Diagnostic screening of COVID-19 based on multiomics data by high-resolution mass spectrometry (MALDI (+)-TOF MS and ESI(±)-Orbitrap MS)

Abstract

Introduction: The urgency for rapid diagnostics during the COVID-19 pandemic in 2020 highlighted the importance of effective methods such as RT-PCR, however multiomics analyses offer a more comprehensive approach, going beyond simple viral detection to the biological understanding of the disease.

Objective: this study aimed to devise an effective multiomic method for differentiating SARS-CoV-2-infected patients, leveraging serum lipid and proteomic profiles.

Method: Electrospray ionization mass spectrometry (ESI-MS) with an Orbitrap analyzer was used to investigate the lipid profile of 239 serum samples (119 positive and 120 negative for test ELISA for COVID-19). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to analyze the proteomic profile of 300 serum samples (150 positive and 150 negative for test ELISA for SARS-CoV-2). After processing MS data and selecting variables, statistical analyses such as the Volcano plot, Heatmap, Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Support Vector Machine (SVM) were performed to distinguish the most relevant variables to classify samples that presented or did not present antibodies for SARS-CoV-2.

Results: Lipidomics analysis using ESI(±)-Orbitrap MS and SVM models, showed sensitivities of 96.67% and 100%, specificities of 82.14% and 96.88%, and accuracies of 89.66% and 98.44% for positive and negative ion mode analyses, respectively. For Proteomics analyses using MALDI(+)-TOF MS, the linear PLS-DA model demonstrated an accuracy of 99.10%.

Conclusion: both ESI-Orbitrap MS and MALDI-TOF MS techniques, combined with chemometrics, demonstrated promising alternatives with high sensitivity and specificity for distinguishing the immune response. However, the investigation of the lipid profile by direct infusion ESI MS represents a valuable and efficient approach that reinforces the application of mass spectrometry in clinical diagnostics, particularly when aiming for high-throughput and minimally invasive analysis.

Keywords: COVID-19; Chemometric; ESI-Orbitrap MS; MALDI-TOF MS; Mass spectrometry.