Establishment of a rapid diagnosis assay for SARS-CoV-2 infection based on MALDI-TOF MS

  Objective  To establish a rapid, high-throughput detection assay of serum peptidome profiling for the diagnosis of SARS-CoV-2 infection based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).

  Methods  MALDI-TOF MS-ClinProTools system was used to construct a genetic algorithm (GA)-based classification model to diagnose SARS-CoV-2 infection in this study. In total, 647 serum samples (228 positive ones, 419 negative ones) were used. Specifically, 160 serum samples (80 positive ones, 80 negative ones) were used for model construction and optimization, and 487 serum samples were used for model validation. Differential proteomics was used to analyze the differences in serum polypeptide between COVID-19 patients and non-COVID-19 patients.

  Results  For the GA screening model, the cross-validation values and the recognition capability values were 99.37% and 100.00%, respectively. Nineteen biomarker peptides were found. The identification accuracy of 487 samples (148 COVID-19 patients and 339 non-COVID-19 patients’ serum samples) was 98.00% (100.00% for positive samples, 96.00% for negative samples). Ninety-five significantly differentially regulated serum proteins were identified between the COVID-19 patients and non-COVID-19 patients by quantification analysis. The assay established in this study can detect 96 serum samples within 3 hours. Only 2 drops of finger blood can meet the detection requirements. The serum is inactivated before use, and there is no potential biosafety hazard. The operation can be carried out in the general molecular biology laboratory.

  Conclusion  This study established a new detection assay with great application potential for the screening and diagnosis of SARS-CoV-2 infection.