Quantitative plasma proteomics of survivor and non-survivor COVID-19 patients admitted to hospital unravels potential prognostic biomarkers and therapeutic targets

Abstract

The development of new approaches that allow early assessment of which cases of COVID-19 will likely become critical and the discovery of new therapeutic targets are urgent demands. In this cohort study, we performed proteomic and laboratorial profiling of plasma from 163 patients admitted to Bauru State Hospital (Bauru, SP, Brazil) between May 4th and July 4th, 2020, who were diagnosed with COVID-19 by RT-PCR nasopharyngeal swab samples. Plasma samples were collected upon admission for routine laboratory analyses and shotgun quantitative label-free proteomics. Based on the course of the disease, the patients were further divided into 3 groups: a) mild symptoms, discharged without admission to an intensive care unit (ICU) (n=76); b) severe symptoms, discharged after admission to an ICU (n=56); c) critical, died after admission to an ICU (n=31). White cells and neutrophils were significantly higher in severe and critical patients compared to mild ones. Lymphocytes were significantly lower in critical patients compared to mild ones and platelets were significantly lower in critical patients compared to mild and severe ones. Ferritin, TGO, urea and creatinine were significantly higher in critical patients compared to mild and severe ones. Albumin, CPK, LDH and D-dimer were significantly higher in severe and critical patients compared to mild ones. PCR was significantly higher in severe patients compared to mild ones. Proteomic analysis revealed marked changes between the groups in plasma proteins related to complement activation, blood coagulation, antimicrobial humoral response, acute inflammatory response, and endopeptidase inhibitor activity. Higher levels of IREB2, GELS, POLR3D, PON1 and ULBP6 upon admission to hospital were found in patients with mild symptoms, while higher levels of Gal-10 were found in critical and severe patients. This needs to be validated in further studies. If confirmed, pathways involving these proteins might be potential new therapeutic targets for COVID-19.

Mass spectrometry applied to diagnosis, prognosis, and therapeutic targets identification for the novel coronavirus SARS-CoV-2: A review

“…In this context, the high use of blood samples and their derivatives in research is notorious. As examples of this statement, three distinct studies stand out as they present important results using LC-MS-based methods for proteomics of blood serum and plasma and peripheral blood mononuclear cells (PBMCs) [ 32 , 70 , 71 ].…”

“…Aiming at identifying potential protein markers present in blood samples from infected, recovered, and deceased patients, seven proteins with potential biomarker application in the prognosis of the disease, which is directly associated with the immune response and cytokine storm, were observed as well [ 71 ]. When comparing three groups of patients (infected, recovered, and deceased), the researchers obtained similar results to the other studies using the same type of sample, where dysregulation was observed in the levels of the proteins IREB2, GELS, POLR3D, PON1, STFPD, ULBP6, SAA1, SAA2, and S-TREM.…”