reliable liquid chromatography/mass spectrometry method for SARS-CoV-2 analysis from gargle solutions and saliva.

We describe a rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the direct detection and quantitation of SARS-CoV-2 nucleoprotein in gargle solutions and saliva. The method is based on a multiple-reaction monitoring (MRM) mass spectrometry approach with a total cycle time of 5 min per analysis and allows the detection and accurate quantitation of SARS-CoV-2 nucleoprotein as low as 500 amol/μL. We improved the sample preparation protocol of our recent piloting SARS-CoV-2 LC-MS study regarding sensitivity, reproducibility, and compatibility with a complementary reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis of the same sample. The aim of this work is to promote diagnostic tools that allow identifying and monitoring SARS-CoV-2 infections by LC-MS/MS methods in a routine clinical environment.

Kipping M ，Tänzler D ，Sinz A 《-》

Saliva metabolomic profile of COVID-19 patients associates with disease severity.

Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages. This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients. LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities. Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine. Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.

Saheb Sharif-Askari N ，Soares NC ，Mohamed HA ，Saheb Sharif-Askari F ，Alsayed HAH ，Al-Hroub H ，Salameh L ，Osman RS ，Mahboub B ，Hamid Q ，Semreen MH ，Halwani R ... -  《-》

A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test.

Lane D ，Allsopp R ，Holmes CW ，Slingsby OC ，Jukes-Jones R ，Bird P ，Anderson NL ，Razavi M ，Yip R ，Pearson TW ，Pope M ，Khunti K ，Doykov I ，Hällqvist J ，Mills K ，Skipp P ，Carling R ，Ng L ，Shaw J ，Gupta P ，Jones DJL ... -  《-》