Machine Learning of Serum Metabolic Patterns Encodes Asymptomatic SARS-CoV-2 Infection

Asymptomatic COVID-19 has become one of the biggest challenges for controlling the spread of the SARS-CoV-2. Diagnosis of asymptomatic COVID-19 mainly depends on quantitative reverse transcription PCR (qRT-PCR), which is typically time-consuming and requires expensive reagents. The application is limited in countries that lack sufficient resources to handle large-scale assay during the COVID-19 outbreak. Here, we demonstrated a new approach to detect the asymptomatic SARS-CoV-2 infection using serum metabolic patterns combined with ensemble learning. The direct patterns of metabolites and lipids were extracted by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) within 1 s with simple sample preparation. A new ensemble learning model was developed using stacking strategy with a new voting algorithm. This approach was validated in a large cohort of 274 samples (92 asymptomatic COVID-19 and 182 healthy control), and provided the high accuracy of 93.4%, with only 5% false negative and 7% false positive rates. We also identified a biomarker panel of ten metabolites and lipids, as well as the altered metabolic pathways during asymptomatic SARS-CoV-2 Infection. The proposed rapid and low-cost approach holds promise to apply in the large-scale asymptomatic COVID-19 screening.