Multi-omics analysis of respiratory specimen characterizes baseline molecular determinants associated with SARS-CoV-2 outcome

呼吸道标本的多组学分析表征了与 SARS-CoV-2 结果相关的基线分子决定因素

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作者:Jaswinder Singh Maras, Shvetank Sharma, Adil Bhat, Sheetalnath Rooge, Reshu Aggrawal, Ekta Gupta, Shiv K Sarin

Abstract

Rapid diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection still remains a major challenge. A multi-omic approach was adopted to analyze the respiratory specimens of 20 SARS-CoV-2-positive, 20 negative and 15 H1N1 pdm 2009 positive cases. Increased basal level of MX1 (MX dynamin-like GTPase 1) and WARS (tryptophan-tRNA ligase) correlated with SARS-CoV-2 infection and its outcome. These markers were further validated in 200 suspects. MX1>30pg/ml and WARS>25ng/ml segregated virus positives [AUC = 94% CI: (0.91-0.97)] and severe patients [AUC>0.85%]. Our results documented significant increase in immune activation; metabolic reprograming and decrease in oxygen transport, wound healing and others linked proteins and metabolites in patients with coronavirus disease 2019 (COVID-19). Multi-omics profiling correlated with viremia and segregated asymptomatic patients with COVID-19. Additionally, we identified increased respiratory pathogens (Burkholderiales, Klebsiella pneumonia) and decreased lactobacillus salivarius (FDR<0.05) in COVID-19 specimens. In conclusion, increased basal MX1 and WARS levels correlates with SARS-CoV-2 infection and could aid in the identification of patient's predisposed to higher severity.

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