Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies

The COVID-19 pandemic caused by SARS-CoV-2 is exerting huge pressure on global healthcare. Understanding of the molecular pathophysiological alterations in COVID-19 patients with different severities during disease is important for effective treatment. In this study, we performed proteomic profiling of 181 serum samples collected at multiple time points from 79 COVID-19 patients with different severity levels (asymptomatic, mild, moderate, and severe/critical) and 27 serum samples from non-COVID-19 control individuals. Dysregulation of immune response and metabolic reprogramming was found in severe/critical COVID-19 patients compared with non-severe/critical patients, whereas asymptomatic patients presented an effective immune response compared with symptomatic COVID-19 patients. Interestingly, the moderate COVID-19 patients were mainly grouped into two distinct clusters using hierarchical cluster analysis, which demonstrates the molecular pathophysiological heterogeneity in COVID-19 patients. Analysis of protein-level alterations during disease progression revealed that proteins involved in complement activation, the coagulation cascade and cholesterol metabolism were restored at the convalescence stage, but the levels of some proteins, such as anti-angiogenesis protein PLGLB1, would not recovered. The higher serum level of PLGLB1 in COVID-19 patients than in control groups was further confirmed by parallel reaction monitoring (PRM). These findings expand our understanding of the pathogenesis and progression of COVID-19 and provide insight into the discovery of potential therapeutic targets and serum biomarkers worth further validation.