Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients

Abstract

This study aimed to understand the pathophysiology of host responses to infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) and Middle East respiratory syndrome coronavirus (MERS-CoV) and to identify proteins for patient stratification with different grades of illness severity. Patients and Methods: Peripheral blood samples from 43 patients with different grades of COVID-19, 7 MERS-CoV patients admitted to the ICU, and 10 healthy subjects were analyzed using label-free quantitative liquid chromatography-mass spectrometry (LC-MS). Results: We identified 193 and 91 proteins that differed significantly between COVID-19 and MERS-CoV sample groups, respectively, and 49 overlapped between datasets. Only 10 proteins are diagnostic of asymptomatic cases, 12 are prognostic of recovery from severe illness, and 28 are prognostic of a fatal outcome of COVID-19. These proteins are implicated in virus-specific/related signaling networks. Notable among the top canonical pathways are humoral immunity, inflammation, acute-phase response signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, coagulation, and the complement system. Furthermore, we confirmed positive viral shedding in 11.76% of 51 additional peripheral blood samples, indicating that caution should be taken to avoid the possible risk of transfusion of infected blood products. Conclusion:We identified COVID-19 and MERS-CoV protein panels that have potential as biomarkers and might assist in the prognosis of SARS-CoV-2 infection. The identified markers further our understanding of COVID-19 disease pathophysiology and may have prognostic or therapeutic potential in predicting or managing host cell responses to human COVID-19 and MERS-CoV infections.

A meta-summary and bioinformatic analysis identified interleukin 6 as a master regulator of COVID-19 severity biomarkers

“…More recent studies of Alaiya et al (2021), Mardani et al (2022), and Tahery et al (2021) showed an elevated levels of CRP alongside other biomarkers in severe vs asymptomatic COVID-19 comparison groups, suggesting the plausibility of CRP as a severity and mortality marker for SARS-CoV-2 infection [50] , [51] , [52] .…”

Saliva changes in composition associated to COVID-19: a preliminary study

“…In this preliminary study, we describe, for the first time, the salivary proteome variations that can be observed in patients with COVID-19. The study of alterations in the plasma proteome of COVID-19 patients has been recently explored with the identification of some proteins that may act as promising biomarkers for the disease physiopathology 15 . Saliva is easier to collect than serum and can be a source of biomarkers for clinical use in COVID-19 4 .…”

Proteomic insights into SARS-CoV-2 infection mechanisms, diagnosis, therapies and prognostic monitoring methods

“…Alaiya et al. ( 66 ) provided a method to objectively predict disease outcome in severe COVID-19 patients using LC−MS/MS for identifying and quantifying proteomic expression in different degrees of COVID-19 peripheral blood samples from patients. They identified 49 differentially expressed proteins that were upregulated in the peripheral blood of critically ill patients; 9 of them were upregulated in asymptomatic patients, and 12 of them had predictive value for recovery from severe disease.…”