Moleküler Biyoloji-genetik ve Biyomühendislik Anabilim Dalı

Investigation of host proteome changes in plasma of COVID-19 Patients

The world has been under the influence of Coronavirus disease 2019 caused by the infection of Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) since December 2019. In this study, by employing an in-depth mass-spectrometry-based proteomics approach, we systematically analyzed the plasma proteome of COVID-19 patients. We aimed to define early severity biomarkers by monitoring different severity grades of COVID-19 patients (moderate, severe, and critical) and periods of infection (early infection, inflammatory response, and recovery). Our analysis identified 111 significantly deregulated plasma proteins out of the total 1147 identified plasma proteins in COVID-19 patients. Also, we checked how the patients are clustered according to their protein profile and concluded that critical patients' plasma proteome samples are intrinsically grouped as a different cluster than the severe and moderate ones. Intriguingly, while proteins identified as upregulated in the critical specific cluster are involved in the pathways of neutrophil degranulation and amyloid formation, the ones that are downregulated in the critical specific cluster play roles mainly in the hemostasis and lipid metabolism. By considering both phases of the COVID-19 and the disease severity grades, CLEC3B, MST1, and ITIH2 proteins are suggested as prognostic biomarkers that can be used in the early prediction of COVID-19 severity. Finally, by taking an integrative approach, we constructed a plasma protein network associated with COVID-19 disease. Besides, we showed the connectedness of the plasma protein network to the viral proteins and focused on the downstream pathways of ORF8 and NSP5 that provides insight into how virus-modulated signaling pathways lead to physiological changes.