Abstract
COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.
Highlights
COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention
Several studies reported symptoms and comorbidities associated with severe COVID-19 complications; early prognostic tools to stratify the risk of developing complications are imperative
We used proteomic panel-profiling of plasma from patients with severe complications versus mildmoderate symptoms and control subjects to characterize biological processes and pathways associated with disease pathogenesis and severity
Summary
COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Several studies reported symptoms and comorbidities associated with severe COVID-19 complications; early prognostic tools to stratify the risk of developing complications are imperative. We hypothesized that changes in plasma proteins offer prognostic molecular profiles and can help identify the most informative clinical features presented at admission, which can predict the risk of developing complications. We used proteomic panel-profiling of plasma from patients with severe complications versus mildmoderate symptoms and control subjects to characterize biological processes and pathways associated with disease pathogenesis and severity. We evaluated the plasma proteins and associated routine clinical tests in an independent cohort and examined candidate FDA-approved drugs targeting multiple upregulated proteins and based on biological pathways specific for patients with severe complications
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