Multi-Omics Analysis of Respiratory Specimen Characterizes Baseline Molecular Determinants Associated with COVID-19 Diagnosis and Outcome

Rapid diagnosis and outcome prediction of SARS-CoV-2 infection remains a major challenge. A multi-omic approach was adopted, and in the discovery phase, respiratory specimens of 20 SARS-CoV-2 positive, 20 negative and 5 H1N1 positive cases were subjected to global proteomics, metaproteomics and metabolomics. We identified MX1 (MX Dynamin like GTPase 1) and WARS (Tryptophan--tRNA ligase) as clues to viral diagnosis and outcome which was validated in 200 SARS-CoV-2 suspects. MX1>30pg/ml and WARS>25ng/ml distinctly segregated virus positives [AUC=94%CI(0.91-0.97)], severe and symptomatic patients [AUC>0.85%]. SARS-CoV-2 infection mediated a distinct increase in immune activation, metabolic reprograming and decrease in oxygen transport, wound healing, vitamin and steroid metabolism. Multi-omics profiling correlated with viraemia and segregated asymptomatic COVID-19 patients. Additionally, we identified increased respiratory pathogens [Burkholderiales, Klebsiella-pneumonia] and decreased lactobacillus salivarius (FDR<0.05) in COVID-19 specimens. Conclusion: Baseline levels of MX1 and WARS can reliably diagnose SARS-CoV-2 infection and identify patient’s predisposed to higher severity. FundIng: The work was supported from project DST (DST-SERB) (EMR/2016/004829). Conflict of Interest: All authors have declared no conflict of interest.