In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over ten million patients worldwide. Although most coronavirus disease 2019 (COVID-19) patients have a good prognosis, some develop severe illness. Markers that define disease severity or predict clinical outcome need to be urgently developed as the mortality rate in critical cases is approximately 61.5%. In the present study, we performed in-depth proteome profiling of undepleted plasma from eight COVID-19 patients. Quantitative proteomic analysis using the BoxCar method revealed that 91 out of 1,222 quantified proteins were differentially expressed depending on the severity of COVID-19. Importantly, we found 76 proteins, previously not reported, which could be novel prognostic biomarker candidates. Our plasma proteome signatures captured the host response to SARS-CoV-2 infection, thereby highlighting the role of neutrophil activation, complement activation, platelet function, and T cell suppression as well as proinflammatory factors upstream and downstream of interleukin-6, interleukin-1B, and tumor necrosis factor. Consequently, this study supports the development of blood biomarkers and potential therapeutic targets to aid clinical decision-making and subsequently improve prognosis of COVID-19.

Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity

“…Similarly, proteomic and metabolomics profiling of serum samples obtained from 46 COVID-19 and 53 control individuals showed deregulation of three major pathways namely complement system, macrophage function and platelet degranulation in severe COVID-19 patients [47]. Study by Park J et al, employed an in-depth proteome profiling of undepleted plasma revealed signatures of proteins involved in neutrophil activation, platelet function, and T cell suppression [3]. Based on the findings, this study's investigators have proposed specific plasma proteins as predictive biomarkers of COVID-19 [3].…”

“…Study by Park J et al, employed an in-depth proteome profiling of undepleted plasma revealed signatures of proteins involved in neutrophil activation, platelet function, and T cell suppression [3]. Based on the findings, this study's investigators have proposed specific plasma proteins as predictive biomarkers of COVID-19 [3]. In a different study, proteomic analysis of serum samples from early COVID-19 patients also identified differentially expressed proteins known to have a function in SARS-CoV-2 infection-associated inflammation and immune signaling [4].…”

Effect of SARS-CoV-2 proteins on vascular permeability

“…On the other hand, some studies suggest that SARS-CoV-2 can be found in the blood, and can induce the disease and cause both cellular and systemic dysfunction 36,42,46 . While this question is beyond the scope of this work, it is important to note that if future studies do identify the active form of SARS-CoV-2 in human blood, then the implications of our findings will apply to this systemic response as well 47,48 .…”

Identifying Transcriptomic Signatures and Rules for SARS-CoV-2 Infection

“…Both have been confirmed to be expressed in upper airway tissues ( Fink et al, 2013 ; Clifford et al, 2016 ). As for their respective capacities for distinguishing upper airway samples from different subjects under various pathological conditions, LAGLS3BP has a specific expression level following the activation of neutrophil-mediated immune responses, which is generally observed during viral infections ( Andres-Terre et al, 2015 ; Xu et al, 2019 ) including but not restricted to SARS-CoV-2 infection ( Didangelos, 2020 ; Park et al, 2020 ). Therefore, LAGLS3BP may also help in distinguishing samples from disease controls and those from patients with viral infection but not the detailed subgrouping of infections.…”